Author Report for: Liu LNo contact information in database for Liu L
Li S, Teguh D, Wu D, Liu L, Hu C, Yuan J, Inderjeeth CA, Xu J Ref: Journal of Cellular Physiology, :, 2023 : PubMed ESTHER: Li_2023_J.Cell.Physiol__ PubMedSearch: Li 2023 J.Cell.Physiol PubMedID: 37334837 Abstract This study was designed to determine whether the use of acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate acetylcholine receptors and are used to treat Alzheimer's disease (AD), is associated with osteoporosis protection and inhibition of osteoclast differentiation and function. Firstly, we examined the effects of AChEIs on RANKL-induced osteoclast differentiation and function with osteoclastogenesis and bone resorption assays. Next, we investigated the impacts of AChEIs on RANKL-induced nuclear factor kappaB and NFATc1 activation and expression of osteoclast marker proteins CA-2, CTSK and NFATc1, and dissected the MAPK signaling in osteoclasts in vitro by using luciferase assay and Western blot. Finally, we assessed the in vivo efficacy of AChEIs using an ovariectomy-induced osteoporosis mouse model, which was analyzed using microcomputed tomography, in vivo osteoclast and osteoblast parameters were assessed using histomorphometry. We found that Donepezil and Rivastigmine inhibited RANKL-induced osteoclastogenesis and impaired osteoclastic bone resorption. Moreover, AChEIs reduced the RANKL-induced transcription of Nfatc1, and expression of osteoclast marker genes to varying degrees (mainly Donepezil and Rivastigmine but not Galantamine). Furthermore, AChEIs variably inhibited RANKL-induced MAPK signaling accompanied by downregulation of AChE transcription. Finally, AChEIs protected against OVX-induced bone loss mainly by inhibiting osteoclast activity. Taken together, AChEIs (mainly Donepezil and Rivastigmine) exerted a positive effect on bone protection by inhibiting osteoclast function through MAPK and NFATc1 signaling pathways through downregulating AChE. Our findings have important clinical implications that elderly patients with dementia who are at risk of developing osteoporosis may potentially benefit from therapy with the AChEI drugs. Our study may influence drug choice in those patients with both AD and osteoporosis. Title: The effects of carvacrol on development and gene expression profiles in Spodoptera frugiperda Liu J, Lin Y, Huang Y, Liu L, Cai X, Lin J, Shu B Ref: Pestic Biochem Physiol, 195:105539, 2023 : PubMed ESTHER: Liu_2023_Pestic.Biochem.Physiol_195_105539 PubMedSearch: Liu 2023 Pestic.Biochem.Physiol 195 105539 PubMedID: 37666589 Abstract The fall armyworm, Spodoptera frugiperda, is a highly polyphagous agricultural pest that is widely distributed around the world and causes severe crop yield loss. Carvacrol showed adverse effects on many pests, such as larval death and growth inhibition. While the effects of carvacrol on S. frugiperda larvae are not yet known. In this study, the effects of carvacrol on S. frugiperda, including larval growth inhibition and mortality induction, were observed. The detoxification and digestive enzyme activities of larvae with 1.0 and 2.0 g/kg carvacrol treatments were analyzed. Carvacrol boosted the enzyme activities of carboxylesterase (CarE) and glutathione S-transferase (GST) while decreasing the activities of alpha-amylase (AMS), lipase (LIP), and trypsin. A total of 3422 differentially expressed genes were identified in the larvae treated with 2.0 g/kg carvacrol, of which the DEGs involved in xenobiotic detoxification, food digestion, and insecticidal targets were further examined. These results suggest that carvacrol could regulate growth and development by affecting the process of food digestion, and exert its toxicity on the larvae through interaction with a variety of insecticidal targets. While the altered expressions of detoxification enzymes might be related to the detoxification and metabolism of carvacrol. Our findings offer a theoretical foundation for the use of carvacrol for S. frugiperda control in the field. Title: OsLDDT1, encoding a transmembrane structural DUF726 family protein, is essential for tapetum degradation and pollen formation in rice Sun Z, Liu K, Chen C, Chen D, Peng Z, Zhou R, Liu L, He D, Duan W and Sun L <7 more author(s)> Sun Z, Liu K, Chen C, Chen D, Peng Z, Zhou R, Liu L, He D, Duan W, Chen H, Huang C, Ruan Z, Zhang Y, Cao L, Zhan X, Cheng S, Sun L (- 7) Ref: Plant Sci, :111596, 2023 : PubMed ESTHER: Sun_2023_Plant.Sci__111596 PubMedSearch: Sun 2023 Plant.Sci 111596 PubMedID: 36657664 Gene_locus related to this paper: orysj-q10ss2 Abstract Formation of the pollen wall, which is mainly composed of lipid substances secreted by tapetal cells, is important to ensure pollen development in rice. Although several regulatory factors related to lipid biosynthesis during pollen wall formation have been identified in rice, the molecular mechanisms controlling lipid biosynthesis are unclear. We isolated the male-sterile rice mutant oslddt1 (leaked and delayed degraded tapetum 1). oslddt1 plants show complete pollen abortion resulting from delayed degradation of the tapetum and blocked formation of Ubisch bodies and pollen walls. OsLDDT1 (LOC_Os03g02170) encodes a DUF726 containing protein of unknown functionwith highly conserved transmembrane and alpha/beta Hydrolase domains. OsLDDT1 localizes to the endoplasmic reticulum and the gene is highly expressed in rice panicles. Genes involved in regulating fatty acid synthesis and formation of sporopollenin and pollen exine during anther developmentshowed significantly different expression patterns in oslddt1 plants. Interestingly, the wax and cutin contents in mature oslddt1-1 anthers were decreased by 74.07% and 72.22% compared to WT, indicating that OsLDDT1 is involved in fatty acid synthesis and affects formation of the anther epidermis. Our results provide as deeper understanding of the role of OsLDDT1 in regulating male sterility and also provide materials for hybrid rice breeding. Title: Sitagliptin attenuates neuronal apoptosis via inhibiting the endoplasmic reticulum stress after acute spinal cord injury Tang C, Xu T, Dai M, Zhong X, Shen G, Liu L Ref: Hum Exp Toxicol, 42:9603271231168761, 2023 : PubMed ESTHER: Tang_2023_Hum.Exp.Toxicol_42_9603271231168761 PubMedSearch: Tang 2023 Hum.Exp.Toxicol 42 9603271231168761 PubMedID: 36977492 Abstract Regulation of endoplasmic reticulum stress (ER) stress-induced apoptosis and nerve regeneration is a hopeful way for acute spinal cord injury (SCI). Sitagliptin (Sita) is one of dipeptidyl peptidase-4 (DPP-4) inhibitor, which is beneficial neurons damaged diseases. However, its protective mechanisms of avoiding nerve injury remain unclear. In this study, we further investigated the mechanism of the anti-apoptotic and neuroprotective effects of Sita in promoting locomotor recovery from SCI. In vivo results showed that Sita treatment reduced neural apoptosis caused by SCI. Moreover, Sita effectively attenuated the ER tress and associated apoptosis in rats with SCI. A striking feature was the occurrence of nerve fiber regeneration at the lesion site, which eventually led to significant locomotion recovery. In vitro results showed that the PC12 cell injury model induced by Thapsigargin (TG) also showed similar neuroprotective effects. Overall, sitagliptin showed potent neuroprotective effects by targeting the ER stress-induced apoptosis both in vivo and vitro, thus facilitating the regeneration of the injured spinal cord. Title: Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma ameliorate scopolamine-induced cognitive impairment by regulating the cholinergic and synaptic associated proteins Xie Y, Liu L, Zheng J, Shi K, Ai W, Zhang X, Wang P, Lan Z, Chen L Ref: J Ethnopharmacol, 311:116400, 2023 : PubMed ESTHER: Xie_2023_J.Ethnopharmacol_311_116400 PubMedSearch: Xie 2023 J.Ethnopharmacol 311 116400 PubMedID: 37003402 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Polygoni Multiflori Radix Praeparata (PMRP) and Acori Tatarinowii Rhizoma (ATR) is often used in traditional Chinese medicine to prevent and treat Alzheimer's disease (AD). However, it is not clear whether the effects and mechanisms of the decoction prepared by traditional decocting method (PA) is different from that prepared by modern decocting method (P + A). AIM OF THE STUDY: The present study aimed to investigate the differences in the protective effects of PA and P + A on scopolamine induced cognitive impairment, and to explore its potential mechanism. MATERIALS AND METHODS: To assess the protective effect of PA and P + A on cognitive dysfunction, the mice were orally administrated with PA (1.56, 6.24 g kg(-1)day(-1)) and P + A (1.56, 6.24 g kg(-1)day(-1)) for 26 days before co-treatment with scopolamine (4 mg kg(-1)day(-1), i.p.). The learning and memory abilities of mice were examined by Morris water maze test, and the expressions of proteins related to cholinergic system and synaptic function were detected by the methods of ELISA, real-time PCR and Western blotting. Then, molecular docking technique was used to verify the effect of active compounds in plasma after PA administration on Acetylcholinesterase (AChE) protein. Finally, the Ellman method was used to evaluate the effects of different concentrations of PA, P + A (1 microg/mL-100 mg/mL) and the compounds (1-100 microM) on AChE activity in vitro. RESULTS: On one hand, in the scopolamine-induced cognitive impairment mouse model, both of PA and P + A could improve the cognitive impairment, while the effect of PA on cognitive amelioration was better than that of P + A. Moreover, PA regulated the cholinergic and synaptic functions by enhancing the concentration of acetylcholine (ACh), the mRNA levels of CHT1, Syn, GAP-43 and PSD-95, and the related proteins (CHT1, VACHT, Syn, GAP-43 and PSD-95), and significantly inhibiting the expression of AChE protein. Meanwhile, P + A only up-regulated the mRNA levels of GAP-43 and PSD-95, increased the expressions of CHT1, VACHT, Syn, GAP-43 and PSD-95 proteins, and inhibited the expression of AChE protein. On the other hand, the in vitro study showed that some compounds including emodin-8-o-beta-d-Glucopyranoside, THSG and alpha-Asarone inhibited AChE protein activity with the IC(50) values 3.65 microM, 5.42 microM and 9.43 microM, respectively. CONCLUSIONS: These findings demonstrate that both of PA and P + A can ameliorate the cognitive deficits by enhancing cholinergic and synaptic related proteins, while PA has the stronger improvement effect on the cholinergic function, which may be attributed to the compounds including THSG, emodin, emodin-8-O-beta-D-glucopyranoside and alpha-asarone. The present study indicated that PA has more therapeutic potential in the treatment of neurodegenerative diseases such as AD. The results provide the experimental basis for the clinical use of PA. Title: A feruloyl esterase/cellulase integrated biological system for high-efficiency and toxic-chemical free isolation of tobacco based cellulose nanofibers Zhao M, An X, Fan Z, Nie S, Cheng Z, Cao H, Zhang X, Mian MM, Liu H, Liu L Ref: Carbohydr Polym, 313:120885, 2023 : PubMed ESTHER: Zhao_2023_Carbohydr.Polym_313_120885 PubMedSearch: Zhao 2023 Carbohydr.Polym 313 120885 PubMedID: 37182973 Abstract Tobacco based cellulose nanofiber (TCNF) is a novel nanocellulose that has recently been used to replace undesirable wood pulp fibers in the preparation of reconstructed tobacco sheets (RTS). However, given the strict requirements for controlling toxic chemical content in tobacco products, there is a global interest in developing a green, efficient, and toxic-chemical free approach to isolate TCNF from tobacco stem as a bioresource. In this study, we propose a creative and environmentally friendly method to efficiently and safely isolate TCNF from tobacco stem pulp, which involves integrated biological pretreatment followed by a facile mechanical defibrillation process. Feruloyl esterase is used to pretreat the stem pulp by disrupting the ether and ester bonds between lignin and polysaccharide carbohydrates within the fiber wall, which effectively facilitates cellulase hydrolysis and swelling of the stem pulp fiber, as well as the following mechanical shearing treatment for TCNF isolation. The results demonstrate that TCNF obtained by the comprehensive feruloyl esterase/cellulase/mechanical process exhibit uniform and well-dispersed nanofiber morphology, higher crystallinity, and stronger mechanical properties than those of the control. The addition of 0.5 % TCNF can replace wood pulp by 18 wt% ~ 25 wt% in the production of RTS samples while maintaining their reasonable strength properties. Title: Mechanism of active acetylcholinesterase inhibition by organic sulfanes in garlic: Non-covalent binding and covalent modifications Zhu Y, Shi D, Chen A, Wang Y, Liu L, Bai B Ref: Int J Biol Macromol, :124972, 2023 : PubMed ESTHER: Zhu_2023_Int.J.Biol.Macromol__124972 PubMedSearch: Zhu 2023 Int.J.Biol.Macromol 124972 PubMedID: 37285891 Abstract Numerous secondary metabolites in medicinal food homology plants such as Allium inhibit the activity of acetylcholinesterase (AChE), but the current understanding of the inhibition mechanism is limited. In this study, we employed ultrafiltration, spectroscopic, molecular docking, and matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS/MS) techniques to investigate the inhibition mechanism of AChE by garlic organic sulfanes, including diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS). The results of UV-spectrophotometry and ultrafiltration experiments showed the inhibition of AChE activity by DAS and DADS was reversible (competitive inhibition), but inhibition by DATS was irreversible. Molecular fluorescence and molecular docking indicated DAS and DADS changed the positions of key amino acids inside the catalytic cavity through hydrophobic interactions with AChE. By using MALDI-TOF-MS/MS, we found DATS irreversibly inhibited AChE activity by opening disulfide-bond switching of disulfide bond 1 (Cys-69 and Cys-96) and disulfide bond 2 (Cys-257 and Cys-272) in AChE, as well as by covalently modifying Cys-272 in disulfide bond 2 to generate AChE-SSA derivatives (strengthened switch). This study provides a basis for further exploration of natural AChE inhibitors using organic active substances in garlic and presents a hypothesis of U-shaped spring force arm effect based on the disulfide bond-switching reaction of DATS that can be used to evaluate the stability of disulfide bonds in proteins. Title: Integrated Proteomic and Metabolomic Analyses of Chicken Ovary Revealed the Crucial Role of Lipoprotein Lipase on Lipid Metabolism and Steroidogenesis During Sexual Maturity Cui Z, Ning Z, Deng X, Du X, Amevor FK, Liu L, Kang X, Tian Y, Wang Y and Zhao X <1 more author(s)> Cui Z, Ning Z, Deng X, Du X, Amevor FK, Liu L, Kang X, Tian Y, Wang Y, Li D, Zhao X (- 1) Ref: Front Physiol, 13:885030, 2022 : PubMed ESTHER: Cui_2022_Front.Physiol_13_885030 PubMedSearch: Cui 2022 Front.Physiol 13 885030 PubMedID: 35574488 Abstract During sexual maturation and ovulatory cycle in chickens, ovaries undergo dynamic morphological and functional changes. The aim of this study was to evaluate the integrated proteome and metabolome analyses of chicken ovaries to characterize the changes in protein and metabolite profiles during sexual maturity. The ovary of Rohman layers before (125 days of age) and after (139 days of age) sexual maturation were collected for proteome and metabolome sequencing. The results showed that a total of 680 differentially expressed proteins (DEPs) and 1,046 differential metabolites (DMs) were identified in the chicken ovary during sexual maturity. Among the DEPs, 595 proteins were up-regulated and 85 were down-regulated, whereas 519 metabolites were up-regulated and 527 were down-regulated. KEGG pathway enrichment analysis showed that DEPs were significantly enriched in glycerolipid metabolism, calcium signaling pathway, folate biosynthesis, fat digestion and absorption, NF-kB signaling pathway, and PPAR signaling pathway. However, DMs were significantly enriched in the metabolism pathways, PPAR signalling pathway, glycerolipid metabolism, ferroptosis, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids. The results of the integrated analyses of DEPs and DMs revealed that the PPAR signaling pathway and glycerolipid metabolism were the most significantly enriched pathways. Among the identified DEPs, lipoprotein lipase (LPL) was upregulated in sexually mature chicken ovaries and was significantly enriched in the glycerolipid metabolism pathway, which may partially explain the possible reasons for steroidogenesis and lipid reserves responsible for oocyte maturation and ovarian follicle development during sexual maturity in chickens. The results further revealed that LPL silencing decreased the content of lipid droplets (LDs), as well as the mRNA expression of lipid metabolism-related genes including; sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FASN); and steroidogenesis-related genes such as; cytochrome P450 11A1 (CYP11A1) and steroidogenic acute regulatory (StAR). The present study revealed that upregulation of LPL in the chicken ovary during sexual maturity promotes granulosa cell (GC) lipid metabolism and steroidogenesis. These findings provide a theoretical support for further studies to elucidate the mechanism of lipid metabolism to regulate the function of avian GCs during sexual maturity in chickens. Title: Tuning the Properties of Ester-Based Degradable Polymers by Inserting Epoxides into Poly(E-caprolactone) Hu S, Liu L, Li H, Pahovnik D, Hadjichristidis N, Zhou X, Zhao J Ref: Chem Asian J, :e202201097, 2022 : PubMed ESTHER: Hu_2022_Chem.Asian.J__e202201097 PubMedSearch: Hu 2022 Chem.Asian.J e202201097 PubMedID: 36424185 Abstract A series of ester-ether copolymers were obtained via the reaction between alpha,omega-dihydroxyl poly(E-caprolactone) (PCL) and ethylene oxide (EO) or monosubstituted epoxides catalyzed by strong phosphazene bases. The two types of monomeric units were distributed in highly random manners due to the concurrence of epoxide ring-opening and fast transesterification reactions. The substituent of epoxide showed an interesting bidirectional effect on the enzymatic degradability of the copolymer. Compared with PCL, copolymers derived from EO exhibited enhanced hydrophilicity and decreased crystallinity which then resulted in higher degradability. For the copolymers derived from propylene oxide and 1,2-butylene oxide, the hydrophobic alkyl pendant groups also allowed lower crystallinity of the copolymers thus higher degradation rates. However, further enlarging the pendant groups by using styrene oxide or 2-ethylhexyl glycidyl ether caused a decrease in the degradation rate, which might be ascribed to the higher bulkiness hindering the contact of ester groups with lipase. Title: Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity Jia Y, Shi S, Cheng B, Cheng S, Liu L, Meng P, Yang X, Chu X, Wen Y and Guo X <1 more author(s)> Jia Y, Shi S, Cheng B, Cheng S, Liu L, Meng P, Yang X, Chu X, Wen Y, Zhang F, Guo X (- 1) Ref: Front Nutr, 9:935112, 2022 : PubMed ESTHER: Jia_2022_Front.Nutr_9_935112 PubMedSearch: Jia 2022 Front.Nutr 9 935112 PubMedID: 35990316 Abstract BACKGROUND: T-2 toxin is recognized as one of the high-risk environmental factors for etiology and pathogenesis of Kashin-Beck disease (KBD). Previous evidence indicates decreased serum fluorine level in KBD patients. However, whether fluoride could regulate carboxylesterase 1 (CES1)-mediated T-2 toxin hydrolysis and alter its chondrocyte toxicity remains largely unknown. METHODS: In this study, in vitro hydrolytic kinetics were explored using recombinant human CES1. HPLC-MS/MS was used to quantitative determination of hydrolytic metabolites of T-2 toxin. HepG2 cells were treated with different concentration of sodium fluoride (NaF). qRT-PCR and western blot analysis were used to compare the mRNA and protein expression levels of CES1. C28/I2 cells were treated with T-2 toxin, HT-2 toxin, and neosolaniol (NEO), and then cell viability was determined by MTT assay, cell apoptosis was determined by Annexin V-FITC/PI, Hoechst 33258 staining, and cleaved caspase-3, and cell cycle was monitored by flow cytometry assay, CKD4 and CDK6. RESULTS: We identified that recombinant human CES1 was involved in T-2 toxin hydrolysis to generate HT-2 toxin, but not NEO, and NaF repressed the formation of HT-2 toxin. Both mRNA and protein expression of CES1 were significantly down-regulated in a dose-dependent manner after NaF treatment in HepG2 cells. Moreover, we evaluated the chondrocyte toxicity of T-2 toxin and its hydrolytic metabolites. Results showed that T-2 toxin induced strongest cell apoptosis, followed by HT-2 toxin and NEO. The decreased the proportion of cells in G0/G1 phase was observed with the descending order of T-2 toxin, HT-2 toxin, and NEO. CONCLUSIONS: This study reveals that CES1 is responsible for the hydrolysis of T-2 toxin, and that fluoride impairs CES1-mediated T-2 toxin detoxification to increase its chondrocyte toxicity. This study provides novel insight into understanding the relationship between fluoride and T-2 toxin in the etiology of KBD. Title: Two New Picoline-Derived Meroterpenoids with Anti-Acetylcholinesterase Activity from Ascidian-Derived Fungus Amphichorda felina Jiang M, Guo H, Wu Q, Yuan S, Liu L Ref: Molecules, 27:, 2022 : PubMed ESTHER: Jiang_2022_Molecules_27_ PubMedSearch: Jiang 2022 Molecules 27 PubMedID: 36014315 Abstract Amphichoterpenoids D (1) and E (2), two new picoline-derived meroterpenoids with a rare 6/6/6 tricyclic pyrano[3,2-c]pyridinyl-gamma-pyranone scaffold, were isolated from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. Their structures, including the absolute configurations, were established by extensive spectroscopic methods (1D and 2D NMR and high-resolution mass spectrometry) and ECD calculations. Compounds 1 and 2 showed anti-acetylcholinesterase (anti-AChE) activities with IC(50) values of 12.5 microM and 11.6 microM, respectively. The binding interactions between 1, 2, and AChE were investigated using molecular docking analyses. Title: Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study Li J, Lin J, Pan Y, Wang M, Meng X, Li H, Wang Y, Zhao X, Qin H, Liu L Ref: J Neuroinflammation, 19:131, 2022 : PubMed ESTHER: Li_2022_J.Neuroinflammation_19_131 PubMedSearch: Li 2022 J.Neuroinflammation 19 131 PubMedID: 35761288 Abstract OBJECTIVE: Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. METHODS: In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A(2) mass (Lp-PLA(2)) and activity (Lp-PLA(2)-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2-6 within 1 year. RESULTS: There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13-1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17-1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06-1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64-2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37-1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37-1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03-1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19-1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01-1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46-1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01-1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001). CONCLUSIONS: In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms. Title: Theophylline Extracted from Fu Brick Tea Affects the Metabolism of Preadipocytes and Body Fat in Mice as a Pancreatic Lipase Inhibitor Liu TT, Liu XT, Huang GL, Liu L, Chen QX, Wang Q Ref: Int J Mol Sci, 23:, 2022 : PubMed ESTHER: Liu_2022_Int.J.Mol.Sci_23_2525 PubMedSearch: Liu 2022 Int.J.Mol.Sci 23 2525 PubMedID: 35269668 Inhibitor(s) related to this paper: Caffeine Abstract The dramatic increase in obesity is putting people under increasing pressure. Lipase inhibitors, as a kind of effective anti-obesity drug, have attracted more and more researchers' attention in recent years because of their advantages of acting on the intestinal tract and having no side effects on the central nervous system. In this study, lipase inhibitor Fu Brick Theophylline (FBT) was screened based on enzyme molecular dynamics, and the inhibition mechanism of lipase inhibitors on obesity was analyzed and discussed at the cellular level and animal model level. We found that FBT had high inhibition effects of lipase with an IC(50) of 1.02~0.03 microg/mL. Firstly, the laboratory used 3T3-L1 proadipocytes as models, flow cytometry was used to detect the effects of FBT on the cycle, apoptosis and intracellular ROS activity of proadipocytes. To study the contents of triglyceride, total cholesterol, related metabolites and related gene and protein expression in adipocytes. The results showed that FBT could reduce ROS production and inflammatory factor mRNA expression during cell differentiation. Secondly, by establishing the animal model of high-fat feed ob nutritional obese mice, the morphological observation and gene expression analysis of body weight, fat rate, adipocyte and hepatocyte metabolism of FBT obese mice were further discussed. It was proven that FBT can effectively reduce the degree of fatty liver, prevent liver fibrosis and fat accumulation, and improve the damage of mitochondrial membrane structure. This study provides a theoretical basis for the screening and clinical treatment of lipase inhibitors. Title: Detoxification mechanism of vinegar-processed Kansui revealed by systematic phytochemical analysis using UPLC-DAD-MS/MS, UPLC-HR-MS and in silico drug target identification Liu L, Li J, Lv J, Jiang H, Chen FE Ref: Rapid Commun Mass Spectrom, :e9332, 2022 : PubMed ESTHER: Liu_2022_Rapid.Commun.Mass.Spectrom__e9332 PubMedSearch: Liu 2022 Rapid.Commun.Mass.Spectrom e9332 PubMedID: 35716385 Abstract RATIONALE: The dried roots of Euphorbia kansui L., known as Kansui, have been used to treat ascites and edema in Traditional Chinese Medicine. However, the toxicity of this herb had seriously restricted its clinical application. A unique vinegar-processing method has been used to reduce its toxicity since ancient China. However, the detoxification mechanism underlying such vinegar-processing has not been fully revealed, to find the answer, the processed-induced components change should be carefully investigated. METHODS: Here we performed systematic analysis of chemical components in raw and vinegar-processed Kansui by UPLC-DAD-MS/MS and UPLC-HR-MS, 31 chemical components in raw and vinegar processed Kansui were found, and the chemical structure of 28 components among them was proposed, and the processed-induced components change was then investigated. RESULTS: A comprehensive conclusion about the processed-induced chemical change was drew. It was found that jatrophane-type diterpenoids decreased markedly after the vinegar-processing, while ingenane-type diterpenoids retained in the vinegar-processing. In silico drug target identification gave hints that jatrophane-type diterpenoids, which decreased markedly during the vinegar-processing, maybe has more intense toxicity involved in cholinesterase and MAPKs, while ingenane-type diterpenoids, which retained in the vinegar-processing, maybe has more intense therapeutic effect involved in carbonic anhydrase. CONCLUSIONS: The possible detoxification mechanism of vinegar-processed Kansui was present. The research has significance on the therapeutic/toxic chemical basis of Kansui, besides, it has significance on drug discovery from terpenoids within the herb. Title: A Three-Dimensional Brain-on-a-Chip Using Human iPSC-Derived GABAergic Neurons and Astrocytes Liu L, Koo Y, Russell T, Yun Y Ref: Methods Mol Biol, 2492:117, 2022 : PubMed ESTHER: Liu_2022_Methods.Mol.Biol_2492_117 PubMedSearch: Liu 2022 Methods.Mol.Biol 2492 117 PubMedID: 35733041 Abstract Brain-on-a-chip is a miniaturized engineering platform to mimic the structural and functional aspects of brain tissue. We describe a method to construct a three-dimensional (3D) brain-on-a-chip in this chapter. We firstly portray the method of a brain-on-a-chip model with cocultured mice neurons, microglia, and astrocytes to mimic brain tissue and membrane-free perfusion with endothelial cells, in which we successfully build the blood-brain barrier to screen neurotoxicity. Then we describe a method to construct a brain-on-a-chip with human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes to simulate human brain behavior. This platform consists of neuronal tissue with extracellular matrix (ECM)-embedded GABAergic neurons and astrocytes and a perfusion channel with dynamic flow. We also include the broader applicability test of this model using an organophosphate (OP), malathion, to induce acute and chronic neurotoxicity, and then using butyrylcholinesterase (BuChE) as an exogenous bioscavenger of OP. Following the methods listed in this chapter, we are able to measure the neurotoxic effects on construct integrity, viability, and total AChE and BuChE activity. Title: An esterase-activatable curcumin prodrug for tumor-targeting therapy Liu L, Zhang L, Tao M, Wang M, Dong L, Hai Z Ref: Chem Commun (Camb), :, 2022 : PubMed ESTHER: Liu_2022_Chem.Commun.(Camb)__ PubMedSearch: Liu 2022 Chem.Commun.(Camb) PubMedID: 36373630 Abstract A tumor-targeting therapy strategy is urgently needed to increase the accumulation of drugs in tumors and reduce the side effects in normal tissues. Herein, we developed an esterase-activatable curcumin prodrug Cur-RGD for tumor-targeting therapy. Armed with the tumor-targeting RGD peptide and in situ esterase-triggered drug release, this prodrug Cur-RGD can efficiently improve the therapeutic effect of curcumin in tumors. Title: Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection Pang Y, Cheng Z, Zhang S, Li S, Li X, Zhang X, Feng Y, Cui H, Chen Z and Feng L <6 more author(s)> Pang Y, Cheng Z, Zhang S, Li S, Li X, Zhang X, Feng Y, Cui H, Chen Z, Liu L, Li Q, Huang J, Zhang M, Zhu S, Wang L, Feng L (- 6) Ref: Cell Rep, 39:110698, 2022 : PubMed ESTHER: Pang_2022_Cell.Rep_39_110698 PubMedSearch: Pang 2022 Cell.Rep 39 110698 PubMedID: 35443182 Abstract Urinary tract infections are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, and pldA expression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulates PIT1 via nuclear factor kappaB (NF-kappaB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection. Title: A symbiotic gut bacterium enhances Aedes albopictus resistance to insecticide Wang H, Liu H, Peng H, Wang Y, Zhang C, Guo X, Liu L, Lv W, Cheng P, Gong M Ref: PLoS Negl Trop Dis, 16:e0010208, 2022 : PubMed ESTHER: Wang_2022_PLoS.Negl.Trop.Dis_16_e0010208 PubMedSearch: Wang 2022 PLoS.Negl.Trop.Dis 16 e0010208 PubMedID: 35245311 Abstract BACKGROUND: The increasing insecticide resistance of Aedes albopictus puts many countries in Asia and Africa, including China, at great risk of a mosquito-borne virus epidemic. To date, a growing number of researches have focused on the relationship between intestinal symbiotic bacteria and their hosts' resistance to insecticides. This provides a novel aspect to the study of resistant mechanisms. METHODS/FINDINGS: This study reveals significant composition and dynamic changes in the intestinal symbiotic bacteria of Ae. albopictus between the resistant and susceptible strains based on full-length sequencing technology. The relative abundance of Serratia oryzae was significantly higher in the resistance strain than in the susceptible strains; also, the relative abundance of S. oryzae was significantly higher in deltamethrin-induced Ae. albopictus than in their counterpart. These suggested that S. oryzae may be involved in the development of insecticide resistance in Ae. albopictus. To explore the insecticide resistance mechanism, adult mosquitoes were fed with GFP-tagged S. oryzae, which resulted in stable bacterial enrichment in the mosquito gut without affecting the normal physiology, longevity, oviposition, and hatching rates of the host. The resistance measurements were made based on bioassays as per the WHO guidelines. The results showed that the survival rate of S. oryzae-enriched Ae. albopictus was significantly higher than the untreated mosquitoes, indicating the enhanced resistance of S. oryzae-enriched Ae. albopictus. Also, the activities of three metabolic detoxification enzymes in S. oryzae-enriched mosquitoes were increased to varying degrees. Meanwhile, the activity of extracellular enzymes released by S. oryzae was measured, but only carboxylesterase activity was detected. HPLC and UHPLC were respectively used to measure deltamethrin residue concentration and metabolite qualitative analysis, showing that the deltamethrin degradation efficiency of S. oryzae was positively correlated with time and bacterial amount. Deltamethrin was broken down into 1-Oleoyl-2-hydroxy-sn-glycero-3-PE and 2',2'-Dibromo-2'-deoxyguanosine. Transcriptome analysis revealed that 9 cytochrome P450s, 8 GSTs and 7 CarEs genes were significantly upregulated. CONCLUSIONS: S. oryzae can be accumulated into adult Ae. albopictus by artificial feeding, which enhances deltamethrin resistance by inducing the metabolic detoxification genes and autocrine metabolic enzymes. S. oryzae is vertically transmitted in Ae. albopictus population. Importantly, S. oryzae can degrade deltamethrin in vitro, and use deltamethrin as the sole carbon source for their growths. Therefore, in the future, S. oryzae may also be commercially used to break down the residual insecticides in the farmland and lakes to protect the environment. Title: Soluble Epoxide Hydrolase Inhibitor t-AUCB Ameliorates Vascular Endothelial Dysfunction by Influencing the NF-kB/miR-155-5p/eNOS/NO/IkB Cycle in Hypertensive Rats Wang X, Han W, Zhang Y, Zong Y, Tan N, Li L, Liu C, Liu L Ref: Antioxidants (Basel), 11:, 2022 : PubMed ESTHER: Wang_2022_Antioxidants.(Basel)_11_ PubMedSearch: Wang 2022 Antioxidants.(Basel) 11 PubMedID: 35883863 Abstract Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated with hypertension, in rats. The hypertensive rats exhibited increased systolic blood pressure, reduced renal blood flow, impaired endothelium-dependent relaxation and eNOS phosphorylation in the renal arteries, elevated ROS production in the endothelium of the renal arteries, and decreased EET levels in plasma, the renal arteries, and endothelial cells; however, t-AUCB reversed all the deleterious effects. Moreover, we found that the stimulation of AMPK/UCP2 scavenged ROS and restored endothelial function in the renal arteries of hypertensive rats undergoing therapy with t-AUCB. In addition, we were the first to reveal the potential role of miR-155-5p in the occurrence and development of vascular endothelial dysfunction in hypertension. Importantly, t-AUCB recovered NO bioavailability by regulating the NF-kappaB/miR-155-5p/eNOS/NO/IkappaB cycle after the activation of AMPK/UCP2 and the subsequent inhibition of ROS in hypertensive rat renal artery endothelial cells. This study will provide evidence for this additional new mechanism, underlying the benefits of EETs and the related agents against hypertensive vasculopathy. Title: Tannic acid reduced apparent protein digestibility and induced oxidative stress and inflammatory response without altering growth performance and ruminal microbiota diversity of Xiangdong black goats Wang Z, Yin L, Liu L, Lan X, He J, Wan F, Shen W, Tang S, Tan Z, Yang Y Ref: Front Vet Sci, 9:1004841, 2022 : PubMed ESTHER: Wang_2022_Front.Vet.Sci_9_1004841 PubMedSearch: Wang 2022 Front.Vet.Sci 9 1004841 PubMedID: 36187804 Abstract The present study was performed to evaluate the impacts of tannic acid (TA) supplementation at different levels on the growth performance, physiological, oxidative and immunological metrics, and ruminal microflora of Xiangdong black goats. Twenty-four goats were randomly assigned to four dietary treatments: the control (CON, basal diet), the low-dose TA group [TAL, 0.3 % of dry matter (DM)], the mid-dose TA group (TAM, 0.6 % of DM), and the high-dose TA group (TAH, 0.9 % of DM). Results showed that the growth performance was unaffected (P > 0.05) by adding TA, whilst the 0.3 % and 0.6 % TA supplementation significantly decreased (P < 0.05) the apparent digestibility of crude protein (CP) and ruminal NH(3)-N concentration, and raised (P < 0.05) the level of total volatile fatty acid (TVFA) in rumen. The increments of alanine aminotransferase (ALT), triglyceride (TG), cortisol (CORT), total antioxidant capacity (T-AOC), interleukin (IL)-1beta, IL-6, and serumamyloid A (SAA), and decrements of globulin (GLB), immunoglobulin G (IgG), cholinesterase (CHE), glutathione reductase (GR), creatinine (CRE), growth hormone (GH), high-density lipoprotein cholesterol (HDLC), and insulin-like growth factor 1 (IGF-1) to different extents by TA addition were observed. Although the Alpha and Beta diversity of rumen bacterial community remained unchanged by supplementing TA, the relative abundance of the predominant genus Prevotella_1 was significantly enriched (P < 0.05) in TAL. It could hence be concluded that the TA supplementation in the present trial generally decreased CP digestion and caused oxidative stress and inflammatory response without influencing growth performance and ruminal microbiota diversity. More research is needed to explore the premium dosage and mechanisms of effects for TA addition in the diet of goats. Title: A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase Xia M, Li C, Liu L, He Y, Li Y, Jiang G, Wang J Ref: Biosensors (Basel), 12:, 2022 : PubMed ESTHER: Xia_2022_Biosensors.(Basel)_12_ PubMedSearch: Xia 2022 Biosensors.(Basel) 12 PubMedID: 35884287 Abstract Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 microU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals. Title: Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals Yang Y, Liu J, Liu L, Zhou Y, Zhang L, Zhong Y, Zhao D, Wang Y Ref: ACS Omega, 7:30720, 2022 : PubMed ESTHER: Yang_2022_ACS.Omega_7_30720 PubMedSearch: Yang 2022 ACS.Omega 7 30720 PubMedID: 36092617 Abstract A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N,N-dimethylammonium cations in the pores of the anionic, biocompatible metal-organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10-50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs. Title: Correlation of lipoprotein-associated phospholipase A2 and cerebral microbleeds in patients with acute ischaemic stroke Zhang X, Liu L, Jiang N, Liu Y, Wang Q, Tang X, Zhai Q, Zhao L Ref: BMC Neurol, 22:482, 2022 : PubMed ESTHER: Zhang_2022_BMC.Neurol_22_482 PubMedSearch: Zhang 2022 BMC.Neurol 22 482 PubMedID: 36517761 Abstract BACKGROUND AND AIMS: Cerebral microbleeds (CMBs) increase the risk of stroke occurrence and recurrence,and affect the prognosis of stroke patients. Therefore, identifying biological markers that predict CMBs after stroke is urgently needed. This study explored whether high levels of lipoprotein-associated phospholipase A2(Lp-PLA2) are associated with an increased risk of CMBs in patients with acute ischaemic stroke (AIS). METHODS: From April 2020 to October 2021, we enrolled 242 patients with AIS. At admission, the plasma levels of Lp-PLA2 were measured in all patients as well as the number of CMBs and white matter lesions. According to the results of the Susceptibility Weighted Imaging (SWI), the patients were divided into a CMB group and a no-CMB group. The groups were compared with univariate and multivariate analyses to clarify the correlation between Lp-PLA2 levels and CMBs, and the optimal cut-off value of Lp-PLA2 that predicted CMBs was determined from the receiver-operating characteristic curve. RESULTS: CMBs were detected in 71 (29.3%) of the 242 AIS patients. The median Lp-PLA2 level was 182.79 ng/ml. Using the 1st quartile of Lp-PLA2 levels (the lowest levels) as the reference group, univariate logistic regression analysis showed that individuals in the 4th quartile (the highest levels) had a higher risk of CMBs (odds ratio [OR] = 1.460, 95% confidence interval [CI]: 1.188-1.795, P = 0.000). This correlation persisted after adjusting for relevant risk factors (OR = 1.370, 95% CI: 1.096-1.713, P = 0.006). The optimal cut-off value of Lp-PLA2 that predicted the occurrence of CMBs was 184.36 ng/ml; at this threshold, the sensitivity was 69.0%, and the specificity was 60.2%. CONCLUSIONS: Our data suggest that a high level of Lp-PLA2 in patients with AIS is a potential risk factor for CMBs. Title: Progesterone activates the cyclic AMP-protein kinase A signalling pathway by upregulating ABHD2 in fertile men Jiang F, Zhu Y, Chen Y, Tang X, Liu L, Chen G, Liu Y, Sun X Ref: J Internal Medicine Res, 49:300060521999527, 2021 : PubMed ESTHER: Jiang_2021_J.Int.Med.Res_49_300060521999527 PubMedSearch: Jiang 2021 J.Int.Med.Res 49 300060521999527 PubMedID: 33752482 Gene_locus related to this paper: human-ABHD2 Abstract OBJECTIVE: This was a prospective study to investigate whether progesterone affects sperm activity by regulating the cyclic AMP-protein kinase A (cAMP-PKA) signalling pathway via alpha/beta hydrolase domain-containing protein 2 (ABHD2). METHODS: Spermatozoa were collected from healthy and infertile men (with oligoasthenospermia or abnormal acrosome; n = 30/group). The expression of and mutations in ABHD2 were detected by quantitative PCR, western blot, and gene sequencing. The expression of ABHD2 in the presence of progesterone was detected in all groups, and cAMP and PKA levels were detected by ELISA in fertile men after treatment with ABHD2 antibody and PKA inhibitor H-89, respectively. RESULTS: Expression of ABHD2 mRNA and protein were reduced in spermatozoa from infertile compared with fertile men. Four gene mutation sites were detected in spermatozoa from the infertile groups. Progesterone increased mRNA and protein levels of ABHD2 in healthy spermatozoa but not in spermatozoa from infertile men. The levels of cAMP and PKA were increased by progesterone in healthy spermatozoa, and the progesterone-increased cAMP and PKA were decreased by ABHD2 antibody and H-89, respectively. CONCLUSION: Progesterone regulates the ABHD2-mediated cAMP-PKA signalling pathway in healthy spermatozoa, which provides a new target for clinical diagnosis and treatment of infertility. Title: mTOR and ERK1/2 signaling participate in the process of acetate regulating lipid metabolism and HSL expression Li Y, Fu C, Liu L, Liu Y, Li F Ref: Anim Biosci, :, 2021 : PubMed ESTHER: Li_2021_Anim.Biosci__ PubMedSearch: Li 2021 Anim.Biosci PubMedID: 34727637 Abstract OBJECTIVE: Acetate plays an important role in host lipid metabolism. However, the network of acetate-regulated lipid metabolism remains unclear. Previous studies show that mitogen-activated protein kinases (MAPKs) and mechanistic target of rapamycin (mTOR) play a crucial role in lipid metabolism. We hypothesize that acetate could affect MAPKs and/or mTOR signaling and then regulate lipid metabolism. The present study investigated whether any cross talk occurs among MAPKs, mTOR and acetate in regulating lipid metabolism. METHODS: The ceramide C6 (an extracellular signaling-regulated kinases 1 and 2 (ERK1/2) activator) and MHY1485 (a mTOR activator) were used to treat rabbit adipose-derived stem cells (ADSCs) with or without acetate, respectively. RESULTS: It indicated that acetate (9 mM) treatment for 48 h decreased the lipid deposition in rabbit ADSCs. Acetate treatment decreased significantly phosphorylated protein levels of ERK1/2 and mTOR but significantly increased mRNA level of hormone-sensitive lipase (HSL). Acetate treatment did not significantly alter the phosphorylated protein level of p38 MAPK and c-Jun aminoterminal kinase (JNK). Activation of ERK1/2 and mTOR by respective addition in media with ceramide C6 and MHY1485 significantly attenuated decreased lipid deposition and increased HSL expression caused by acetate. CONCLUSION: Our results suggest that ERK1/2 and mTOR signaling pathways are associated with acetate regulated HSL gene expression and lipid deposition. Title: Chemical Constituents and their Antioxidant, Anti-Inflammatory and Anti-Acetylcholinesterase Activities from Pholidota cantonensis Liu L, Zou M, Zeng K, Ye X, Wang R, Wang W, Zhang X Ref: Plant Foods Hum Nutr, 76:105, 2021 : PubMed ESTHER: Liu_2021_Plant.Foods.Hum.Nutr_76_105 PubMedSearch: Liu 2021 Plant.Foods.Hum.Nutr 76 105 PubMedID: 33620638 Abstract Alzheimer's disease (AD) has the third highest health expenditures after heart disease and cancer. It has emerged as a serious global health issue. The discovery of new drugs to prevent and treat AD is of utmost importance. Pholidota cantonensis is an edible medicinal plant consumed in China. It is widely used in traditional Chinese medicine to treat various diseases. P. cantonensis has been reported to have antioxidant, anti-inflammatory, antitumor and antibacterial activities. Among these properties, its potent antioxidant activity has attracted our attention, since oxidative stress is one of the important pathological mechanisms involved in AD. This study aimed to isolate the compounds from the active extract and evaluate their bioactivities. Fifteen compounds, including one new compound, were obtained. The isolates were tested for 2,2'-diphenyl-1-picrylhydrazyl (DPPH)/2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, anti-acetylcholinesterase (anti-AChE) activities and inhibitory effects on nitrogen monoxide (NO) release in the BV-2 cells. Compounds 1, 2, 4, 6, 8, and 13-15 exhibited two kinds of AD-associated bioactivities. More importantly, compound 13 showed more potent NO inhibitory activity (IC(50) = 0.72 +/- 0.08 microM) than the positive control quercetin (IC(50) = 12.94 +/- 0.08 microM). Compound 13 also had a higher inhibitory rate (99.59 +/- 0.43%) on AChE than that of the positive control galantamine (78.32 +/- 1.16%) at the concentrate of 50 microg/mL. Our studies provide new insights into this plant in terms of its potential in the development of new multi-target anti-Alzheimer's disease (anti-AD) drugs. Title: Elsholtzia rugulosa: Phytochemical Profile and Antioxidant, Anti-Alzheimer's Disease, Antidiabetic, Antibacterial, Cytotoxic and Hepatoprotective Activities Liu L, Gao Q, Zhang Z, Zhang X Ref: Plant Foods Hum Nutr, :, 2021 : PubMed ESTHER: Liu_2021_Plant.Foods.Hum.Nutr__ PubMedSearch: Liu 2021 Plant.Foods.Hum.Nutr PubMedID: 34853948 Abstract Elsholtzia rugulosa Hemsl., a species of the Labiatae family, has a long history of use as a honey plant, herbal tea, and folk medicine in China. However, little is known about its composition and biological activities. The present study aimed to investigate the total phenol and flavonoid contents, phytochemical composition, and multiple biological activities of this plant. The total flavonoid content of the ethyl acetate fraction (EAF) was higher than those of the petroleum ether fraction (PEF), n-butanol fraction (NBF), and water fraction (WF). The EAF also had much stronger antioxidant, cytotoxic, hepatoprotective, and acetylcholinesterase (AChE) and alpha-glucosidase inhibitory activities than the PEF, NBF, and WF. More importantly, the IC(50) values of the EAF and NBF against alpha-glucosidase were much lower than that of the positive control acarbose, indicating their potent alpha-glucosidase inhibitory activities. The isolation of the EAF led to the acquisition of 9 compounds, four of which (beta-daucosterol, methyl rosmarinate, betulinic acid, and oleanolic acid) possessed significant alpha-glucosidase inhibitory activities. Maltol 6'-O-(5-O-p-coumaroyl)-beta-D-apiofuranosyl-beta-D-glucopyranoside and rosmarinic acid were the major phenolic compounds in the EAF according to the HPLC-DAD analysis. All these findings indicate that the EAF, NBF, and some isolated compounds have the potential to be developed as antidiabetic drugs. Moreover, the dual inhibition of AChE and butyrylcholinesterase (BChE) of certain fractions indicates their potential in the development of anti-Alzheimer's disease drugs. The present study provides a new understanding of the phytochemistry and bioactivity of E. rugulosa. Title: Protection studies of an excretory-secretory protein HcABHD against Haemonchus contortus infection Lu M, Tian X, Zhang Y, Wang W, Tian AL, Aimulajiang K, Liu L, Li C, Yan R and Li X <2 more author(s)> Lu M, Tian X, Zhang Y, Wang W, Tian AL, Aimulajiang K, Liu L, Li C, Yan R, Xu L, Song X, Li X (- 2) Ref: Vet Res, 52:3, 2021 : PubMed ESTHER: Lu_2021_Vet.Res_52_3 PubMedSearch: Lu 2021 Vet.Res 52 3 PubMedID: 33407892 Gene_locus related to this paper: haeco-CDJ88804 Abstract Unlike the successful immunization of native H. contortus antigens that contributed to the realization of the first commercial vaccine Barbervax, not many studies revealed the encouraging protective efficacies of recombinant H. contortus antigens in laboratory trials or under field conditions. In our preliminary study, H. contortus alpha/beta-hydrolase domain protein (HcABHD) was demonstrated to be an immunomodulatory excretory-secretory (ES) protein that interacts with goat T cells. We herein evaluated the protective capacities of two HcABHD preparations, recombinant HcABHD (rHcABHD) antigen and anti-rHcABHD IgG, against H. contortus challenge via active and passive immunization trials, respectively. Parasitological parameter, antibody responses, hematological pathology and cytokine profiling in unchallenged and challenged goats were monitored and determined throughout both trials. Subcutaneous administration of rHcABHD with Freund adjuvants elicited protective immune responses in challenged goats, diminishing cumulative fecal egg counts (FEC) and total worm burden by 54.0% and 74.2%, respectively, whereas passive immunization with anti-rHcABHD IgG conferred substantial protection to challenged goats by generating a 51.5% reduction of cumulative FEC and a 73.8% reduction of total worm burden. Additionally, comparable changes of mucosal IgA levels, circulating IgG levels, hemoglobin levels, and serum interleukin (IL)-4 and IL-17A levels were observed in rHcABHD protein/anti-rHcABHD IgG immunized goats in both trials. Taken together, the recombinant version of HcABHD might have further application under field conditions in protecting goats against H. contortus infection, and the integrated immunological pipeline of ES antigen identification, screening and characterization may provide new clues for further development of recombinant subunit vaccines to control H. contortus. Title: Arabidopsis Carboxylesterase 20 Binds Strigolactone and Increases Branches and Tillers When Ectopically Expressed in Arabidopsis and Maize Roesler K, Lu C, Thomas J, Xu Q, Vance P, Hou Z, Williams RW, Liu L, Owens MA, Habben JE Ref: Front Plant Sci, 12:639401, 2021 : PubMed ESTHER: Roesler_2021_Front.Plant.Sci_12_639401 PubMedSearch: Roesler 2021 Front.Plant.Sci 12 639401 PubMedID: 33986761 Gene_locus related to this paper: arath-AT5G62180 Abstract Severe drought stress can delay maize silk emergence relative to the pollen shedding period, resulting in poor fertilization and reduced grain yield. Methods to minimize the delay in silking could thus improve yield stability. An Arabidopsis enhancer-tagged carboxylesterase 20 (AtCXE20) line was identified in a drought tolerance screen. Ectopic expression of AtCXE20 in Arabidopsis and maize resulted in phenotypes characteristic of strigolactone (SL)-deficient mutants, including increased branching and tillering, decreased plant height, delayed senescence, hyposensitivity to ethylene, and reduced flavonols. Maize silk growth was increased by AtCXE20 overexpression, and this phenotype was partially complemented by exogenous SL treatments. In drought conditions, the transgenic maize plants silked earlier than controls and had decreased anthesis-silking intervals. The purified recombinant AtCXE20 protein bound SL in vitro, as indicated by SL inhibiting AtCXE20 esterase activity and altering AtCXE20 intrinsic fluorescence. Homology modeling of the AtCXE20 three-dimensional (3D) protein structure revealed a large hydrophobic binding pocket capable of accommodating, but not hydrolyzing SLs. The AtCXE20 protein concentration in transgenic maize tissues was determined by mass spectrometry to be in the micromolar range, well-above known endogenous SL concentrations. These results best support a mechanism where ectopic expression of AtCXE20 with a strong promoter effectively lowers the concentration of free SL by sequestration. This study revealed an agriculturally important role for SL in maize silk growth and provided a new approach for altering SL levels in plants. Title: Molecular cloning and characterization of an atypical butyrylcholinesterase-like protein in zebrafish Tan KS, Zhang Y, Liu L, Li S, Zou X, Zeng W, Cheng G, Wang D, Tan W Ref: Comparative Biochemistry & Physiology B Biochem Mol Biol, :110590, 2021 : PubMed ESTHER: Tan_2021_Comp.Biochem.Physiol.B.Biochem.Mol.Biol__110590 PubMedSearch: Tan 2021 Comp.Biochem.Physiol.B.Biochem.Mol.Biol 110590 PubMedID: 33662568 Gene_locus related to this paper: danre-a0a0r4iu19.1 Abstract Cholinesterases act as bio scavengers to clear organophosphorus (OP) compounds and prodrugs. The butyrylcholinesterase (BChE) gene has been found in several types of teleost fish but this gene has yet to be identified in cyprinid fish. Indeed, BChE homologs have not been found in the zebrafish (Danio rerio) genomic database. Here, we demonstrate that BChE activity is present in zebrafish, in line with other groups' findings. Using in-gel native-PAGE enzymatic activity staining and LC-MS/MS technique, an atypical BChE-like protein was identified in zebrafish. The si:ch211-93f2.1 gene was cloned, and His-tagged recombinant protein was expressed using the Pichia yeast system. The purified protein (molecular weight ~ 180 kDa) showed BChE activity, and degraded acetylcholinesterase (ACh) at a higher rate than BCh. However, phylogram analysis shows that this novel cholinesterase shared an evolutionary origin with carboxylic esterase rather than BChE. The zebrafish BChE-like protein shares structural characteristics with cholinesterase and carboxylesterase. The 2-arachidonoylglycerol (2-AG), nicosulfuron, and triacetin exhibited a higher binding affinity to the zebrafish BChE-like protein than BCh and ACh. With the identification of BChE-like protein in zebrafish, this study could shed light on the origin of BChE and may contribute towards the development of a BChE knockout zebrafish model for sensitive drug or toxin screening. Title: The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L and Wang A <3 more author(s)> Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L, Zhou G, Cui Y, Liu L, Wang A (- 3) Ref: Ecotoxicology & Environmental Safety, 228:112959, 2021 : PubMed ESTHER: Wang_2021_Ecotoxicol.Environ.Saf_228_112959 PubMedSearch: Wang 2021 Ecotoxicol.Environ.Saf 228 112959 PubMedID: 34808511 Abstract Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence. Title: Triphenyl phosphate disturbs the lipidome and induces endoplasmic reticulum stress and apoptosis in JEG-3 cells Wang Y, Hong J, Shi M, Guo L, Liu L, Tang H, Liu X Ref: Chemosphere, 275:129978, 2021 : PubMed ESTHER: Wang_2021_Chemosphere_275_129978 PubMedSearch: Wang 2021 Chemosphere 275 129978 PubMedID: 33662732 Inhibitor(s) related to this paper: TPHP Abstract Triphenyl phosphate (TPP) is a frequently used aryl organophosphate flame retardant. Epidemiological studies have shown that TPP and its metabolite diphenyl phosphate (DPP) can accumulate in the placenta, and positively correlated with abnormal birth outcomes. TPP can disturb placental hormone secretion through the peroxisome proliferator-activated receptor gamma (PPARgamma) pathway. However, the extent and mechanism of placental toxicity mediation by TPP remains unknown. In this study, we used JEG-3 cells to investigate the role of PPARgamma-regulated lipid metabolism in TPP-mediated placental toxicity. The results of lipidomic analysis showed that TPP increased the production of triglycerides (TG), fatty acids (FAs), and phosphatidic acid (PA), but decreased the levels of phosphatidylethanol (PE), phosphatidylserine (PS), and sphingomyelin (SM). TG accumulation was accompanied by increased levels of sterol regulatory element binding transcription factor 1 (SREBP1), acetyl-coA carboxylase (ACC), and fatty acid transport protein (CD36). Although PPARgamma and its target CCAAT/enhancer binding proteins (C/EBPalpha) was decreased, the TG content and gene expression of SREBP1, ACC, and CD36 decreased when TPP was co-exposed to the PPARgamma antagonist GW9662. TPP also induced inflammatory responses, endoplasmic reticulum stress (ERS), and cell apoptosis. Expression of genes related to ERS and apoptosis were attenuated by GW9662. Together, these results show that TPP can disturb lipid metabolism and cause lipid accumulation through PPARgamma, induce ERS, and cell apoptosis. Our findings reveal that the developmental toxicity of TPP through placental toxicity should not be ignored. Title: Case Report/Case Series: Rare case of anti-LGI1 limbic encephalitis with rapidly progressive dementia, psychiatric symptoms, and frequently seizures: A case report Wu H, Mei F, Liu L, Zhang L, Hao H, Zhang S Ref: Medicine (Baltimore), 100:e26654, 2021 : PubMed ESTHER: Wu_2021_Medicine.(Baltimore)_100_e26654 PubMedSearch: Wu 2021 Medicine.(Baltimore) 100 e26654 PubMedID: 34398024 Abstract RATIONALE: Anti leucine-rich glioma inactivated 1 (LGI1) limbic encephalitis (LE) is rare autoimmune encephalitis, characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, mental disorders, and refractory hyponatremia. As a type of treatable rapidly progressive dementia with a good prognosis, early, and accurate diagnosis is essential. We present a case of anti-LGI1 LE who was initially misdiagnosed with Alzheimer disease because his clinical manifestations were similar to Alzheimer disease. PATIENT CONCERNS: A male patient presenting with rapidly progressive dementia, faciobrachial dystonic seizures, psychiatric disturbance, and refractory hyponatremia was admitted. The scores of Mini-Mental State Examination, Montreal Cognitive Assessment, and Neuropsychiatric Inventory were 19/30, 16/30, and 91/144, respectively. Brain magnetic resonance images indicated moderate atrophy of the hippocampus and abnormally hyperintensities in the left medial temporal and hippocampus. DIAGNOSIS: The patient was diagnosed with anti-LGI1 LE based on the presence of LGI-1 antibodies in the cerebrospinal fluid and serum and clinical manifestations. INTERVENTIONS: Patient was treated with glucocorticoid against LGI1, antiepileptic drug, cholinesterase inhibitors, and other adjuvant therapy. OUTCOMES: The patient showed marked improvement on immunotherapy. Clinical symptoms were disappeared and the LGI-1 antibodies in cerebrospinal fluid and serum were both negative at the time of discharge. CONCLUSIONS: Recognition of the specific symptoms and LGI-1 antibody test will be helpful for the early diagnosis, prompt immunotherapy, and good prognosis. This case raises the awareness that rapidly progressive dementia with frequent seizures could be caused by immunoreactions. Title: Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1 Zhou L, Zhang C, Yang X, Liu L, Hu J, Hou Y, Tao H, Sugimura H, Chen Z and Chen K <1 more author(s)> Zhou L, Zhang C, Yang X, Liu L, Hu J, Hou Y, Tao H, Sugimura H, Chen Z, Wang L, Chen K (- 1) Ref: Clin Transl Med, 11:e449, 2021 : PubMed ESTHER: Zhou_2021_Clin.Transl.Med_11_e449 PubMedSearch: Zhou 2021 Clin.Transl.Med 11 e449 PubMedID: 34185414 Gene_locus related to this paper: human-CES1 Abstract BACKGROUND: Androgen deprivation therapy (ADT) is the main clinical treatment for patients with advanced prostate cancer (PCa). However, PCa eventually progresses to castration-resistant prostate cancer (CRPC), largely because of androgen receptor variation and increased intratumoral androgen synthesis. Several studies have reported that one abnormal lipid accumulation is significantly related to the development of PCa. Melatonin (MLT) is a functionally pleiotropic indoleamine molecule and a key regulator of energy metabolism. The aim of our study is finding the links between CRPC and MLT and providing the basis for MLT treatment for CRPC. METHODS: We used animal CRPC models with a circadian rhythm disorder, and PCa cell lines to assess the role of melatonin in PCa. RESULTS: We demonstrated that MLT treatment inhibited tumor growth and reversed enzalutamide resistance in animal CRPC models with a circadian rhythm disorder. A systematic review and meta-analysis demonstrated that MLT is positively associated with an increased risk of developing advanced PCa. Restoration of carboxylesterase 1 (CES1) expression by MLT treatment significantly reduced lipid droplet (LD) accumulation, thereby inducing apoptosis by increasing endoplasmic reticulum stress, reducing de novo intratumoral androgen synthesis, repressing CRPC progression and reversing the resistance to new endocrine therapy. Mechanistic investigations demonstrated that MLT regulates the epigenetic modification of CES1. Ces1-knockout (Ces(-/-) ) mice verified the important role of endogenous Ces1 in PCa. CONCLUSIONS: Our findings provide novel preclinical and clinical information about the role of melatonin in advanced PCa and characterize the importance of enzalutamide combined with MLT administration as a therapy for advanced PCa. Title: Goodyschle A, a new butenolide with significant BchE inhibitory activity from Goodyera schlechtendaliana Dai LY, Yin QM, Qiu JK, Zhang ZY, Li G, Huang MN, Liu L Ref: Nat Prod Res, :1, 2020 : PubMed ESTHER: Dai_2020_Nat.Prod.Res__1 PubMedSearch: Dai 2020 Nat.Prod.Res 1 PubMedID: 32208851 Inhibitor(s) related to this paper: Goodyschle-A Abstract Goodyschle A (1), a new butenolide, was isolated from the whole grass of Goodyera schlechtendaliana, an orchidaceous edible medicinal plant. The structure of the new compound was elucidated by 1 D and 2 D NMR experiments in addition to HRESIMS analyses. Compound 1 was evaluated for its bioactivities including cytotoxic activity against human gastric cancer (SGC-7901) and human hepatocellular carcinoma (HepG2) cell lines, inhibitory activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and DPPH radical scavenging activity. As a result, compound 1 showed potent BChE inhibitory activity (IC50 value = 6.88 +/- 1.63 muM), moderate DPPH radical scavenging activity (IC50 value = 16.25 +/- 0.21 muM), and slight AChE inhibitory and cytotoxic activities. These findings suggest that compound 1 is worthy for further investigations in terms of its selective BChE inhibitory activity. Title: Discovery and characterization of tannase genes in plants: roles in hydrolysis of tannins Dai X, Liu Y, Zhuang J, Yao S, Liu L, Jiang X, Zhou K, Wang Y, Xie D and Xia T <2 more author(s)> Dai X, Liu Y, Zhuang J, Yao S, Liu L, Jiang X, Zhou K, Wang Y, Xie D, Bennetzen JL, Gao L, Xia T (- 2) Ref: New Phytol, 226:1104, 2020 : PubMed ESTHER: Dai_2020_New.Phytol_226_1104 PubMedSearch: Dai 2020 New.Phytol 226 1104 PubMedID: 32061142 Gene_locus related to this paper: camsi-a0a5b9g8c2, jugre-JrTA, fraan-FaTA, vitvi-VvTA, citcl-CcTA, dioka-DkTA, camsi-CsTA Abstract Plant tannins, including condensed tannins (CTs) and hydrolyzable tannins (HTs), are widely distributed in the plant kingdom. To date, tannase (TA) - is a type of tannin acyl-hydrolase hydrolyzing HTs, CT monomer gallates and depsides - has been reported in microbes only. Whether plants express TA remains unknown. Herein, we report plant TA genes. A native Camellia sinensis TA (CsTA) is identified from leaves. Six TAs are cloned from tea, strawberry (Fragariasxsananassa, Fa) and four other crops. Biochemical analysis shows that the native CsTA and six recombinant TAs hydrolyze tannin compounds, depsides and phenolic glycosides. Transcriptional and metabolic analyses reveal that the expression of CsTA is oppositely associated with the accumulation of galloylated catechins. Moreover, the transient overexpression and RNA interference of FaTA are positively associated with the accumulation of ellagitannins in strawberry fruit. Phylogenetic analysis across different kingdoms shows that 29 plant TA homologs are clustered as a plant-specific TA clade in class I carboxylesterases. Further analysis across the angiosperms reveals that these TA genes are dispersed in tannin-rich plants, which share a single phylogenetic origin c. 120 million yr ago. Plant TA is discovered for the first time in the plant kingdom and is shown to be valuable to improve tannin compositions in plants. Title: miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2 He Y, Yang Y, Liao Y, Xu J, Liu L, Li C, Xiong X Ref: Mol Ther Oncolytics, 17:83, 2020 : PubMed ESTHER: He_2020_Mol.Ther.Oncolytics_17_83 PubMedSearch: He 2020 Mol.Ther.Oncolytics 17 83 PubMedID: 32322665 Gene_locus related to this paper: human-ABHD2 Abstract Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed abhydrolase domain containing 2 (ABHD2) to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, in vivo results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2. Title: Admission serum cholinesterase concentration for prediction of in-hospital mortality in very elderly patients with acute ischemic stroke: a retrospective study Li M, Chen Y, Zhang Y, Liu X, Xie T, Yin J, Wang L, Gang S, Chen J and Geng T <2 more author(s)> Li M, Chen Y, Zhang Y, Liu X, Xie T, Yin J, Wang L, Gang S, Chen J, Liu L, Yang F, Geng T (- 2) Ref: Aging Clin Exp Res, :, 2020 : PubMed ESTHER: Li_2020_Aging.Clin.Exp.Res__ PubMedSearch: Li 2020 Aging.Clin.Exp.Res PubMedID: 32067216 Abstract BACKGROUND: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (>/= 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged >/= 80 years) with acute ischemic stroke. METHODS: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged >/= 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. RESULTS: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34-0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. CONCLUSIONS: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS. Title: Three-dimensional brain-on-chip model using human iPSC-derived GABAergic neurons and astrocytes: Butyrylcholinesterase post-treatment for acute malathion exposure Liu L, Koo Y, Russell T, Gay E, Li Y, Yun Y Ref: PLoS ONE, 15:e0230335, 2020 : PubMed ESTHER: Liu_2020_PLoS.One_15_e0230335 PubMedSearch: Liu 2020 PLoS.One 15 e0230335 PubMedID: 32163499 Abstract Organophosphates (OPs) induce acute and chronic neurotoxicity, primarily by inhibiting acetylcholinesterase (AChE) activity as well as by necrosis, and apoptosis. Butyrylcholinesterase (BuChE), an exogenous bioscavenger of OPs, can be used as a treatment for OP exposure. It is prerequisite to develop in vitro brain models that can study BuChE post-treatment for acute OP exposure. In this study, we developed a three-dimensional (3D) brain-on-chip platform with human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes to simulate human brain behavior. The platform consists of two compartments: 1) a hydrogel embedded with human iPSC-derived GABAergic neurons and astrocytes and 2) a perfusion channel with dynamic medium flow. The brain tissue constructs were exposed to Malathion (MT) at various concentrations and then treated with BuChE after 20 minutes of MT exposure. Results show that the iPSC-derived neurons and astrocytes directly interacted and formed synapses in the 3D matrix, and that treatment with BuChE improved viability after MT exposure up to a concentration of 10-3 M. We conclude that the 3D brain-on-chip platform with human iPSC-derived brain cells is a suitable model to study the neurotoxicity of OP exposure and evaluate therapeutic compounds for treatment. Title: Neuroprotective Effects of D-(-)-Quinic Acid on Aluminum Chloride-Induced Dementia in Rats Liu L, Liu Y, Zhao J, Xing X, Zhang C, Meng H Ref: Evid Based Complement Alternat Med, 2020:5602597, 2020 : PubMed ESTHER: Liu_2020_Evid.Based.Complement.Alternat.Med_2020_5602597 PubMedSearch: Liu 2020 Evid.Based.Complement.Alternat.Med 2020 5602597 PubMedID: 32454864 Abstract Objective: The present study was designed to evaluate the neuroprotective effects of D-(-)-quinic acid on aluminum chloride- (AlCl3-) induced neurobehavioral and biochemical changes in rats. This study showed the behavioral and biochemical effects of D-(-)-quinic acid on rats with particular emphasis on the hippocampus and frontal cortex which are associated with memory. Materials and Methods: Chronic administration of aluminum chloride at a dose of 175 mg/kg, p.o. for a period of 25 days markedly increased the level of acetylcholinesterase (AChE) activity and reduced the levels of antioxidant enzymes in the brain. Two doses of D-(-)-quinic acid (200 mg/kg and 400 mg/kg) were selected based on previous safety/toxicity studies and administered orally from the 26th day to the 36th day of the trial. Behavioral parameters were assessed using the Morris water maze test and an actophotometer in rats. Biochemical parameter content and histology of brain tissue were assessed on the final day of the experiment. Results: D-(-)-Quinic acid (200 mg/kg and 400 mg/kg) orally administered alongside AlCl3 rescued AChE activity and the behavioral impairments caused by aluminum. There was significant inhibition of MAO-B in D-(-)-quinic acid-treated rats. Histopathological studies in the hippocampus and cortex of the rat brain also supported that D-(-)-quinic acid markedly reduced the toxicity of AlCl3 and preserved the normal histoarchitecture pattern of the hippocampus and cortex. These results indicate that D-(-)-quinic acid can reverse memory loss caused by aluminum intoxication by attenuating AChE activity and rescuing the deleterious effect of AlCl3. Title: ABHD11 Is Critical for Embryonic Stem Cell Expansion, Differentiation and Lipid Metabolic Homeostasis Liu G, Ruan Y, Zhang J, Wang X, Wu W, He P, Wang J, Xiong J, Cheng Y and Jian R <3 more author(s)> Liu G, Ruan Y, Zhang J, Wang X, Wu W, He P, Wang J, Xiong J, Cheng Y, Liu L, Yang Y, Tian Y, Jian R (- 3) Ref: Front Cell Developmental Biology, 8:570, 2020 : PubMed ESTHER: Liu_2020_Front.Cell.Dev.Biol_8_570 PubMedSearch: Liu 2020 Front.Cell.Dev.Biol 8 570 PubMedID: 32733886 Gene_locus related to this paper: human-ABHD11 Abstract Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, alpha/beta-hydrolase domain-containing (ABHD) proteins have emerged as novel pivotal regulators in lipid synthesis or degradation while their functions in ESCs have not been investigated. In this study, we revealed the role of ABHD11 in ESC function using classical loss and gain of function experiments. Knockout of Abhd11 hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast, Abhd11 overexpression exerted anti-apoptotic effects in ESCs. Moreover, Abhd11 knockout disturbed GSK3beta/beta-Catenin and ERK signaling transduction. Finally, Abhd11 knockout led to the misexpression of key metabolic enzymes related to lipid synthesis, glycolysis, and amino acid metabolism, and ABHD11 contributed to the homeostasis of lipid metabolism. These findings provide new insights into the broad role of ABHD proteins and highlight the significance of regulators of lipid metabolism in the control of stem cell function. Title: MicroRNA-544 attenuates diabetic renal injury via suppressing glomerulosclerosis and inflammation by targeting FASN Sun T, Liu Y, Liu L, Ma F Ref: Gene, 723:143986, 2020 : PubMed ESTHER: Sun_2020_Gene_723_143986 PubMedSearch: Sun 2020 Gene 723 143986 PubMedID: 31323309 Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Accumulating evidence shows that microRNAs play important roles in diabetic kidney. However, the potential role of MicroRNA-544 (miR-544) in DN remains unclear. In this study, we explored the role of miR-544 on inflammation and fibrosis in diabetic kidney using db/db mice. Renal expression of miR-544 was decreased in mice, companied by increased the expression of FASN. The dual luciferase assay confirmed FASN as a direct target of miR-544. Over-expression of miR-544 significantly ameliorated renal injury, mesangial matrix and renal fibrosis. In addition, over-expression of miR-544 significantly attenuated inflammatory cells infiltration and IL-1, IL-6, TNF- and iNOS production in DN. Furthermore, miR-544 over-expression inhibited the activation of NF-kB signal pathway in DN. In conclusion, our finding demonstrated that miR-544 attenuates diabetic renal injury via suppressing glomerulosclerosis and inflammation by targeting FASN, suggesting that miR-544 might have therapeutic potential for the treatment of DN. Title: Physiologically-Based Pharmacokinetic-Pharmacodynamics Model Characterizing CYP2C19 Polymorphisms to Predict Clopidogrel Pharmacokinetics and Its Anti-Platelet Aggregation Effect Following Oral Administration to Coronary Artery Disease Patients With or Without Diabetes Xu RJ, Kong WM, An XF, Zou JJ, Liu L, Liu XD Ref: Front Pharmacol, 11:593982, 2020 : PubMed ESTHER: Xu_2020_Front.Pharmacol_11_593982 PubMedSearch: Xu 2020 Front.Pharmacol 11 593982 PubMedID: 33519456 Abstract Background and Objective: Clopidogrel (CLOP) is commonly used in coronary artery disease (CAD) patients with or without diabetes (DM), but these patients often suffer CLOP resistance, especially those with diabetes. This study was aimed to develop a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to describe the pharmacokinetics and pharmacodynamics of clopidogrel active metabolite (CLOP-AM) in CAD patients with or without DM. Methods: The PBPK-PD model was first established and validated in healthy subjects and then in CAD patients with or without DM. The influences of CYP2C19, CYP2C9, CYP3A4, carboxylesterase 1 (CES1), gastrointestinal transit rates (K (t,i)) and platelets response to CLOP-AM (k (irre)) on predicted pharmacokinetics and pharmacodynamics were investigated, followed with their individual and integrated effects on CLOP-AM pharmacokinetics due to changes in DM status. Results: Most predictions fell within 0.5-2.0 folds of observations, indicating successful predictions. Sensitivity analysis showed that contributions of interested factors to pharmacodynamics were CES1> k (irre)> K (t,i)> CYP2C19 > CYP3A4> CYP2C9. Mimicked analysis showed that the decreased exposure of CLOP-AM by DM was mainly attributed to increased CES1 activity, followed by decreased CYP2C19 activity. Conclusion: The pharmacokinetics and pharmacodynamics of CLOP-AM were successfully predicted using the developed PBPK-PD model. Clopidogrel resistance by DM was the integrated effects of altered K (t,i), CYP2C19, CYP3A4, CES1 and k (irre). Title: FAM172A promotes follicular thyroid carcinogenesis and may be a marker of FTC Xu PP, Zeng S, Xia XT, Ye ZH, Li MF, Chen MY, Xia T, Xu JJ, Jiao Q and Guo MG <2 more author(s)> Xu PP, Zeng S, Xia XT, Ye ZH, Li MF, Chen MY, Xia T, Xu JJ, Jiao Q, Liu L, Li LX, Guo MG (- 2) Ref: Endocr Relat Cancer, 27:657, 2020 : PubMed ESTHER: Xu_2020_Endocr.Relat.Cancer_27_657 PubMedSearch: Xu 2020 Endocr.Relat.Cancer 27 657 PubMedID: 33095186 Gene_locus related to this paper: mouse-f172a, human-f172a Abstract Our aims were to uncover the role of FAM172A (Family with sequence similarity 172 member A) in the pathogenesis of follicular thyroid carcinoma (FTC) and to evaluate its value in the differential diagnosis between malignant and benign thyroid follicular lesions. FAM172A expression was evaluated by q-PCR, immunoblotting and immunohistochemistry (IHC). The ability of proliferation, migration and invasion of cells were assessed by Cell Counting Kit-8 assay (CCK8), clone-formation and Transwell assays. Nude mouse tumorigenicity assays were used to investigate the role of FAM172A in the pathogenesis of FTC in vivo. The value of FAM172A in the differential diagnosis for FTC was assessed using 120 formalin-fixed paraffin-embedded (FFPE) tissues after the operation and 81 fine-needle aspiration biopsy (FNAB) samples before the operation. FAM172A was highly expressed in FTC tissues and FTC cell lines. Downregulation of FAM172A inhibited the proliferation, invasion and migration of FTC cells through Erk1/2 and JNK pathways. Subcutaneous tumorigenesis in nude mice showed that knockdown of FAM172A inhibited tumor growth and progression in vivo. The FAM172A IHC scores of 3.5 had 92% sensitivity and 63% specificity to separate FTC from benign/borderline thyroid follicular lesions, and 92% sensitivity and 80% specificity to discriminate FTC from benign thyroid follicular lesions in postoperative FFPE samples. The corresponding values were 75 and 78%, and 75 and 89% in preoperative FNA samples, respectively. FAM172A plays an important role in the pathogenesis of FTC through Erk1/2 and JNK pathways. FAM172A may be a potential marker for the preoperative diagnosis of FTC based on the IHC results of thyroid FNAB samples. Title: A Soluble Epoxide Hydrolase Inhibitor Upregulated KCNJ12 and KCNIP2 by Downregulating MicroRNA-29 in a Mouse Model of Myocardial Infarction Zhang X, Liao C, Sun K, Liu L, Xu D Ref: Heart Surg Forum, 23:E579, 2020 : PubMed ESTHER: Zhang_2020_Heart.Surg.Forum_23_E579 PubMedSearch: Zhang 2020 Heart.Surg.Forum 23 E579 PubMedID: 32990585 Abstract BACKGROUND: Soluble epoxide hydrolase inhibitors (sEHi) have anti-arrhythmic effects, and we previously found that the novel sEHi t-AUCB (trans-4[-4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) significantly inhibited ventricular arrhythmias after myocardial infarction (MI). However, the mechanism is unknown. It's known that microRNA-29 (miR-29) participates in the occurrence of arrhythmias. In this study, we investigated whether sEHi t-AUCB was protective against ischemic arrhythmias by modulating miR-29 and its target genes KCNJ12 and KCNIP2. METHODS: Male 8-week-old C57BL/6 mice were divided into five groups and fed distilled water only or distilled water with t-AUCB of different dosages for seven days. Then, the mice underwent MI or sham surgery. The ischemic region of the myocardium was obtained 24 hours after MI to detect miR-29, KCNJ12, and KCNIP2 mRNA expression levels via real-time PCR and KCNJ12 and KCNIP2 protein expression levels via western blotting. RESULTS: MiR-29 expression levels were significantly increased in the ischemic region of MI mouse hearts and the mRNA and protein expression levels of its target genes KCNJ12 and KCNIP2 were significantly decreased. T-AUCB prevented these changes dose-dependently. CONCLUSION: The sEHi t-AUCB regulates the expression levels of miR-29 and its target genes KCNJ12 and KCNIP2, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmia. Title: The discovery of azetidine-piperazine di-amides as potent, selective and reversible monoacylglycerol lipase (MAGL) inhibitors Zhu B, Connolly PJ, Zhang YM, McDonnell ME, Bian H, Lin SC, Liu L, Zhang SP, Chevalier KM and Macielag MJ <3 more author(s)> Zhu B, Connolly PJ, Zhang YM, McDonnell ME, Bian H, Lin SC, Liu L, Zhang SP, Chevalier KM, Brandt MR, Milligan CM, Flores CM, Macielag MJ (- 3) Ref: Bioorganic & Medicinal Chemistry Lett, 30:127243, 2020 : PubMed ESTHER: Zhu_2020_Bioorg.Med.Chem.Lett_30_127243 PubMedSearch: Zhu 2020 Bioorg.Med.Chem.Lett 30 127243 PubMedID: 32527545 Gene_locus related to this paper: human-MGLL Abstract Monoacylglycerol lipase (MAGL) is the enzyme that is primarily responsible for hydrolyzing the endocannabinoid 2-arachidononylglycerol (2-AG) to arachidonic acid (AA). It has emerged in recent years as a potential drug target for a number of diseases. Herein, we report the discovery of compound 6g from a series of azetidine-piperazine di-amide compounds as a potent, selective, and reversible inhibitor of MAGL. Oral administration of compound 6g increased 2-AG levels in rat brain and produced full efficacy in the rat complete Freund's adjuvant (CFA) model of inflammatory pain. Title: Effects of Bread Yeast Cell Wall Beta-Glucans on Mice with Loperamide-Induced Constipation Chen Z, Lin S, Jiang Y, Liu L, Jiang J, Chen S, Tong Y, Wang P Ref: J Med Food, 22:1009, 2019 : PubMed ESTHER: Chen_2019_J.Med.Food_22_1009 PubMedSearch: Chen 2019 J.Med.Food 22 1009 PubMedID: 31536448 Abstract Constipation is a common gastrointestinal disorder characterized by changes in intestinal habits. Increasing evidence indicates that long-term use of irritant laxatives causes serious side effects. Meanwhile, more than 50% of patients are dissatisfied with sense of use of non-prescriptional laxatives. beta-glucans are natural polysaccharides widely found in yeast, fungus, and plants, which have been reported to exhibit various pharmacological effects. The aim of this study was to characterize the effect of beta-glucans extracted from the bread yeast cell wall on loperamide-induced constipation mice. Forty mice were fed with loperamide (10 mg/kg) to make the constipation model and a diet supplemented with 2.5, 5, and 10 mg/kg beta-glucan. We assessed the defecation frequency, intestinal transit function of mice, as well as used high-throughput sequencing to analyze the intestinal microbiota composition and functional biological profiles data. Meanwhile, we detected expression of neurotransmitters including acetylcholinesterase, substance P, and serotonin (5-HT) and expression of tight junction protein (TJP) including zonula occludens-1 and mucin-2 in distal colon to characterize the possible molecular mechanisms. beta-glucans significantly enhanced intestinal motility and provided a possibility to regulate the expression of neurotransmitters and TJP in mice. The intestinal microecological portion of the treatment group partially recovered and was closer to the normal group. This study showed that beta-glucans can influence the intestinal microbiota and restore microecological balance to regulate the express of neurotransmitters and TJP to recover intestinal epithelial mechanical barrier. We suggested that beta-glucans could be used as an active nutritional supplement to protect the damaged intestinal barrier and help patients who have constipation complications and dysbiosis. Title: Chemical characterization of the main bioactive polyphenols from the roots of Morus australis (mulberry) Guo S, Liu L, Zhang S, Yang C, Yue W, Zhao H, Ho CT, Du J, Zhang H, Bai N Ref: Food Funct, 10:6915, 2019 : PubMed ESTHER: Guo_2019_Food.Funct_10_6915 PubMedSearch: Guo 2019 Food.Funct 10 6915 PubMedID: 31588440 Abstract Morus species, commonly known as mulberry, is widely distributed in China. The mulberry tree is a high-value plant in agriculture. Morus australis is one of the major Morus species growing in Northern China. However, the biological properties of the main constituents of M. australis roots were not well studied. In the present study, through extensive chromatographic and spectral analysis, 12 phenolic compounds were isolated and identified from the M. australis roots. Compounds 1, 2, 8, 9 and 12 were isolated from M. australis roots for the first time. Antitumor activities of these polyphenols were studied on the A549 cell line. Compounds 1, 5 and 6 exhibited cytotoxicity on A549 cells and induced apoptosis in A549 cells via the intrinsic mitochondrial pathway. They also mediated inhibition of autophagic flux contributed cell death via the PI3k/Akt/mTOR pathway. In order to explore more potential bioactivities of these isolates, alpha-glucosidase, acetylcholinesterase and tyrosinase inhibitory activities were studied, and the results demonstrated that the inhibitory activity of these polyphenols on enzymes was not defined by their basic structural skeletons, but by the substituted position. Title: Long noncoding RNA ABHD11-AS1 promote cells proliferation and invasion of colorectal cancer via regulating the miR-1254-WNT11 pathway He D, Yue Z, Liu L, Fang X, Chen L, Han H Ref: Journal of Cellular Physiology, 234:12070, 2019 : PubMed ESTHER: He_2019_J.Cell.Physiol_234_12070 PubMedSearch: He 2019 J.Cell.Physiol 234 12070 PubMedID: 30537177 Gene_locus related to this paper: human-ABHD11 Abstract The purpose of our study was to investigate the effects of the long noncoding RNA (lncRNA) ABHD11-AS1 on colorectal cancer (CRC) progression and further explore its possible underlying mechanisms. In the study, we found that ABHD11-AS1 was highly expressed in CRC tissues and cell lines. High ABHD11-AS1 expression was correlated with poor overall survival of patients with CRC. ABHD11-AS1 knockdown reduced CRC cell proliferation, in vitro invasion, and in vivo tumor growth. Investigation of the underlying mechanism showed that ABHD11-AS1 could act as a molecular sponge of miR-1254, and WNT11 was a downstream target of miR-1254 in CRC. Moreover, there was a negative association between ABHD11-AS1 expression (or WNT11) and miR-1254 in CRC tissues. The rescue assays showed that WNT11 overexpression partially rescued the effects of ABHD11-AS1 inhibition on CRC progression. Thus, we demonstrated that ABHD11-AS1 promotes CRC progression through the miR-1254-WNT11 pathway, which provides a new insight into the therapeutic strategies for CRC. Title: New biphenanthrenes with butyrylcholinesterase inhibitory activitiy from Cremastra appendiculata Liu L, Yin QM, Gao Q, Li J, Jiang Y, Tu PF Ref: Nat Prod Res, :1, 2019 : PubMed ESTHER: Liu_2019_Nat.Prod.Res__1 PubMedSearch: Liu 2019 Nat.Prod.Res 1 PubMedID: 31117825 Abstract Encouraged by the in vitro potent inhibitory activity on butyrylcholinesterase (BChE) of 95% ethanol extract of Cremastra appendiculata (D. Don) Makino tubers, a further phytochemical investigation on C. appendiculata tubers was conducted, which led to the isolation of a pair of new biphenanthrene atropisomers, namely cremaphenanthrene F-G (1-2). Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical method. It is the first time that biphenanthrene atropisomers have been isolated from the plant kingdom. Compound 1 showed potent BChE inhibitory effect with IC50 value of 14.62 +/- 2.15 muM. Compound 2 exhibited weak BChE inhibitory effect with IC50 value of 79.56 +/- 0.78 muM. Meanwhile, 1 and 2 were found to be inactive for acetylcholinesterase (AChE) inhibition. These findings suggested that compound 1 was a promising selective BChE inhibitor for AD prevention and treatment. Title: Structural and functional abnormalities of motor endplates in rat skeletal model of myofascial trigger spots Liu QG, Huang QM, Liu L, Nguyen TT Ref: Neuroscience Letters, :134417, 2019 : PubMed ESTHER: Liu_2019_Neurosci.Lett__134417 PubMedSearch: Liu 2019 Neurosci.Lett 134417 PubMedID: 31398457 Abstract Myofascial trigger points (MTrPs) are defined as hyperirritable spots in a palpable taut band (TB) of skeletal muscle fibers. Knowing the formation and location of MTrPs is a great help to prevent their development and inactivate existing MTrPs. This study aimed to obtain new evidence that myofascial trigger spots (MTrSs), which are similar to human MTrPs, are found in dysfunctional motor endplates by observing the morphological characteristics of muscles and changes in biochemical substances. A total of 32 male Sprague Dawley rats were randomly divided into four groups: two control groups (i.e., C1 and C2) and two model groups (i.e., M1 and M2). C1 and M1 were used for acetylcholine (ACh) content measurement, while C2 and M2 were utilized for acetylcholinesterase (AChE) staining. In the model groups, blunt striking injury was induced and eccentric exercise was applied to the left gastrocnemius for 8 weeks. After 1 month, spontaneous electrical activity(SEA), AChE optical density (OD), muscle fiber diameter, and ACh content were measured. The results showed that extensive abnormal endplate noise (aEPN), including positive neurons, fibrillation potentials, fasciculation potential, and high amplitude (endplate spikes [EPS]), is present at MTrSs in M1. Quantitative electromyography results showed that the amplitudes of aEPN and frequency of EPS in M1 were significantly higher than those of C1. The ACh content of MTrSs in M1 was significantly higher than that in C1. The AChE OD value of M2 was significantly lower than that of C2. In addition, the diameter of the muscle fibers in the AChE-stained area was longer in M2 than in C2. In conclusion, MTrSs formed at the motor endplate with a larger diameter of muscle fibers. Excessive ACh release and decreased AChE activity at MTrSs stimulated muscle action potential and muscle contraction. Title: Three-dimensional (3D) brain microphysiological system for organophosphates and neurochemical agent toxicity screening Liu L, Koo Y, Akwitti C, Russell T, Gay E, Laskowitz DT, Yun Y Ref: PLoS ONE, 14:e0224657, 2019 : PubMed ESTHER: Liu_2019_PLoS.One_14_e0224657 PubMedSearch: Liu 2019 PLoS.One 14 e0224657 PubMedID: 31703066 Abstract We investigated a potential use of a 3D tetraculture brain microphysiological system (BMPS) for neurotoxic chemical agent screening. This platform consists of neuronal tissue with extracellular matrix (ECM)-embedded neuroblastoma cells, microglia, and astrocytes, and vascular tissue with dynamic flow and membrane-free culture of the endothelial layer. We tested the broader applicability of this model, focusing on organophosphates (OPs) Malathion (MT), Parathion (PT), and Chlorpyrifos (CPF), and chemicals that interact with GABA and/or opioid receptor systems, including Muscimol (MUS), Dextromethorphan (DXM), and Ethanol (EtOH). We validated the BMPS platform by measuring the neurotoxic effects on barrier integrity, acetylcholinesterase (AChE) inhibition, viability, and residual OP concentration. The results show that OPs penetrated the model blood brain barrier (BBB) and inhibited AChE activity. DXM, MUS, and EtOH also penetrated the BBB and induced moderate toxicity. The results correlate well with available in vivo data. In addition, simulation results from an in silico physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model that we generated show good agreement with in vivo and in vitro data. In conclusion, this paper demonstrates the potential utility of a membrane-free tetraculture BMPS that can recapitulate brain complexity as a cost-effective alternative to animal models. Title: Cholinergic M4 receptors are involved in morphine-induced expression of behavioral sensitization by regulating dopamine function in the nucleus accumbens of rats Ruan H, Sun J, Liu X, Liu L, Cui R, Li X Ref: Behavioural Brain Research, 360:128, 2019 : PubMed ESTHER: Ruan_2019_Behav.Brain.Res_360_128 PubMedSearch: Ruan 2019 Behav.Brain.Res 360 128 PubMedID: 30529589 Abstract Repeated administration of morphine profoundly influences the dopaminergic and cholinergic systems in the nucleus accumbens [including the shell of the nucleus accumbens (NAcS)]. Further, dopamine release is regulated by the cholinergic system, especially the M4 receptor. Drug priming is one of the main factors that induces relapse in drug addiction. The present study first investigated how activation of the M4 receptor in the NAcS affects the expression of morphine-induced behavioral sensitization, through the administration of an M4 agonist (LY2033298) and antagonist (tropicamide), as well as a combination of an acetylcholinesterase inhibitor and M4 antagonist (huperzine-A + tropicamide). Additionally, the influence of a dopamine receptor agonist, in conjunction with an M4 agonist (i.e., SKF38393 + LY2033298), was also examined. Behavioral sensitization was established by exposure to 5 mg/kg morphine once every three days for a total of three exposures. The expression of behavioral sensitization was challenged by 5 mg/kg morphine. Results showed that (1) microinjection of the M4 receptor agonist LY2033298 (0.2 mug/side), but not the antagonist tropicamide (5, 10, or 20 muM/side) into the NAcS blocked the expression of behavioral sensitization; (2) tropicamide (20 muM/side) reversed the inhibition effect of huperzine-A on this behavior; and (3) SKF38393 (1 mug/side) reversed the inhibitory effect of LY2033298 on the expression of morphine-induced behavioral sensitization. These results suggest that the cholinergic M4 receptor in the NAcS plays an important role in the morphine-induced expression of behavioral sensitization through the regulation of dopamine function in rats. Title: Determination of Genetic Effects of LIPK and LIPJ Genes on Milk Fatty Acids in Dairy Cattle Shi L, Han B, Liu L, Lv X, Ma Z, Li C, Xu L, Li Y, Zhao F and Sun D <1 more author(s)> Shi L, Han B, Liu L, Lv X, Ma Z, Li C, Xu L, Li Y, Zhao F, Yang Y, Sun D (- 1) Ref: Genes (Basel), 10:, 2019 : PubMed ESTHER: Shi_2019_Genes.(Basel)_10_ PubMedSearch: Shi 2019 Genes.(Basel) 10 PubMedID: 30696079 Gene_locus related to this paper: bovin-e1bnt1, bovin-f1msa3, human-LIPJ, human-LIPK Abstract In our previous genome-wide association study (GWAS) on milk fatty acids (FAs) in Chinese Holstein, we discovered 83 genome-wide significant single nucleotide polymorphisms (SNPs) associated with milk FAs. Two of them were close to lipase family member K (LIPK) and lipase family member J (LIPJ), respectively. Hence, this study is a follow-up to verify whether the LIPK and LIPJ have significant genetic effects on milk FAs in dairy cattle. By re-sequencing the entire exons, and 3 kb of 5' and 3' flanking regions, two and seven SNPs were identified in LIPK and LIPJ, respectively, including a novel SNP, ss158213049726. With the Haploview 4.1 software, we found that five of the SNPs in LIPJ formed a haplotype block (D' = 0.96 ~ 1.00). Single-locus association analyses revealed that each SNP in LIPK and LIPJ was significantly associated with at least one milk FA (p = < 1.00x10(-4) ~ 4.88x10(-2)), and the haplotype-based association analyses showed significant genetic effects on nine milk FAs (p = < 1.00x10(-4) ~ 3.98x10(-2)). Out of these SNPs, the missense mutation in LIPK gene, rs42774527, could change the protein secondary structure and function predicted by SOPMA, SIFT, and PROVEAN softwares. With the Genomatix software, we predicted that two SNPs, rs110322221 in LIPK and rs211373799 in LIPJ, altered the transcription factors binding sites (TFBSs), indicating their potential regulation on promoter activity of the genes. Furthermore, we found that both LIPK and LIPJ had relatively high expressions in the mammary gland. In conclusion, our research is the first to demonstrate that LIPK and LIPJ genes have significant associations with milk FAs, and the identified SNPs might be served as genetic markers to optimize breeding programs for milk FAs in dairy cattle. This research deserves in-depth verification. Title: Accumulation, biodegradation and toxicological effects of N-ethyl perfluorooctane sulfonamidoethanol on the earthworms Eisenia fetida exposed to quartz sands Zhao S, Liu T, Wang B, Fu J, Liang T, Zhong Z, Zhan J, Liu L Ref: Ecotoxicology & Environmental Safety, 181:138, 2019 : PubMed ESTHER: Zhao_2019_Ecotoxicol.Environ.Saf_181_138 PubMedSearch: Zhao 2019 Ecotoxicol.Environ.Saf 181 138 PubMedID: 31176248 Abstract While N-ethyl perfluorooctane sulfonamidoethanol (EtFOSE) is a precursor of perfluorooctane sulfonate (PFOS), its bioaccumulation, transformation and toxicological effects in earthworms (Eisenia fetida) exposed to quartz sands are poorly understood. The present study showed that except for parent EtFOSE, N-ethylperfluorooctane sulfonamide acetate (EtFOSAA), N-ethyl perfluorooctane sulfonamide (EtFOSA), perfluorooctane sulfonamide acetate (FOSAA), perfluorooctane sulfonamide (FOSA) and PFOS were detected in earthworms, with EtFOSAA as the primary biotransformation product. The biota-to-sand accumulation factor (BSAF) and uptake rate coefficient (ku) of EtFOSE were 5.7 and 0.542/d, respectively. The elimination rate constants (ke) decreased in the order EtFOSA (0.167/d) approximately FOSAA (0.147/d)>FOSA (0.119/d) approximately EtFOSAA (0.117/d)>EtFOSE (0.095/d)>PFOS (0.069/d). No significant effects were observed in malondialdehyde (MDA) contents and acetylcholinesterase (AChE) activities between EtFOSE treatments and controls. EtFOSE could cause significant accumulation of reactive oxygen species (ROS) in earthworms. Peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were significantly activated by 41.4-74.3%, 37.2-44.4% and 32.4-52.3% from day 4-10, respectively, while 8-Hydroxy-2-deoxyguanosine (8-OHdG) levels were elevated by 47.7-70.3% from day 8-10, demonstrating that EtFOSE induced oxidative stress and oxidative DNA damage in earthworms. Significant increase of glutathione-S-transferase (GST) with 41.6-62.8% activation (8-10d) gave indirect evidence on the conjugation of EtFOSE or its corresponding metabolites during phase II of detoxication. This study provides important information on the fate and potential risks of EtFOSE to terrestrial invertebrates. Title: Inhibiting Abeta toxicity in Alzheimer's disease by a pyridine amine derivative Zhu Z, Yang T, Zhang L, Liu L, Yin E, Zhang C, Guo Z, Xu C, Wang X Ref: Eur Journal of Medicinal Chemistry, 168:330, 2019 : PubMed ESTHER: Zhu_2019_Eur.J.Med.Chem_168_330 PubMedSearch: Zhu 2019 Eur.J.Med.Chem 168 330 PubMedID: 30826509 Abstract Alzheimer's disease (AD) is a neurodegenerative disorder with no radical therapy. Aggregation of amyloid beta-peptide (Abeta) induced by various factors is associated with pathogenesis of AD. A pyridine amine derivative, 3-bis(pyridin-2-ylmethyl)aminomethyl-5-hydroxybenzyltriphenylphosphonium bromide (PAT), is synthesized. The inhibition of self- and metal-induced Abeta aggregation by PAT is confirmed by thioflavine T fluorescence, circular dichroism spectroscopy, and TEM. Western blot, RT-PCR and fluorescence imaging indicate that PAT can alleviate the Abeta-induced paralysis, reduce the production of ROS, and protect the mitochondrial function in transgenic C. elegans. Genetic analyses indicate that heat shock protein is involved in the alleviation of Abeta toxicity. PAT also inhibits the activity of acetylcholinesterase in C. elegans. Morris water maze test shows that the memory and cognitive ability of APP/PS1 AD model mice are significantly improved by PAT. Both in vitro and in vivo studies demonstrate that PAT is effective in counteracting Abeta toxicity and ameliorating cognitive functions in AD mice, and therefore a potential lead compound of anti-AD drugs. Title: Structure of the G119S Mutant Acetylcholinesterase of the Malaria Vector Anopheles gambiae Reveals Basis of Insecticide Resistance Cheung J, Mahmood A, Kalathur R, Liu L, Carlier PR Ref: Structure, 26:130, 2018 : PubMed ESTHER: Cheung_2018_Structure_26_130 PubMedSearch: Cheung 2018 Structure 26 130 PubMedID: 29276037 Gene_locus related to this paper: anoga-ACHE1 Inhibitor(s) related to this paper: Difluoromethyl-ketone-BT7 Abstract Malaria is a devastating disease in sub-Saharan Africa and is transmitted by the mosquito Anopheles gambiae. While indoor residual spraying of anticholinesterase insecticides has been useful in controlling the spread of malaria, widespread application of these compounds has led to the rise of an insecticide-resistant mosquito strain that harbors a G119S mutation in the nervous system target enzyme acetylcholinesterase. We demonstrate the atomic basis of insecticide resistance through structure determination of the G119S mutant acetylcholinesterase of An. gambiae in the ligand-free state and bound to a potent difluoromethyl ketone inhibitor. These structures reveal specific features within the active-site gorge distinct from human acetylcholinesterase, including an open channel at the base of the gorge, and provide a means for improving species selectivity in the rational design of improved insecticides for malaria vector control. Title: Structure-activity relationship investigation of tertiary amine derivatives of cinnamic acid as acetylcholinesterase and butyrylcholinesterase inhibitors: compared with that of phenylpropionic acid, sorbic acid and hexanoic acid Gao X, Tang J, Liu H, Liu L, Kang L, Chen W Ref: J Enzyme Inhib Med Chem, 33:519, 2018 : PubMed ESTHER: Gao_2018_J.Enzyme.Inhib.Med.Chem_33_519 PubMedSearch: Gao 2018 J.Enzyme.Inhib.Med.Chem 33 519 PubMedID: 29447012 Abstract In the present investigation, 48 new tertiary amine derivatives of cinnamic acid, phenylpropionic acid, sorbic acid and hexanoic acid (4d-6g, 10d-12g, 16d-18g and 22d-24g) were designed, synthesized and evaluated for the effect on AChE and BChE in vitro. The results revealed that the alteration of aminoalkyl types and substituted positions markedly influences the effects in inhibiting AChE. Almost of all cinnamic acid derivatives had the most potent inhibitory activity than that of other acid derivatives with the same aminoalkyl side chain. Unsaturated bond and benzene ring in cinnamic acid scaffold seems important for the inhibitory activity against AChE. Among them, compound 6g revealed the most potent AChE inhibitory activity (IC50 value: 3.64 micromol/L) and highest selectivity over BChE (ratio: 28.6). Enzyme kinetic study showed that it present a mixed-type inhibition against AChE. The molecular docking study suggested that it can bind with the catalytic site and peripheral site of AChE. Title: Transfection of neurotrophin-3 into neural stem cells using ultrasound with microbubbles to treat denervated muscle atrophy Gong L, Jiang C, Liu L, Wan S, Tan W, Ma S, Jia X, Wang M, Hu A and Chen Y <4 more author(s)> Gong L, Jiang C, Liu L, Wan S, Tan W, Ma S, Jia X, Wang M, Hu A, Shi Y, Zhang Y, Shen Y, Wang F, Chen Y (- 4) Ref: Exp Ther Med, 15:620, 2018 : PubMed ESTHER: Gong_2018_Exp.Ther.Med_15_620 PubMedSearch: Gong 2018 Exp.Ther.Med 15 620 PubMedID: 29403547 Abstract Neurotrophin-3 (NT-3) has potential as a therapeutic agent for the treatment of patients with denervated muscle atrophy. However, the endogenous secretion of NT-3 is low and exogenous NT-3 lacks sufficient time to accumulate due to its short half-life. The transfection of NT-3 has been demonstrated to have a beneficial effect on denervated muscle and motor endplates. Neural stem cells (NSCs) differentiate into neurons and form motor endplate nerve-muscle connections. It has been previously demonstrated that local and noninvasive transfection can be performed using ultrasound with microbubbles (MBs). In the current study, hematoxylin and eosin, acetylcholinesterase and gold chloride staining, as well as transmission electron microscopy, were performed to verify the effects of this treatment strategy. The results demonstrated that using ultrasound with MBs for the transfection of NT-3 into NSCs, and their subsequent transplantation in vivo, attenuated the atrophy of denervated muscle and reduced motor endplate degeneration. This noninvasive, efficient and targeted treatment strategy may therefore be a potential treatment for patients with denervated muscle atrophy. Title: Fluorescein as a Visible-Light-Induced Oxidase Mimic for Signal-Amplified Colorimetric Assay of Carboxylesterase by an Enzymatic Cascade Reaction Liu L, Sun C, Yang J, Shi Y, Long Y, Zheng H Ref: Chemistry, 24:6148, 2018 : PubMed ESTHER: Liu_2018_Chemistry_24_6148 PubMedSearch: Liu 2018 Chemistry 24 6148 PubMedID: 29493016 Abstract We have found that fluorescein possesses high visible-light-induced oxidase mimetic activity and could transform colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB) without unstable and destructive H2 O2 under visible-light illumination. Instead, fluorescein uses oxygen as a mild and green electron acceptor, and its activity can be easily controlled by the switching "on/off" of visible light. In addition, the visible-light-induced catalytic mechanism was elucidated in detail and, as the main reactive species h(+) and O2(.-) accounted for TMB oxidation. Based on the fact that fluorescein diacetate (FDA) possessed no activity and generated active fluorescein in situ in the presence of carboxylesterase (CaE), a signal-amplified sensing platform through a cascade reaction for CaE detection was constructed. Our proposed sensing system displayed excellent analytical performance for the detection of CaE in a wide linear range from 0.040 to 20 U L(-1) with a low detection limit of 0.013 U L(-1) . This work not only changes the conventional concept that fluorescein is generally considered to be photocatalytically inert, but also provides a novel sensing strategy by tailoring the enzyme mimetic activity of fluorescein derivatives with analyte. Title: Two new prenylated C6-C3 compounds from Illicium micranthum Dunn Liu L, Lv XM, Hua T, Khan A, Huang XB, Wang YF, Zhou ZH Ref: Nat Prod Res, :1, 2018 : PubMed ESTHER: Liu_2018_Nat.Prod.Res__1 PubMedSearch: Liu 2018 Nat.Prod.Res 1 PubMedID: 30450961 Abstract Phytochemical investigation of Illicium micranthum led to the isolation of two new prenylated C6-C3 compounds, 12-O-methyl-2,3-dehydroillifunone C (1) and illiciminone A (2), together with three known analogues (3-5) and one known sesquiterpene lactone (6). The structures were established by extensive spectroscopic characterization and the reported data. All the isolates were evaluated for their acetylcholinesterase (AChE) inhibition activity. Compound 5 showed weak inhibitory activity (46.0%) at 50 muM concentration. Title: Production enhancement of the extracellular lipase LipA in Bacillus subtilis: Effects of expression system and Sec pathway components Ma RJ, Wang YH, Liu L, Bai LL, Ban R Ref: Protein Expr Purif, 142:81, 2018 : PubMed ESTHER: Ma_2018_Protein.Expr.Purif_142_81 PubMedSearch: Ma 2018 Protein.Expr.Purif 142 81 PubMedID: 28963005 Abstract Lipases are among the most versatile biocatalysts, and are used in a range of industrially relevant bioconversion reactions. However, the production of LipA in recombinant Bacillus subtilis is still limited, due to unresolved issues surrounding the regulation of the expression and secretion systems. In this study, the gene encoding LipA from B. subtilis 168 was expressed in BNA under the control of the P(43) and the P(AE) promoter. The extracellular lipase activity of the resulting strains BNACL and BNAAL was 7.8 U ml(-1) and 12.6 U ml(-1), respectively. To further enhance the expression of LipA, pHP13L was constructed by inserting the P(AE)-lip into the shuttle vector pHP13, which produced an extracellular lipase activity of 180.5 U ml(-1) of BNA/pHP13L. The strain BNAY8 described in Supplement data which lacks eight extracellular proteins was constructed and the deletion a few of the much weaker secreting proteins had no significant effect on the secretion of LipA. Moreover, the four Sec pathway components, secA-prfB, secDF, secYEG, prsA, were individually overexpressed in BNA. The overexpression of secDF and prsA enhanced the production of LipA by 28% and 49%, respectively. Furthermore, the co-overexpression of secDF with prsA improved the extracellular amount of LipA by 59% over that of BNA/pHP13L, reaching 287.8 U ml(-1). It can therefore be said that both regulatory elements and secretion pathway had an impact on the production of secreted LipA. Their optimization and modification is a useful strategy to improve the homologous overproduction of other extracellular proteins in B. subtilis. Title: Molluscicidal activity of Solidago canadensis L. extracts on the snail Pomacea canaliculata Lam Shen X, Wang Z, Liu L, Zou Z Ref: Pestic Biochem Physiol, 149:104, 2018 : PubMed ESTHER: Shen_2018_Pestic.Biochem.Physiol_149_104 PubMedSearch: Shen 2018 Pestic.Biochem.Physiol 149 104 PubMedID: 30033006 Abstract Extracts from the aerial parts of Solidago canadensis L. were evaluated for molluscicidal activity against Pomacea canaliculata Lam. using an immersion bioassay method. The petroleum ether fraction of the ethanolic extract (PEEE) from S. canadensis exhibited strong molluscicidal activity. The PEEE mode of action in the hepatopancreas tissue of P. canaliculata was tested at several concentrations. Biochemical parameters, namely, soluble sugar content, protein, malondialdehyde (MDA), acetylcholinesterase (AChE) activity, alanine aminotransferase (ALT), and aspartate transaminase (AST) were significantly decreased or increased after exposure to PEEE for 48 h (p<0.05). Histological assessment results showed that hepatopancreas tissue structure was destroyed by exposure to PEEE. Gas chromatography-mass spectrometry analysis (GC-MS) was used to identify 15 compounds that could contribute to the molluscicidal efficacy of the PEEE. Molluscicidal assay, biochemical tests and histological assessments suggest that the PEEE from S. canadensis has potential utility as a molluscicide. Title: Protective effects of evodiamine in experimental paradigm of Alzheimer's disease Wang D, Wang C, Liu L, Li S Ref: Cogn Neurodyn, 12:303, 2018 : PubMed ESTHER: Wang_2018_Cogn.Neurodyn_12_303 PubMedSearch: Wang 2018 Cogn.Neurodyn 12 303 PubMedID: 29765479 Inhibitor(s) related to this paper: Evodiamine Abstract Evodiamine, a major component of Evodia rutaecarpa, has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidative stress, and neuroprotective effects. Our previous study has shown that the potential effects of evodiamine on the learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). The present study was designed to investigate neuroprotective mechanism and therapeutic potential of evodiamine against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic Alzheimer's disease in mice. STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily oral administration with evodiamine (50 or 100 mg/kg per day) starting from the first dose of STZ for 21 days showed an improvement in STZ induced cognitive deficits as assessed by novel object recognition and Morris water maze test. Evodiamine significantly decreased STZ induced elevation in acetylcholinesterase activity and malondialdehyde level, and significantly increased STZ induced reduction in glutathione activities and superoxide dismutase activities in the hippocampus compared to control. Furthermore, evodiamine inhibited significantly glial cell activation and neuroinflammation (TNF-alpha, IL-1beta, and IL-6 levels) in the hippocampus. Moreover, evodiamine increased the activity of AKT/GSK-3beta signalling pathway and inhibited the activity of nuclear factor kappaB. In summary, our study suggests that evodiamine can be a novel therapeutic agent for the management of sporadic AD. Title: Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-alpha and IL-1beta in an Abeta25-35-induced Rat Model of Alzheimer's Disease Li L, Xu S, Liu L, Feng R, Gong Y, Zhao X, Li J, Cai J, Feng N and Peng Y <2 more author(s)> Li L, Xu S, Liu L, Feng R, Gong Y, Zhao X, Li J, Cai J, Feng N, Wang L, Wang X, Peng Y (- 2) Ref: J Alzheimers Dis, 56:1403, 2017 : PubMed ESTHER: Li_2017_J.Alzheimers.Dis_56_1403 PubMedSearch: Li 2017 J.Alzheimers.Dis 56 1403 PubMedID: 28157092 Abstract The dyshomeostasis of transition metal ions, accumulation of amyloid-beta (Abeta) senile plaques and neuroinflammatory response found in the brain of patients with Alzheimer's disease (AD) have been suggested to be involved in AD pathogenesis. Novel compounds capable of targeting metal-Abeta species and neuroinflammation would be valuable. AD-35 is such a patented small-molecule compound derived from innovative modification of the chemical structure of donepezil. This compound could moderately inhibit acetylcholinesterase and metal-induced Abeta aggregation in vitro and showed disassembly of Abeta aggregates. The effects of AD-35 on cognitive impairments and neuroinflammatory changes caused by intracerebroventricular injection of Abeta25-35 were studied in rats. Compared to sham group, Abeta25-35 injection significantly led to learning and memory deficits, astrocyte activation, and pro-inflammatory cytokines releases (TNF-alpha and IL-1beta). Further studies indicated that the phosphorylation of extracellular signal-regulated kinase was involved in astrocyte activation and pro-inflammatory cytokines production. Oral administration of AD-35 could markedly attenuate Abeta25-35 injection-induced astrocyte activation, pro-inflammatory cytokines TNF-alpha and IL-1beta release, and memory deficits. On the contrary, donepezil only showed inhibition of IL-1beta production, but failed to block astrocyte activation and TNF-alpha production. These results showed that AD-35 would be a novel multi-mechanism drug for the prevention and/or treatment of AD. Title: A new facet of NDRG1 in pancreatic ductal adenocarcinoma: Suppression of glycolytic metabolism Liu W, Zhang B, Hu Q, Qin Y, Xu W, Shi S, Liang C, Meng Q, Xiang J and Xu J <9 more author(s)> Liu W, Zhang B, Hu Q, Qin Y, Xu W, Shi S, Liang C, Meng Q, Xiang J, Liang D, Ji S, Liu J, Hu P, Liu L, Liu C, Long J, Ni Q, Yu X, Xu J (- 9) Ref: Int J Oncol, 50:1792, 2017 : PubMed ESTHER: Liu_2017_Int.J.Oncol_50_1792 PubMedSearch: Liu 2017 Int.J.Oncol 50 1792 PubMedID: 28350132 Abstract N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1alpha level. Moreover, NDRG1 has a unique role in modulating cancer metabolism of pancreatic ductal adenocarcinoma (PDAC). The mechanism accounting for NDRG1 in modulating aerobic glycolysis, at least partly, relied on its regulation of glycolysis genes including GLUT1, HK2, LDHA and PDK1. Additionally, NDRG1 is shown to suppress the activity of HIF1alpha, which is responsible for regulation of glycolysis enzymes. The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC. Title: Neurexin Restricts Axonal Branching in Columns by Promoting Ephrin Clustering Liu L, Tian Y, Zhang XY, Zhang X, Li T, Xie W, Han J Ref: Dev Cell, 41:94, 2017 : PubMed ESTHER: Liu_2017_Dev.Cell_41_94 PubMedSearch: Liu 2017 Dev.Cell 41 94 PubMedID: 28366281 Abstract Columnar restriction of neurites is critical for forming nonoverlapping receptive fields and preserving spatial sensory information from the periphery in both vertebrate and invertebrate nervous systems, but the underlying molecular mechanisms remain largely unknown. Here, we demonstrate that Drosophila homolog of alpha-neurexin (DNrx) plays an essential role in columnar restriction during L4 axon branching. Depletion of DNrx from L4 neurons resulted in misprojection of L4 axonal branches into neighboring columns due to impaired ephrin clustering. The proper ephrin clustering requires its interaction with the intracellular region of DNrx. Furthermore, we find that Drosophila neuroligin 4 (DNlg4) in Tm2 neurons binds to DNrx and initiates DNrx clustering in L4 neurons, which subsequently induces ephrin clustering. Our study demonstrates that DNrx promotes ephrin clustering and reveals that ephrin/Eph signaling from adjacent L4 neurons restricts axonal branches of L4 neurons in columns. Title: Glycoengineering of Esterase Activity through Metabolic Flux-Based Modulation of Sialic Acid Mathew MP, Tan E, Labonte JW, Shah S, Saeui CT, Liu L, Bhattacharya R, Bovonratwet P, Gray JJ, Yarema KJ Ref: Chembiochem, 18:1204, 2017 : PubMed ESTHER: Mathew_2017_Chembiochem_18_1204 PubMedSearch: Mathew 2017 Chembiochem 18 1204 PubMedID: 28218815 Abstract This report describes the metabolic glycoengineering (MGE) of intracellular esterase activity in human colon cancer (LS174T) and Chinese hamster ovary (CHO) cells. In silico analysis of carboxylesterases CES1 and CES2 suggested that these enzymes are modified with sialylated N-glycans, which are proposed to stabilize the active multimeric forms of these enzymes. This premise was supported by treating cells with butanolylated ManNAc to increase sialylation, which in turn increased esterase activity. By contrast, hexosamine analogues not targeted to sialic acid biosynthesis (e.g., butanoylated GlcNAc or GalNAc) had minimal impact. Measurement of mRNA and protein confirmed that esterase activity was controlled through glycosylation and not through transcription or translation. Azide-modified ManNAc analogues widely used in MGE also enhanced esterase activity and provided a way to enrich targeted glycoengineered proteins (such as CES2), thereby providing unambiguous evidence that the compounds were converted to sialosides and installed into the glycan structures of esterases as intended. Overall, this study provides a pioneering example of the modulation of intracellular enzyme activity through MGE, which expands the value of this technology from its current status as a labeling strategy and modulator of cell surface biological events. Title: The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke Raju SV, Lin VY, Liu L, McNicholas CM, Karki S, Sloane PA, Tang L, Jackson PL, Wang W and Rowe SM <8 more author(s)> Raju SV, Lin VY, Liu L, McNicholas CM, Karki S, Sloane PA, Tang L, Jackson PL, Wang W, Wilson L, Macon KJ, Mazur M, Kappes JC, DeLucas LJ, Barnes S, Kirk K, Tearney GJ, Rowe SM (- 8) Ref: American Journal of Respiratory Cellular & Molecular Biology, 56:99, 2017 : PubMed ESTHER: Raju_2017_Am.J.Respir.Cell.Mol.Biol_56_99 PubMedSearch: Raju 2017 Am.J.Respir.Cell.Mol.Biol 56 99 PubMedID: 27585394 Abstract Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-mum resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis. Title: Next-generation sequencing reveals lymph node metastasis associated genetic markers in colorectal cancer Xie N, Yao Y, Wan L, Zhu T, Liu L, Yuan J Ref: Exp Ther Med, 14:338, 2017 : PubMed ESTHER: Xie_2017_Exp.Ther.Med_14_338 PubMedSearch: Xie 2017 Exp.Ther.Med 14 338 PubMedID: 28672935 Abstract Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4. The SNPs in solute carrier family 28 member 3 (SLC28A3), breast cancer 1 (BRCA1), ribonucleotide reductase regulators subunit M2 (RRM2), PMS1 homolog 2 (PMS2), cytidine deaminase (CDA), epoxide hydrolase 1 (EPHX1), heterogenous ribonucleoprotein particle-associated with lethal yellow (RALY), Siglec-3 (CD33), B cell lymphoma 10 (BCL10), ETS variant 1 (ETV1), macrophage stimulating 1 receptor 1 (MST1R), lysine methyltransferase 2B (KMT2B), B cell lymphoma 2 (BCL2), U6 small nuclear RNA-associated Sm-like protein 3 (LSM3), thyroid transcription factor 1 (TTF1) and mitogen-activated protein 3 kinase 1 (MAP3K1) were significantly associated with lymphatic metastasis (P<0.05). EGF and NFKB1 were both observed to be significantly downregulated in the lymph node metastases group (P<0.05). Although no association between CNVs and lymph node metastases in patients with colorectal cancer was observed in the present study, SNPs in SLC28A3, BRCA1, RRM2, PMS2, CDA, EPHX1, RALY, CD33, BCL10, ETV1, MST1R, KMT2B, BCL2, LSM3, TTF1 and MAP3K1 were significantly associated with colorectal cancer. Downregulation of EGF and NFKB1 was also identified to be associated with lymph node metastases in colorectal cancer. The findings of the current study provide a scientific basis for the clinical inspection of lymphatic metastasis and prognosis prediction, intervention and guidance therapy for patients with colorectal cancer. Title: Ultrahigh pressure-assisted enzymatic extraction maximizes the yield of longan pulp polysaccharides and their acetylcholinesterase inhibitory activity in vitro Bai Y, Liu L, Zhang R, Huang F, Deng Y, Zhang M Ref: Int J Biol Macromol, 96:214, 2016 : PubMed ESTHER: Bai_2016_Int.J.Biol.Macromol_96_214 PubMedSearch: Bai 2016 Int.J.Biol.Macromol 96 214 PubMedID: 27908719 Abstract An extraction method employing ultrahigh pressure-assisted enzymatic treatment was developed and optimized by response surface methodology to increase the yield of longan pulp polysaccharides (LP-UE). A maximum polysaccharides yield of 8.55% was obtained under the optimal conditions of 407MPa ultrahigh pressure maintained for 6min with an enzyme to pretreated material ratio of 1:100, an enzymolysis time of 1.7h and a water to pretreated material ratio of 42ml/g. Subsequently, the physicochemical properties and acetylcholinesterase (AChE) inhibitory activity of LP-UE were compared to those of longan pulp polysaccharides (LP) extracted by hot water (LP-H), ultrahigh pressure (LP-U) or enzymatic treatment (LP-E). Results demonstrated that the extraction yield, hexuronic acid content and AChE inhibitory activity of LP-UE was the highest among the four LP samples. LP-UE was primarily made up of arabinose, glucose, and galactose and was linked mainly by beta-type glycosidic linkage. The FTIR spectrum of LP-UE was very similar to those of LP-H, LP-U, and LP-E. In summary, ultrahigh pressure-assisted enzymatic treatment is a more efficient technique for extracting LP with considerable improvement of both yield and memory enhancement function. Title: Draft Genome Sequence of Aspergillus niger Strain An76 Gong W, Cheng Z, Zhang H, Liu L, Gao P, Wang L Ref: Genome Announc, 4:, 2016 : PubMed ESTHER: Gong_2016_Genome.Announc_4_e01700 PubMedSearch: Gong 2016 Genome.Announc 4 e01700 PubMedID: 26893421 Gene_locus related to this paper: aspna-g3y5a6, aspna-g3xpw9, aspkw-g7xq95, aspng-a0a100iew6, asptc-a0a1l9nby7, aspng-a0a100i8t9 Abstract The filamentous fungus Aspergillus niger has become one of the most important fungi in industrial biotechnology, and it can efficiently secrete both polysaccharide-degrading enzymes and organic acids. We report here the 6,074,961,332-bp draft sequence of A. niger strain An76, and the findings provide important information related to its lignocellulose-degrading ability. Title: Overexpression of CXCL3 can enhance the oncogenic potential of prostate cancer Gui SL, Teng LC, Wang SQ, Liu S, Lin YL, Zhao XL, Liu L, Sui HY, Yang Y and Wang WQ <5 more author(s)> Gui SL, Teng LC, Wang SQ, Liu S, Lin YL, Zhao XL, Liu L, Sui HY, Yang Y, Liang LC, Wang ML, Li XY, Cao Y, Li FY, Wang WQ (- 5) Ref: International Urology & Nephrology, 48:701, 2016 : PubMed ESTHER: Gui_2016_Int.Urol.Nephrol_48_701 PubMedSearch: Gui 2016 Int.Urol.Nephrol 48 701 PubMedID: 26837773 Abstract PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis. Title: Behavioural and biochemical alterations in Penaeus monodon post-larvae diet-exposed to inorganic mercury Harayashiki CA, Reichelt-Brushett AJ, Liu L, Butcher P Ref: Chemosphere, 164:241, 2016 : PubMed ESTHER: Harayashiki_2016_Chemosphere_164_241 PubMedSearch: Harayashiki 2016 Chemosphere 164 241 PubMedID: 27591375 Abstract Mercury is a metal naturally present in the environment with concentrations in aquatic systems increasing annually due to human activities. This represents a great concern mainly due to its high toxicity to organisms and consequences for human health. Most studies regarding the toxic effect of mercury have focussed on freshwater species using water as the exposure and uptake pathway. In contrast, the present study investigated the effects of dietary exposure of mercury to the marine crustacean Penaeus monodon post-larvae during 96 h to evaluate changes in behaviour (swimming activity and risk taken) and in biochemical biomarkers [acetylcholinesterase (AChE) and glutathione S-transferase (GST)]. Results showed a decrease in swimming activity with an increase in mercury exposure, but no changes were observed regarding the behavioural response 'risk taken'. Prawns from medium (0.56 mug g-1) and high (1.18 mug g-1) treatments had their GST activity reduced in relation to the beginning of experiment (time 0), while AChE activity was increased in the low (0.15 mug g-1) treatment in relation to time 0. In the present study, behaviour analysis were clearer than biochemical biomarkers and results might indicate P. monodon populations from a mercury contaminated environment might be at risk, since the behavioural alterations observed increases the risk of predation. Title: Computational analysis and enzyme assay of inhibitor response to disease single nucleotide polymorphisms (SNPs) in lipoprotein lipase He D, Huang L, Xu Y, Pan X, Liu L Ref: J Bioinform Comput Biol, :1650028, 2016 : PubMed ESTHER: He_2016_J.Bioinform.Comput.Biol__1650028 PubMedSearch: He 2016 J.Bioinform.Comput.Biol 1650028 PubMedID: 27427383 Abstract Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins, chylomicrons, and very low-density lipoproteins. The enzyme has been established as an efficacious and safe therapeutic target for the management of obesity. Here, a systematic profile of the lipase inhibitor response of three anti-obesity agents (Orlistat, Lipstatin, and Cetilistat) to clinical LPL missense mutations arising from disease single nucleotide polymorphisms (SNPs) was established by integrating complex structure modeling, virtual mutagenesis, molecular dynamics (MD) simulations, binding energy analysis, and radiolabeled TG hydrolysis assays. The profile was then used to characterize the resistance and sensitivity of systematic mutation-inhibitor pairs. It is suggested that the Orlistat and Lipstatin have a similar response profile to the investigated mutations due to their homologous chemical structures, but exhibit a distinct profile to that of Cetilistat. Most mutations were predicted to have a modest or moderate effect on inhibitor binding; they are located far away from the enzyme active site and thus can only influence the binding limitedly. A number of mutations were found to sensitize or cause resistance for lipase inhibitors by directly interacting with the inhibitor ligands or by indirectly addressing allosteric effect on enzyme active site. Long-term MD simulations revealed a different noncovalent interaction network at the complex interfaces of Orlistat with wild-type LPL as well as its sensitized mutant H163R and resistant mutant I221T. Title: Identification of biotransformation enzymes in the antennae of codling moth Cydia pomonella Huang X, Liu L, Su X, Feng J Ref: Gene, 580:73, 2016 : PubMed ESTHER: Huang_2016_Gene_580_73 PubMedSearch: Huang 2016 Gene 580 73 PubMedID: 26778204 Abstract Biotransformation enzymes are found in insect antennae and play a critical role in degrading xenobiotics and odorants. In Cydia pomonella, we identified 26 biotransformation enzymes. Among these enzymes, twelve carboxylesterases (CXEs), two aldehyde oxidases (AOXs) and six alcohol dehydrogenases (ADs) were predominantly expressed in antennae. Each of the CpomCXEs presents a conserved catalytic triad "Ser-His-Glu", which is the structural characteristic of known insect CXEs. CpomAOXs present two redox centers, a FAD-binding domain and a molybdenum cofactor/substrate-binding domain. The antennal CpomADs are from two protein families, short-chain dehydrogenases/reducetases (SDRs) and medium-chain dehydrogenases/reducetases (MDRs). Putative catalytic active domain and cofactor binding domain were found in these CpomADs. Potential functions of these enzymes were determined by phylogenetic analysis. The results showed that these enzymes share close relationship with odorant degrading enzymes (ODEs) and resistance-associated enzymes of other insect species. Because of commonly observed roles of insect antennal biotransformation enzymes, we suggest antennal biotransformation enzymes presented here are candidate that involved in degradation of odorants and xenobiotics within antennae of C. pomonella. Title: Phomopsichin A-D; Four New Chromone Derivatives from Mangrove Endophytic Fungus Phomopsis sp. 33 Huang M, Li J, Liu L, Yin S, Wang J, Lin Y Ref: Mar Drugs, 14:, 2016 : PubMed ESTHER: Huang_2016_Mar.Drugs_14_ PubMedSearch: Huang 2016 Mar.Drugs 14 PubMedID: 27879655 Abstract Four new chromone derivatives, phomopsichins A-D (1-4), along with a known compound, phomoxanthone A (5), were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated based on comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction or theoretical calculations of electronic circular dichroism (ECD). They feature a tricyclic framework, in which a dihydropyran ring is fused with the chromone ring. Compounds 1-5 showed weak inhibitory activities on acetylcholinesterase as well as alpha-glucosidase, weak radical scavenging effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as OH, and weak antimicrobial activities. Compounds 1-4 showed no cytotoxic activity against MDA-MB-435 breast cancer cells. Their other bioactivities are worthy of further study, considering their unique molecular structures. Title: Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting Li XQ, Ma N, Li XG, Wang B, Sun SS, Gao F, Mo DP, Song LG, Sun X and Miao ZR <5 more author(s)> Li XQ, Ma N, Li XG, Wang B, Sun SS, Gao F, Mo DP, Song LG, Sun X, Liu L, Zhao XQ, Wang YL, Wang YJ, Zhao ZG, Miao ZR (- 5) Ref: PLoS ONE, 11:e0148891, 2016 : PubMed ESTHER: Li_2016_PLoS.One_11_e0148891 PubMedSearch: Li 2016 PLoS.One 11 e0148891 PubMedID: 26870959 Abstract BACKGROUND AND PURPOSE: Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes. Title: Novel ferulic amide derivatives with tertiary amine side chain as acetylcholinesterase and butyrylcholinesterase inhibitors: The influence of carbon spacer length, alkylamine and aromatic group Liu H, Liu L, Gao X, Liu Y, Xu W, He W, Jiang H, Tang J, Fan H, Xia X Ref: Eur Journal of Medicinal Chemistry, 126:810, 2016 : PubMed ESTHER: Liu_2016_Eur.J.Med.Chem_126_810 PubMedSearch: Liu 2016 Eur.J.Med.Chem 126 810 PubMedID: 27951489 Abstract Based on our recent investigations on chalcone derivatives as AChE inhibitors, a series of ferulic acid (FA) tertiary amine derivatives similar to chalcone compounds were designed and synthesized. The results of bioactivity evaluation revealed that most of new synthesized compounds had comparable or more potent AChE inhibitory activity than the control drug Rivastigmine. The alteration of carbon chain linking tertiary amine groups and ferulic acid scaffold markedly influenced the inhibition activity against AChE. Among them the inhibitory activity of compound 6d (IC50: 0.71 +/- 0.09 mumol/L) and 6e (IC50: 1.11 +/- 0.17 mumol/L) was equal to 15-fold and 9-fold than that of Rivastigmine against AChE (IC50: 10.54 +/- 0.86 mumol/L), respectively. Moreover, compound 6d shows the highest selectivity for AChE over butyrylcholinesterase(BuChE) (ratio: 18.3). The kinetic study suggested that compound 6d revealed a mixed-type inhibition against AChE. The result of molecular docking showed that compound 6d combines to AChE with three amino acid sites(Trp84, Tyr334 and Trp279), while combines to BuChE with two amino acid sites (Tyr67 and Gly66) in enzyme domains, respectively. Compound 6d might act as a potential agent for the treatment of Alzheimer's diseases (AD). Title: Arsenicitalea aurantiaca gen. nov., sp. nov., a new member of the family Hyphomicrobiaceae, isolated from high-arsenic sediment Mu Y, Zhou L, Zeng XC, Liu L, Pan Y, Chen X, Wang J, Li S, Li WJ, Wang Y Ref: Int J Syst Evol Microbiol, 66:5478, 2016 : PubMed ESTHER: Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478 PubMedSearch: Mu 2016 Int.J.Syst.Evol.Microbiol 66 5478 PubMedID: 27902179 Gene_locus related to this paper: 9rhiz-a0a433xfq5 Abstract A novel arsenic-resistant bacterium, designated 42-50T, was isolated from the high-arsenic sediment of Jianghan Plain, Hubei Province, China. Phylogenetic and biochemical analysis indicated that this bacterium represents the first species of a novel genus belonging to the family Hyphomicrobiaceae. The 16S rRNA gene of strain 42-50T shares 96.3-94.2, 96.3, 96.2 and 94.9-93.8 % sequence identities to those of species from the genera Devosia, Youhaiella, Paradevosia and Pelagibacterium, respectively. The major cellular fatty acids are C16 : 0, C18 : 0, C18 : 1omega7c 11-methyl and summed feature 8 (comprising C18 : 1omega7c and C18 : 1omega6c). The predominant polar lipids are diphosphatidylglycerol, phosphatidylglycerol and two unidentified glycolipids. The predominant respiratory quinone is ubiquinone-10 (Q-10). The DNA G+C content of strain 42-50T is 73.7 mol%. The distinct phylogenetic lineage and unique cellular fatty acids suggest that strain 42-50T represents a novel species of a new genus affiliated with the family Hyphomicrobiaceae, for which the name Arsenicitalea aurantiaca gen. nov., sp. nov. is proposed. The type strain is 42-50T (=CCTCC AB 2014325T=KCTC 42825T). Title: De novo transcriptome analysis in radish (Raphanus sativus L.) and identification of critical genes involved in bolting and flowering Nie S, Li C, Xu L, Wang Y, Huang D, Muleke EM, Sun X, Xie Y, Liu L Ref: BMC Genomics, 17:389, 2016 : PubMed ESTHER: Nie_2016_BMC.Genomics_17_389 PubMedSearch: Nie 2016 BMC.Genomics 17 389 PubMedID: 27216755 Gene_locus related to this paper: rapsa-a0a6j0lzs2 Abstract BACKGROUND: The appropriate timing of bolting and flowering is pivotal for reproductive success in Brassicaceae crops including radish (Raphanus sativus L.). Although several flowering regulatory pathways had been described in some plant species, no study on genetic networks of bolting and flowering regulation was performed in radish. In this study, to generate dataset of radish unigene sequences for large-scale gene discovery and functional pathway identification, a cDNA library from mixed radish leaves at different developmental stages was subjected to high-throughput RNA sequencing (RNA-seq). RESULTS: A total of 54.64 million clean reads and 111,167 contigs representing 53,642 unigenes were obtained from the radish leaf transcriptome. Among these, 50,385 unigenes were successfully annotated by BLAST searching against the public protein databases. Functional classification and annotation indicated that 42,903 and 15,382 unique sequences were assigned to 55 GO terms and 25 COG categories, respectively. KEGG pathway analysis revealed that 25,973 unigenes were classified into 128 functional pathways, among which 24 candidate genes related to plant circadian rhythm were identified. Moreover, 142 potential bolting and flowering-related genes involved in various flowering pathways were identified. In addition, seven critical bolting and flowering-related genes were isolated and profiled by T-A cloning and RT-qPCR analysis. Finally, a schematic network model of bolting and flowering regulation and pathways was put forward in radish. CONCLUSIONS: This study is the first report on systematic identification of bolting and flowering-related genes based on transcriptome sequencing and assembly in radish. These results could provide a foundation for further investigating bolting and flowering regulatory networks in radish, and facilitate dissecting molecular genetic mechanisms underlying bolting and flowering in Brassicaceae vegetable crops. Title: Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender Shi J, Wang X, Nguyen JH, Bleske BE, Liang Y, Liu L, Zhu HJ Ref: Biochemical Pharmacology, 119:76, 2016 : PubMed ESTHER: Shi_2016_Biochem.Pharmacol_119_76 PubMedSearch: Shi 2016 Biochem.Pharmacol 119 76 PubMedID: 27614009 Gene_locus related to this paper: human-CES1 Abstract The oral anticoagulant prodrug dabigatran etexilate (DABE) is sequentially metabolized by intestinal carboxylesterase 2 (CES2) and hepatic carboxylesterase 1 (CES1) to form its active metabolite dabigatran (DAB). A recent genome-wide association study reported that the CES1 single nucleotide polymorphisms (SNPs) rs2244613 and rs8192935 were associated with lower DAB plasma concentrations in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) study participants. In addition, gender differences in exposure to DAB were observed in clinical studies. The aim of this study was to examine the effect of CES1 genetic polymorphisms and gender on DABE activation using several in vitro approaches. The genotypes of the CES1 SNPs rs2244613, rs8192935, and the known loss-of-function CES1 variant rs71647871 (G143E), and the activation of DABE and its intermediate metabolites M1 and M2 were determined in 104 normal human liver samples. DABE, M1, and M2 activations were found to be impaired in human livers carrying the G143E variant. However, neither rs2244613 nor rs8192935 was associated with the activation in human livers. The incubation study of DABE with supernatant fractions (S9) prepared from the G143E-transfected cells showed that the G143E is a loss-of-function variant for DABE metabolism. Moreover, hepatic CES1 activity on M2 activation was significantly higher in female liver samples than male. Our data suggest that CES1 genetic variants and gender are important contributing factors to variability in DABE activation in humans. A personalized DABE treatment approach based on patient-specific CES1 genotypes and sex may have the potential to improve the efficacy and safety of DABE pharmacotherapy. Title: Association of Oseltamivir Activation with Gender and Carboxylesterase 1 Genetic Polymorphisms Shi J, Wang X, Eyler RF, Liang Y, Liu L, Mueller BA, Zhu HJ Ref: Basic Clin Pharmacol Toxicol, 119:555, 2016 : PubMed ESTHER: Shi_2016_Basic.Clin.Pharmacol.Toxicol_119_555 PubMedSearch: Shi 2016 Basic.Clin.Pharmacol.Toxicol 119 555 PubMedID: 27228223 Gene_locus related to this paper: human-CES1 Abstract Oseltamivir, an inactive anti-influenza virus prodrug, is activated (hydrolysed) in vivo by carboxylesterase 1 (CES1) to its active metabolite oseltamivir carboxylate. CES1 functions are significantly associated with certain CES1 genetic variants and some non-genetic factors. The purpose of this study was to investigate the effect of gender and several CES1 genetic polymorphisms on oseltamivir activation using a large set of individual human liver samples. CES1-mediated oseltamivir hydrolysis and CES1 genotypes, including the G143E (rs71647871), rs2244613, rs8192935, the -816A>C (rs3785161) and the CES1P1/CES1P1VAR, were determined in 104 individual human livers. The results showed that hepatic CES1 protein expression in females was 17.3% higher than that in males (p = 0.039), while oseltamivir activation rate in the livers from female donors was 27.8% higher than that from males (p = 0.076). As for CES1 genetic polymorphisms, neither CES1 protein expression nor CES1 activity on oseltamivir activation was significantly associated with the rs2244613, rs8192935, -816A>C or CES1P1/CES1P1VAR genotypes. However, oseltamivir hydrolysis in the livers with the genotype 143G/E was approximately 40% of that with the 143G/G genotype (0.7 +/- 0.2 versus 1.8 +/- 1.1 nmole/mg protein/min, p = 0.005). In summary, the results suggest that hepatic oseltamivir activation appears to be more efficient in females than that in males, and the activation can be impaired by functional CES1 variants, such as the G143E. However, clinical implication of CES1 gender differences and pharmacogenetics in oseltamivir pharmacotherapy warrants further investigations. Title: Targeted absolute quantitative proteomics with SILAC internal standards and unlabeled full-length protein calibrators (TAQSI) Wang X, Liang Y, Liu L, Shi J, Zhu HJ Ref: Rapid Commun Mass Spectrom, 30:553, 2016 : PubMed ESTHER: Wang_2016_Rapid.Commun.Mass.Spectrom_30_553 PubMedSearch: Wang 2016 Rapid.Commun.Mass.Spectrom 30 553 PubMedID: 26842578 Abstract RATIONALE: Liquid Chromatography/Mass Spectrometry (LC/MS)-based proteomics for absolute protein quantification has been increasingly utilized in both basic and clinical research. There is a great need to overcome some major hurdles of current absolute protein quantification methods, such as significant inter-assay variability and the high cost associated with the preparation of purified stable-isotope-labeled peptide/protein standards. Title: Exonuclease I-aided homogeneous electrochemical strategy for organophosphorus pesticide detection based on enzyme inhibition integrated with a DNA conformational switch Wang X, Dong S, Hou T, Liu L, Liu X, Li F Ref: Analyst, 141:1830, 2016 : PubMed ESTHER: Wang_2016_Analyst_141_1830 PubMedSearch: Wang 2016 Analyst 141 1830 PubMedID: 26839920 Abstract A novel enzyme inhibition-based homogeneous electrochemical biosensing strategy was designed for an organophosphorus pesticide assay based on exploiting the resistance of a mercury ion-mediated helper probe (HP) toward nuclease-catalyzed digestion and the remarkable diffusivity difference between HPs and the mononucleotides toward a negatively charged indium tin oxide (ITO) electrode. In particular, the mercury ion-mediated T-Hg(2+)-T base pairs facilitate the HP labeled with methylene blue (MB) to fold into a hairpin structure, preventing its digestion by exonuclease I, and thus resulting in a low electrochemical response because of the large electrostatic repulsion between the negatively charged ITO electrode and the HPs. The competitive binding by a thiol group (-SH), produced in the hydrolysis reaction of acetylthiocholine (ACh) chloride with acetylcholinesterase (AChE), removes mercury ions from the base pairs, causing a nuclease-catalyzed digestion, and the subsequent electrochemical response increase due to the weak electrostatic repulsion between the product-mononucleotides and the ITO electrode. Mercury ion-mediated HPs were first designed for pesticide detection and diazinon was chosen as the model target. Under the optimal experimental conditions, the approach exhibited high sensitivity for diazinon detection with a detection limit of 0.25 mug L(-1). The satisfactory results in the determination of diazinon in real samples demonstrate that the method possesses great potential for detecting organophosphorus pesticides. This new approach is expected to promote the exploitation of mercury-mediated base pair-based homogenous electrochemical biosensors in biochemical studies and in the food safety field. Title: Carboxylesterase-mediated insecticide resistance: Quantitative increase induces broader metabolic resistance than qualitative change Cui F, Li MX, Chang HJ, Mao Y, Zhang HY, Lu LX, Yan SG, Lang ML, Liu L, Qiao CL Ref: Pestic Biochem Physiol, 121:88, 2015 : PubMed ESTHER: Cui_2015_Pestic.Biochem.Physiol_121_88 PubMedSearch: Cui 2015 Pestic.Biochem.Physiol 121 88 PubMedID: 26047115 Abstract Carboxylesterases are mainly involved in the mediation of metabolic resistance of many insects to organophosphate (OP) insecticides. Carboxylesterases underwent two divergent evolutionary events: (1) quantitative mechanism characterized by the overproduction of carboxylesterase protein; and (2) qualitative mechanism caused by changes in enzymatic properties because of mutation from glycine/alanine to aspartate at the 151 site (G/A151D) or from tryptophan to leucine at the 271 site (W271L), following the numbering of Drosophila melanogaster AChE. Qualitative mechanism has been observed in few species. However, whether this carboxylesterase mutation mechanism is prevalent in insects remains unclear. In this study, wild-type, G/A151D and W271L mutant carboxylesterases from Culex pipiens and Aphis gossypii were subjected to germline transformation and then transferred to D. melanogaster. These germlines were ubiquitously expressed as induced by tub-Gal4. In carboxylesterase activity assay, the introduced mutant carboxylesterase did not enhance the overall carboxylesterase activity of flies. This result indicated that G/A151D or W271L mutation disrupted the original activities of the enzyme. Less than 1.5-fold OP resistance was only observed in flies expressing A. gossypii mutant carboxylesterases compared with those expressing A. gossypii wild-type carboxylesterase. However, transgenic flies universally showed low resistance to OP insecticides compared with non-transgenic flies. The flies expressing A. gossypii W271L mutant esterase exhibited 1.5-fold resistance to deltamethrin, a pyrethroid insecticide compared with non-transgenic flies. The present transgenic Drosophila system potentially showed that a quantitative increase in carboxylesterases induced broader resistance of insects to insecticides than a qualitative change. Title: pH effects on the structural dynamics of cutinase from Trichoderma reesei: insights from molecular dynamics simulations Duan ML, Liu L, Du J, Yao XJ Ref: Mol Biosyst, 11:3149, 2015 : PubMed ESTHER: Duan_2015_Mol.Biosyst_11_3149 PubMedSearch: Duan 2015 Mol.Biosyst 11 3149 PubMedID: 26387959 Abstract Cutinases are utilized in a variety of industries for the hydrolysis of a broad range of substrates, such as cutin, polyesters, soluble esters, insoluble short- and long-chain triglycerides. The novel cutinase from Trichoderma reesei (Tr) attracted much attention due to its two rare characteristics distinct from the classical cutinases: it possesses a lid covering its active site and its optimal activity at acidic pH. However, the structural basis for pH preference and the function of lid is still not well understood. In this work, total of six initial systems were set up either under acidic or basic pH conditions (closed-apo, open-apo and open-holo). Then, molecular dynamics (MD) simulations were performed to make a better understanding of structural dynamics of Tr cutinase under different pH conditions for the first time. The results mainly suggest that it is easier to open for the lid under an acidic pH condition. In addition, the binding of long-chain triglyceride is more stable at lower pH than higher pH. These findings elucidate that how pH influences Tr cutinase at the atomistic level. The structural and dynamic details would be useful for rational enzyme design for acidic cutinase. Title: A Randomized, Prospective, Double-Blinded Study of Physostigmine to Prevent Sedation-Induced Ventilatory Arrhythmias Karan SB, Rackovsky E, Voter WA, Kanel JA, Farris N, Jensen J, Liu L, Ward DS Ref: Anesthesia & Analgesia, 121:652, 2015 : PubMed ESTHER: Karan_2015_Anesth.Analg_121_652 PubMedSearch: Karan 2015 Anesth.Analg 121 652 PubMedID: 26200465 Abstract BACKGROUND: Physostigmine, a centrally acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the postanesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep-disordered breathing. We investigated whether physostigmine was effective in decreasing the frequency of ventilatory arrhythmias produced during moderate sedation with midazolam and remifentanil during the conditions of breathing room air or 2 L/min nasal O2. Title: Neurotoxic effect of triazophos on goldfish (Carassius auratus) and tissue specific antioxidant responses Liu L, Zhu B, Gong YX, Liu GL, Wang GX Ref: Ecotoxicology & Environmental Safety, 116:68, 2015 : PubMed ESTHER: Liu_2015_Ecotoxicol.Environ.Saf_116_68 PubMedSearch: Liu 2015 Ecotoxicol.Environ.Saf 116 68 PubMedID: 25768424 Abstract Due to the high chemical and photochemical stability, an organophosphorus pesticide triazophos might enter aquatic ecosystems and impose negative effect on aquatic organisms. In order to investigate short-term toxicity of triazophos on goldfish (Carassius auratus), antioxidant response in brain, spleen, kidney and liver was tested in this study. As a confirmation, the impact of triazophos on acetyl cholinesterase (AChE) activity was found a reduction in all studied tissues, especially in brain. In addition, 0.1 and 0.5mgL-1 triazophos induced MDA level increased, while glutathione content (GSH), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) activities decreased. Of note, more prominent oxidative stress was provoked in kidney and liver, but weaker in brain and spleen. These results revealed that triazophos could cause a generalized oxidative stress and tissue specific antioxidant response in goldfish. Furthermore, neuroendocrine-growth-related gene expression (growth hormone (GH), luteinizing hormone (LH) and peptide YY) in brain was also changed by exposed to triazophos during 4 and 7d exposure periods. Linked with the above results, the present study pointed out that triazophos might induce a neurotoxic effect and oxidative damage in goldfish, and the goldfish brain should be a critical target for triazophos-induced damage. Title: Associations of ABHD2 Genetic Variations with Risks for Chronic Obstructive Pulmonary Disease in a Chinese Han Population Liu L, Li X, Yuan R, Zhang H, Qiang L, Shen J, Jin S Ref: PLoS ONE, 10:e0123929, 2015 : PubMed ESTHER: Liu_2015_PLoS.One_10_e0123929 PubMedSearch: Liu 2015 PLoS.One 10 e0123929 PubMedID: 25880496 Gene_locus related to this paper: human-ABHD2 Abstract The human alpha/beta hydrolase domain-containing protein 2 gene (ABHD2) plays a critical role in pulmonary emphysema, a major subset of the clinical entity known as chronic obstructive pulmonary disease (COPD). Here, we evaluated genetic variation in the ABHD2 gene in a Chinese Han population of 286 COPD patients and 326 control subjects. The rs12442260 CT/CC genotype was associated with COPD (P < 0.001) under a dominant model. In the former-smoker group, the rs12442260 TT genotype was associated with a decreased risk of developing COPD after adjusting for age, gender and pack-years (P = 0.012). Rs12442260 was also associated with pre-FEV1 (the predicted bronchodilator forced expiratory volume in the first second) in controls (P = 0.027), but with FEV1/ forced vital capacity (FVC) ratios only in COPD patients (P = 0.012) under a dominant model. Results from the current study suggest that ABHD2 gene polymorphisms contribute to COPD susceptibility in the Chinese Han population. Title: Design, synthesis and preliminary structure-activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives Liu H, Fan H, Gao X, Huang X, Liu X, Liu L, Zhou C, Tang J, Wang Q, Liu W Ref: J Enzyme Inhib Med Chem, :1, 2015 : PubMed ESTHER: Liu_2015_J.Enzyme.Inhib.Med.Chem__1 PubMedSearch: Liu 2015 J.Enzyme.Inhib.Med.Chem 1 PubMedID: 26186269 Abstract In order to study the structure-activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a-8d) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro. The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound 6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 mumol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound 6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE. Title: Genomic information of the arsenic-resistant bacterium Lysobacter arseniciresistens type strain ZS79(T) and comparison of Lysobacter draft genomes Liu L, Zhang S, Luo M, Wang G Ref: Stand Genomic Sci, 10:88, 2015 : PubMed ESTHER: Liu_2015_Stand.Genomic.Sci_10_88 PubMedSearch: Liu 2015 Stand.Genomic.Sci 10 88 PubMedID: 26516404 Gene_locus related to this paper: 9gamm-a0a0a0f4f2 Abstract Lysobacter arseniciresistens ZS79(T) is a highly arsenic-resistant,rod-shaped, motile, non-spore-forming, aerobic, Gram-negative bacterium. In this study, four Lysobacter type strains were sequenced and the genomic information of L. arseniciresistens ZS79(T) and the comparative genomics results of the Lysobacter strains were described. The draft genome sequence of the strain ZS79(T) consists of 3,086,721 bp and is distributed in 109 contigs. It has a G+C content of 69.5 % and contains 2,363 protein-coding genes including eight arsenic resistant genes. Title: Strategy to Overcome Effect of Raw Materials on Enzymatic Process of Biodiesel from Non-edible Oils Using Candida sp. 99-125 Lipase Nie K, Wang F, Tan T, Liu L Ref: Appl Biochem Biotechnol, 177:1176, 2015 : PubMed ESTHER: Nie_2015_Appl.Biochem.Biotechnol_177_1176 PubMedSearch: Nie 2015 Appl.Biochem.Biotechnol 177 1176 PubMedID: 26280803 Abstract Non-edible oils are preferred raw materials for biodiesel production. However, the properties of raw materials significantly affect the synthesis process, leading to difficulties to design one process suitable for any kind of raw material. In this study, the composition of five typical non-edible oils was analyzed. The major difference was the content of free fatty acids, reflected from their acid values. The influence of different oils was investigated by using lipase from Candida sp. 99-125. At low lipase dosage and low water content, the conversion was found proportional to the acid value. However, by increasing the water content or lipase dosage, we observed that the conversions for all kinds of oils used in this study could exceed 80 %. Time course analysis indicates that the lipase used in this study catalyzed hydrolysis followed by esterification, rather than direct transesterification. Accumulation of free fatty acids at the very beginning was necessary. A high water content facilitated the hydrolysis of oils with low acid value. This lipase showed capability to transform all the oils by controlling the water content. Title: A Novel Reaction Mediated by Human Aldehyde Oxidase: Amide Hydrolysis of GDC-0834 Sodhi JK, Wong S, Kirkpatrick DS, Liu L, Khojasteh SC, Hop CE, Barr JT, Jones JP, Halladay JS Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 43:908, 2015 : PubMed ESTHER: Sodhi_2015_Drug.Metab.Dispos_43_908 PubMedSearch: Sodhi 2015 Drug.Metab.Dispos 43 908 PubMedID: 25845827 Abstract GDC-0834, a Bruton's tyrosine kinase inhibitor investigated as a potential treatment of rheumatoid arthritis, was previously reported to be extensively metabolized by amide hydrolysis such that no measurable levels of this compound were detected in human circulation after oral administration. In vitro studies in human liver cytosol determined that GDC-0834 (R)-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo- 4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b] thiophene-2-carboxamide) was rapidly hydrolyzed with a CLint of 0.511 ml/min per milligram of protein. Aldehyde oxidase (AO) and carboxylesterase (CES) were putatively identified as the enzymes responsible after cytosolic fractionation and mass spectrometry-proteomics analysis of the enzymatically active fractions. Results were confirmed by a series of kinetic experiments with inhibitors of AO, CES, and xanthine oxidase (XO), which implicated AO and CES, but not XO, as mediating GDC-0834 amide hydrolysis. Further supporting the interaction between GDC-0834 and AO, GDC-0834 was shown to be a potent reversible inhibitor of six known AO substrates with IC50 values ranging from 0.86 to 1.87 muM. Additionally, in silico modeling studies suggest that GDC-0834 is capable of binding in the active site of AO with the amide bond of GDC-0834 near the molybdenum cofactor (MoCo), orientated in such a way to enable potential nucleophilic attack on the carbonyl of the amide bond by the hydroxyl of MoCo. Together, the in vitro and in silico results suggest the involvement of AO in the amide hydrolysis of GDC-0834. Title: Genomic and transcriptomic analysis of the endophytic fungus Pestalotiopsis fici reveals its lifestyle and high potential for synthesis of natural products Wang X, Zhang X, Liu L, Xiang M, Wang W, Sun X, Che Y, Guo L, Liu G and Liu X <3 more author(s)> Wang X, Zhang X, Liu L, Xiang M, Wang W, Sun X, Che Y, Guo L, Liu G, Wang C, Yin WB, Stadler M, Liu X (- 3) Ref: BMC Genomics, 16:28, 2015 : PubMed ESTHER: Wang_2015_BMC.Genomics_16_28 PubMedSearch: Wang 2015 BMC.Genomics 16 28 PubMedID: 25623211 Gene_locus related to this paper: 9pezi-w3wud0, 9pezi-w3xja3, pesfw-w3wz53, pesfw-w3x341, pesfw-w3whp0, pesfw-w3xc39, pesfw-w3wrn9, pesfw-pfmab, pesfw-pfmae Abstract BACKGROUND: In recent years, the genus Pestalotiopsis is receiving increasing attention, not only because of its economic impact as a plant pathogen but also as a commonly isolated endophyte which is an important source of bioactive natural products. Pestalotiopsis fici Steyaert W106-1/CGMCC3.15140 as an endophyte of tea produces numerous novel secondary metabolites, including chloropupukeananin, a derivative of chlorinated pupukeanane that is first discovered in fungi. Some of them might be important as the drug leads for future pharmaceutics. Title: Huperzine A Alleviates Mechanical Allodynia but Not Spontaneous Pain via Muscarinic Acetylcholine Receptors in Mice Zuo ZX, Wang YJ, Liu L, Wang Y, Mei SH, Feng ZH, Wang M, Li XY Ref: Neural Plast, 2015:453170, 2015 : PubMed ESTHER: Zuo_2015_Neural.Plast_2015_453170 PubMedSearch: Zuo 2015 Neural.Plast 2015 453170 PubMedID: 26697233 Abstract Chronic pain is a major health issue and most patients suffer from spontaneous pain. Previous studies suggest that Huperzine A (Hup A), an alkaloid isolated from the Chinese herb Huperzia serrata, is a potent analgesic with few side effects. However, whether it alleviates spontaneous pain is unclear. We evaluated the effects of Hup A on spontaneous pain in mice using the conditioned place preference (CPP) behavioral assay and found that application of Hup A attenuated the mechanical allodynia induced by peripheral nerve injury or inflammation. This effect was blocked by atropine. However, clonidine but not Hup A induced preference for the drug-paired chamber in CPP. The same effects occurred when Hup A was infused into the anterior cingulate cortex. Furthermore, ambenonium chloride, a competitive inhibitor of acetylcholinesterase, also increased the paw-withdrawal threshold but failed to induce place preference in CPP. Therefore, our data suggest that acetylcholinesterase in both the peripheral and central nervous systems is involved in the regulation of mechanical allodynia but not the spontaneous pain. Title: Site-directed mutagenesis studies of the aromatic residues at the active site of a lipase from Malassezia globosa Gao C, Lan D, Liu L, Zhang H, Yang B, Wang Y Ref: Biochimie, 102:29, 2014 : PubMed ESTHER: Gao_2014_Biochimie_102_29 PubMedSearch: Gao 2014 Biochimie 102 29 PubMedID: 24556587 Gene_locus related to this paper: malgo-a8puy1 Abstract The lipase from Malassezia globosa (SMG1) has specific activity on mono- and diacylglycerol but not on triacylglycerol. The structural analysis of SMG1 structure shows that two bulky aromatic residues, W116 and W229, lie at the entrance of the active site. To study the functions of these two residues in the substrate recognition and the catalytic reaction, they were mutated to a series of amino acids. Subsequently, biochemical properties of these mutants were investigated. Although the activities decrease, W229L and W116A show a significant shift in substrate preference. W229L has an increased preference for short-chain substrates whereas W116A has preference for long-chain substrates. Besides, the half-lives of W116A and W116H at 45 degrees C are 346.6 min and 115.5 min respectively, which improve significantly compared to that of native enzyme. Moreover, the optimum substrate of W116A, W116F and W229F mutants shifted from p-nitrophenyl caprylate to p-nitrophenyl myristate. These findings not only shed light onto the lipase structure/function relationship but also lay the framework for the potential industrial applications. Title: Genome and transcriptome analysis of the fungal pathogen Fusarium oxysporum f. sp. cubense causing banana vascular wilt disease Guo L, Han L, Yang L, Zeng H, Fan D, Zhu Y, Feng Y, Wang G, Peng C and Huang J <9 more author(s)> Guo L, Han L, Yang L, Zeng H, Fan D, Zhu Y, Feng Y, Wang G, Peng C, Jiang X, Zhou D, Ni P, Liang C, Liu L, Wang J, Mao C, Fang X, Peng M, Huang J (- 9) Ref: PLoS ONE, 9:e95543, 2014 : PubMed ESTHER: Guo_2014_PLoS.ONE_9_E95543 PubMedSearch: Guo 2014 PLoS.ONE 9 E95543 PubMedID: 24743270 Gene_locus related to this paper: fusox-w9hvf0, fusox-x0d9n6 Abstract BACKGROUND: The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing vascular wilt disease is one of the most devastating pathogens of banana (Musa spp.). To understand the molecular underpinning of pathogenicity in Foc, the genomes and transcriptomes of two Foc isolates were sequenced. METHODOLOGY/PRINCIPAL FINDINGS: Genome analysis revealed that the genome structures of race 1 and race 4 isolates were highly syntenic with those of F. oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence associated genes were identified in both Foc genomes, including genes putatively involved in root attachment, cell degradation, detoxification of toxin, transport, secondary metabolites biosynthesis and signal transductions. Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate (Foc4) has evolved with some expanded gene families of transporters and transcription factors for transport of toxins and nutrients that may facilitate its ability to adapt to host environments and contribute to pathogenicity to banana. Transcriptome analysis disclosed a significant difference in transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the banana 'Brazil' in comparison with the vegetative growth stage. Of particular note, more virulence-associated genes were up regulated in Foc4 than in Foc1. Several signaling pathways like the mitogen-activated protein kinase Fmk1 mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway and a pathogenicity associated two-component system were activated in Foc4 rather than in Foc1. Together, these differences in gene content and transcription response between Foc1 and Foc4 might account for variation in their virulence during infection of the banana variety 'Brazil'. CONCLUSIONS/SIGNIFICANCE: Foc genome sequences will facilitate us to identify pathogenicity mechanism involved in the banana vascular wilt disease development. These will thus advance us develop effective methods for managing the banana vascular wilt disease, including improvement of disease resistance in banana. Title: Fatty acid specificity of T1 lipase and its potential in acylglycerol synthesis Qin XL, Lan DM, Zhong JF, Liu L, Wang YH, Yang B Ref: J Sci Food Agric, 94:1614, 2014 : PubMed ESTHER: Qin_2014_J.Sci.Food.Agric_94_1614 PubMedSearch: Qin 2014 J.Sci.Food.Agric 94 1614 PubMedID: 24338705 Gene_locus related to this paper: bacsp-lip Abstract BACKGROUND: T1 lipase has received considerable attention due to its thermostability. Fatty acid specificity of T1 lipase (crude and purified) was investigated, and its potential in the synthesis of acylglycerols was also evaluated. Title: Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1 Wang X, Wang Q, Zhang W, Wang Y, Li L, Wen T, Zhang T, Zhang Y, Xu J and Li J <9 more author(s)> Wang X, Wang Q, Zhang W, Wang Y, Li L, Wen T, Zhang T, Zhang Y, Xu J, Hu J, Li S, Liu L, Liu J, Jiang W, Tian J, Li Y, Schuler D, Wang L, Li J (- 9) Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Wang_2014_Genome.Announc_2_e00171 PubMedSearch: Wang 2014 Genome.Announc 2 e00171 PubMedID: 24625872 Gene_locus related to this paper: maggm-v6ezc0 Abstract We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and "domestication" by accelerated evolution of the strain upon repeated passaging. Title: Nanomaterials-Based Optical Techniques for the Detection of Acetylcholinesterase and Pesticides Xia N, Wang Q, Liu L Ref: Sensors (Basel), 15:499, 2014 : PubMed ESTHER: Xia_2014_Sensors.(Basel)_15_499 PubMedSearch: Xia 2014 Sensors.(Basel) 15 499 PubMedID: 25558991 Abstract The large amount of pesticide residues in the environment is a threat to global health by inhibition of acetylcholinesterase (AChE). Biosensors for inhibition of AChE have been thus developed for the detection of pesticides. In line with the rapid development of nanotechnology, nanomaterials have attracted great attention and have been intensively studied in biological analysis due to their unique chemical, physical and size properties. The aim of this review is to provide insight into nanomaterial-based optical techniques for the determination of AChE and pesticides, including colorimetric and fluorescent assays and surface plasmon resonance. Title: Structural insights into enzymatic degradation of oxidized polyvinyl alcohol Yang Y, Ko TP, Liu L, Li J, Huang CH, Chan HC, Ren F, Jia D, Wang AH and Du G <2 more author(s)> Yang Y, Ko TP, Liu L, Li J, Huang CH, Chan HC, Ren F, Jia D, Wang AH, Guo RT, Chen J, Du G (- 2) Ref: Chembiochem, 15:1882, 2014 : PubMed ESTHER: Yang_2014_Chembiochem_15_1882 PubMedSearch: Yang 2014 Chembiochem 15 1882 PubMedID: 25044912 Gene_locus related to this paper: psesp-OPH, sphs1-OPH Inhibitor(s) related to this paper: Diethylene-glycol-monoethyl-ether, Acetylacetone, Octanoate Abstract The ever-increasing production and use of polyvinyl alcohol (PVA) threaten our environment. Yet PVA can be assimilated by microbes in two steps: oxidation and cleavage. Here we report novel alpha/beta-hydrolase structures of oxidized PVA hydrolase (OPH) from two known PVA-degrading organisms, Sphingopyxis sp. 113P3 and Pseudomonas sp. VM15C, including complexes with substrate analogues, acetylacetone and caprylate. The active site is covered by a lid-like beta-ribbon. Unlike other esterase and amidase, OPH is unique in cleaving the CC bond of beta-diketone, although it has a catalytic triad similar to that of most alpha/beta-hydrolases. Analysis of the crystal structures suggests a double-oxyanion-hole mechanism, previously only found in thiolase cleaving beta-ketoacyl-CoA. Three mutations in the lid region showed enhanced activity, with potential in industrial applications. Title: Roles of tryptophan residue and disulfide bond in the variable lid region of oxidized polyvinyl alcohol hydrolase Yang Y, Ko TP, Liu L, Li J, Huang CH, Chen J, Guo RT, Du G Ref: Biochemical & Biophysical Research Communications, 452:509, 2014 : PubMed ESTHER: Yang_2014_Biochem.Biophys.Res.Commun_452_509 PubMedSearch: Yang 2014 Biochem.Biophys.Res.Commun 452 509 PubMedID: 25173935 Gene_locus related to this paper: sphs1-OPH Inhibitor(s) related to this paper: Diethylene-glycol-monoethyl-ether, DMSO Abstract Oxidized polyvinyl alcohol hydrolase (OPH) catalyzes the cleavage of C-C bond in beta-diketone. It belongs to the alpha/beta-hydrolase family and contains a unique lid region that covers the active site. The lid is the most variable region when pOPH from Pseudomonas sp. VM15C and sOPH from Sphingopyxis sp. 113P3 are compared. The wild-type enzymes and the pOPH mutants W255A, W255Y and W255F were analyzed for lipase activity by using p-nitrophenyl (pNP) esters as the substrates. The wild-type enzymes showed increased Km and decreased kcat/Km with the acyl chain length, and the mutants showed reduced kcat/Km for pNP acetate, indicating the importance of Trp255 in sequestering the active site from solvent. The significantly lower activity for pNP butyrate can be a result of product inhibition, as suggested by the complex crystal structures, in which butyric acid, DMSO or PEG occupied the same substrate-binding cleft. The mutant activity was retained with pNP caprylate and pNP laurate as the substrates, reflecting the amphipathic nature of the cleft. Moreover, the disulfide bond formation of Cys257/267 is important for the activity of pOPH, but it is not essential for sOPH, which has a shorter lid structure. Title: Biochemical characterization and high-level production of oxidized polyvinyl alcohol hydrolase from Sphingopyxis sp. 113P3 expressed in methylotrophic Pichia pastoris Yang Y, Liu L, Li J, Du G, Chen J Ref: Bioprocess Biosyst Eng, 37:777, 2014 : PubMed ESTHER: Yang_2014_Bioprocess.Biosyst.Eng_37_777 PubMedSearch: Yang 2014 Bioprocess.Biosyst.Eng 37 777 PubMedID: 24068496 Abstract The Sphingopyxis sp. 113P3 gene oph, encoding oxidized polyvinyl alcohol hydrolase (OPH), was optimized with the preferred codons of Pichia pastoris and ligated into the pPIC9K vector behind the alpha-factor signal sequence. The vector was then transfected into P. pastoris GS115 and genomic integration was confirmed. Large-scale production of recombinant protein was performed by induction with 14.4 g/L methanol at 22 degrees C in a 3-L bioreactor. The maximal OPH activity obtained was 68.4 U/mL, which is the highest activity reported. The optimal pH and temperature of recombinant OPH were 8.0 and 45 degrees C, respectively. OPH activity was stable over a pH range of 5.0-8.5, and at a maximal temperature of 45 degrees C. The K cat /K m of recombinant OPH was 598 mM(-1) s(-1), which was 4.27-fold higher than that of recombinant OPH derived from Escherichia coli. The improved catalytic efficiency of OPH expressed in recombinant P. pastoris makes it favorable for industrial applications. Title: Triazole-induced toxicity in developing rare minnow (Gobiocypris rarus) embryos Zhu B, Liu L, Gong YX, Ling F, Wang GX Ref: Environ Sci Pollut Res Int, 21:13625, 2014 : PubMed ESTHER: Zhu_2014_Environ.Sci.Pollut.Res.Int_21_13625 PubMedSearch: Zhu 2014 Environ.Sci.Pollut.Res.Int 21 13625 PubMedID: 25028328 Abstract Using rare minnow (Gobiocypris rarus) at early-life stages as experimental models, the developmental toxicity of five widely used triazole fungicides (myclobutanil, fluconazole, flusilazole, triflumizole, and epoxiconazole) were investigated following exposure to 1-15 mg/L for 72 h. Meanwhile, morphological parameters (body length, body weight, and heart rate), enzyme activities (superoxide dismutase (SOD), glutathione S-transferase (GST), adenosine triphosphatase (ATPase), and acetyl cholinesterase (AChE)), and mRNA levels (hsp70, mstn, mt, apaf1, vezf1, and cyp1a) were also recorded following exposure to 0.2, 1.0, and 5.0 mg/L for 72 h. Results indicated that increased malformation and mortality, decreased body length, body weight, and heart rate provide a concentration-dependent pattern; values of 72 h LC50 (median lethal concentration) and EC50 (median effective concentration) ranged from 3 to 12 mg/L. Most importantly, the results of the present study suggest that even at the lowest concentration, 0.2 mg/L, five triazole fungicides also caused notable changes in enzyme activities and mRNA levels. Overall, the present study points out that those five triazole fungicides are highly toxic to the early development of G. rarus embryos. The information presented in this study will be helpful in better understanding the toxicity induced by triazole fungicides in fish embryos. Title: Sesquineolignans and terpene-sesquineolignans: anti-acetylcholinesterase constituents from Illicium simonsii Dong C, Liu L, Li X, Guan Z, Luo H, Wang Y Ref: Planta Med, 79:338, 2013 : PubMed ESTHER: Dong_2013_Planta.Med_79_338 PubMedSearch: Dong 2013 Planta.Med 79 338 PubMedID: 23468312 Abstract Chemical investigation of the aerial parts of Illicium simonsii resulted in the isolation of nine new compounds, simonsols A-E (1-5), simonsins A-B (7-8), terpene-sesquineolignans, clovanedunnianol (9), and p-menthadunnianol (10). Compound 5 was equilibrated with 7 as an inseparable mixture. The structures were elucidated by extensive NMR and MS analysis. Compounds 9, 10, and the mixture of 5 and 7 moderately inhibited acetylcholinesterase with IC50 values of 4.58 microM, 6.55 microM, and 10.34 microM, respectively. Title: A New Anti-acetylcholinesterase alpha-Pyrone Meroterpene, Arigsugacin I, from Mangrove Endophytic Fungus Penicillium sp. sk5GW1L of Kandelia candel Huang X, Sun X, Ding B, Lin M, Liu L, Huang H, She Z Ref: Planta Med, 79:1572, 2013 : PubMed ESTHER: Huang_2013_Planta.Med_79_1572 PubMedSearch: Huang 2013 Planta.Med 79 1572 PubMedID: 24081685 Abstract Arigsugacin I (1), a new alpha-pyrone meroterpene, along with two known compounds, arigsugacins F (2) and territrem B (3), were isolated from the mangrove endophytic fungus Penicillium sp. sk5GW1L from Kandelia candel. Their structures were identified through mass spectrometry and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low-temperature (100 K) single crystal X-ray diffraction with Cu Kalpha radiation. The absolute configuration of compound 2 was first reported by using X-ray copper radiation. Compounds 1-3 showed inhibitory activities against acetylcholinesterase with IC50 values of 0.64 +/- 0.08 microM, 0.37 +/- 0.11 microM, and 7.03 +/- 0.20 nM, respectively. Title: Nicotinic acetylcholine receptors containing the alpha4 subunit modulate alcohol reward Liu L, Hendrickson LM, Guildford MJ, Zhao-Shea R, Gardner PD, Tapper AR Ref: Biological Psychiatry, 73:738, 2013 : PubMed ESTHER: Liu_2013_Biol.Psychiatry_73_738 PubMedSearch: Liu 2013 Biol.Psychiatry 73 738 PubMedID: 23141806 Abstract BACKGROUND: Nicotine and alcohol are the two most co-abused drugs in the world, suggesting a common mechanism of action might underlie their rewarding properties. Although nicotine elicits reward by activating ventral tegmental area dopaminergic (DAergic) neurons via high-affinity neuronal nicotinic acetylcholine receptors (nAChRs), the mechanism by which alcohol activates these neurons is unclear. Title: Nicotinic acetylcholine receptors containing the alpha6 subunit contribute to ethanol activation of ventral tegmental area dopaminergic neurons Liu L, Zhao-Shea R, McIntosh JM, Tapper AR Ref: Biochemical Pharmacology, 86:1194, 2013 : PubMed ESTHER: Liu_2013_Biochem.Pharmacol_86(8)_1194 PubMedSearch: Liu 2013 Biochem.Pharmacol 86(8) 1194 PubMedID: 23811312 Abstract Nicotine and alcohol are often co-abused suggesting a common mechanism of action may underlie their reinforcing properties. Both drugs acutely increase activity of ventral tegmental area (VTA) dopaminergic (DAergic) neurons, a phenomenon associated with reward behavior. Recent evidence indicates that nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels activated by ACh and nicotine, may contribute to ethanol-mediated activation of VTA DAergic neurons although the nAChR subtype(s) involved has not been fully elucidated. Here we show that expression and activation of nAChRs containing the alpha6 subunit contribute to ethanol-induced activation of VTA DAergic neurons. In wild-type (WT) mouse midbrain sections that contain the VTA, ethanol (50 or 100 mM) significantly increased firing frequency of DAergic neurons. In contrast, ethanol did not significantly increase activity of VTA DAergic neurons in mice that do not express CHRNA6, the gene encoding the alpha6 nAChR subunit (alpha6 knock-out (KO) mice). Ethanol-induced activity in WT slices was also reduced by pre-application of the alpha6 subtype-selective nAChR antagonist, alpha-conotoxin MII[E11A]. When co-applied, ethanol potentiated the response to ACh in WT DAergic neurons; whereas co-application of ACh and ethanol failed to significantly increase activity of DAergic neurons in alpha6 KO slices. Finally, pre-application of alpha-conotoxin MII[E11A] in WT slices reduced ethanol potentiation of ACh responses. Together our data indicate that alpha6-subunit containing nAChRs may contribute to ethanol activation of VTA DAergic neurons. These receptors are predominantly expressed in DAergic neurons and known to be critical for nicotine reinforcement, providing a potential common therapeutic molecular target to reduce nicotine and alcohol co-abuse. Title: [Effect of Huperzine A on neural lesion of acute organophosphate poisoning in mice] Liu L, Wang J, Xie G, Sun J Ref: Wei Sheng Yan Jiu, 42:419, 2013 : PubMed ESTHER: Liu_2013_Wei.Sheng.Yan.Jiu_42_419 PubMedSearch: Liu 2013 Wei.Sheng.Yan.Jiu 42 419 PubMedID: 23805518 Abstract OBJECTIVE: Effects of neurophathologic changes and expression of Glu and 60 nNOS were observed in acute isocarbophos and phoxim poisoning in mice. Title: Evaluating the cognitive effects of donepezil 23 mg/d in moderate and severe Alzheimer's disease: analysis of effects of baseline features on treatment response Sabbagh M, Cummings J, Christensen D, Doody R, Farlow M, Liu L, Mackell J, Fain R Ref: BMC Geriatr, 13:56, 2013 : PubMed ESTHER: Sabbagh_2013_BMC.Geriatr_13_56 PubMedSearch: Sabbagh 2013 BMC.Geriatr 13 56 PubMedID: 23742728 Abstract BACKGROUND: Treatment of Alzheimer's disease with acetylcholinesterase inhibitors can result in symptomatic benefits, but patients often show variable responses. The objective of this post hoc analysis was to investigate relationships between easily identifiable baseline characteristics/demographics and cognitive response in patients treated with either donepezil 23 mg/d or 10 mg/d and to identify factors potentially influencing response. Title: Complete Genome Sequence of an Oral Commensal, Streptococcus oligofermentans Strain AS 1.3089 Tong H, Shang N, Liu L, Wang X, Cai J, Dong X Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Tong_2013_Genome.Announc_1_ PubMedSearch: Tong 2013 Genome.Announc 1 PubMedID: 23788543 Gene_locus related to this paper: strcr-n0c7c9 Abstract Streptococcus oligofermentans, an oral commensal, inhibits the growth of the dental caries pathogen Streptococcus mutans by producing large amounts of hydrogen peroxide. Therefore, it can be a potential probiotic for oral health. Here we report the complete genome sequence of S. oligofermentans strain AS 1.3089. Title: Heterologous expression and characterization of a malathion-hydrolyzing carboxylesterase from a thermophilic bacterium, Alicyclobacillus tengchongensis Xie Z, Xu B, Ding J, Liu L, Zhang X, Li J, Huang Z Ref: Biotechnol Lett, 35:1283, 2013 : PubMed ESTHER: Xie_2013_Biotechnol.Lett_35_1283 PubMedSearch: Xie 2013 Biotechnol.Lett 35 1283 PubMedID: 23801110 Gene_locus related to this paper: 9bacl-j9e7t9 Abstract A carboxylesterase gene from thermophilic bacterium, Alicyclobacillus tengchongensis, was cloned and expressed in Escherichia coli BL21 (DE3). The gene coded for a 513 amino acid protein with a calculated molecular mass of 57.82 kDa. The deduced amino acid sequence had structural features highly conserved among serine hydrolases, including Ser204, Glu325, and His415 as a catalytic triad, as well as type-B carboxylesterase serine active site (FGGDPENITIGGQSAG) and type-B carboxylesterase signature 2 (EDCLYLNIWTP). The purified enzyme exhibited optimum activity with beta-naphthyl acetate at 60 degrees C and pH 7 as well as stability at 25 degrees C and pH 7. One unit of the enzyme hydrolyzed 5 mg malathion l(-1) by 50 % within 25 min and 89 % within 100 min. The enzyme strongly degraded malathion and has a potential use for the detoxification of malathion residues. Title: Activation of GABAergic neurons in the interpeduncular nucleus triggers physical nicotine withdrawal symptoms Zhao-Shea R, Liu L, Pang X, Gardner PD, Tapper AR Ref: Current Biology, 23:2327, 2013 : PubMed ESTHER: Zhao-Shea_2013_Curr.Biol_23_2327 PubMedSearch: Zhao-Shea 2013 Curr.Biol 23 2327 PubMedID: 24239118 Abstract BACKGROUND: Chronic exposure to nicotine elicits physical dependence in smokers, yet the mechanism and neuroanatomical bases for withdrawal symptoms are unclear. As in humans, rodents undergo physical withdrawal symptoms after cessation from chronic nicotine characterized by increased scratching, head nods, and body shakes. Title: Lecithin:cholesterol acyltransferase deficiency protects against cholesterol-induced hepatic endoplasmic reticulum stress in mice Hager L, Li L, Pun H, Liu L, Hossain MA, Maguire GF, Naples M, Baker C, Magomedova L and Ng DS <4 more author(s)> Hager L, Li L, Pun H, Liu L, Hossain MA, Maguire GF, Naples M, Baker C, Magomedova L, Tam J, Adeli K, Cummins CL, Connelly PW, Ng DS (- 4) Ref: Journal of Biological Chemistry, 287:20755, 2012 : PubMed ESTHER: Hager_2012_J.Biol.Chem_287_20755 PubMedSearch: Hager 2012 J.Biol.Chem 287 20755 PubMedID: 22500017 Abstract We recently reported that lecithin:cholesterol acyltransferase (LCAT) knock-out mice, particularly in the LDL receptor knock-out background, are hypersensitive to insulin and resistant to high fat diet-induced insulin resistance (IR) and obesity. We demonstrated that chow-fed Ldlr-/-xLcat+/+ mice have elevated hepatic endoplasmic reticulum (ER) stress, which promotes IR, compared with wild-type controls, and this effect is normalized in Ldlr-/-xLcat-/- mice. In the present study, we tested the hypothesis that hepatic ER cholesterol metabolism differentially regulates ER stress using these models. We observed that the Ldlr-/-xLcat+/+ mice accumulate excess hepatic total and ER cholesterol primarily attributed to increased reuptake of biliary cholesterol as we observed reduced biliary cholesterol in conjunction with decreased hepatic Abcg5/g8 mRNA, increased Npc1l1 mRNA, and decreased Hmgr mRNA and nuclear SREBP2 protein. Intestinal NPC1L1 protein was induced. Expression of these genes was reversed in the Ldlr-/-xLcat-/- mice, accounting for the normalization of total and ER cholesterol and ER stress. Upon feeding a 2% high cholesterol diet (HCD), Ldlr-/-xLcat-/- mice accumulated a similar amount of total hepatic cholesterol compared with the Ldlr-/-xLcat+/+ mice, but the hepatic ER cholesterol levels remained low in conjunction with being protected from HCD-induced ER stress and IR. Hepatic ER stress correlates strongly with hepatic ER free cholesterol but poorly with hepatic tissue free cholesterol. The unexpectedly low ER cholesterol seen in HCD-fed Ldlr-/-xLcat-/- mice was attributable to a coordinated marked up-regulation of ACAT2 and suppressed SREBP2 processing. Thus, factors influencing the accumulation of ER cholesterol may be important for the development of hepatic insulin resistance. Title: [Wolman disease with novel mutation of LIPA gene in a Chinese infant] Huang YL, Sheng HY, Zhao XY, Yu JK, Li L, Liu HS, Gu CM, He DM, Liu L Ref: Zhonghua Er Ke Za Zhi, 50:601, 2012 : PubMed ESTHER: Huang_2012_Zhonghua.Er.Ke.Za.Zhi_50_601 PubMedSearch: Huang 2012 Zhonghua.Er.Ke.Za.Zhi 50 601 PubMedID: 23158738 Gene_locus related to this paper: human-LIPA Abstract OBJECTIVE To explore the clinical characteristics of Wolman disease and diagnostic methods using enzymatic and molecular analysis METHOD Lysosomal acid lipase activity was measured using 4-methylumbelliferyl oleate in the leukocytes of an infant suspected of Wolman disease and LIPA gene mutational analysis was performed by PCR and direct sequencing in the proband and his parents After the diagnosis was confirmed the clinical biochemical radiological and histopathological findings in this case of Wolman disease were retrospectively reviewed RESULT The sixteen-day-old boy was failing to thrive with progressive vomiting abdominal distention and hepatosplenomegaly Abdominal X-ray revealed adrenal calcifications which were confirmed on abdominal CT scan Xanthomatosis were observed on enlarged liver spleen and lymph nodes during abdominal surgery Liver and lymph node biopsy showed foamy histiocytes The lysosomal acid lipase activity in leukocytes was 3.5 nmol/(mg.h control 35.5 105.8 nmol/(mg.h Serum chitotriosidase activity was 315.8 nmol/(ml.h control Title: Molecular characterization of two acetylcholinesterase genes from the brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae) Li BL, Chen W, Liu L, Zhang XC, Bao YY, Cheng JA, Zhu ZR, Zhang CX Ref: Pesticide Biochemistry and Physiology, 102:198, 2012 : PubMed ESTHER: Li_2012_Pestic.Biochem.Physiol_102_198 PubMedSearch: Li 2012 Pestic.Biochem.Physiol 102 198 Gene_locus related to this paper: nillu-ACHE1, nillu-ACHE2 Abstract Acetylcholinesterase (AChE), which is encoded by the ace gene, catalyzes the hydrolysis of the neurotransmitter acetylcholine to terminate nerve impulses at the postsynaptic membrane. AChE is a primary target of many insecticides including organophosphates (OP) and carbamates (CB). In this study, full-length cDNA sequences of two ace genes (Nlace1 and Nlace2) were sequenced from the brown planthopper (BPH) Nilaparvata lugens, the most destructive insect pest of rice crops. Nlace1 cDNA is 2842 nucleotides long and contains an ORF potentially encoding a 790 amino acid peptide. Nlace2 cDNA is 2852 bp in length and contains an ORF that potentially encodes a 672 amino acid peptide. NlAChE1 has an identity of 40% with NlAChE2 at the amino acid sequence level. Phylogenetic analysis of 59 AChEs from 32 animal species showed that NlAChE1 is most closely related to AChE1s from Blattella germanica and Nephotettix cincticeps, while NlAChE2 is most closely related to AChE2 from N. cincticeps. Quantitative RT-PCR analysis showed that Nlace1 is expressed at a much higher level than Nlace2 in all developmental stages and tissues, demonstrating that NlAChE1 may be the dominant AChE form of the two enzymes. This result will help reveal the resistance mechanism of N. lugens to organophosphorous and carbamate insecticides and promote development of more selective insecticides targeting the main NlAChE1. Title: Protective effects of nizofenone administration on the cognitive impairments induced by chronic restraint stress in mice Liu Y, Zhuang X, Gou L, Ling X, Tian X, Liu L, Zheng Y, Zhang L, Yin X Ref: Pharmacol Biochem Behav, 103:474, 2012 : PubMed ESTHER: Liu_2012_Pharmacol.Biochem.Behav_103_474 PubMedSearch: Liu 2012 Pharmacol.Biochem.Behav 103 474 PubMedID: 23026061 Abstract The present study was aimed to investigate the effects of nizofenone administration on the chronic restraint stress-induced cognitive impairments in mice. Adult male mice were randomized into five groups: control group, nizofenone control group, chronic restraint stress group, and nizofenone treatment groups (3.0mg/kg and 9.0mg/kg). The changes of cognitive performances were examined by Morris water maze (MWM), open field and step-through tests. Our results showed that the cognitive performances in CRS group were markedly deteriorated, accompanied by noticeable alterations in oxidative parameters, acetylcholinesterase activity and catecholamines levels in the hippocampus and the prefrontal cortex. These changes could be reversed by nizofenone treatment. Moreover, CRS group showed higher corticosterone levels and lower catecholamines levels in the serum, which were reversed in the nizofenone treatment groups. Collectively, the present results suggested the potential of nizofenone in attenuating the CRS-induced cognitive impairments. Title: Nicotine persistently activates ventral tegmental area dopaminergic neurons via nicotinic acetylcholine receptors containing alpha4 and alpha6 subunits Liu L, Zhao-Shea R, McIntosh JM, Gardner PD, Tapper AR Ref: Molecular Pharmacology, 81:541, 2012 : PubMed ESTHER: Liu_2012_Mol.Pharmacol_81_541 PubMedSearch: Liu 2012 Mol.Pharmacol 81 541 PubMedID: 22222765 Abstract Nicotine is reinforcing because it activates dopaminergic (DAergic) neurons within the ventral tegmental area (VTA) of the brain's mesocorticolimbic reward circuitry. This increase in activity can occur for a period of several minutes up to an hour and is thought to be a critical component of nicotine dependence. However, nicotine concentrations that are routinely self-administered by smokers are predicted to desensitize high-affinity alpha4beta2 neuronal nicotinic acetylcholine receptors (nAChRs) in seconds. Thus, how physiologically relevant nicotine concentrations persistently activate VTA DAergic neurons is unknown. Here we show that nicotine can directly and robustly increase the firing frequency of VTA DAergic neurons for several minutes. In mouse midbrain slices, 300 nM nicotine elicited a persistent inward current in VTA DAergic neurons that was blocked by alpha-conotoxin MII[H9A;L15A], a selective antagonist of nAChRs containing the alpha6 subunit. alpha-conotoxin MII[H9A;L15A] also significantly reduced the long-lasting increase in DAergic neuronal activity produced by low concentrations of nicotine. In addition, nicotine failed to significantly activate VTA DAergic neurons in mice that did not express either alpha4 or alpha6 nAChR subunits. Conversely, selective activation of nAChRs containing the alpha4 subunit in knock-in mice expressing a hypersensitive version of these receptors yielded a biphasic response to nicotine consisting of an acute desensitizing increase in firing frequency followed by a sustained increase that lasted several minutes and was sensitive to alpha-conotoxin MII[H9A;L15A]. These data indicate that nicotine persistently activates VTA DAergic neurons via nAChRs containing alpha4 and alpha6 subunits. Title: Molecular basis for substrate selectivity of a mono- and diacylglycerol lipase from Malassezia globosa Liu L, Gao C, Lan D, Yang B, Wang Y Ref: Biochemical & Biophysical Research Communications, 424:285, 2012 : PubMed ESTHER: Liu_2012_Biochem.Biophys.Res.Commun_424_285 PubMedSearch: Liu 2012 Biochem.Biophys.Res.Commun 424 285 PubMedID: 22750000 Gene_locus related to this paper: malgo-a8puy1 Abstract The lipase from Malassezia globosa (SMG1) was identified to be strictly specific for mono- and diacylglycerol but not triacylglycerol. The crystal structures of SMG1 were solved in the closed conformation, but they failed to provide direct evidence of factors responsible for this unique selectivity. To address this problem, we constructed a structure in the open, active conformation and modeled a diacylglycerol analogue into the active site. Molecular dynamics simulations were performed on this enzyme-analogue complex to relax steric clashes. This bound diacylglycerol analogue unambiguously identified the position of two pockets which accommodated two alkyl chains of substrate. The structure of SMG1-analogue complex revealed that Leu103 and Phe278 divided the catalytic pocket into two separated moieties, an exposed groove and a narrow tunnel. Analysis of the binding model suggested that the unique selectivity of this lipase mainly resulted from the shape and size of this narrow tunnel, in which there was no space for the settlement of the third chain of triacylglycerol. These results expand our understanding on the mechanism underlying substrate selectivity of enzyme, and could pave the way for site-directed mutagenesis experiments to improve the enzyme for application. Title: Purification and characterization of a novel galloyltransferase involved in catechin galloylation in the tea plant (Camellia sinensis) Liu Y, Gao L, Liu L, Yang Q, Lu Z, Nie Z, Wang Y, Xia T Ref: Journal of Biological Chemistry, 287:44406, 2012 : PubMed ESTHER: Liu_2012_J.Biol.Chem_287_44406 PubMedSearch: Liu 2012 J.Biol.Chem 287 44406 PubMedID: 23132863 Gene_locus related to this paper: camsi-SCPL13 Abstract Catechins (flavan-3-ols), the most important secondary metabolites in the tea plant, have positive effects on human health and are crucial in defense against pathogens of the tea plant. The aim of this study was to elucidate the biosynthetic pathway of galloylated catechins in the tea plant. The results suggested that galloylated catechins were biosynthesized via 1-O-glucose ester-dependent two-step reactions by acyltransferases, which involved two enzymes, UDP-glucose:galloyl-1-O-beta-D-glucosyltransferase (UGGT) and a newly discovered enzyme, epicatechin:1-O-galloyl-beta-D-glucose O-galloyltransferase (ECGT). In the first reaction, the galloylated acyl donor beta-glucogallin was biosynthesized by UGGT from gallic acid and uridine diphosphate glucose. In the second reaction, galloylated catechins were produced by ECGT catalysis from beta-glucogallin and 2,3-cis-flavan-3-ol. 2,3-cis-Flavan-3-ol and 1-O-galloyl-beta-D-glucose were appropriate substrates of ECGT rather than 2,3-trans-flavan-3-ol and 1,2,3,4,6-pentagalloylglucose. Purification by more than 1641-fold to apparent homogeneity yielded ECGT with an estimated molecular mass of 241 to 121 kDa by gel filtration. Enzyme activity and SDS-PAGE analysis indicated that the native ECGT might be a dimer, trimer, or tetramer of 60- and/or 58-kDa monomers, and these monomers represent a heterodimer consisting of pairs of 36- or 34- of and 28-kDa subunits. MALDI-TOF-TOF MS showed that the protein SCPL1199 was identified. Epigallocatechin and epicatechin exhibited higher substrate affinities than beta-glucogallin. ECGT had an optimum temperature of 30 degreesC and maximal reaction rates between pH 4.0 and 6.0. The enzyme reaction was inhibited dramatically by phenylmethylsulfonyl fluoride, HgCl(2), and sodium deoxycholate. Title: Crystal structure of a mono- and diacylglycerol lipase from Malassezia globosa reveals a novel lid conformation and insights into the substrate specificity Xu T, Liu L, Hou S, Xu J, Yang B, Wang Y, Liu J Ref: J Struct Biol, 178:363, 2012 : PubMed ESTHER: Xu_2012_J.Struct.Biol_178_363 PubMedSearch: Xu 2012 J.Struct.Biol 178 363 PubMedID: 22484238 Gene_locus related to this paper: malgo-a8puy1 Abstract Most lipases contain a lid domain to shield the hydrophobic binding site from the water environment. The lid, mostly in helical form, can undergo a conformational change to expose the active cleft during the interfacial activation. Here we report the crystal structures of Malassezia globosa LIP1 (SMG1) at 1.45 and 2.60 resolution in two crystal forms. The structures present SMG1 in its closed form, with a novel lid in loop conformation. SMG1 is one of the few members in the fungal lipase family that has been found to be strictly specific for mono- and diacylglycerol. To date, the mechanism for this substrate specificity remains largely unknown. To investigate the substrate binding properties, we built a model of SMG1 in open conformation. Based on this model, we found that the two bulky hydrophobic residues adjacent to the catalytic site and the N-terminal hinge region of the lid both may act as steric hindrances for triacylglycerols binding. These unique structural features of SMG1 will provide a better understanding on the substrate specificity of mono- and diacylglycerol lipases and a platform for further functional study of this enzyme. Title: Comparative analysis of the genomes of two field isolates of the rice blast fungus Magnaporthe oryzae Xue M, Yang J, Li Z, Hu S, Yao N, Dean RA, Zhao W, Shen M, Zhang H and Peng YL <8 more author(s)> Xue M, Yang J, Li Z, Hu S, Yao N, Dean RA, Zhao W, Shen M, Zhang H, Li C, Liu L, Cao L, Xu X, Xing Y, Hsiang T, Zhang Z, Xu JR, Peng YL (- 8) Ref: PLoS Genet, 8:e1002869, 2012 : PubMed ESTHER: Xue_2012_PLoS.Genet_8_E1002869 PubMedSearch: Xue 2012 PLoS.Genet 8 E1002869 PubMedID: 22876203 Gene_locus related to this paper: maggr-q0pnd2, mago7-g4mk92, mago7-g4mkc6, mago7-g4mkk9, mago7-g4mns9, mago7-g4ms19, mago7-g4mvm8, mago7-g4mvw5, mago7-g4mvw6, mago7-g4n6j4, mago7-g4nal1, mago7-g4nba0, mago7-g4nbs0, mago7-g4nc41, mago7-g4ncz9, mago7-g4nhn9, mago7-g4nil3, mago7-g4nky6, mago7-g5ehg6, mago7-g5ehv6, mago7-g4msm5, magoy-l7il05, magoy-l7i6m7, magoy-l7ic25 Abstract Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases of rice worldwide. The fungal pathogen is notorious for its ability to overcome host resistance. To better understand its genetic variation in nature, we sequenced the genomes of two field isolates, Y34 and P131. In comparison with the previously sequenced laboratory strain 70-15, both field isolates had a similar genome size but slightly more genes. Sequences from the field isolates were used to improve genome assembly and gene prediction of 70-15. Although the overall genome structure is similar, a number of gene families that are likely involved in plant-fungal interactions are expanded in the field isolates. Genome-wide analysis on asynonymous to synonymous nucleotide substitution rates revealed that many infection-related genes underwent diversifying selection. The field isolates also have hundreds of isolate-specific genes and a number of isolate-specific gene duplication events. Functional characterization of randomly selected isolate-specific genes revealed that they play diverse roles, some of which affect virulence. Furthermore, each genome contains thousands of loci of transposon-like elements, but less than 30% of them are conserved among different isolates, suggesting active transposition events in M. oryzae. A total of approximately 200 genes were disrupted in these three strains by transposable elements. Interestingly, transposon-like elements tend to be associated with isolate-specific or duplicated sequences. Overall, our results indicate that gain or loss of unique genes, DNA duplication, gene family expansion, and frequent translocation of transposon-like elements are important factors in genome variation of the rice blast fungus. Title: Molecular Cloning and Heterologous Expression of a True Lipase in Pichia pastoris Isolated via a Metagenomic Approach Zheng J, Liu L, Liu C, Jin Q Ref: J Molecular Microbiology Biotechnol, 22:300, 2012 : PubMed ESTHER: Zheng_2012_J.Mol.Microbiol.Biotechnol_22_300 PubMedSearch: Zheng 2012 J.Mol.Microbiol.Biotechnol 22 300 PubMedID: 23128414 Abstract Lipases are important enzymes for various biotechnological applications. By using functional expression screening, lipZ03, a novel lipase gene, was isolated from a soil-derived metagenomic library. The gene was supposed to encode a protein of 617 amino acids with a C-terminal targeting signal region and four potential N-linked glycosylation sites. The protein sequence shared a conserved GXSXG motif (X represents any amino acid residue) with other microbial lipases. Gene lipZ03 was expressed in Pichia pastoris and the molecular weight was estimated to be approximately 65 kDa by electrophoresis. The optimum reaction temperature and pH value for LipZ03 was 50C and 9.0, respectively. The enzyme was highly stable in the temperature range of 40-60C and under alkaline conditions (pH 8-10). Lipolytic activity was significantly enhanced by Ca(2+) and Mg(2+) ions, but dramatically inhibited by Cu(2+), Ni(2+) and Hg(2+) ions and EDTA. The purified enzyme preferentially hydrolyzed relatively long-chain triacylglycerols and was a true lipase rather than an esterase. Using a multi-stepwise methanol supply, the purified LipZ03 achieved a conversion yield of biodiesel production up to 74% after 36 h. Some interesting characteristics described here showed that the recombinant lipase may have potential to be a useful enzyme in industrial applications. Title: Complete genome sequence of Bacillus amyloliquefaciens LL3, which exhibits glutamic acid-independent production of poly-gamma-glutamic acid Geng W, Cao M, Song C, Xie H, Liu L, Yang C, Feng J, Zhang W, Jin Y and Wang S <1 more author(s)> Geng W, Cao M, Song C, Xie H, Liu L, Yang C, Feng J, Zhang W, Jin Y, Du Y, Wang S (- 1) Ref: Journal of Bacteriology, 193:3393, 2011 : PubMed ESTHER: Geng_2011_J.Bacteriol_193_3393 PubMedSearch: Geng 2011 J.Bacteriol 193 3393 PubMedID: 21551302 Gene_locus related to this paper: baca2-a7z811 Abstract Bacillus amyloliquefaciens is one of most prevalent Gram-positive aerobic spore-forming bacteria with the ability to synthesize polysaccharides and polypeptides. Here, we report the complete genome sequence of B. amyloliquefaciens LL3, which was isolated from fermented food and presents the glutamic acid-independent production of poly-gamma-glutamic acid. Title: Azaphilones and p-terphenyls from the mangrove endophytic fungus Penicillium chermesinum (ZH4-E2) isolated from the South China Sea Huang H, Feng X, Xiao Z, Liu L, Li H, Ma L, Lu Y, Ju J, She Z, Lin Y Ref: Journal of Natural Products, 74:997, 2011 : PubMed ESTHER: Huang_2011_J.Nat.Prod_74_997 PubMedSearch: Huang 2011 J.Nat.Prod 74 997 PubMedID: 21510637 Abstract Eight secondary metabolites, including three new azaphilones (chermesinones A-C, 1-3), three new p-terphenyls (6'-O-desmethylterphenyllin, 4; 3-hydroxy-6'-O-desmethylterphenyllin, 5; 3''-deoxy-6'-O-desmethylcandidusin B, 7), and two known p-terphenyls (6, 8), were isolated from the culture of the mangrove endophytic fungus Penicillium chermesinum (ZH4-E2). Their structures were established by spectroscopic analysis. The absolute configuration of 1 was determined by X-ray crystallography. Terphenyls 4, 5, and 6 exhibited strong inhibitory effects against alpha-glucosidase with IC50 values of 0.9, 4.9, and 2.5 muM, respectively. Terphenyls 7 and 8 showed inhibitory activity toward acetylcholinesterase with IC50 values of 7.8 and 5.2 muM. Title: Visual detection of organophosphorus pesticides represented by mathamidophos using Au nanoparticles as colorimetric probe Li H, Guo J, Ping H, Liu L, Zhang M, Guan F, Sun C, Zhang Q Ref: Talanta, 87:93, 2011 : PubMed ESTHER: Li_2011_Talanta_87_93 PubMedSearch: Li 2011 Talanta 87 93 PubMedID: 22099654 Abstract With citrate-coated Au nanoparticles as colorimetric probe, a novel visual method for rapid assay of organophosphorus pesticides has been developed. The assay principle is based on catalytic hydrolysis of acetylthiocholine into thiocholine by acetylcholinesterase, which induces the aggregation of Au nanoparticles and the color change from claret-red to purple or even grey. The original plasmon absorption of Au nanoparticles at 522 nm decreases, and simultaneously, a new absorption band appears at 675 nm. The irreversible inhibition of organophosphorus pesticides on acetylcholinesterase prevents aggregation of Au nanoparticles. Under optimum conditions, the absorbance at 522 nm of Au nanoparticles is related linearly to the concentration of mathamidophos in the range of 0.02-1.42 mug/mL with a detection limit of 1.40 ng/mL. This colorimetric method has been successfully utilized to detect mathamidophos in vegetables with satisfactory results. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for the analysis of organophosphorus pesticides. Title: Complete genome sequence of the industrial strain Ketogulonicigenium vulgare WSH-001 Liu L, Li Y, Zhang J, Zhou Z, Liu J, Li X, Zhou J, Du G, Wang L, Chen J Ref: Journal of Bacteriology, 193:6108, 2011 : PubMed ESTHER: Liu_2011_J.Bacteriol_193_6108 PubMedSearch: Liu 2011 J.Bacteriol 193 6108 PubMedID: 21994934 Gene_locus related to this paper: ketvy-e3f614, ketvw-f9yby2 Abstract Ketogulonicigenium vulgare is an industrial organism commonly used in the vitamin C industry. Here, we report the finished, annotated, and compared 3.28-Mbp high-quality genome sequence of Ketogulonicigenium vulgare WSH-001, a 2-keto-l-gulonic acid-producing industrial strain stocked in our laboratory. Title: Complete genome sequence of the industrial strain Bacillus megaterium WSH-002 Liu L, Li Y, Zhang J, Zou W, Zhou Z, Liu J, Li X, Wang L, Chen J Ref: Journal of Bacteriology, 193:6389, 2011 : PubMed ESTHER: Liu_2011_J.Bacteriol_193_6389 PubMedSearch: Liu 2011 J.Bacteriol 193 6389 PubMedID: 22038958 Gene_locus related to this paper: bacmd-d5dhr4, bacmd-d5dlu4, bacmd-d5dna5, bacme-g2rqm9, bacme-g2rsv7, bacme-g9bex6 Abstract Bacillus megaterium, an industrial strain, has been widely used in protein production and the vitamin C industry. Here we reported a finished, annotated, and compared 4.14-Mbp high-quality genome sequence of B. megaterium WSH-002, which is the companion strain for Ketogulonicigenium vulgare in the vitamin C industry and is stocked in our laboratory. Title: Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 A resolution Schalk-Hihi C, Schubert C, Alexander R, Bayoumy S, Clemente JC, Deckman I, Desjarlais RL, Dzordzorme KC, Flores CM and Kuo LC <12 more author(s)> Schalk-Hihi C, Schubert C, Alexander R, Bayoumy S, Clemente JC, Deckman I, Desjarlais RL, Dzordzorme KC, Flores CM, Grasberger B, Kranz JK, Lewandowski F, Liu L, Ma H, Maguire D, Macielag MJ, McDonnell ME, Mezzasalma Haarlander T, Miller R, Milligan C, Reynolds C, Kuo LC (- 12) Ref: Protein Science, 20:670, 2011 : PubMed ESTHER: Schalk-Hihi_2011_Protein.Sci_20_670 PubMedSearch: Schalk-Hihi 2011 Protein.Sci 20 670 PubMedID: 21308848 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: ZYH Abstract A high-resolution structure of a ligand-bound, soluble form of human monoglyceride lipase (MGL) is presented. The structure highlights a novel conformation of the regulatory lid-domain present in the lipase family as well as the binding mode of a pharmaceutically relevant reversible inhibitor. Analysis of the structure lacking the inhibitor indicates that the closed conformation can accommodate the native substrate 2-arachidonoyl glycerol. A model is proposed in which MGL undergoes conformational and electrostatic changes during the catalytic cycle ultimately resulting in its dissociation from the membrane upon completion of the cycle. In addition, the study outlines a successful approach to transform membrane associated proteins, which tend to aggregate upon purification, into a monomeric and soluble form. Title: Effect of acute soman exposure on GABA(A) receptors in rat hippocampal slices and cultured hippocampal neurons Wang Y, Liu L, Weiss T, Stewart C, Mikler J Ref: Neurotox Res, 20:343, 2011 : PubMed ESTHER: Wang_2011_Neurotox.Res_20_343 PubMedSearch: Wang 2011 Neurotox.Res 20 343 PubMedID: 21643853 Abstract Exposure of the central nervous system to organophosphorus (OP) nerve agents causes seizures and neuronal cell death. Benzodiazepines are commonly used to treat seizures induced by OPs. However, it is known that soman-induced seizures are particularly resistant to benzodiazepine treatment, as compared with other OPs. This study investigated the effect of soman on gamma-aminobutyric acid (GABA) neurotransmission in acute rat hippocampal slices and the surface expression of GABA(A) receptors in cultured rat hippocampal neurons. Results showed that GABA-mediated inhibitory post synaptic currents (IPSCs) are significantly reduced by soman in a concentration-dependent manner in acute rat hippocampal slices. Furthermore, confocal microscopic and cell-based ELISA assays revealed that soman caused rapid internalization of GABA(A) receptors in cultured rat hippocampal neurons. The effect of soman on GABA(A)R endocytosis was not due to inhibition of acetylcholinesterase (AChE) because (1) the acetylcholine muscarinic receptor antagonist atropine did not block soman-induced GABA(A)R endocytosis; and (2) physostigmine, at concentrations that completely inhibit AChE activity, did not cause GABA(A)R endocytosis. Moreover, blocking of the N-methyl-D-aspartate (NMDA) receptors by 2-amino-5-phosphonovalerate (APV) had no effect on soman-induced GABA(A)R endocytosis, suggesting that the soman effect was not secondary to glutamate receptor over activation. Regardless of the exact mechanism, the observation that soman induces rapid GABA(A)R endocytosis may have significant implications in the development of effective countermeasures against soman-induced seizures. Title: Complete genome sequence of the plant pathogen Ralstonia solanacearum strain Po82 Xu J, Zheng HJ, Liu L, Pan ZC, Prior P, Tang B, Xu JS, Zhang H, Tian Q and Feng J <1 more author(s)> Xu J, Zheng HJ, Liu L, Pan ZC, Prior P, Tang B, Xu JS, Zhang H, Tian Q, Zhang LQ, Feng J (- 1) Ref: Journal of Bacteriology, 193:4261, 2011 : PubMed ESTHER: Xu_2011_J.Bacteriol_193_4261 PubMedSearch: Xu 2011 J.Bacteriol 193 4261 PubMedID: 21685279 Gene_locus related to this paper: ralso-PCAD, ralso-RSP1108, ralsl-y0kx85 Abstract Ralstonia solanacearum strain Po82, a phylotype IIB/sequevar 4 strain, was found to be pathogenic to both solanaceous plants and banana. Here, we report the complete genome sequence of Po82 and its comparison with seven published R. solanacearum genomes. Title: Nicotine-mediated activation of dopaminergic neurons in distinct regions of the ventral tegmental area Zhao-Shea R, Liu L, Soll LG, Improgo MR, Meyers EE, McIntosh JM, Grady SR, Marks MJ, Gardner PD, Tapper AR Ref: Neuropsychopharmacology, 36:1021, 2011 : PubMed ESTHER: Zhao-Shea_2011_Neuropsychopharmacology_36_1021 PubMedSearch: Zhao-Shea 2011 Neuropsychopharmacology 36 1021 PubMedID: 21289604 Abstract Nicotine activation of nicotinic acetylcholine receptors (nAChRs) within the dopaminergic (DAergic) neuron-rich ventral tegmental area (VTA) is necessary and sufficient for nicotine reinforcement. In this study, we show that rewarding doses of nicotine activated VTA DAergic neurons in a region-selective manner, preferentially activating neurons in the posterior VTA (pVTA) but not in the anterior VTA (aVTA) or in the tail VTA (tVTA). Nicotine (1 muM) directly activated pVTA DAergic neurons in adult mouse midbrain slices, but had little effect on DAergic neurons within the aVTA. Quantification of nAChR subunit gene expression revealed that pVTA DAergic neurons expressed higher levels of alpha4, alpha6, and beta3 transcripts than did aVTA DAergic neurons. Activation of nAChRs containing the alpha4 subunit (alpha4(*) nAChRs) was necessary and sufficient for activation of pVTA DAergic neurons: nicotine failed to activate pVTA DAergic neurons in alpha4 knockout animals; in contrast, pVTA alpha4(*) nAChRs were selectively activated by nicotine in mutant mice expressing agonist-hypersensitive alpha4(*) nAChRs (Leu9'Ala mice). In addition, whole-cell currents induced by nicotine in DAergic neurons were mediated by alpha4(*) nAChRs and were significantly larger in pVTA neurons than in aVTA neurons. Infusion of an alpha6(*) nAChR antagonist into the VTA blocked activation of pVTA DAergic neurons in WT mice and in Leu9'Ala mice at nicotine doses, which only activate the mutant receptor indicating that alpha4 and alpha6 subunits coassemble to form functional receptors in these neurons. Thus, nicotine selectively activates DAergic neurons within the pVTA through alpha4alpha6(*) nAChRs. These receptors represent novel targets for smoking-cessation therapies. Title: Inhibition of soluble epoxide hydrolase preserves cardiomyocytes: role of STAT3 signaling Merkel MJ, Liu L, Cao Z, Packwood W, Young J, Alkayed NJ, Van Winkle DM Ref: American Journal of Physiology Heart Circ Physiol, 298:H679, 2010 : PubMed ESTHER: Merkel_2010_Am.J.Physiol.Heart.Circ.Physiol_298_H679 PubMedSearch: Merkel 2010 Am.J.Physiol.Heart.Circ.Physiol 298 H679 PubMedID: 20008276 Abstract Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs), primarily 14,15-EET. EETs are derived from arachidonic acid via P-450 epoxygenases and are cardioprotective. We tested the hypothesis that sEH deficiency and pharmacological inhibition elicit tolerance to ischemia via EET-mediated STAT3 signaling in vitro and in vivo. In addition, the relevance of single nucleotide polymorphisms (SNPs) of EPHX2 (the gene encoding sEH) on tolerance to oxygen and glucose deprivation and reoxygenation and glucose repletion (OGD/RGR) was assessed in male C57BL\6J (WT) or sEH knockout (sEHKO) cardiomyocytes by using transactivator of transcription (TAT)-mediated transduction with sEH mutant proteins. Cell death and hydrolase activity was lower in Arg287Gln EPHX2 mutants vs. nontransduced controls. Excess 14,15-EET and SEH inhibition did not improve cell survival in Arg287Gln mutants. In WT cells, the putative EET receptor antagonist, 14,15-EEZE, abolished the effect of 14,15-EET and sEH inhibition. Cotreatment with 14,15-EET and SEH inhibition did not provide increased protection. In vitro, STAT3 inhibition blocked 14,15-EET cytoprotection, but not the effect of SEH inhibition. However, STAT3 small interfering RNA (siRNA) abolished cytoprotection by 14,15-EET and sEH inhibition, but cells pretreated with JAK2 siRNA remained protected. In vivo, STAT3 inhibition abolished 14,15-EET-mediated infarct size reduction. In summary, the Arg287Gln mutation is associated with improved tolerance against ischemia in vitro, and inhibition of sEH preserves cardiomyocyte viability following OGD/RGR via an EET-dependent mechanism. In vivo and in vitro, 14,15-EET-mediated protection is mediated in part by STAT3. Title: Modulation of glucagon-like peptide-1 release by berberine: in vivo and in vitro studies Yu Y, Liu L, Wang X, Liu X, Xie L, Wang G Ref: Biochemical Pharmacology, 79:1000, 2010 : PubMed ESTHER: Yu_2010_Biochem.Pharmacol_79_1000 PubMedSearch: Yu 2010 Biochem.Pharmacol 79 1000 PubMedID: 19945441 Inhibitor(s) related to this paper: Berberine Abstract Glucagon-like peptide (GLP)-1 is a potent glucose-dependent insulinotropic gut hormone released from intestinal L cells. Our previous studies showed that berberine increased GLP-1 secretion in streptozotocin-induced diabetic rats. The aim of this study was to investigate whether berberine affected GLP-1 release in normal rats and in NCI-H716 cells. Proglucagon and prohormone convertase 3 genes regulating GLP-1 biosynthesis were analyzed by RT-PCR. Effects of pharmacological inhibitors on berberine-mediated GLP-1 release were studied. In vivo, 5-week treatment of berberine enhanced GLP-1 secretion induced by glucose load and promoted proglucagon mRNA expression as well as L cell proliferation in intestine. In vitro, berberine concentration-dependently stimulated GLP-1 release in NCI-H716 cells. Berberine also promoted both prohormone convertase 3 and proglucagon mRNA expression. Chelerythrine (inhibitor of PKC) concentration-dependently suppressed berberine-mediated GLP-1 secretion. Compound C (inhibitor of AMPK) also inhibited berberine-mediated GLP-1 secretion. But only low concentrations of H89 (inhibitor of PKA) showed inhibitory effects on berberine-mediated GLP-1 release. The present results demonstrated that berberine showed its modulation on GLP-1 via promoting GLP-1 secretion and GLP-1 biosynthesis. Some signal pathways including PKC-dependent pathway were involved in this process. Elucidation of mechanisms controlling berberine-mediated GLP-1 secretion may facilitate the understanding of berberine's antidiabetic effects. Title: Complete genome sequence of citrus huanglongbing bacterium, 'Candidatus Liberibacter asiaticus' obtained through metagenomics Duan Y, Zhou L, Hall DG, Li W, Doddapaneni H, Lin H, Liu L, Vahling CM, Gabriel DW and Gottwald T <3 more author(s)> Duan Y, Zhou L, Hall DG, Li W, Doddapaneni H, Lin H, Liu L, Vahling CM, Gabriel DW, Williams KP, Dickerman A, Sun Y, Gottwald T (- 3) Ref: Mol Plant Microbe Interact, 22:1011, 2009 : PubMed ESTHER: Duan_2009_Mol.Plant.Microbe.Interact_22_1011 PubMedSearch: Duan 2009 Mol.Plant.Microbe.Interact 22 1011 PubMedID: 19589076 Gene_locus related to this paper: libap-c6xhk4, libap-c6xgr3 Abstract Citrus huanglongbing is the most destructive disease of citrus worldwide. It is spread by citrus psyllids and is associated with a low-titer, phloem-limited infection by any of three uncultured species of alpha-Proteobacteria, 'Candidatus Liberibacter asiaticus', 'Ca. L. americanus', and 'Ca. L. africanus'. A complete circular 'Ca. L. asiaticus' genome has been obtained by metagenomics, using the DNA extracted from a single 'Ca. L. asiaticus'-infected psyllid. The 1.23-Mb genome has an average 36.5% GC content. Annotation revealed a high percentage of genes involved in both cell motility (4.5%) and active transport in general (8.0%), which may contribute to its virulence. 'Ca. L. asiaticus' appears to have a limited ability for aerobic respiration and is likely auxotrophic for at least five amino acids. Consistent with its intracellular nature, 'Ca. L. asiaticus' lacks type III and type IV secretion systems as well as typical free-living or plant-colonizing extracellular degradative enzymes. 'Ca. L. asiaticus' appears to have all type I secretion system genes needed for both multidrug efflux and toxin effector secretion. Multi-protein phylogenetic analysis confirmed 'Ca. L. asiaticus' as an early-branching and highly divergent member of the family Rhizobiaceae. This is the first genome sequence of an uncultured alpha-proteobacteria that is both an intracellular plant pathogen and insect symbiont. Title: Procyanidins extracted from the lotus seedpod ameliorate scopolamine-induced memory impairment in mice Xu J, Rong S, Xie B, Sun Z, Zhang L, Wu H, Yao P, Zhang Y, Liu L Ref: Phytother Res, 23:1742, 2009 : PubMed ESTHER: Xu_2009_Phytother.Res_23_1742 PubMedSearch: Xu 2009 Phytother.Res 23 1742 PubMedID: 19367674 Abstract The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) in mice. The capacities of memory and learning were evaluated by the Morris water maze and the step-down avoidance test. LSPC (50, 100, 150 mg/kg BW, p.o.) significantly reversed scopolamine-induced learning and memory impairments in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. In the step-down avoidance test, LSPC (50, 100, 150 mg/kg BW, p.o.) treatment significantly reduced the number of errors and shortened latency compared with that of scopolamine. In addition, LSPC was also found to inhibit acetyl cholinesterase (AChE) activity. These results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by AD and aging. Title: Rejuvenation of antioxidant and cholinergic systems contributes to the effect of procyanidins extracted from the lotus seedpod ameliorating memory impairment in cognitively impaired aged rats Xu J, Rong S, Xie B, Sun Z, Zhang L, Wu H, Yao P, Zhang X, Zhang Y, Liu L Ref: European Neuropsychopharmacology, 19:851, 2009 : PubMed ESTHER: Xu_2009_Eur.Neuropsychopharmacol_19_851 PubMedSearch: Xu 2009 Eur.Neuropsychopharmacol 19 851 PubMedID: 19716273 Abstract The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments in cognitively impaired aged rats. Based on Morris water maze performance compared with young female rats, aged unimpaired (AU) and aged impaired (AI) rats were chosen from aged female rats. LSPC supplementation (50, 100 mg/kg BW, p.o.) for 7 weeks significantly improved learning and memory impairments in AI animals in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. Aged rats had significantly declined antioxidant defense capacities and significantly increased lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex than young rats. Further, AI group had higher protein oxidation level compared with AU group. LSPC (50, 100 mg/kg BW, p.o.) significantly reversed the decline of antioxidant defense capacities and significantly reduced lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex of AI rats. In addition, LSPC significantly restored acetylcholine (ACh) contents and acetylcholinesterase (AChE) activities in hippocampus and cerebral cortex of AI animals. The results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by Alzheimer's disease and aging. Title: [Cloning, expression and characterization of a novel lipase gene lipB from Aspergillus niger F044] Yang J, Zhang Z, Liu L, Yan Y Ref: Wei Sheng Wu Xue Bao, 49:1095, 2009 : PubMed ESTHER: Yang_2009_Wei.Sheng.Wu.Xue.Bao_49_1095 PubMedSearch: Yang 2009 Wei.Sheng.Wu.Xue.Bao 49 1095 PubMedID: 19835173 Abstract OBJECTIVE: We cloned, expressed and characterized a novel lipase gene lipB from Aspergillus niger F044, to facilitate the large scale production and application of that enzyme. METHOD: We cloned lipB gene and the cDNA sequence by PCR and RT-PCR, and then cloned the open reading frame of lipB into pET28a vector and expressed by isopropyl beta-D-1-thiogalactopyranoside (IPTG) induction. After Ni-agarose purification, the characteristics were determined and the conformation change was checked by circular dichroism methods. RESULTS: The novel lipase genes cDNA of lipB were cloned from Aspergillus niger F044 (GenBank: FJ536287, FJ536288) and expressed in Escherichia coli. The molecular weight of LipB was about 43 kDa. The optimal substrate of this enzyme is 4-nitrophenyl octanoate (pNPC-C8) with Km = 5.98 mmol/L. The optimal temperature and pH was 50 degrees C and pH 6.0. The enzyme was stable below 40 degrees C. After incubated at 60 degrees C for 1 h, only 18.8% activity remained. After treated by 2 mmol/L Ca2+ for 1 h, the activity improved 2.6-fold. CONCLUSION: Enzymatic characteristics of LipB determined showed this enzyme might have potential in industrial applications. Title: In situ electrodeposited nanoparticles for facilitating electron transfer across self-assembled monolayers in biosensor design Du D, Ding J, Cai J, Zhang J, Liu L Ref: Talanta, 74:1337, 2008 : PubMed ESTHER: Du_2008_Talanta_74_1337 PubMedSearch: Du 2008 Talanta 74 1337 PubMedID: 18371787 Abstract Gold nanoparticles (AuNPs) were synthesized in situ and electrodeposited onto Au substrate. The AuNPs modified interface facilitates electron transfer across self-assembled monolayers (SAMs) of 11-mercaptoundecanoic acid (MUA). After activation of surface carboxyl groups with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, the interface displayed good stability for immobilization of biomolecules. These modification processes were characterized by contact angle measurement, cyclic voltammetry and electrochemical impedance spectra. The immobilized acetylcholinesterase (AChE), as a model, showed excellent activity to its substrate, leading to a stable AChE biosensor. Under the optimal experimental conditions, the inhibition of malathion on AChE biosensor was proportional to its concentration in two ranges, from 0.001 to 0.1 microg mL(-1) and from 0.1 to 25 microg mL(-1), with detection limit of 0.001 microg mL(-1). The simple method showed good reproducibility and acceptable stability, which had potential application in biosensor design. Title: [Cutinase production from short-chain organic acids by Thermobifida fusca] He G, Du G, Liu L, Liu H, Huo G, Chen J Ref: Sheng Wu Gong Cheng Xue Bao, 24:821, 2008 : PubMed ESTHER: He_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_821 PubMedSearch: He 2008 Sheng.Wu.Gong.Cheng.Xue.Bao 24 821 PubMedID: 18724703 Abstract We studied cutinase production from short-chain organic acids by Thermobifida fusca WSH03-11 to evaluate the possibility of converting municipal sludge to high value-added products. The optimum organic acid (8.0 g/L) and nitrogen source (1.5 g/L) concentrations were determined by the single factor experiments with butyric acid, propionic acid and acetic acid as the carbon sources. When lactic acid was used as the carbon source, the optimum organic acid (3.0 g/L) and nitrogen source (1.0 g/L) concentrations were obtained. Cutinase production by T. fusca WSH03-11 was further improved with butyric acid (by 31.0%), propionic acid (by 13.3%), acetic acid (by 43.8%) and lactic acid (by 73.2%) as carbon source, respectively, with the optimized cutin concentrations. Among these four short-chain organic acids, the average specific consumption rate of acetic acid was the highest, higher than that of propionic acid 1.3-folds, butyric acid 2.0-folds and lactic acid 2.2-folds. The highest cutinase activity reached 52.4 u/mL with butyric acid (8 g/L) as the sole carbon source, higher than that of lactic acid (3 g/L) 1.7-folds, acetic acid (8 g/L) 2.5-folds and propionic acid (8 g/L) 3.2-folds. The yield of cutinase activity on lactic acid (12.70 u/mg) higher than that of butyric acid 1.4-folds, propionic acid 3.0-folds and acetic acid 3.8-folds. T. fusca WSH03-11 consumed acetic acid firstly in mixed acids carbon sources, and the consumption of butyric acid was inhibited. Further studies indicated that the consumption rate of butyrate was decreased by 66.7% in the presence of 0.5 g/L acetic acid in the mixed acids. This was the first report concerning the production of cutinase by T. fusca with mixed organic acids as the carbon sources. The results presented here provided a novel and efficient approach to produce high value-add products from municipal sludge, and also established a foundation for the industrial production of cutinase by T. fusca WSH03-11 with cheap carbon sources from the processing of municipal sludge. Title: L- and N-current but not M-current inhibition by M1 muscarinic receptors requires DAG lipase activity Liu L, Heneghan JF, Michael GJ, Stanish LF, Egertova M, Rittenhouse AR Ref: Journal of Cellular Physiology, 216:91, 2008 : PubMed ESTHER: Liu_2008_J.Cell.Physiol_216_91 PubMedSearch: Liu 2008 J.Cell.Physiol 216 91 PubMedID: 18247369 Inhibitor(s) related to this paper: Rhc80267 Abstract Stimulation of postsynaptic M(1) muscarinic receptors (M(1)Rs) increases firing rates of both sympathetic and central neurons that underlie increases in vasomotor tone, heart rate, and cognitive memory functioning. At the cellular level, M(1)R stimulation modulates currents through various voltage-gated ion channels, including KCNQ K+ channels (M-current) and both L- and N-type Ca2+ channels (L- and N-current) by a pertussis toxin-insensitive, slow signaling pathway. Depletion of phosphatidylinositol-4,5-bisphosphate (PIP2) during M(1)R stimulation suffices to inhibit M-current. We found previously that following PIP2 hydrolysis by phospholipase C, activation of phospholipase A2 and liberation of a lipid metabolite, most likely arachidonic acid (AA) are necessary for L- and N-current modulation. Here we examined the involvement of a third lipase, diacylglycerol lipase (DAGL), in the slow pathway. We documented the presence of DAGL in superior cervical ganglion neurons, and then tested the highly selective DAGL inhibitor, RHC-80267, for its capacity to antagonize M(1)R-mediated modulation of whole-cell Ca2+ currents. RHC-80267 significantly reduced L- and N-current inhibition by the muscarinic agonist oxotremorine-M (Oxo-M) but did not affect their inhibition by exogenous AA. Moreover, voltage-dependent inhibition of N-current by Oxo-M remained in the presence of RHC-80267, indicating selective action on the slow pathway. RHC also blocked inhibition of recombinant N-current. In contrast, RHC-80267 had no effect on native M-current inhibition. These data are consistent with a role for DAGL in mediating L- and N-current inhibition. These results extend our previous findings that the signaling pathway mediating L- and N-current inhibition diverges from the pathway initiating M-current inhibition. Title: Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo Motoki A, Merkel MJ, Packwood WH, Cao Z, Liu L, Iliff J, Alkayed NJ, Van Winkle DM Ref: American Journal of Physiology Heart Circ Physiol, 295:H2128, 2008 : PubMed ESTHER: Motoki_2008_Am.J.Physiol.Heart.Circ.Physiol_295_H2128 PubMedSearch: Motoki 2008 Am.J.Physiol.Heart.Circ.Physiol 295 H2128 PubMedID: 18835921 Gene_locus related to this paper: human-EPHX2 Inhibitor(s) related to this paper: nbAUDA Abstract Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death. Deletion of sEH has been shown to be protective against myocardial ischemia in the isolated heart preparation. We tested the hypothesis that sEH inactivation by targeted gene deletion or pharmacological inhibition reduces infarct size (I) after regional myocardial ischemia-reperfusion injury in vivo. Male C57BL\6J wild-type or sEH knockout mice were subjected to 40 min of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 min before LCA occlusion or during ischemia 10 min before reperfusion. 14,15-EET, the main substrate for sEH, was administered intravenously 15 min before LCA occlusion or during ischemia 5 min before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 min before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and triphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15-EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15-EEZE. Immunohistochemistry revealed abundant sEH protein expression in left ventricular tissue. Strategies to increase 14,15-EET, including sEH inactivation, may represent a novel therapeutic approach for cardioprotection against myocardial ischemia-reperfusion injury. Title: Crystallization and preliminary crystallographic analysis of Gibberella zeae extracellular lipase Sun Y, Li M, Zhang Y, Liu L, Liu Y, Liu Z, Li X, Lou Z Ref: Acta Crystallographica Sect F Struct Biol Cryst Commun, 64:813, 2008 : PubMed ESTHER: Sun_2008_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_64_813 PubMedSearch: Sun 2008 Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun 64 813 PubMedID: 18765911 Gene_locus related to this paper: gibze-q6wer3 Abstract Fusarium head blight, one of the most destructive crop diseases, is mainly caused by Fusarium graminearum (known in its sexual stage as Gibberella zeae). F. graminearum secretes various extracellular enzymes that have been hypothesized to be involved in host infection. One of the extracellular enzymes secreted by this organism is the G. zeae extracellular lipase (GZEL), which is encoded by the FGL1 gene. In order to solve the crystal structure of GZEL and to gain a better understanding of the biological functions of the protein and of possible inhibitory mechanisms of lipase inhibitors, recombinant GZEL was crystallized at 291 K using PEG 3350 as a precipitant. A data set was collected to 2.8 A resolution from a single flash-cooled crystal (100 K). The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 78.4, b = 91.0, c = 195.8 A, alpha = beta = gamma = 90 degrees . The presence of four molecules was assumed per asymmetric unit, which gave a Matthews coefficient of 2.6 A(3) Da(-1). Title: Genome biology of Actinobacillus pleuropneumoniae JL03, an isolate of serotype 3 prevalent in China Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W and Chen H <16 more author(s)> Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W, Jin H, Kang M, Dalai B, Li T, Liu L, Cheng Y, Zhang L, Xu T, Zheng H, Pu S, Wang B, Gu W, Zhang XL, Zhu GF, Wang S, Zhao GP, Chen H (- 16) Ref: PLoS ONE, 3:e1450, 2008 : PubMed ESTHER: Xu_2008_PLoS.ONE_3_E1450 PubMedSearch: Xu 2008 PLoS.ONE 3 E1450 PubMedID: 18197260 Gene_locus related to this paper: actp2-a3n347, actp7-b3h2v1, actp7-b3h2x2, actpj-b0bpm3, actpj-b0bqd8 Abstract Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a cause of considerable world wide economic losses in the swine industry. We sequenced the complete genome of A. pleuropneumoniae, JL03, an isolate of serotype 3 prevalent in China. Its genome is a single chromosome of 2,242,062 base pairs containing 2,097 predicted protein-coding sequences, six ribosomal rRNA operons, and 63 tRNA genes. Preliminary analysis of the genomic sequence and the functions of the encoded proteins not only confirmed the present physiological and pathological knowledge but also offered new insights into the metabolic and virulence characteristics of this important pathogen. We identified a full spectrum of genes related to its characteristic chemoheterotrophic catabolism of fermentation and respiration with an incomplete TCA system for anabolism. In addition to confirming the lack of ApxI toxin, identification of a nonsense mutation in apxIVA and a 5'-proximal truncation of the flp operon deleting both its promoter and the flp1flp2tadV genes have provided convincing scenarios for the low virulence property of JL03. Comparative genomic analysis using the available sequences of other serotypes, probable strain (serotype)-specific genomic islands related to capsular polysaccharides and lipopolysaccharide O-antigen biosyntheses were identified in JL03, which provides a foundation for future research into the mechanisms of serotypic diversity of A. pleuropneumoniae. Title: Sequence variation and molecular evolution of hormone-sensitive lipase genes in species of bovidae Ma Z, Zhong J, Cheng Z, Liu L, Chang H, Luo X Ref: J Genet Genomics, 34:26, 2007 : PubMed ESTHER: Ma_2007_J.Genet.Genomics_34_26 PubMedSearch: Ma 2007 J.Genet.Genomics 34 26 PubMedID: 17469775 Abstract The partial sequences of exon I of hormone-sensitive lipase (HSL) genes in yak (Bos grunniens), cattle (Bos taurus), zebu (Bos indicus), and buffalo (Bubalus bubalis) were analyzed. Comparisons of these sequences and the deduced amino acid sequences with the homologous HSL gene and protein sequences in other mammalian species including pig (Sus scrofa), human (Homo sapiens), mouse (Mus musculus), and rat (Rattus sp.) retrieved from the GenBank were carried out and finally a phylogenetic tree was constructed using the partial DNA sequences of the HSL genes in all species. The results showed that the homologies of the partial exon I sequences of the HSL genes between yak and cattle, zebu, buffalo, pig, human, mouse, and rat were as high as 99.8%, 99.6%, 97.4%, 90.6%, 88.4%, 83.5%, and 82.3%, respectively. This was accompanied by highly homologous amino acid sequences of the HSLs: 100%, 100%, 98.2%, 94.0%, 92.2%, 89.8%, and 89.8% identity, respectively. There are more transitions, less transversions, and no insertion or deletion in variable nucleotides of the HSL genes between the yak and other species. The majority of the variable mutations was synonymous and was found most frequently at the third codon, followed by the first and second codons, a finding that was in accordance with the neutralism hypothesis for molecular evolution. In the phylogenetic tree, the cattle and zebu were clustered together first, followed by the yak, buffalo, pig, human, mouse, and rat. This was in agreement with taxonomy suggesting that the partial sequences of exon I of the HSL genes were useful in constructing the phylogenetic tree of mammalian species. Among the four species of Bovidae, genetic differentiation in the HSL genes between yak and buffalo is equivalent to that between buffalo and cattle and between buffalo and zebu. Furthermore, the genetic distances in the HSL genes are much smaller between yak, cattle, and zebu than those between each of the three species and the buffalo. Therefore, it is reasonable to consider yak as an independent species of the genus Bos. Title: Crystal structure of homoserine O-acetyltransferase from Leptospira interrogans Wang M, Liu L, Wang Y, Wei Z, Zhang P, Li Y, Jiang X, Xu H, Gong W Ref: Biochemical & Biophysical Research Communications, 363:1050, 2007 : PubMed ESTHER: Wang_2007_Biochem.Biophys.Res.Commun_363_1050 PubMedSearch: Wang 2007 Biochem.Biophys.Res.Commun 363 1050 PubMedID: 17927957 Gene_locus related to this paper: lepin-METX Abstract Homoserine O-acetyltransferase (HTA, EC 2.3.1.31) initiates methionine biosynthesis pathway by catalyzing the transfer of acetyl group from acetyl-CoA to homoserine. This study reports the crystal structure of HTA from Leptospira interrogans determined at 2.2A resolution using selenomethionyl single-wavelength anomalous diffraction method. HTA is modular and consists of two structurally distinct domains--a core alpha/beta domain containing the catalytic site and a helical bundle called the lid domain. Overall, the structure fold belongs to alpha/beta hydrolase superfamily with the characteristic 'catalytic triad' residues in the active site. Detailed structure analysis showed that the catalytic histidine and serine are both present in two conformations, which may be involved in the catalytic mechanism for acetyl transfer. Title: Acetylcholinesterase inhibitors and sleep architecture in patients with Alzheimer's disease Cooke JR, Loredo JS, Liu L, Marler M, Corey-Bloom J, Fiorentino L, Harrison T, Ancoli-Israel S Ref: Drugs & Aging, 23:503, 2006 : PubMed ESTHER: Cooke_2006_Drugs.Aging_23_503 PubMedSearch: Cooke 2006 Drugs.Aging 23 503 PubMedID: 16872233 Abstract BACKGROUND AND OBJECTIVE Studies suggest that some acetylcholinesterase inhibitors (AChEIs) increase rapid eye movement (REM) sleep and nightmares in patients with Alzheimer's disease (AD) but few have studied their effect on other sleep parameters. The objective of this study was to examine differences in sleep architecture in AD patients taking different AChEIs. METHODS: 76 participants (51 men, 25 women) [mean age = 78.2 years; SD = 7.7] with mild to moderate AD underwent medication history screening as well as polysomnography to determine the percentage of each sleep stage. Participants were divided into groups based on AChEI used: donepezil (n = 41), galantamine (n = 15), rivastigmine (n = 8) or no AChEI (n = 12). General univariate linear model analyses were performed. RESULTS: AChEI therapy had a significant effect on the percentage of stage 1 (p = 0.01) and stage 2 (p = 0.03) sleep. Patients in the donepezil group had a significantly lower percentage of stage 1 sleep than patients in the galantamine group (mean = 17.3%, SD = 11.7 vs 29.2%, SD = 15.0, respectively; p = 0.01), but there was no significant difference between the donepezil group and the rivastigmine (mean = 25.0%, SD = 12.3) or no AChEI groups (mean = 27.6%, SD = 17.7) in this respect. No significant differences in percentage of stage 1 between other groups were seen. Patients in the donepezil group also had a significantly higher percentage of stage 2 sleep than patients in the no AChEI group (mean = 63.6%, SD = 14.4 vs 51.4%, SD = 16.9, respectively; p = 0.04), but there was no significant difference between the donepezil group and either the galantamine group (mean = 56.5%, SD = 8.7) or the rivastigmine group (mean = 59.9%, SD = 8.4). There were no significant differences between groups in terms of percentage REM sleep or other sleep parameters. CONCLUSION: Subgroups of AD patients (classified according to AChEI treatment) in this study differed with respect to the amount of stage 1 and stage 2 sleep experienced, with the donepezil-treated group having the lowest percentage of stage 1 sleep and the highest percentage of stage 2 sleep. There was no significant difference in the amount of REM sleep between the groups. Our data suggest that sleep architecture may be affected by the use of donepezil in patients with AD. Although not elicited in this study because of the small sample size, there may be a class effect of AChEIs on sleep architecture. Double-blind, placebo-controlled studies are needed to better understand causality and the effect of each AChEI on sleep architecture in patients with AD. Title: Identification of open reading frames unique to a select agent: Ralstonia solanacearum race 3 biovar 2 Gabriel DW, Allen C, Schell M, Denny TP, Greenberg JT, Duan YP, Flores-Cruz Z, Huang Q, Clifford JM and Mikhailova N <18 more author(s)> Gabriel DW, Allen C, Schell M, Denny TP, Greenberg JT, Duan YP, Flores-Cruz Z, Huang Q, Clifford JM, Presting G, Gonzalez ET, Reddy J, Elphinstone J, Swanson J, Yao J, Mulholland V, Liu L, Farmerie W, Patnaikuni M, Balogh B, Norman D, Alvarez A, Castillo JA, Jones J, Saddler G, Walunas T, Zhukov A, Mikhailova N (- 18) Ref: Mol Plant Microbe Interact, 19:69, 2006 : PubMed ESTHER: Gabriel_2006_Mol.Plant.Microbe.Interact_19_69 PubMedSearch: Gabriel 2006 Mol.Plant.Microbe.Interact 19 69 PubMedID: 16404955 Gene_locus related to this paper: ralsl-a3rp80, ralso-a3rpz2, ralso-a3rqm7, ralso-a3rwb6, ralso-a3s0y6, ralso-b5sl67, ralso-b5slf2, ralso-DEHH, ralso-METX, ralso-PCAD, ralso-PCAD2, ralso-PHAZ, ralso-PHBC, ralso-RSC0268, ralso-RSC0439, ralso-RSC0563, ralso-RSC1770, ralso-RSC1772, ralso-RSC1887, ralso-RSC2328, ralso-RSC3346, ralso-RSP0196, ralso-RSP1108, ralso-RSP1248, ralso-RSP1484, ralso-RSP1521, ralsl-y0kx85 Abstract An 8x draft genome was obtained and annotated for Ralstonia solanacearum race 3 biovar 2 (R3B2) strain UW551, a United States Department of Agriculture Select Agent isolated from geranium. The draft UW551 genome consisted of 80,169 reads resulting in 582 contigs containing 5,925,491 base pairs, with an average 64.5% GC content. Annotation revealed a predicted 4,454 protein coding open reading frames (ORFs), 43 tRNAs, and 5 rRNAs; 2,793 (or 62%) of the ORFs had a functional assignment. The UW551 genome was compared with the published genome of R. solanacearum race 1 biovar 3 tropical tomato strain GMI1000. The two phylogenetically distinct strains were at least 71% syntenic in gene organization. Most genes encoding known pathogenicity determinants, including predicted type III secreted effectors, appeared to be common to both strains. A total of 402 unique UW551 ORFs were identified, none of which had a best hit or >45% amino acid sequence identity with any R. solanacearum predicted protein; 16 had strong (E < 10(-13)) best hits to ORFs found in other bacterial plant pathogens. Many of the 402 unique genes were clustered, including 5 found in the hrp region and 38 contiguous, potential prophage genes. Conservation of some UW551 unique genes among R3B2 strains was examined by polymerase chain reaction among a group of 58 strains from different races and biovars, resulting in the identification of genes that may be potentially useful for diagnostic detection and identification of R3B2 strains. One 22-kb region that appears to be present in GMI1000 as a result of horizontal gene transfer is absent from UW551 and encodes enzymes that likely are essential for utilization of the three sugar alcohols that distinguish biovars 3 and 4 from biovars 1 and 2. Title: [Effect of HuperzineA on neurophathologic change of mouse exposed by isocarbophos and phoxim] Xie GY, Liu L, Wang J, Zhao WJ Ref: Wei Sheng Yan Jiu, 35:339, 2006 : PubMed ESTHER: Xie_2006_Wei.Sheng.Yan.Jiu_35_339 PubMedSearch: Xie 2006 Wei.Sheng.Yan.Jiu 35 339 PubMedID: 16921763 Inhibitor(s) related to this paper: Isocarbophos Abstract OBJECTIVE: In order to assessment the Huperzine A (HupA) on CNS of mice exposed by phoxim and isocarbophos. Title: [Clinical analysis of successful treatment of 12 cases with acute organophosphorus pesticide poisoning.] Chen HY, Sun YL, Liu L Ref: Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 17:334, 2005 : PubMed ESTHER: Chen_2005_Zhongguo.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_17_334 PubMedSearch: Chen 2005 Zhongguo.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue 17 334 PubMedID: 15970095 Title: [Advances on study of organophosphate poisoning prevented by Huperzine A] Liu L, Sun JX Ref: Wei Sheng Yan Jiu, 34:224, 2005 : PubMed ESTHER: Liu_2005_Wei.Sheng.Yan.Jiu_34_224 PubMedSearch: Liu 2005 Wei.Sheng.Yan.Jiu 34 224 PubMedID: 15952670 Abstract Currently, it is a concerned project in medicine to study the effective methods for treatment of organophosphate (OP) poisoning. Huperzine A is a potent, reversible red cells acetylcholinesterases (AChE) inhibitor, which shows high specificity for AChE preserving scavenger capacity of plasma butyrylcholinesterase (BuChE) for OP agents, and cross the blood-brain barrier smoothly preventing the AChE in CNS, so the CNS damages induced by the acute OP poisoning were prevented. These review summarizes the results of experimental in animals, prevention mechanism, and prevention value of HupA against OP poison. Title: Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing Mansfield KJ, Liu L, Mitchelson FJ, Moore KH, Millard RJ, Burcher E Ref: British Journal of Pharmacology, 144:1089, 2005 : PubMed ESTHER: Mansfield_2005_Br.J.Pharmacol_144_1089 PubMedSearch: Mansfield 2005 Br.J.Pharmacol 144 1089 PubMedID: 15723094 Abstract 1. We investigated muscarinic receptors in the detrusor and mucosa of the human bladder body. Radioligand-binding studies with [(3)H]QNB were conducted using specimens collected from patients (36-77 years) with normal bladder function, undergoing surgery. For RT-PCR, biopsies of normal bladder were obtained from patients (30-88 years) undergoing check cystoscopy. 2. Binding of [(3)H]QNB in detrusor (n=20) was of high affinity (K(D) 77.1 (55.2-99.0) pM) and capacity (B(max) 181+/-7 fmol mg protein(-1)). Similar values were obtained in mucosa (n=6) (K(D) 100.5 (41.2-159.9) pM; B(max) 145+/-9 fmol mg protein(-1)). 3. Competition-binding experiments in detrusor membranes with muscarinic receptor antagonists including trospium, darifenacin, 4-DAMP, methoctramine, AQ-RA 741, AF-DX 116 and pirenzepine indicated a receptor population of 71% M(2), 22% M(3) and 7% M(1). In the mucosa, 75% of sites were M(2) receptors, with 25% M(3)/M(5). 4. Using RT-PCR, expression of M(1), M(2), M(3) and M(5) mRNA was demonstrated in both detrusor and mucosa. 5. The presence of a high density of mainly M(2) muscarinic receptors in the mucosa appears to be a novel finding and raises the question of their physiological significance and the source of their endogenous ligand. 6. There was a negative correlation of receptor number (B(max)) with age in detrusor muscle from male patients (P=0.02). Quantitative competitive RT-PCR demonstrated a selective age-related decrease in mRNA for muscarinic M(3) but not M(2) receptors, in both male (P<0.0001) and female (P=0.019) detrusor. These findings correspond with reports of decreased detrusor contractility with ageing. Title: Lipase-catalyzed biodegradation of poly(epsilon-caprolactone) blended with various polylactide-based polymers Li S, Liu L, Garreau H, Vert M Ref: Biomacromolecules, 4:372, 2003 : PubMed ESTHER: Li_2003_Biomacromolecules_4_372 PubMedSearch: Li 2003 Biomacromolecules 4 372 PubMedID: 12625734 Abstract Poly(epsilon-caprolactone) was blended with various polylactide-based polymers and processed to films by the solution casting method. Blends of 25/75, 50/50, 75/25, 90/10, and 95/5 (w/w) poly(epsilon-caprolactone)/poly(l-lactide), a 95/5 (w/w) blend of poly(epsilon-caprolactone) with a poly(d-lactide), a 50/50 (w/w) poly(l-lactide)-poly(d-lactide) mixture, and a poly(l-lactide-co-epsilon-caprolactone) copolymer were considered comparatively. The various phase-separated films were allowed to degrade in the presence of Pseudomonas lipase, biodegradation being monitored by proton nuclear magnetic resonance, size exclusion chromatography, differential scanning calorimetry, X-ray diffraction, and environmental scanning electron microscopy. The formation of separated phases during solvent evaporation and their morphologies are discussed. The introduction of poly(l-lactide) dramatically decreased the degradation rate of poly(epsilon-caprolactone)/poly(l-lactide) blends. The higher the percentage of poly(l-lactide), the slower the degradation, while the presence of cracks and increasing the lipase concentration acted in favor of the enzymatic degradation. Long-term enzymatic degradation of the various 95/5 blends was investigated over 480 h. The poly(epsilon-caprolactone) phase was enzymatically degraded by the lipase regardless of the blend type, the degradation rate depending on the nature of the co-components. Title: Functional profiling of the Saccharomyces cerevisiae genome Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, Dow S, Lucau-Danila A, Anderson K and Johnston M <63 more author(s)> Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, Dow S, Lucau-Danila A, Anderson K, Andre B, Arkin AP, Astromoff A, El-Bakkoury M, Bangham R, Benito R, Brachat S, Campanaro S, Curtiss M, Davis K, Deutschbauer A, Entian KD, Flaherty P, Foury F, Garfinkel DJ, Gerstein M, Gotte D, Guldener U, Hegemann JH, Hempel S, Herman Z, Jaramillo DF, Kelly DE, Kelly SL, Kotter P, LaBonte D, Lamb DC, Lan N, Liang H, Liao H, Liu L, Luo C, Lussier M, Mao R, Menard P, Ooi SL, Revuelta JL, Roberts CJ, Rose M, Ross-Macdonald P, Scherens B, Schimmack G, Shafer B, Shoemaker DD, Sookhai-Mahadeo S, Storms RK, Strathern JN, Valle G, Voet M, Volckaert G, Wang CY, Ward TR, Wilhelmy J, Winzeler EA, Yang Y, Yen G, Youngman E, Yu K, Bussey H, Boeke JD, Snyder M, Philippsen P, Davis RW, Johnston M (- 63) Ref: Nature, 418:387, 2002 : PubMed ESTHER: Giaever_2002_Nature_418_387 PubMedSearch: Giaever 2002 Nature 418 387 PubMedID: 12140549 Abstract Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics. Title: The effects of long-term treatment with metrifonate, a cholinesterase inhibitor, on cholinergic activity, amyloid pathology, and cognitive function in APP and PS1 doubly transgenic mice Liu L, Ikonen S, Heikkinen T, Tapiola T, van Groen T, Tanila H Ref: Experimental Neurology, 173:196, 2002 : PubMed ESTHER: Liu_2002_Exp.Neurol_173_196 PubMedSearch: Liu 2002 Exp.Neurol 173 196 PubMedID: 11822883 Abstract Recent studies in cell cultures have shown that modulating the cholinergic activity can influence the processing and metabolism of amyloid precursor protein (APP). To investigate whether acetylcholinesterase inhibitors (ChEIs) could decrease production of amyloid beta-peptide (A(beta)) and slow down the accumulation of A(beta) also in vivo, we chronically administered metrifonate (100 mg/kg, po), a second-generation ChEI, to 7-month-old doubly transgenic APP+PS1 mice and their nontransgenic littermate controls for 7 months. Behavioral studies, including open field test, T maze, and water maze, were conducted after 6 months treatment with metrifonate, and the mice were sacrificed at the age of 14 months for biochemical and histological analyses. The long-term treatment with metrifonate failed to inhibit the marked overproduction and deposition of A(beta) in the APP+PS1 mice; in contrast, it increased both A(beta)40 and A(beta)42 levels in the hippocampus. However, the A(beta)42 to 40 ratio was significantly reduced by the treatment. In addition, the number of amyloid plaques in the hippocampus did not differ between the treatment and the control groups. Tolerance to cholinesterase inhibition might be induced in the mouse brain because the inhibition rate of AChE was attenuated from about 80 to 50% during the experiment in both APP+PS1 and nontransgenic mice. The metrifonate treatment did not affect cognitive testing parameters but reduced swimming speed and locomotor activity in both genotypes. Our results do not support the idea that ChEIs would slow down the progression of amyloid pathology in Alzheimer's disease. Title: Fimbria-fornix lesion does not affect APP levels and amyloid deposition in the hippocampus of APP+PS1 double transgenic mice Liu L, Ikonen S, Tapiola T, Tanila H, van Groen T Ref: Experimental Neurology, 177:565, 2002 : PubMed ESTHER: Liu_2002_Exp.Neurol_177_565 PubMedSearch: Liu 2002 Exp.Neurol 177 565 PubMedID: 12429202 Abstract The deposition of amyloid beta peptides (Abeta) and cholinergic dysfunction are two characteristic features of Alzheimer's disease. Several studies have suggested that a compromised cholinergic transmission can increase the amount of amyloid precursor protein (APP) in the denervated cortex (or hippocampus); however, whether this will increase Abeta production is unknown. To investigate the relation between cholinergic neurotransmission and APP metabolism, and the possible role of cholinergic dysfunction in the development of amyloid neuropathology, we lesioned the fimbria-fornix pathway in APP+PS1 double transgenic mice, at 5 and 7 months of age. Three months and 11 months postlesion, the mice were sacrificed for biochemical and histopathological analyses. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus at both time points. Three months postlesion, hippocampal APP and Abeta levels were not significantly changed. At 11 months postlesion, the fimbria-fornix lesion did not result in an alteration in either the hippocampal Abeta levels or the extent of Abeta deposition, as assessed by amyloid plaque counts and image analysis of Abeta load in the 18-month-old APP+PS1 mice. Our findings indicate that APP metabolism in mice may be dissociated from cholinergic neurotransmission rather than related as previously suggested in other mammalian species. Title: Human and rodent carboxylesterases: immunorelatedness, overlapping substrate specificity, differential sensitivity to serine enzyme inhibitors, and tumor-related expression Xie M, Yang D, Liu L, Xue B, Yan B Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 30:541, 2002 : PubMed ESTHER: Xie_2002_Drug.Metab.Dispos_30_541 PubMedSearch: Xie 2002 Drug.Metab.Dispos 30 541 PubMedID: 11950785 Abstract Carboxylesterases hydrolyze numerous endogenous and foreign compounds with diverse structures. Humans and rodents express multiple forms of carboxylesterases, which share a high degree of sequence identity (approximately 70%). Alignment analyses locate in carboxylesterases several functional subsites such the catalytic triad as seen in acetylcholinesterase. The aim of this study was to determine among human and rodent carboxylesterases the immunorelatedness, overlapping substrate specificity, differential sensitivity to serine enzyme inhibitors, tissue distribution, and tumor-related expression. Six antibodies against whole carboxylesterases or synthetic peptides were tested for their reactivity toward 11 human or rodent recombinant carboxylesterases. The antibodies against whole proteins generally exhibited a broader cross-reactivity than the anti-peptide antibodies. All carboxylesterases hydrolyzed para-nitrophenylacetate and para-nitrophenylbutyrate. However, the relative activity varied markedly from enzyme to enzyme (>20-fold), and some carboxylesterases showed a clear substrate preference. Carboxylesterases with the same functional subsites had a similar profile on substrate specificity and sensitivity toward phenylmethylsulfonyl fluoride (PMSF) and paraoxon, suggesting that these subsites play determinant roles in the recognition of substrates and inhibitors. Among three human carboxylesterases, HCE-1 hydrolyzed both substrates to a similar extent, whereas HCE-2 and HCE-3 showed an opposite substrate preference. All three enzymes were inhibited by PMSF and paraoxon, but they showed a marked difference in relative sensitivities. Based on immunoblotting analyses, HCE-1 was present in all tissues examined, whereas HCE-2 and HCE-3 were expressed in a tissue-restricted pattern. Colon carcinomas expressed slightly higher levels of HCE-1 and HCE-2 than the adjacent normal tissues, whereas the opposite was true with HCE-3. Title: Neuronal-glial interactions mediated by interleukin-1 enhance neuronal acetylcholinesterase activity and mRNA expression Li Y, Liu L, Kang J, Sheng JG, Barger SW, Mrak RE, Griffin WS Ref: Journal of Neuroscience, 20:149, 2000 : PubMed ESTHER: Li_2000_J.Neurosci_20_149 PubMedSearch: Li 2000 J.Neurosci 20 149 PubMedID: 10627591 Abstract Cholinergic dysfunction in Alzheimer's disease has been attributed to stress-induced increases in acetylcholinesterase (AChE) activity. Interleukin-1 (IL-1) is overexpressed in Alzheimer's disease, and stress-related changes in long-term potentiation, an ACh-related cerebral function, are triggered by interleukin-1. Microglial cultures (N9) synthesized and released IL-1 in response to conditioned media obtained from glutamate-treated primary neuron cultures or PC12 cells. This conditioned media contained elevated levels of secreted beta-amyloid precursor protein (sAPP). Naive PC12 cells cocultured with stimulated N9 cultures showed increased AChE activity and mRNA expression. These effects on AChE expression and activity could be blocked by either preincubating the glutamate-treated PC12 supernatants with anti-sAPP antibodies or preincubating naive PC12 cells with IL-1 receptor antagonist. These findings were confirmed in vivo; IL-1-containing pellets implanted into rat cortex also increased AChE mRNA levels. Neuronal stress in Alzheimer's disease may induce increases in AChE expression and activity through a molecular cascade that is mediated by sAPP-induced microglial activation and consequent overexpression of IL-1. | |||||||
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