Author Report for: Sun JNo contact information in database for Sun J
Chen Y, Wang Y, Xu Y, Sun J, Yang L, Feng C, Wang J, Zhou Y, Zhang ZM Ref: Commun Chem, 6:45, 2023 : PubMed ESTHER: Chen_2023_Commun.Chem_6_45 PubMedSearch: Chen 2023 Commun.Chem 6 45 PubMedID: 36859434 Gene_locus related to this paper: 9acto-q2mhh5 Abstract Phthalate acid esters (PAEs), a group of xenobiotic compounds used extensively as plasticizers, have attracted increasing concern for adverse effects to human health and the environment. Microbial degradation relying on PAE hydrolases is a promising treatment. However, only a limited number of PAE hydrolases were characterized to date. Here we report the structures of MehpH, a monoalkyl phthalate (MBP) hydrolase that catalyzes the reaction of MBP to phthalic acid and the corresponding alcohol, in apo and ligand-bound form. The structures reveal a positively-charged catalytic center, complementary to the negatively-charged carboxyl group on MBP, and a penetrating tunnel that serves as exit of alcohol. The study provides a first glimpse into the enzyme-substrate binding model for PAE hydrolases, leading strong support to the development of better enzymes in the future. Title: Improved Production of Recombinant Carboxylesterase FumDM by Co-Expressing Molecular Chaperones in Pichia pastoris Jiang L, Guan X, Liu H, Chang X, Sun J, Sun C, Zhao C Ref: Toxins (Basel), 15:, 2023 : PubMed ESTHER: Jiang_2023_Toxins.(Basel)_15_ PubMedSearch: Jiang 2023 Toxins.(Basel) 15 PubMedID: 36828470 Gene_locus related to this paper: sphmc-FumD Abstract Fumonisins (FBs) are mycotoxins that threaten public health and food safety worldwide. Enzymatic degradation of Fumonisin B1 (FB(1)) through decarboxylation has attracted much attention, whereas application of FB(1) carboxylesterase in detoxification requires more effective expression of the recombinant carboxylesterase. In this study, the carboxylesterase FumDM from Sphingopyxis sp. ASAG22 was codon-optimized and co-expressed with five different molecular chaperones (PDI, CPR5, ERO1, HAC1, and Bip) in order to improve the expression level of FumDM in Pichia pastoris (also known as Komagataella phaffii) GS115. The co-expression of different chaperones caused varying degrees of improvement in FumDM activity for FB(1). The enzyme activities of recombinant strains over-expressing PDI and CPR5 reached the highest levels of 259.47 U/mL and 161.34 U/mL, 635% and 357% higher than the original enzyme activity, respectively. Transcriptomic analysis of the two recombinant strains in comparison with the control strain showed that the correct folding of proteins assisted by molecular chaperones played a key role in the improvement of FumDM expression and its enzyme activity. This study demonstrated that co-expression of carboxylesterase FumDM and folding chaperones was an efficient strategy and therefore might inspire new perspectives on the improvement of carboxylesterase for detoxification of FB(1). Title: Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase Wang Y, Sun J, Zhang M, Pan K, Liu T, Zhang T, Luo X, Zhao J, Li Z Ref: Foods, 12:, 2023 : PubMed ESTHER: Wang_2023_Foods_12_ PubMedSearch: Wang 2023 Foods 12 PubMedID: 36673508 Abstract Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries. Title: A Sensitive and Selective Colorimetric Method Based on the Acetylcholinesterase-like Activity of Zeolitic Imidazolate Framework-8 and Its Applications Chen X, He X, Sun J, Wang Z, Chen GY, Qian ZM, Yin SJ, Zhou X, Yang FQ Ref: Molecules, 27:, 2022 : PubMed ESTHER: Chen_2022_Molecules_27_ PubMedSearch: Chen 2022 Molecules 27 PubMedID: 35458616 36364318 Abstract In this study, a simple colorimetric method was established to detect copper ion (Cu(2+)), sulfathiazole (ST), and glucose based on the acetylcholinesterase (AChE)-like activity of zeolitic imidazolate framework-8 (ZIF-8). The AChE-like activity of ZIF-8 can hydrolyze acetylthiocholine chloride (ATCh) to thiocholine (TCh), which will further react with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) to generate 2-nitro-5-thiobenzoic acid (TNB) that has a maximum absorption peak at 405 nm. The effects of different reaction conditions (buffer pH, the volume of ZIF-8, reaction temperature and time, and ATCh concentration) were investigated. Under the optimized conditions, the value of the Michaelis-Menten constant (K(m)) is measured to be 0.83 mM, which shows a high affinity toward the substrate (ATCh). Meanwhile, the ZIF-8 has good storage stability, which can maintain more than 80.0% of its initial activity after 30 days of storage at room temperature, and the relative standard deviation (RSD) of batch-to-batch (n = 3) is 5.1%. The linear dependences are obtained based on the AChE-like activity of ZIF-8 for the detection of Cu(2+), ST, and glucose in the ranges of 0.021-1.34 and 5.38-689.66 M, 43.10-517.24 M, and 0.0054-1.40 mM, respectively. The limit of detections (LODs) are calculated to be 20.00 nM, 9.25 M, and 5.24 M, respectively. Moreover, the sample spiked recoveries of Cu(2+) in lake water, ST in milk, and glucose in strawberry samples were measured, and the results are in the range of 98.4-115.4% with the RSD (n = 3) lower than 3.3%. In addition, the method shows high selectivity in the real sample analysis. Title: Defining the Chemical Additives Driving In Vitro Toxicities of Plastics Chen W, Gong Y, McKie M, Almuhtaram H, Sun J, Barrett H, Yang D, Wu M, Andrews RC, Peng H Ref: Environ Sci Technol, :, 2022 : PubMed ESTHER: Chen_2022_Environ.Sci.Technol__ PubMedSearch: Chen 2022 Environ.Sci.Technol PubMedID: 36173153 Abstract Increases in the global use of plastics have caused concerns regarding potential adverse effects on human health. Plastic products contain hundreds of potentially toxic chemical additives, yet the exact chemicals which drive toxicity currently remain unknown. In this study, we employed nontargeted analysis and in vitro bioassays to identify the toxicity drivers in plastics. A total of 56 chemical additives were tentatively identified in five commonly used plastic polymer pellets (i.e., PP, LDPE, HDPE, PET, and PVC) by employing suspect screening and nontargeted analysis. Phthalates and organophosphates were found to be dominant in PVC pellets. Triphenyl phosphate and 2-ethylhexyl diphenyl phosphate accounted for a high amount (53.6%) of the inhibition effect of PVC pellet extract on human carboxylesterase 1 (hCES1) activity. Inspired by the high abundances of chemical additives in PVC pellets, six different end-user PVC-based products including three widely used PVC water pipes were further examined. Among them, extracts of PVC pipe exerted the strongest PPARgamma activity and cell viability suppression. Organotins were identified as the primary drivers to these in vitro toxicities induced by the PVC pipe extracts. This study clearly delineates specific chemical additives responsible for hCES1 inhibition, PPARgamma activity, and cell viability suppression associated with plastic. Title: Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain Du F, Cao R, Chen L, Sun J, Shi Y, Fu Y, Hammock BD, Zheng Z, Liu Z, Chen G Ref: Acta Pharm Sin B, 12:1377, 2022 : PubMed ESTHER: Du_2022_Acta.Pharm.Sin.B_12_1377 PubMedSearch: Du 2022 Acta.Pharm.Sin.B 12 1377 PubMedID: 35530144 Inhibitor(s) related to this paper: EC5026 Abstract Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (+/-)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain. Title: Development of 5-hydroxyl-1-azabenzanthrone derivatives as dual binding site and selective acetylcholinesterase inhibitors Sun X, Wang Y, Lei Z, Yue S, Chen L, Sun J Ref: Eur Journal of Medicinal Chemistry, 234:114210, 2022 : PubMed ESTHER: Sun_2022_Eur.J.Med.Chem_234_114210 PubMedSearch: Sun 2022 Eur.J.Med.Chem 234 114210 PubMedID: 35303485 Abstract A series of novel 5-hydroxyl-1-azabenzanthrone derivatives were designed, synthesized and evaluated as dual binding site acetylcholinesterase inhibitors for the treatment of Alzheimer's disease (AD). The most effective Compound 16 showed selective inhibition of acetylcholinesterase (eeAChE IC(50) = 0.045 microM; eeBuChE IC(50) = 19.68 microM; SI = 437.33). Most of the compounds showed cytoprotective effects on PC12 cells damaged by hydrogen peroxide, which might be related to their antioxidant activity. Further experiments confirmed that 16 exhibited anti-apoptotic effects at low concentrations and reduced the relative level of ROS generation in PC12 cells. The expression level of proteins related to antioxidant stress pathway in PC12 cells was relatively increased after administrated with 16, which may be beneficial to delay the progression of the disease. Moreover, 16 was evaluated to be safe in vivo and in vitro, and showed good overall pharmacokinetic performance and high bioavailability (Foral = 55.5%). Besides, 16 showed comparable performance in ameliorating the scopolamine-induced cognition impairment to donepezil. In addition, in vitro BBB permeability experiments confirmed that 16 had high BBB permeability. Title: Colorimetric Assay for Acetylcholinesterase Activity and Inhibitor Screening Based on Metal-Organic Framework Nanosheets Wang Y, Xue Y, Zhao Q, Wang S, Sun J, Yang X Ref: Analytical Chemistry, 94:16345, 2022 : PubMed ESTHER: Wang_2022_Anal.Chem_94_16345 PubMedSearch: Wang 2022 Anal.Chem 94 16345 PubMedID: 36444539 Abstract Alzheimer's disease (AD) is a common chronic neurodegenerative disease that manifests as cognitive impairment and behavioral deficits and severely threatens the health of the elderly. Acetylcholinesterase (AChE) plays a vital role in biological signaling and is an essential target for the early diagnosis and treatment of AD. Herein, 2D Zn-TCPP(Fe) nanosheets (NSs) employing Zn(2+) and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were prepared through a surfactant-assisted synthetic method. The ultrathin two-dimensional (2D) metal-organic framework structures exhibited high peroxidase-like activity, which allowed the catalysis of the H(2)O(2)-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (ox-TMB). Such catalytic performance inspired us to develop a convenient, rapid, and sensitive acetylcholinesterase activity assay, during which AChE can catalyze the substrate acetylthiocholine (ATCh) to produce thiocholine (TCh), and TCh could especially enable the degradation of 2D Zn-TCPP(Fe) NSs accompanied by the reduction of ox-TMB production. Our proposed sensing system exhibited favorable selectivity and sensitivity (LOD of 0.029 mU/mL) and has excellent potential to evaluate AChE activity in human serum samples and to screen AChE inhibitors. This colorimetric assay could provide an alternative pathway for early diagnosis and drug screening of AD, facilitating the development of AD therapy. Title: A preliminary study of the chemical composition and bioactivity of Bombax ceiba L. flower and its potential mechanism in treating type 2 diabetes mellitus using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry and network pharmacology analysis Yin K, Yang J, Wang F, Wang Z, Xiang P, Xie X, Sun J, He X, Zhang X Ref: Front Nutr, 9:1018733, 2022 : PubMed ESTHER: Yin_2022_Front.Nutr_9_1018733 PubMedSearch: Yin 2022 Front.Nutr 9 1018733 PubMedID: 36313078 Abstract This study aimed to preliminary investigate the phytochemistry, bioactivity, hypoglycemic potential, and mechanism of action of Bombax ceiba L. flower (BCF), a wild edible and food plant in China. By using methanol extraction and liquid-liquid extraction, the crude extract (CE) of BCF and its petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and aqueous (AQ) fractions were obtained, and their chemical components and biological activities were evaluated. Further high-performance liquid chromatography (HPLC) analysis was carried out to identify and quantify the active constituents of BFC and its five fractions, and the phytochemical composition of the best-performing fraction was then analyzed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC/Q-TOF-MS). Finally, a network pharmacology strategy based on the chemical profile of this fraction was applied to speculate its main hypoglycemic mechanism. Results revealed the excellent biological activities of BCF, especially the EtOAc fraction. In addition to the highest total flavonoid content (TFC) (367.72 microg RE/mg E) and total phenolics content (TPC) (47.97 microg GAE/mg E), EtOAc showed the strongest DPPH scavenging ability (IC(50) value = 29.56 microg/mL), ABTS (+) scavenging ability (IC(50) value = 84.60 microg/mL), and ferric reducing antioxidant power (FRAP) (889.62 microg FeSO(4)/mg E), which were stronger than the positive control BHT. EtOAc also exhibited the second-best alpha-glucosidase inhibitory capacity and second-best acetylcholinesterase (AChE) inhibitory capacity with the IC(50) values of 2.85 and 3.27 mg/mL, respectively. Also, EtOAc inhibited HepG2, MCF-7, Raw264.7, and A549 cell with IC(50) values of 1.08, 1.62, 0.77, and 0.87 mg/mL, which were the second or third strongest in all fractions. Additionally, HPLC analysis revealed significant differences in the compounds' abundance between different fractions. Among them, EtOAc had the most detected compounds and the highest content. According to the results of UPLC/Q-TOF-MS, 38 compounds were identified in EtOAc, including 24 phenolic acids and 6 flavonoids. Network pharmacological analysis further confirmed 41 potential targets of EtOAc in the treatment of type 2 diabetes, and intracellular receptor signaling pathways, unsaturated fatty acid, and DNA transcription pathways were the most possible mechanisms. These findings suggested that BCF was worthwhile to be developed as an antioxidant and anti-diabetic food/drug. Title: Advances in enzyme biocatalysis for the preparation of functional lipids Zhang H, Secundo F, Sun J, Mao X Ref: Biotechnol Adv, :108036, 2022 : PubMed ESTHER: Zhang_2022_Biotechnol.Adv__108036 PubMedSearch: Zhang 2022 Biotechnol.Adv 108036 PubMedID: 36130694 Abstract Functional lipids, mainly omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic (DHA; 22:6n-3), are known to have a variety of health benefits. Lipases and phospholipases are widely used to prepare different forms of structured lipids, since biocatalytic methods can be carried out under mild conditions, preserving the quality of the products. On the other hand, many processes still are conducted at high temperatures and with organic solvents, which are conditions unfavorable for the production of nutritional products. This article gives an updated overview of enzyme biocatalysis methods for the preparation of different derivatives containing n-3 PUFAs, including specific reactions, enzyme immobilization research for high-efficiency catalysis, and enzyme engineering technologies (higher selectivity, stability, and activity). Furthermore, advanced control strategies of biocatalytic processes and reactors are presented. The future prospect and opportunities for marine functional lipids are also discussed. Therefore, the obtainment of enzymes endowed with superior properties and the development of optimized processes, still have to be pursued to achieve greener bio-catalyzed processes. Title: Huperzine-A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation Zhang T, Kim MJ, Wu X, Yang HJ, Yuan H, Huang S, Yoon SM, Kim KN, Park S and Wang J <46 more author(s)> Zhang T, Kim MJ, Wu X, Yang HJ, Yuan H, Huang S, Yoon SM, Kim KN, Park S, Zhang Y, Yao J, Yin K, Liu Z, Deng C, Liu J, Hou S, Zhang H, Yu D, Zhao N, Zhao R, Chen S, Zhang ZP, Bai X, Cui WB, Chen XH, Liu X, Zhi DJ, Zhang ZX, Fei DQ, Wang DS, Zhang X, Wang Y, Zhu H, Zhong Z, Zhang CY, Tan XH, Yang HH, Jin L, Hong JR, Zhou Y, Huang XT, Zhang M, Xiang R, Glorieux C, Huang P, Young C, Morishita Y, Kim K, Kabil OO, Clarke OB, Di Jeso B, Arvan P, Wang D, Sun J, Wu S, Wang J (- 46) Ref: Int J Mol Sci, 23:, 2022 : PubMed ESTHER: Zhang_2022_Int.J.Mol.Sci_23_ PubMedSearch: Zhang 2022 Int.J.Mol.Sci 23 PubMedID: 35328781 35563299 35743309 35887300 35897843 36233022 36362390 36555825 Abstract Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1beta, IL-18, CD16, and TNF-alpha). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation. Title: Plastic wastes biodegradation: Mechanisms, challenges and future prospects Ali SS, Elsamahy T, Al-Tohamy R, Zhu D, Mahmoud YA, Koutra E, Metwally MA, Kornaros M, Sun J Ref: Sci Total Environ, 780:146590, 2021 : PubMed ESTHER: Ali_2021_Sci.Total.Environ_780_146590 PubMedSearch: Ali 2021 Sci.Total.Environ 780 146590 PubMedID: 34030345 Abstract The growing accumulation of plastic wastes is one of the main environmental challenges currently faced by modern societies. These wastes are considered a serious global problem because of their effects on all forms of life. There is thus an urgent need to demonstrate effective eco-environmental techniques to overcome the hazardous environmental impacts of traditional disposal paths. However, our current knowledge on the prevailing mechanisms and the efficacy of synthetic plastics' biodegradation still appears limited. Under this scope, our review aims to comprehensively highlight the role of microbes, with special emphasis on algae, on the entire plastic biodegradation process focusing on the depolarization of various synthetic plastic types. Moreover, our review emphasizes on the ability of insects; gut microbial consortium to degrade synthetic plastic wastes. In this view, we discuss the schematic pathway of the biodegradation process of six types of synthetic plastics. These findings may contribute to establishing bio-upcycling processes of plastic wastes towards biosynthesis of valuable metabolic products. Finally, we discuss the challenges and opportunities for microbial valorization of degraded plastic wastes. Title: Development of a highly-specific (18)F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping Chen Z, Mori W, Rong J, Schafroth MA, Shao T, Van RS, Ogasawara D, Yamasaki T, Hiraishi A and Liang SH <12 more author(s)> Chen Z, Mori W, Rong J, Schafroth MA, Shao T, Van RS, Ogasawara D, Yamasaki T, Hiraishi A, Hatori A, Chen J, Zhang Y, Hu K, Fujinaga M, Sun J, Yu Q, Collier TL, Shao Y, Cravatt BF, Josephson L, Zhang MR, Liang SH (- 12) Ref: Acta Pharm Sin B, 11:1686, 2021 : PubMed ESTHER: Chen_2021_Acta.Pharm.Sin.B_11_1686 PubMedSearch: Chen 2021 Acta.Pharm.Sin.B 11 1686 PubMedID: 34221877 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: PF-06795071 Abstract As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile S(N)Ar reaction to form 2-[(18)F]fluoropyridine scaffold. Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [(18)F]14 (also named as [(18)F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent (18)F-labeled MAGL PET tracers. Title: Identification of a GDSL lipase from Streptomyces bacillaris and its application in the preparation of free astaxanthin Gao K, Wang X, Jiang H, Sun J, Mao X Ref: J Biotechnol, 325:280, 2021 : PubMed ESTHER: Gao_2021_J.Biotechnol_325_280 PubMedSearch: Gao 2021 J.Biotechnol 325 280 PubMedID: 33049356 Abstract Astaxanthin shows multiple biological activities, but it is usually linked to different fatty acids and exists in the form of esters. The complexity of astaxanthin esters limits their application in the preparation of sophisticated drugs. Herein, a novel lipase from Streptomyces bacillaris that could hydrolyze astaxanthin esters, named OUC-Sb-lip12, was expressed in Bacillus subtilis. The active site of OUC-Sb-lip12 is probably composed of a dyad of Ser48 and His254, instead of a typical catalytic triad. The lipase was identified to be a GDSL hydrolase, and it showed highest activity at 45 degreesC and pH 9.0 (glycine-NaOH buffer). OUC-Sb-lip12 showed a good stability at its optimum temperature or a higher temperature, retaining 88.4% and 80.6% of its activity after incubating for 36 h at 45 degreesC and 55 degreesC, respectively. OUC-Sb-lip12 could effectively hydrolyze astaxanthin esters in Haematococcus pluvialis oil, generating free astaxanthin. Under the optimum conditions, 96.29% astaxanthin esters were hydrolyzed in 12 h. In addition, B.subtilis is a GRAS model strain and it could efficiently secrete lipase in 9 h, making the lipase potential for scale production of free astaxanthin, which could be further used in the preparation of specific astaxanthin esters with specific functions. Title: A Roadmap to the Structure-Related Metabolism Pathways of Per- and Polyfluoroalkyl Substances in the Early Life Stages of Zebrafish (Danio rerio) Han J, Gu W, Barrett H, Yang D, Tang S, Sun J, Liu J, Krause HM, Houck KA, Peng H Ref: Environmental Health Perspectives, 129:77004, 2021 : PubMed ESTHER: Han_2021_Environ.Health.Perspect_129_77004 PubMedSearch: Han 2021 Environ.Health.Perspect 129 77004 PubMedID: 34288731 Abstract BACKGROUND: Thousands of per- and polyfluoroalkyl substances (PFAS) with diverse structures have been detected in the ambient environment. Apart from a few well-studied PFAS, the structure-related toxicokinetics of a broader set of PFAS remain unclear. OBJECTIVES: To understand the toxicokinetics of PFAS, we attempted to characterize the metabolism pathways of 74 structurally diverse PFAS samples from the U.S. Environmental Protection Agency's PFAS screening library. METHODS: Using the early life stages of zebrafish (Danio rerio) as a model, we determined the bioconcentration factors and phenotypic toxicities of 74 PFAS. Then, we applied high-resolution mass spectrometry-based nontargeted analysis to identify metabolites of PFAS in zebrafish larvae after 5 d of exposure by incorporating retention time and mass spectra. In vitro enzymatic activity experiments with human recombinant liver carboxylesterase (hCES1) were employed to validate the structure-related hydrolysis of 11 selected PFAS. RESULTS: Our findings identified five structural categories of PFAS prone to metabolism. The metabolism pathways of PFAS were highly related to their structures as exemplified by fluorotelomer alcohols that the predominance of beta-oxidation or taurine conjugation pathways were primarily determined by the number of hydrocarbons. Hydrolysis was identified as a major metabolism pathway for diverse PFAS, and perfluoroalkyl carboxamides showed the highest in vivo hydrolysis rates, followed by carboxyesters and sulfonamides. The hydrolysis of PFAS was verified with recombinant hCES1, with strong substrate preferences toward perfluoroalkyl carboxamides. CONCLUSIONS: We suggest that the roadmap of the structure-related metabolism pathways of PFAS established in this study would provide a starting point to inform the potential health risks of other PFAS. https://doi.org/10.1289/EHP7169. Title: GRAPE, a greedy accumulated strategy for computational protein engineering Sun J, Cui Y, Wu B Ref: Methods Enzymol, 648:207, 2021 : PubMed ESTHER: Sun_2021_Methods.Enzymol_648_207 PubMedSearch: Sun 2021 Methods.Enzymol 648 207 PubMedID: 33579404 Gene_locus related to this paper: idesa-peth Abstract Nature harbors fascinating enzymatic catalysts with high efficiency, chemo-, regio- and stereoselectivity. However, the insufficient stability of the enzymes often prevents their widespread utilization for industrial processes. Not content with the finite repertoire of naturally occurring enzymes, protein engineering holds promises to extend the applications of the improved enzymes with desired physical and catalytic properties. Herein, we devised a computational strategy (greedy accumulated strategy for protein engineering, GRAPE) to enhance the thermostability of enzymes. Through scanning of all point mutations of the structural and evolutionary consensus analysis, a library containing fewer than 100 mutations was established for characterization. After preliminary experimental verification, effective mutations are clustered in a multidimensional physical property space and then accumulated via the greedy algorithm to produce the final designed enzyme. Using the recently reported IsPETase from Ideonella sakaiensis that decomposes PET under ambient temperatures as a starting point, we adopted the GRAPE strategy to come up with a DuraPETase (T(M)=77 degreesC, raised by 31 degreesC) which showed drastically enhanced degradation performance (300-fold) on semicrystalline PET films at 40 degreesC. Title: An integrated approach using chemical ecological risk assessment and multi-integrated biomarker indexes approach to assess pollution: A case study of Ruditapes philippinarum in four bays on the Shandong Peninsula in China Sun J, Ma Y, Qin H, Li Z, Pan L Ref: Environ Research, :111793, 2021 : PubMed ESTHER: Sun_2021_Environ.Res__111793 PubMedSearch: Sun 2021 Environ.Res 111793 PubMedID: 34339694 Abstract Considering the ecological risks of polycyclic aromatic hydrocarbons (PAHs) to the marine environment, it is urgent to find scientific and effective monitoring methods. In this study, an integrated approach combining chemical ecological risk assessment and multi-integrated biomarker indexes approach was used to assess the marine environment. Samples included seawater, sediments, and clam Ruditapes philippinarum were collected from four bays on the Shandong Peninsula, China in the four seasons of 2019. The concentrations, composition, potential sources, and ecological risk of PAHs were investigated in seawater and sediments. Risk quotient (RQ) and sediment quality guidelines (SQGs) were calculated to assess the ecological risks of PAHs in seawater and sediment, respectively. And then, clam Ruditapes philippinarum's multi-level biological response, including its ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), lipid peroxidation (LPO), and acetylcholinesterase (AChE) were investigated in-depth, by which multi-integrated biomarker indexes approach were calculated to evaluate marine environmental quality. Taken together, the results showed that the concentration of PAHs was in good agreement with the response of biomarkers, and the usefulness of the combined use of chemical ecological risk assessment and integrated biomarker indexes to assess PAHs pollution was verified. Title: Triglyceride-Mimetic Structure-Gated Prodrug Nanoparticles for Smart Cancer Therapy Tian C, Guo J, Miao Y, Zheng S, Sun B, Sun M, Ye Q, Liu W, Zhou S and Sun J <2 more author(s)> Tian C, Guo J, Miao Y, Zheng S, Sun B, Sun M, Ye Q, Liu W, Zhou S, Kamei KI, He Z, Sun J (- 2) Ref: Journal of Medicinal Chemistry, :, 2021 : PubMed ESTHER: Tian_2021_J.Med.Chem__ PubMedSearch: Tian 2021 J.Med.Chem PubMedID: 34723524 Abstract Off-target drug release and insufficient drug delivery are the main obstacles for effective anticancer chemotherapy. Prodrug-based self-assembled nanoparticles bioactivated under tumor-specific conditions are one of the effective strategies to achieve on-demand drug release and effective tumor accumulation. Herein, stimuli-activable prodrugs are designed yielding smart tumor delivery by combination of the triglyceride-mimic (TG-mimetic) prodrug structure and disulfide bond. Surprisingly, these prodrugs can self-assemble into uniform nanoparticles (NPs) with a high drug loading (over 40%) and accumulate in tumor sites specifically. The super hydrophobic TG structure can act as a gate that senses lipase to selectively control over NP dissociation and affect the glutathione-triggered prodrug activation. In addition, the impacts of the double bonds in the prodrug NPs on parent drug release and the following cytotoxicity, pharmacokinetics, and antitumor efficiency are further demonstrated. Our findings highlight the promising potential of TG-mimetic structure-gated prodrug nanoparticles for tumor-specific drug delivery. Title: Acupuncture therapy for Alzheimer's disease: The effectiveness and potential mechanisms Yin W, Lv G, Li C, Sun J Ref: Anatomical Record (Hoboken), :, 2021 : PubMed ESTHER: Yin_2021_Anat.Rec.(Hoboken)__ PubMedSearch: Yin 2021 Anat.Rec.(Hoboken) PubMedID: 34623030 Abstract Alzheimer's disease (AD) is a common neurodegenerative disease that accounts for approximately 70% of dementia. Following the global escalation of the aging process, the morbidity of AD is increasing rapidly. The current treatment for AD is mainly limited to medications, such as acetylcholinesterase inhibitors. However, the efficacy of acetylcholinesterase inhibitors in improving memory and cognitive functions is not satisfactory. It is a challenge to find an effective alternative therapy for ameliorating AD symptoms. As an important therapeutic technique in traditional Chinese medicine, acupuncture has been proved effective in treating many neurologic diseases including AD. The efficacy of acupuncture is also acknowledged by the National Institutes of Health of the United States. Here, we summarized the effectiveness of acupuncture for treating AD. Especially, the role of acupuncture at certain acupuncture points in modulating the brain function through meridians activity based on Chinese meridian theory is discussed. How acupuncture at a certain acupoint can improve AD symptoms is also described. Furthermore, the possible molecular mechanisms of acupuncture for AD are reviewed, and the role of acupuncture in modulating signaling molecules in neural protection and homeostasis is highlighted. This study may help to understand the theoretical basis and potential molecular mechanisms of acupuncture therapy for AD. Title: Synthesis and biological evaluation of 2-arylbenzofuran derivatives as potential anti-Alzheimer's disease agents Yun Y, Miao Y, Sun X, Sun J, Wang X Ref: J Enzyme Inhib Med Chem, 36:1346, 2021 : PubMed ESTHER: Yun_2021_J.Enzyme.Inhib.Med.Chem_36_1346 PubMedSearch: Yun 2021 J.Enzyme.Inhib.Med.Chem 36 1346 PubMedID: 34134572 Abstract Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and beta-secretase inhibitory activity. The IC(50) value of compound 20 against acetylcholinesterase inhibition (0.086 +/- 0.01 micromol.L(-1)) is similar to donepezil (0.085 +/- 0.01 micromol.L(-1)) and is better than baicalein (0.404 +/- 0.04 micromol.L(-1)). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 +/- 0.03 micromol.L(-1)). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD. Title: Construction of a new lipase- and xylanase-producing oleaginous yeast consortium capable of reactive azo dye degradation and detoxification Ali SS, Al-Tohamy R, Xie R, El-Sheekh MM, Sun J Ref: Bioresour Technol, 313:123631, 2020 : PubMed ESTHER: Ali_2020_Bioresour.Technol_313_123631 PubMedSearch: Ali 2020 Bioresour.Technol 313 123631 PubMedID: 32540694 Abstract A new oleaginous yeast consortium Y-BC-SH which stands for molecularly identified species Yarrowia sp., Barnettozyma californica and Sterigmatomyces halophilus was successfully constructed in this study. This multipurpose oleaginous yeast consortium was developed based on its higher ability to accumulate large amounts of lipids in the form of triacylglycerol, grow on xylose, produce lipase and xylanase and it could rapidly decolorize and degrade commonly-used textile reactive azo dyes. The specific enzyme activities of lipase, xylanase, xylan esterase, beta-xylosidase, CMCase, beta-glucosidase and cellobiohydrolase produced by Y-BC-SH were significantly higher than that of individual strains. As chemical oxygen demand reduction had occurred in the dye mixture solutions, it was evidence of their color removal and mineralization by Y-BC-SH. The significant induction of oxidoreductive enzymes by Y-BC-SH was probably due to the coordinated metabolic interactions of the individual strains. Phytotoxicity assay confirmed that metabolites generated after dye degradation by Y-BC-SH are non-toxic. Title: Identification of an alkaline lipase capable of better enrichment of EPA than DHA due to fatty acids selectivity and regioselectivity Gao K, Chu W, Sun J, Mao X Ref: Food Chem, 330:127225, 2020 : PubMed ESTHER: Gao_2020_Food.Chem_330_127225 PubMedSearch: Gao 2020 Food.Chem 330 127225 PubMedID: 32569931 Abstract The whole genome of Streptomyces violascens (=ATCC 27968) was sequenced and the cloning and expression of OUC-Lipase 6 were conducted in Bacillus subtilis WB800. The recombinant enzyme belongs to the lipolytic enzymes family V. OUC-Lipase 6 showed optimal activity at 30 degrees C and pH 9.0, and retained 90.2% of its activity in an alkaline buffer (pH 8.0, 30 degrees C and 96 h). OUC-Lipase 6 showed good stability under medium temperature conditions (residual activity of 68.8%, pH 8.0, 45 degrees C and 96 h). OUC-Lipase 6 could selectively hydrolyze fatty acids on the glyceride backbone, thus improving the contents of DHA and EPA in codfish oil. OUC-Lipase 6 also showed regioselectivity, resulting in a better enrichment efficiency for EPA than DHA. After hydrolyzing for 36 h via OUC-Lipase 6, the contents of EPA and DHA were improved to 3.24-fold and 1.98-fold, respectively. Title: Separation of saturated fatty acids from docosahexaenoic acid-rich algal oil by enzymatic ethanolysis in tandem with molecular distillation He J, Hong B, Lu R, Zhang R, Fang H, Huang W, Bai K, Sun J Ref: Food Sci Nutr, 8:2234, 2020 : PubMed ESTHER: He_2020_Food.Sci.Nutr_8_2234 PubMedSearch: He 2020 Food.Sci.Nutr 8 2234 PubMedID: 32405380 Abstract Algal oil, rich in docosahexaenoic acid (DHA) and an environmentally sustainable source of omega-3 fatty acids, is receiving increasing attention. In the present study, a novel approach combining ethanolysis with a 1,3-specific immobilized lipase (Lipozyme() TL IM) and molecular distillation was investigated to increase the DHA content of algal oil. Algal oil with a 45.94% DHA content was mixed with ethanol, pumped into a column filled with Lipozyme() TL IM, and then circulated for 4 hr at room temperature. The ethanol was then recycled by vacuum distillation. At an evaporator temperature of 150 degC, the residue was separated by molecular distillation into a heavy component enriched with DHA glycerides (in the form of triglyceride (TG), diglyceride (DG), and monoglyceride (MG)) and a light component enriched with palmitic acid (PA) and DHA ethyl ester (EE). As a result, 76.55% of the DHA from the algal oil was present in the heavy component, whose DHA content was 70.27%. DHA-MG was collected in the heavy component mostly in the form of 1-MG. Lipozyme() TL IM appeared to specifically target PA rather than DHA at the sn-1(3) position. The Lipozyme() TL IM allowed 90.03% of the initial DHA yield to be retained after seven reaction cycles. Therefore, an eco-friendly and simple method for increasing the DHA content in algal oil has been developed. Title: Reduced insecticide sensitivity of the wheat aphid Sitobion miscanthi after infection by the secondary bacterial symbiont Hamiltonella defensa Li Q, Sun J, Qin Y, Fan J, Zhang Y, Tan X, Hou M, Chen J Ref: Pest Manag Sci, 77:1936, 2020 : PubMed ESTHER: Li_2020_Pest.Manag.Sci_77_1936 PubMedSearch: Li 2020 Pest.Manag.Sci 77 1936 PubMedID: 33300163 Abstract BACKGROUND: Bacterial symbionts in insects, especially aphids, have a major influence on host adaptation. The authors previously showed that infection with the secondary symbiont Hamiltonella defensa increases the fitness of the wheat aphid Sitobion miscanthi, yielding increases in fitness parameters such as adult weight and offspring number. However, whether H. defensa affects the sensitivity of host aphids to insecticides remains unknown. RESULTS: We tested the effects of H. defensa on host aphid susceptibility to the insecticides chlorpyrifos methyl, imidacloprid, cyantraniliprole and acetamiprid. Our results showed that compared with Hamiltonella-free aphid clones, Hamiltonella-infected aphid clones exhibited lower sensitivity to most of the tested insecticides at low concentrations. Quantitative PCR showed that the density of H. defensa in the infected clones was slightly decreased at 24 h but then sharply increased until the late stage after treatment with the different insecticides. H. defensa in the host aphids was detected by fluorescence in situ hybridization and was localized to the aphid hindgut. The levels of the detoxification enzymes acetylcholinesterase (AChE), glutathione transferase (GST) and carboxylesterase (CarE) were significantly higher in the Hamiltonella-infected clones than in the Hamiltonella-free clones. CONCLUSIONS: The findings indicated that infection with H. defensa reduced aphid sensitivity to the investigated insecticides at low concentrations, potentially by increasing detoxification enzyme activity in the host. Therefore, symbiont-mediated insecticide resistance should be taken into account when performing resistance-monitoring studies. Studies of symbiont-mediated insecticide resistance may enhance our understanding of the emergence of insecticide resistance in agricultural systems. This article is protected by copyright. All rights reserved. Title: Biomonitoring of polycyclic aromatic hydrocarbons (PAHs) from Manila clam Ruditapes philippinarum in Laizhou, Rushan and Jiaozhou, bays of China, and investigation of its relationship with human carcinogenic risk Sun J, Pan L, Cao Y, Li Z Ref: Mar Pollut Bull, 160:111556, 2020 : PubMed ESTHER: Sun_2020_Mar.Pollut.Bull_160_111556 PubMedSearch: Sun 2020 Mar.Pollut.Bull 160 111556 PubMedID: 32836194 Abstract This study examined the marine environment and seafood safety using chemical monitoring and multiple biomarkers. Samples were collected from three bays on the Shandong Peninsula in China, Laizhou, Rushan and Jiaozhou, in March, May, August, and October of 2018 and 2019. The polycyclic aromatic hydrocarbon (PAH) concentrations in sediments and tissue samples from the clam Ruditapes philippinarum and multiple biomarkers were measured. All the sampling sites were found to be medium-PAH-contaminated areas (100-1000 ng/g d.w.). According to the correlation analysis, ethoxyresorufin-o-deethylase (EROD) and superoxide dismutase (SOD) activity in the clam's digestive gland were sensitive to PAHs (p < .05), but the incremental lifetime cancer risk (ILCR) was lower than the priority risk level (10(-4)) at most sampling sites. EROD, SOD and acetylcholinesterase activity exhibited significant correlations with the ILCR values (p < .01), suggesting that they may serve as good indicators for assessing safe seafood consumption levels for human beings. Title: Whole-Genome Sequencing and Bioinformatics Analysis of Apiotrichum mycotoxinivorans: Predicting Putative Zearalenone-Degradation Enzymes Sun J, Xia Y, Ming D Ref: Front Microbiol, 11:1866, 2020 : PubMed ESTHER: Sun_2020_Front.Microbiol_11_1866 PubMedSearch: Sun 2020 Front.Microbiol 11 1866 PubMedID: 32849454 Abstract Biological detoxification techniques have been developed by using microorganisms such as bacteria, yeast, and fungi to eliminate mycotoxin contamination. However, due to the lack of molecular details of related enzymes, the underlying mechanism of detoxification of many mycotoxins remain unclear. On the other hand, the next generation sequencing technology provides a large number of genomic data of microorganisms that can degrade mycotoxins, which makes it possible to use bioinformatics technology to study the molecular details of relevant enzymes. In this paper, we report the whole-genome sequencing of Apiotrichum mycotoxinivorans (Trichosporon mycotoxinivorans in old taxonomy) and the putative Baeyer-Villiger monooxygenases (BVMOs) and carboxylester hydrolases for zearalenone (ZEA) degradation through bioinformatic analysis. In particular, we developed a working pipeline for genome-scaled prediction of substrate-specific enzyme (GPSE, available at https://github.com/JinyuanSun/GPSE), which ultimately builds homologous structural and molecular docking models to demonstrate how the relevant degrading enzymes work. We expect that the enzyme-prediction woroflow process GPSE developed in this study might help accelerate the discovery of new detoxification enzymes. Title: Sanger's Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions Wei T, Lu S, Sun J, Xu Z, Yang X, Wang F, Ma Y, Shi Y, Chen X Ref: Journal of the American Chemical Society, :, 2020 : PubMed ESTHER: Wei_2020_J.Am.Chem.Soc__ PubMedSearch: Wei 2020 J.Am.Chem.Soc PubMedID: 32023409 Abstract Photolabile groups offer promising tools to study biological processes with highly spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-D-aspartate receptors (NMDARs) and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways. Title: Synthesis and biological evaluation of 3-arylbenzofuranone derivatives as potential anti-Alzheimer's disease agents Yang J, Yun Y, Miao Y, Sun J, Wang X Ref: J Enzyme Inhib Med Chem, 35:805, 2020 : PubMed ESTHER: Yang_2020_J.Enzyme.Inhib.Med.Chem_35_805 PubMedSearch: Yang 2020 J.Enzyme.Inhib.Med.Chem 35 805 PubMedID: 32183602 Abstract Multi-target drugs can better address the cascade of events involved in oxidative stress and the reduction in cholinergic transmission that occur in Alzheimer's disease than cholinesterase inhibitors alone. We synthesised a series of 3-arylbenzofuranone derivatives and evaluated their antioxidant activity, cholinesterase inhibitory activity, and monoamine oxidase inhibitory activity. 3-Arylbenzofuranone compounds exhibit good antioxidant activity as well as selective acetylcholinesterase inhibitory activity. The IC50 value of anti-acetylcholinesterase inhibition of Compound 20 (0.089 +/- 0.01 muM) is similar to the positive drug donepezil (0.059 +/- 0.003 muM). According to the experimental results, Compounds 7, 13 show a certain effect in the in vitro evaluation performed and have the potential as drug candidates for the treatment of Alzheimer's disease. Title: Effect of Massa Medicata Fermentata on the Gut Microbiota of Dyspepsia Mice Based on 16S rRNA Technique Zhang X, Zhang H, Huang Q, Sun J, Yao R, Wang J Ref: Evid Based Complement Alternat Med, 2020:7643528, 2020 : PubMed ESTHER: Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_7643528 PubMedSearch: Zhang 2020 Evid.Based.Complement.Alternat.Med 2020 7643528 PubMedID: 33029172 Abstract Massa Medicata Fermentata (MMF) is a traditional Chinese medicine (TCM) for treating indigestion and its related disorders. This study analyzes the effect of MMF on intestinal microorganisms in dyspepsia mice based on 16S rRNA technology. We take a dyspepsia model caused by a high-protein, high-calorie, high-fat diet. The 60 specific-pathogen free Kunming (SPF KM) mice were randomly divided into a model group (n=12), an MMF group (LSQ group, n=12), a Jianweixiaoshi group (JWXS group, n=12), a domperidone group (DP group, n=12), and a blank group (n=12). On the seventh day of administration, mice were fasted and deprived of water. After 24 h, take the second feces of stress defecation in mice under strict aseptic conditions and quickly transfer them to a sterile cryotube. This study comprehensively evaluates the alpha-diversity, beta-diversity, flora abundance and composition of each group of mice's intestinal microorganisms, and their correlation with functional dyspepsia based on the 16S rRNA gene sequencing technology. After modeling, some dyspepsia reactions, proximal gastric relaxation reduction, and intestinal microflora changes were noted. Dyspepsia mice showed dyspepsia reactions and proximal gastric relaxation reduction, characterized by a significant decrease of contents of gastrin (P < 0.01) and cholinesterase (P < 0.01). MMF can improve dyspepsia symptoms and promote proximal gastric relaxation. Significant intestinal flora disorders were found in dyspepsia mice, including downregulation of Bacteroidetes, Lactobacillus, and Prevotellaceae and upregulation of Proteobacteria, Verrucomicrobia, Epsilonbacteraeota, Firmicutes, Lachnospiraceae NK4A136 group, and Lachnospiraceae. MMF could alleviate intestinal microflora disturbance, and the regulation effect of MMF on Bacteroidetes, Verrucomicrobia, and Epsilonbacteraeota was more reliable than that of Jianweixiaoshi tables and domperidone. The intestinal microflora may be correlated with the promoted digestion of MMF. Title: Assessment of phthalate ester residues and distribution patterns in Baijiu raw materials and Baijiu Dong W, Guo R, Sun X, Li H, Zhao M, Zheng F, Sun J, Huang M, Wu J Ref: Food Chem, 283:508, 2019 : PubMed ESTHER: Dong_2019_Food.Chem_283_508 PubMedSearch: Dong 2019 Food.Chem 283 508 PubMedID: 30722905 Abstract Phthalate esters (PAEs) are harmful to human health and have been repeatedly identified in Baijiu samples. In our study, the distribution and degradation characteristics of 14 PAEs in Baijiu raw materials (BRMs) and Baijiu during distillation were detected using QuEChERS or vortex-assisted surfactant-enhanced-emulsification liquid-liquid micro-extraction (VSLLME) methods coupled with gas chromatography-mass spectrometry. The same five PAEs were detected in all tested samples, values ranged from 0.003 to 0.292 mg/kg; however, higher concentrations existed in BRMs compared to Baijiu samples. Using multivariate statistical analysis, detailed distinctions between different varieties of Baijiu and BRMs and separation-related PAE markers were revealed. PAEs concentration during Baijiu distillation showed a decreasing trend. The highest concentrations detected in distillate heads, were 1.6-, 2.3-, and 8.1-fold higher than those in heart1, heart2, and tail distillates, respectively. These findings revealed that PAEs may migrate from BRMs; moreover, that PAEs content can be regulated by distillation. Title: Stoichiometry and Kinetics of Sequential Dimethacrylate Enzymolysis Frukhtbeyn S, Van Dongen K, Sun J Ref: J Dent Res, 98:1037, 2019 : PubMed ESTHER: Frukhtbeyn_2019_J.Dent.Res_98_1037 PubMedSearch: Frukhtbeyn 2019 J.Dent.Res 98 1037 PubMedID: 31329048 Abstract The increasing use of methacrylate-based materials in tissue engineering and dental restorations demands detailed evaluation of enzymolysis of these materials due to toxicity, durability, and biocompatibility concerns. The objective of this study is to develop tools for assessing and ranking the enzymolysis kinetics of dimethacrylate (DMA) compounds. Triethyleneglycol DMA and diurethane DMA are employed as model DMAs for kinetic studies of 2-step enzymolysis by 2 esterases, pseudocholine esterase and cholesterol esterase. In addition, the intermediate hydrolysis products, mono-methacrylates (mono-MAs), are prepared via esterases. The kinetics of DMA enzymolysis are evaluated per the concentrations of DMA. The enzymolysis products are quantified by high-performance liquid chromatography. Additionally, stoichiometric analysis and a Berkeley Madonna model are employed to compare the efficacy of esterases in DMA enzymolysis. The chemical structure of mono-MAs is verified by proton and heteronuclear single quantum coherence (2D (1)H-(13)C) nuclear magnetic resonance spectroscopy and mass spectrometry. In evaluating the ratio of sequential and simultaneous degradations of DMA and mono-MA, the stoichiometric analysis draws the same conclusions without using [mono-MA] as the experimental observation using [mono-MA]. The majority of the 4 esterase-DMA combinations undergo the sequential enzyme-catalyzed hydrolysis, from DMA to mono-MA to diol. However, cholesterol esterase is more effective than pseudocholine esterase in maintaining sequential degradation until >90% of DMA is decomposed. Both enzymolysis steps are first-order reactions. The mono-MAs are more hydrolysis resistant than DMAs. Moreover, esterase efficacy and selectivity on DMA enzymolysis are presented. The stoichiometric analysis provides valuable tools in assessing DMA enzymolysis when mono-MA is difficult to be obtained. The resistance of mono-MAs to enzymolysis suggests a need for thorough toxicity evaluations of these intermediate compounds. It also advocates the alternative approaches in designing and developing durable and biocompatible materials. Title: Synthesis and biological evaluation of 3-(4-aminophenyl)-coumarin derivatives as potential anti-Alzheimer's disease agents Hu YH, Yang J, Zhang Y, Liu KC, Liu T, Sun J, Wang XJ Ref: J Enzyme Inhib Med Chem, 34:1083, 2019 : PubMed ESTHER: Hu_2019_J.Enzyme.Inhib.Med.Chem_34_1083 PubMedSearch: Hu 2019 J.Enzyme.Inhib.Med.Chem 34 1083 PubMedID: 31117844 Abstract The work is focused on the design of drugs that prevent and treat Alzheimer's disease (AD) and its complications. A series of 3-(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 +/- 0.011 microM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 +/- 0.017 microM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications. Title: Carboxylesterase 2 and Intestine Transporters Contribute to the Low Bioavailability of Allisartan, a Prodrug of Exp3174 for Hypertension Treatment in Humans Li X, Sun J, Guo Z, Zhong D, Chen X Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 47:843, 2019 : PubMed ESTHER: Li_2019_Drug.Metab.Dispos_47_843 PubMedSearch: Li 2019 Drug.Metab.Dispos 47 843 PubMedID: 31076412 Abstract Exp3174 is an active metabolite of losartan for the treatment of hypertension. Allisartan (ALS3) is a marketed ester prodrug of Exp3174 to reduce bioavailability variation of losartan in China. However, ALS3 exhibited a lower oral absorption than losartan in humans. In this study, the enzymes and transporters involved in ALS3 and Exp3174 disposition were investigated to clarify the mechanisms. ALS3 underwent extensive hydrolysis to Exp3174 in S9 of Caco-2 cells, human intestine microsomes (HIM), recombinant carboxylesterase (rCES) 1, and rCES2. ALS3 exhibited similar affinity in HIM and rCES2 with K m values of 6.92 and 6.77 muM, respectively, indicating that ALS3 is mainly hydrolyzed to Exp3174 in human intestine by CES2. Transport assays of ALS3 and Exp3174 suggested that ALS3 and Exp3174 are substrates of P-glycoprotein, breast cancer resistance protein, and multidrug resistance protein 2 with poor permeability. Organic anion-transporting polypeptide 2B1 showed higher affinity and clearance toward ALS3 (K m 0.75 muM and intrinsic clearance 215 mul/min/mg) than those of Exp3174 (K m 7.85 muM and intrinsic clearance 16.1 mul/min/mg), indicating that ALS3 is preferred to be uptaken into intestinal epithelia. Hydrolysis of ALS3 was increased from approximately 30% to 55% in CES2-transfected human embryonic kidney 293-OATP2B1 cells, indicating the possible interplay between OATP2B1 and CES2. The influx and efflux of ALS3 across Caco-2 cells increased the potential of ALS3 hydrolysis to Exp3174, and the produced Exp3174 was rapidly pumped out, which led to undetectable ALS3 and Exp3174 in basolateral (receiver) side in Caco-2 cells. Overall, our study provided supportive evidences that the interplay between CES2 and transporters in intestine contributes to the low bioavailability of ALS3 in humans. Title: Identification of Carassius auratus gibelio liver cell proteins interacting with the GABAA receptor gamma2 subunit using a yeast two-hybrid system Ma RR, Sun J, Fang WH, Dong YP, Ruan JM, Yang XL, Hu K Ref: Fish Physiol Biochem, 45:199, 2019 : PubMed ESTHER: Ma_2019_Fish.Physiol.Biochem_45_199 PubMedSearch: Ma 2019 Fish.Physiol.Biochem 45 199 PubMedID: 30242696 Abstract The gamma-aminobutyric acid type A (GABAA) receptor is an important pentameric inhibitory neurotransmitter receptor, and the gamma2 subunit of this receptor plays a key role in potentiation of the GABAA response. We previously detected that the expression of GABAA receptor in the livers of Carassius auratus gibelio significantly increased after medication (avermectin and difloxacin treatment). In order to better understand the mechanism of action of the GABAA receptor gamma2 subunit in the livers of C. auratus gibelio, we constructed a C. auratus gibelio liver cDNA library (the titer value of 1.2 x 10(6) cfu/mL) and identified the proteins that interact with the GABAA receptor gamma2 subunit by using a yeast two-hybrid assay. The yeast two-hybrid screening yielded seven positive clones, namely, prelid3b, cdc42, sgk1, spg21, proteasome, chia.5, and AP-3 complex subunit beta-1, all of which have been annotated by the NCBI database. The functions of these proteins are complex; therefore, additional studies are required to determine the specific interactions of these proteins with the GABAA receptor gamma2 subunit in the liver of C. auratus gibelio. Although the interactions identified by the yeast two-hybrid system should be considered as preliminary results, the findings of this study may provide further direction and a foundation for future research focusing on the mechanisms of the GABAA receptor gamma2 subunit in C. auratus gibelio livers. 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: In vitro and in vivo Metabolism of a Potent Inhibitor of Soluble Epoxide Hydrolase, 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea Wan D, Yang J, McReynolds CB, Barnych B, Wagner KM, Morisseau C, Hwang SH, Sun J, Blocher R, Hammock BD Ref: Front Pharmacol, 10:464, 2019 : PubMed ESTHER: Wan_2019_Front.Pharmacol_10_464 PubMedSearch: Wan 2019 Front.Pharmacol 10 464 PubMedID: 31143115 Abstract 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (TPPU) is a potent soluble epoxide hydrolase (sEH) inhibitor that is used extensively in research for modulating inflammation and protecting against hypertension, neuropathic pain, and neurodegeneration. Despite its wide use in various animal disease models, the metabolism of TPPU has not been well-studied. A broader understanding of its metabolism is critical for determining contributions of metabolites to the overall safety and effectiveness of TPPU. Herein, we describe the identification of TPPU metabolites using LC-MS/MS strategies. Four metabolites of TPPU (M1-M4) were identified from rat urine by a sensitive and specific LC-MS/MS method with double precursor ion scans. Their structures were further supported by LC-MS/MS comparison with synthesized standards. Metabolites M1 and M2 were formed from hydroxylation on a propionyl group of TPPU; M3 was formed by amide hydrolysis of the 1-propionylpiperdinyl group on TPPU; and M4 was formed by further oxidation of the hydroxylated metabolite M2. Interestingly, the predicted alpha-keto amide metabolite and 4-(trifluoromethoxy)aniline (metabolite from urea cleavage) were not detected by the LC-MRM-MS method. This indicates that if formed, the two potential metabolites represent <0.01% of TPPU metabolism. Species differences in the formation of these four identified metabolites was assessed using liver S9 fractions from dog, monkey, rat, mouse, and human. M1, M2, and M3 were generated in liver S9 fractions from all species, and higher amounts of M3 were generated in monkey S9 fractions compared to other species. In addition, rat and human S9 metabolism showed the highest species similarity based on the quantities of each metabolite. The presence of all four metabolites were confirmed in vivo in rats over 72-h post single oral dose of TPPU. Urine and feces were major routes for TPPU excretion. M1, M4 and parent drug were detected as major substances, and M2 and M3 were minor substances. In blood, M1 accounted for ~9.6% of the total TPPU-related exposure, while metabolites M2, M3, and M4 accounted for <0.4%. All four metabolites were potent inhibitors of human sEH but were less potent than the parent TPPU. In conclusion, TPPU is metabolized via oxidation and amide hydrolysis without apparent breakdown of the urea. The aniline metabolites were not observed either in vitro or in vivo. Our findings increase the confidence in the ability to translate preclinical PK of TPPU in rats to humans and facilitates the potential clinical development of TPPU and other sEH inhibitors. Title: Synthesis and biological evaluation of 3-arylcoumarins as potential anti-Alzheimer's disease agents Yang J, Zhang P, Hu Y, Liu T, Sun J, Wang X Ref: J Enzyme Inhib Med Chem, 34:651, 2019 : PubMed ESTHER: Yang_2019_J.Enzyme.Inhib.Med.Chem_34_651 PubMedSearch: Yang 2019 J.Enzyme.Inhib.Med.Chem 34 651 PubMedID: 30746966 Abstract Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Most of the compounds exhibited high activity; therefore 3-arylcoumarin compounds have the potential as drug candidates for the treatment of Alzheimer's disease. Title: Screening and determination for potential acetylcholinesterase inhibitory constituents from ginseng stem-leaf saponins using ultrafiltration (UF)-LC-ESI-MS(2) Yang Y, Liang X, Jin P, Li N, Zhang Q, Yan W, Zhang H, Sun J Ref: Phytochem Anal, 30:26, 2019 : PubMed ESTHER: Yang_2019_Phytochem.Anal_30_26 PubMedSearch: Yang 2019 Phytochem.Anal 30 26 PubMedID: 30159954 Abstract INTRODUCTION: Previous studies have demonstrated that several ginsenosides have remarkable inhibitory effect on acetylcholinesterase (AChE). In the present study, ginseng stem-leaf saponins (GSLS) can improve learning and memory of Alzheimer's disease patients. However, much comprehensive information regarding AChE inhibition of GSLS and its metabolites is yet unknown. OBJECTIVE: The present study aims to screen and determine the potential of AChE inhibitors (AChEIs) from GSLS. METHODOLOGY: The active fraction of the GSLS detected in vitro AChE inhibition assays was selected as a starting material for the screening of the potential of AChEIs using ultrafiltration liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (UF-LC-ESI-MS(2) ). RESULTS: The results showed that 31 ginsenosides were identified with analysis using rapid resolution liquid chromatography with a diode array detector combined with electrospray ionisation tandem mass spectrometry (RRLC-DAD-ESI-MS(2) ) from the active fraction, and there are 27 compounds with AChE binding activity. Among them, 11 ginsenosides were evaluated and confirmed using in vitro enzymatic assay, and ginsenosides F1 , Rd, Rk3 , 20(S)-Rg3 , F2 and Rb2 were found to possess strong AChE inhibitory activities. CONCLUSION: The proposed UF-LC-ESI-MS(2) method was a powerful tool for the discovery of AChEIs from traditional Chinese medicine (TCM). Title: Characterization of the prognostic values of the NDRG family in gastric cancer Yu C, Hao X, Zhang S, Hu W, Li J, Sun J, Zheng M Ref: Therap Adv Gastroenterol, 12:1756284819858507, 2019 : PubMed ESTHER: Yu_2019_Therap.Adv.Gastroenterol_12_1756284819858507 PubMedSearch: Yu 2019 Therap.Adv.Gastroenterol 12 1756284819858507 PubMedID: 31384305 Abstract Background: The N-myc downstream-regulated gene (NDRG) family, NDRG1-4, has been involved in a wide spectrum of biological functions in multiple cancers. However, their prognostic values remain sparse in gastric cancer (GC). Therefore, it is crucial to systematically investigate the prognostic values of the NDRG family in GC. Methods: The prognostic values of the NDRG family were evaluated by Kaplan-Meier Plotter and SurvExpress. The mRNA of the NDRG family was investigated in The Cancer Genome Atlas (TCGA). Transcription factors (TFs) and miRNAs associated with the NDRG family were predicted by NetworkAnalysis. The prognostic values of DNA methylation levels were analyzed by MethSurv. The correlation between immune cells and the NDRG family was evaluated by the Tumor Immune Estimation Resource (TIMER) database. Results: High levels of mRNA expression of NDRG2 and NDRG3 were associated with a favorable prognosis in all GCs. In HER2 (-) GC, NDRG1 was significantly associated with a poor prognosis of GC [hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.16-2.33, p = 0.0046]. In HER2 (+) GC, NDRG4 showed a poor prognosis (HR = 1.4, 95% CI: 1.06-1.85, p = 0.017). NDRG4 was an independent prognostic factor in recurrence-free survival by TCGA cohort. The low-risk NDRG-signature group displayed a significantly favorable survival outcome than the high-risk group (HR = 1.76, 95% CI: 1.2-2.59, p = 0.00385). The phosphorylated protein NDRG1 (NDRG1_pT346) displayed a favorable overall survival and was significantly associated with HER2 and phosphorylated HER2. Epidermis development was the top biological process (BP) for coexpressed genes associated with NDRG1 and NDRG4, while mitotic nuclear division and mitotic cell processes were the top BPs for NDRG2 and NDRG3, respectively. Overall, 6 CpGs of NDRG1, 4 CpGs of NDRG2, 3 CpGs of NDRG3 and 24 CpGs of NDRG4 were associated with significant prognosis. CD4(+) T-cells showed the highest correlation with NDRG4 (correlation = 0.341, p = 2.14e(-11)). Furthermore, BCL6 in follicular helper T-cells (Tfh) cells showed the highest association with NDRG4 (correlation = 0.438, p = 00e(+)00). Conclusions: This study analyzed the multilevel prognostic values and biological roles of the NDRG family in GC. Title: Synthesis and biological evaluation of 4-arylcoumarins as potential anti-Alzheimer's disease agents Yun Y, Yang J, Miao Y, Wang X, Sun J Ref: Bioorganic & Medicinal Chemistry Lett, :126900, 2019 : PubMed ESTHER: Yun_2019_Bioorg.Med.Chem.Lett__126900 PubMedSearch: Yun 2019 Bioorg.Med.Chem.Lett 126900 PubMedID: 31882295 Abstract Alzheimer's disease (AD) is a progressive neurological degenerative disease that has complex pathogenesis. A variety of studies in humans indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted 4-arylcoumarin derivatives were synthesised, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity, MAO inhibitory activity, and antioxidant activity. Most of the compounds were found to exhibit high inhibitory activity, and individual compounds have extremely excellent activities. Therefore 4-arylcoumarins provides an idea for drugs design for the development of therapeutic or preventive agents for AD. Title: Novel Dual-Functional Enzyme Lip10 Catalyzes Lipase and Acyltransferase Activities in the Oleaginous Fungus Mucor circinelloides Zan X, Cui F, Sun J, Zhou S, Song Y Ref: Journal of Agricultural and Food Chemistry, 67:13176, 2019 : PubMed ESTHER: Zan_2019_J.Agric.Food.Chem_67_13176 PubMedSearch: Zan 2019 J.Agric.Food.Chem 67 13176 PubMedID: 31690075 Gene_locus related to this paper: muccl-a0a168kyh0, muccl-a0a168mc90, muccl-a0a168nw20 Abstract Lipases or triacylglycerol (TAG) lipases belong to the alpha/beta-hydrolases superfamily, which are enzymes capable of catalyzing the hydrolysis of the ester bond between fatty acids and glycerol. Interestingly, some lipases have been found to not only possess hydrolysis activity but also acyltransferase activity in yeasts and microalgae. Our present study reported a novel dual-functional Mucor circinelloides lipase Lip10 with a slight lipolysis activity but a noteworthy phospholipid/diacylglycerol acyltransferase (PDAT) activity. The purified Lip10 mutants prefer to utilize phosphatidyl serine to form TAG over phosphatidyl ethanolamine and phosphatidylcholine. Site-directed mutagenesis indicated that the histidine residue in the acyltransferase motif H-(X)4-D is indispensable for the PDAT activity of Lip10. Overexpression of the acyltransferase motif of Lip10 promoted cell growth by 12% and increased lipid production by 14% compared to the control, whilst overexpression of the lipase motif induced lipid degradation in M. circinelloides. Title: Compartmentalized biosynthesis of mycophenolic acid Zhang W, Du L, Qu Z, Zhang X, Li F, Li Z, Qi F, Wang X, Jiang Y and Li S <6 more author(s)> Zhang W, Du L, Qu Z, Zhang X, Li F, Li Z, Qi F, Wang X, Jiang Y, Men P, Sun J, Cao S, Geng C, Wan X, Liu C, Li S (- 6) Ref: Proc Natl Acad Sci U S A, 116:13305, 2019 : PubMed ESTHER: Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305 PubMedSearch: Zhang 2019 Proc.Natl.Acad.Sci.U.S.A 116 13305 PubMedID: 31209052 Gene_locus related to this paper: penbr-mpaH, penbr-mpac Abstract Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic to be isolated and crystallized, and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, some key biosynthetic mechanisms of such an old and important molecule have remained unclear. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and beta-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB' as the long-sought key enzyme responsible for the oxidative cleavage of the farnesyl side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC' and O-methyltransferase MpaG', the Golgi apparatus-associated prenyltransferase MpaA', the endoplasmic reticulum-bound oxygenase MpaB' and P450-hydrolase fusion enzyme MpaDE', and the peroxisomal acyl-coenzyme A (CoA) hydrolase MpaH'. The whole pathway is elegantly comediated by these compartmentalized enzymes, together with the peroxisomal beta-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic steps, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis. Title: Repellent action and contact toxicity mechanisms of the essential oil extracted from Chinese chive against Plutella xylostella larvae Gao Q, Song L, Sun J, Cao HQ, Wang L, Lin H, Tang F Ref: Archives of Insect Biochemistry & Physiology, :e21509, 2018 : PubMed ESTHER: Gao_2018_Arch.Insect.Biochem.Physiol__e21509 PubMedSearch: Gao 2018 Arch.Insect.Biochem.Physiol e21509 PubMedID: 30390324 Abstract Botanical pesticides play increasingly important roles in the control of agricultural pests. In this study, the insecticidal effects, specifically the repellent action and contact toxicity, of the essential oil extracted from Chinese chive (EOC) against Plutella xylostella larvae were confirmed. The mechanisms of repellent's action were studied using electroantennograms (EAGs), and the effects on glutathione S-transferase (GST), carboxylesterase (CarE), and acetyl cholinesterase were investigated after EOC treatments. The EOC affected the EAG results and inhibited the activities of GST and CarE in treated P. xylostella larvae, which could explain its insecticidal effects. And, four pyrazines showed greater repellent activities than that of the EOC, which was confirmed as the main active compounds of EOC. Title: Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality Wei C, Yang H, Wang S, Zhao J, Liu C, Gao L, Xia E, Lu Y, Tai Y and Wan X <33 more author(s)> Wei C, Yang H, Wang S, Zhao J, Liu C, Gao L, Xia E, Lu Y, Tai Y, She G, Sun J, Cao H, Tong W, Gao Q, Li Y, Deng W, Jiang X, Wang W, Chen Q, Zhang S, Li H, Wu J, Wang P, Li P, Shi C, Zheng F, Jian J, Huang B, Shan D, Shi M, Fang C, Yue Y, Li F, Li D, Wei S, Han B, Jiang C, Yin Y, Xia T, Zhang Z, Bennetzen JL, Zhao S, Wan X (- 33) Ref: Proc Natl Acad Sci U S A, 115:E4151, 2018 : PubMed ESTHER: Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151 PubMedSearch: Wei 2018 Proc.Natl.Acad.Sci.U.S.A 115 E4151 PubMedID: 29678829 Gene_locus related to this paper: camsi-a0a4s4dr18, camsi-a0a4s4etg9, camsi-a0a4s4e3j5, camsi-a0a4s4d2s5, camsi-a0a4s4duc4, camsi-a0a4v3wr80 Abstract Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties. Title: IMA Genome-F 9: Draft genome sequence of Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina, and Morchella septimelata Wingfield BD, Bills GF, Dong Y, Huang W, Nel WJ, Swalarsk-Parry BS, Vaghefi N, Wilken PM, An Z and Zhang X <22 more author(s)> Wingfield BD, Bills GF, Dong Y, Huang W, Nel WJ, Swalarsk-Parry BS, Vaghefi N, Wilken PM, An Z, de Beer ZW, De Vos L, Chen L, Duong TA, Gao Y, Hammerbacher A, Kikkert JR, Li Y, Li H, Li K, Li Q, Liu X, Ma X, Naidoo K, Pethybridge SJ, Sun J, Steenkamp ET, van der Nest MA, van Wyk S, Wingfield MJ, Xiong C, Yue Q, Zhang X (- 22) Ref: IMA Fungus, 9:199, 2018 : PubMed ESTHER: Wingfield_2018_IMA.Fungus_9_199 PubMedSearch: Wingfield 2018 IMA.Fungus 9 199 PubMedID: 30018880 Gene_locus related to this paper: 9helo-a0a370tge3, 9helo-a0a3d8spg6, 9euro-a0a3d8t2t6, 9euro-a0a3d8t644, 9helo-a0a370te58, 9helo-a0a370tt42, 9helo-a0a370u2s4, 9helo-a0a3d8s0y2, 9helo-a0a3d8stp9, 9helo-a0a370u370, 9euro-a0a3d8rk78, 9helo-a0a370tat5, 9helo-a0a3d8qpi0 Abstract Draft genomes of the species Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina and Morchella septimelata are presented. Both mating types (MAT1-1 and MAT1-2) of Cercospora beticola are included. Two strains of Coleophoma cylindrospora that produce sulfated homotyrosine echinocandin variants, FR209602, FR220897 and FR220899 are presented. The sequencing of Aspergillus mulundensis, Coleophoma cylindrospora and Phialophora cf. hyalina has enabled mapping of the gene clusters encoding the chemical diversity from the echinocandin pathways, providing data that reveals the complexity of secondary metabolism in these different species. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity (in some cases), biology and toxin production of these economically important fungi. Title: Butyrylcholinesterase Levels on Admission Predict Severity and 12-Month Mortality in Hospitalized AIDS Patients Xu L, Zhu B, Huang Y, Yang Z, Sun J, Xu Y, Zheng J, Kinloch S, Yin MT and Wu N <1 more author(s)> Xu L, Zhu B, Huang Y, Yang Z, Sun J, Xu Y, Zheng J, Kinloch S, Yin MT, Weng H, Wu N (- 1) Ref: Mediators Inflamm, 2018:5201652, 2018 : PubMed ESTHER: Xu_2018_Mediators.Inflamm_2018_5201652 PubMedSearch: Xu 2018 Mediators.Inflamm 2018 5201652 PubMedID: 29736152 Abstract Background: Butyrylcholinesterase (BChE) is synthesized mainly in the liver and an important marker in many infectious/inflammatory diseases, but its role in acquired immunodeficiency syndrome (AIDS) patients is not clear. We wished to ascertain if BChE level is associated with the progression/prognosis of AIDS patients. Methods: BChE levels (in U/L) were measured in 505 patients; <4500 was defined as "low" and >/=4500 as "normal." Associations between BChE level and CD4 count, WHO stage, body mass index (BMI), C-reactive protein (CRP) level, and duration of hospitalization were assessed. Kaplan-Meier curves and Cox proportional hazards model were used to assess associations between low BChE levels and mortality, after adjustment for age, CD4 count, WHO stage, and laboratory parameters. Results: A total of 129 patients (25.5%) had a lower BChE level. BChE was closely associated with CD4 count, WHO stage, CRP level, and BMI (all P < 0.001). Eighty-four patients (16.6%) died in the first year of follow-up. One-year survival was 64.5 +/- 4.5% for patients with low BChE and 87.6 +/- 1.8% for those with normal BChE (log-rank, P < 0.001). After adjustment for sex, age, BMI, WHO stage, and CD4 count, as well as serum levels of hemoglobin, sodium, and albumin, the hazard ratio was 1.8 (95% confidence interval, 1.0-3.2) for patients with a low BChE compared with those with a normal BChE (P = 0.035). Conclusion: BChE level is associated with HIV/AIDS severity and is an independent risk factor for increased mortality in AIDS patients. Title: Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry Zhang H, Guo Y, Meng L, Sun H, Yang Y, Gao Y, Sun J Ref: Pharmacogn Mag, 14:248, 2018 : PubMed ESTHER: Zhang_2018_Pharmacogn.Mag_14_248 PubMedSearch: Zhang 2018 Pharmacogn.Mag 14 248 PubMedID: 29720840 Abstract Background: At present, approximately 17-25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. Objective: To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). Materials and Methods: In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro. Results: The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. Conclusion: The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. SUMMARY: A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF-LC-ESI-MS/MS): ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry; (AChEIs): acetylcholinesterase inhibitors. Title: Oxoisoaporphine Alkaloids: Prospective Anti-Alzheimer's Disease, Anticancer, and Antidepressant Agents Zhang J, Chen L, Sun J Ref: ChemMedChem, 13:1262, 2018 : PubMed ESTHER: Zhang_2018_ChemMedChem_13_1262 PubMedSearch: Zhang 2018 ChemMedChem 13 1262 PubMedID: 29696800 Abstract Oxoisoaporphine alkaloids are a family of oxoisoquinoline-derived alkaloids that were first isolated from the rhizome of Menispermum dauricum DC. (Menispermaceae). It has been demonstrated that oxoisoaporphine alkaloids possess various biological properties, such as cholinesterase and beta-amyloid inhibition, acting as a topoisomerase intercalator, monoamine oxidase A inhibition, and are expected to become anti-Alzheimer's disease, anticancer, and antidepressant drugs. This review provides an overview of natural sources, synthetic routes, bioactivities, structure-function relationship, and modification investigations into oxoisoaporphine alkaloids, with the aim of providing references to the structure-activity relationships for the design and development of oxoisoaporphine derivatives with higher efficacy and therapeutic potential. Title: A pH-responsive colorimetric strategy for DNA detection by acetylcholinesterase catalyzed hydrolysis and cascade amplification Guo Y, Yang K, Sun J, Wu J, Ju H Ref: Biosensors & Bioelectronics, 94:651, 2017 : PubMed ESTHER: Guo_2017_Biosens.Bioelectron_94_651 PubMedSearch: Guo 2017 Biosens.Bioelectron 94 651 PubMedID: 28388529 Abstract A pH-responsive colorimetric strategy was designed for sensitive and convenient biosensing by introducing acetylcholinesterase (AChE) catalyzed hydrolysis of acetylcholine to change solution pH and phenol red as an indicator. Using DNA as a target model, this technique was successfully employed for sensitive DNA analysis by labeling AChE to DNA. The sensitivity could be greatly improved by coupling a newly designed magnetic probe with target DNA-triggered nonenzymatic cascade amplification. In the presence of a help DNA (H) and the functional probe, the cascade assembly via toehold-mediated strand displacement released the AChE-conjugated sequence from magnetic beads, which could be simply separated from the reaction mixture to catalyze the hydrolysis of ACh in detection solution. The color change of detection solution from pink to orange-red, orange-yellow and ultimately yellow could be used for target DNA detection by naked eye and colorimetry with the absorbance ratio of detection solution at 558nm to 432nm as the signal. The nonenzymatically sensitized colorimetric strategy showed a linear range from 50pM to 50nM with a detection limit of 38pM, indicating a promising application in DNA analysis. Title: Assessment of the inhibitory effects of pyrethroids against human carboxylesterases Lei W, Wang DD, Dou TY, Hou J, Feng L, Yin H, Luo Q, Sun J, Ge GB, Yang L Ref: Toxicol Appl Pharmacol, 321:48, 2017 : PubMed ESTHER: Lei_2017_Toxicol.Appl.Pharmacol_321_48 PubMedSearch: Lei 2017 Toxicol.Appl.Pharmacol 321 48 PubMedID: 28242322 Abstract Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibition towards CES1. The IC50 values of deltamethrin against CES1-mediated BMBT, DME, and DMCB hydrolysis were determined as 1.58muM, 2.39muM, and 3.3muM, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation. The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1. Title: Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice Li N, Liu C, Jing S, Wang M, Wang H, Sun J, Wang C, Chen J, Li H Ref: Evid Based Complement Alternat Med, 2017:8632016, 2017 : PubMed ESTHER: Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016 PubMedSearch: Li 2017 Evid.Based.Complement.Alternat.Med 2017 8632016 PubMedID: 28814961 Abstract Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement. Title: The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M and Sun J <2 more author(s)> Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M, Zheng M, Ji J, Sun J (- 2) Ref: Oncogene, 36:4323, 2017 : PubMed ESTHER: Mi_2017_Oncogene_36_4323 PubMedSearch: Mi 2017 Oncogene 36 4323 PubMedID: 28346422 Gene_locus related to this paper: human-NDRG1 Abstract N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer. Title: Aqueous extracts from asparagus stems prevent memory impairments in scopolamine-treated mice Sui Z, Qi C, Huang Y, Ma S, Wang X, Le G, Sun J Ref: Food Funct, 8:1460, 2017 : PubMed ESTHER: Sui_2017_Food.Funct_8_1460 PubMedSearch: Sui 2017 Food.Funct 8 1460 PubMedID: 28275781 Abstract Aqueous extracts from Asparagus officinalis L. stems (AEAS) are rich in polysaccharides, gamma-amino butyric acid (GABA), and steroidal saponin. This study was designed to investigate the effects of AEAS on learning, memory, and acetylcholinesterase-related activity in a scopolamine-induced model of amnesia. Sixty ICR mice were randomly divided into 6 groups (n = 10) including the control group (CT), scopolamine group (SC), donepezil group (DON), low, medium, and high dose groups of AEAS (LS, MS, HS; 1.6 mL kg-1, 8 mL kg-1, 16 mL kg-1). The results showed that 8 mL kg-1 of AEAS used in this study significantly reversed scopolamine-induced cognitive impairments in mice in the novel object recognition test (P < 0.05) and the Y-maze test (P < 0.05), and also improved the latency to escape in the Morris water maze test (P < 0.05). Moreover, it significantly increased acetylcholine and inhibited acetylcholinesterase activity in the hippocampus, which was directly related to the reduction in learning and memory impairments. It also reversed scopolamine-induced reduction in the hippocampal brain-derived neurotrophic factor (BDNF) and the cAMP response element-binding protein (CREB) mRNA expression. AEAS protected against scopolamine-induced memory deficits. In conclusion, AEAS protected learning and memory function in mice by enhancing the activity of the cholinergic nervous system, and increasing BDNF and CREB expression. This suggests that AEAS has the potential to prevent cognitive impairments in age-related diseases, such as Alzheimer's disease. Title: Huperzine A inhibits immediate addictive behavior but not behavioral sensitization following repeated morphine administration in rats Sun J, Tian L, Cui R, Li X Ref: Exp Ther Med, 13:1584, 2017 : PubMed ESTHER: Sun_2017_Exp.Ther.Med_13_1584 PubMedSearch: Sun 2017 Exp.Ther.Med 13 1584 PubMedID: 28413513 Abstract Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to treat addiction. The current study aimed to examine the effects of huperzine A, a cholinesterase inhibitor, on behavioral sensitization induced by repeated morphine administration and relapse induced by contextual conditioning. The present study also assessed whether the state-dependency hypothesis may explain the results. Adult rats were divided into four groups (n=8) and intraperitoneally injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for 5 days. The effect of repeated huperzine A administration alone on locomotor activity was assessed. For the experiments that analyzed the development of morphine-induced sensitization, 40 rats were divided into five groups (n=8): Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine. Following a withdrawal period of 7 days, all animals were administered saline or morphine, as appropriate. To test the state-dependency hypothesis, the rats in the Saline+Morphine group were injected with saline and morphine, while the other three groups were administered different doses of huperzine A and morphine. To examine the effect of huperzine A on the expression of morphine-induced sensitization, the rats in huperzine A+Morphine groups were injected with appropriate concentrations of huperzine A, and morphine. The current results indicated that the administration of huperzine A alone did not affect locomotor activity, while higher doses of huperzine A inhibited the addictive behavior induced by morphine at the development phase. Additionally, huperzine A administration during the expression phase of morphine sensitization did not inhibit the relapse induced by administration of saline. Furthermore, 0.4 mg/kg huperzine A inhibited the expression of morphine-induced behavioral sensitization. Therefore, the results of the current study do not support the state-dependency hypothesis. Title: Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis Xie Q, Zheng Z, Shao B, Fu W, Xia Z, Li W, Sun J, Zheng W, Zhang W and Qiu Z <4 more author(s)> Xie Q, Zheng Z, Shao B, Fu W, Xia Z, Li W, Sun J, Zheng W, Zhang W, Sheng W, Zhang Q, Chen H, Wang H, Qiu Z (- 4) Ref: J Enzyme Inhib Med Chem, 32:659, 2017 : PubMed ESTHER: Xie_2017_J.Enzyme.Inhib.Med.Chem_32_659 PubMedSearch: Xie 2017 J.Enzyme.Inhib.Med.Chem 32 659 PubMedID: 28274151 Abstract Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer's disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (-)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC50 31.6 nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-beta (Abeta) lowering effects (51.9% decrease of Abeta42) superior to phenserine (31% decrease of total Abeta) in SH-SY5Y-APP695 cells at 50 microM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents. Title: N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2 Yang X, Zhu F, Yu C, Lu J, Zhang L, Lv Y, Sun J, Zheng M Ref: Oncotarget, 8:47709, 2017 : PubMed ESTHER: Yang_2017_Oncotarget_8_47709 PubMedSearch: Yang 2017 Oncotarget 8 47709 PubMedID: 28537875 Gene_locus related to this paper: human-NDRG1 Abstract N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Calpha (PKCalpha), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug. Title: Effects and mechanism of cerebroprotein hydrolysate on learning and memory ability in mice An L, Han X, Li H, Ma Y, Shi L, Xu G, Yuan G, Sun J, Zhao N and Du P <2 more author(s)> An L, Han X, Li H, Ma Y, Shi L, Xu G, Yuan G, Sun J, Zhao N, Sheng Y, Wang M, Du P (- 2) Ref: Genet Mol Res, 15:, 2016 : PubMed ESTHER: An_2016_Genet.Mol.Res_15_ PubMedSearch: An 2016 Genet.Mol.Res 15 PubMedID: 27525868 Abstract Cerebroprotein hydrolysate is an extract from porcine brain tissue that acts on the central nervous system in various ways to protect neurons and improve memory, attention, and vigilance. This study examined the effect and mechanism of cerebroprotein hydrolysate on learning and memory in mice with scopolamine-induced impairment. Mice were given an intraperitoneal injection of scopolamine hydrobromide to establish a murine model of learning and memory impairment. After 35 successive days of cerebroprotein hydrolysate treatment, their behaviors were observed in the Morris water maze and step-down test. Superoxide dismutase (SOD), Na+-K+-ATPase, and acetylcholinesterase (AChE) activity, and malondialdehyde (MDA), gamma-aminobutyric acid (GABA), and glutamic acid (Glu) levels in the brain tissue of the mice were determined, and pathological changes in the hippocampus were examined. The results of the water-maze test showed that cerebroprotein hydrolysate shortened the escape latency and increased the number of platform crossings. In the step-down test, cerebroprotein hydrolysate treatment prolonged the step-down latency and reduced the number of errors; cerebroprotein hydrolysate increased the activity of SOD, Na+-K+-ATPase, and AChE, reduced the levels of MDA, decreased the Glu/GABA ratio in brain tissue, and reduced pathological changes in the hippocampus. The results indicate that cerebroprotein hydrolysate can improve learning and memory in mice with scopolamine-induced impairment. This effect may be associated with its ability to reduce injury caused by free radicals, improve acetylcholine function, and modulate the Glu/GABA learning and memory regulation system, reducing excitotoxicity caused by Glu. Title: High expression of NDRG3 associates with positive lymph node metastasis and unfavourable overall survival in laryngeal squamous cell carcinoma Ma J, Liu S, Zhang W, Zhang F, Wang S, Wu L, Yan R, Wang C, Zha Z, Sun J Ref: Pathology, 48:691, 2016 : PubMed ESTHER: Ma_2016_Pathology_48_691 PubMedSearch: Ma 2016 Pathology 48 691 PubMedID: 27780595 Abstract N-myc downstream-regulated gene 3 (NDRG3), which belongs to the NDRG family, is believed to play important roles in human cancer. In this present study, one-step quantitative reverse transcription-polymerase chain reaction (qPCR) and western blotting tests with 10 fresh-frozen laryngeal squamous cell carcinoma (LSCC) samples and immunohistochemistry (IHC) analysis in 109 LSCC cases were performed to investigate the relationship between NDRG3 expression and the clinicopathological characteristics of LSCC. Results demonstrated that NDRG3 mRNA and protein expression levels were statistically higher in LSCC tissues than that in non-cancerous tissues (all p<0.05). IHC data showed that the NDRG3 protein expression was remarkably correlated with lymph node metastasis (p=0.043). Univariate and multivariate survival analysis implied that high NDRG3 expression (p=0.004), lymph node metastasis (p=0.044) and TNM stage (p=0.020) were independently associated with the unfavourable overall survival of patients with LSCC. The above findings suggested that NDRG3 may be identified as a novel biomarker predicting the prognosis of LSCC. Title: Lipolytic enzymes involving lipolysis in Teleost: Synteny, structure, tissue distribution, and expression in grass carp (Ctenopharyngodon idella) Sun J, Ji H, Li XX, Shi XC, Du ZY, Chen LQ Ref: Comparative Biochemistry & Physiology B Biochem Mol Biol, 198:110, 2016 : PubMed ESTHER: Sun_2016_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_198_110 PubMedSearch: Sun 2016 Comp.Biochem.Physiol.B.Biochem.Mol.Biol 198 110 PubMedID: 27131420 Abstract Lipolysis is the biochemical pathway responsible for the sequential hydrolysis of triacylglycerols (TAGs) stored in cellular lipid droplets. Three enzymes are known to participate in TAGs hydrolysis, including adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase (MGL), and each is present in mammals as only one isoform. Here we show that the genome of grass carp (Ctenopharyngodon idella) and other teleosts codes for one ATGL, two HSLs, and one MGL isoforms. Two isoforms of HSL gene, HSLa and HSLb, derived from paralogous genes that could be originated from teleost-specific genome duplication (TSGD) event. The genes encoding for fish ATGL and MGL were conserved and contained nine and seven coding exons, respectively. However, two isoforms of HSL gene had a remarkable variation in gene structure, such as HSLa gene contained ten and HSLb contained thirteen exons. All three enzymes, including two isoforms of HSL, were expressed in a wide range of tissues, but the abundance of each gene mRNA showed the tissue-dependent expression patterns. During fasting, only ATGL and HSLa showed a significant increase in adipose tissue and adipocyte, indicating that ATGL and HSLa may be the main rate-limiting enzymes controlling the hydrolysis of TAGs in fasting-induced lipolysis. Different expression of HSLa and HSLb suggests that they might serve different roles in fasting-induced lipolysis. These results provide evidence about the conservation and divergence of genes of fish lipolytic enzymes. Title: Carbon dots-assisted colorimetric and fluorometric dual-mode protocol for acetylcholinesterase activity and inhibitors screening based on the inner filter effect of silver nanoparticles Zhao D, Chen C, Sun J, Yang X Ref: Analyst, 141:3280, 2016 : PubMed ESTHER: Zhao_2016_Analyst_141_3280 PubMedSearch: Zhao 2016 Analyst 141 3280 PubMedID: 27099097 Abstract In this work, we proposed an original and versatile dual-readout (colorimetric and fluorometric) protocol by means of silver nanoparticles (AgNPs) and fluorescent carbon dots (CDs), which was amenable to rapid, ultrasensitive assay of acetylcholinesterase (AChE) activity and its inhibitors. The sensing mechanism was based on the non-fluorescence state of CDs resulting from the inner filter effect (IFE) of AgNPs and the specific AChE-catalyzed hydrolysis of acetylthiocholine (ATCh) into thiocholine (TCh). Herein, the generated positively-charged and thiol-bearing TCh at trace concentration levels could trigger the aggregation of AgNPs through the well-known electrostatic and Ag-SH interactions, thereby turning the sensing solutions grey and recovering the IFE-quenched fluorescence simultaneously. Furthermore, the existence of IFE mechanism was conceivably confirmed by combining the zeta potentials, fluorescence spectra, UV-vis spectra, fluorescence lifetime and TEM measurements. As far as we know, the present study has reported the first dual-mode proposal for assessing AChE activity by using a CDs-based IFE sensing strategy, where the detection limit was as low as 0.021 mU mL(-1) and 0.016 mU mL(-1) by colorimetric and fluorometric measurements, respectively. On the other hand, the proposed assay was feasible to screen AChE inhibitors such as tacrine and carbaryl. Meanwhile, this rationally designed dual-mode sensing platform featured simplicity, rapidity, flexibility and diversity, which was demonstrated by the quantitative detection of spiked carbaryl in apple juice samples with satisfactory results. Title: [Effect of Bacillus thuringiensis var. israelensis (Bti) on detoxification en- zyme activity of larvae of Culex pipiens pallens and Aedes aegypti] Han GJ, Li CM, Sun J, Liu Q, Zhao S, Qi JH, Xu J Ref: Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi, 27:385, 2015 : PubMed ESTHER: Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385 PubMedSearch: Han 2015 Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi 27 385 PubMedID: 26767261 Abstract OBJECTIVE: To investigate the effect of Bacillus thuringiensis var. israelensis (Bti) on the activities of three detoxification enzymes of Culex pipiens pallens and Aedes aegypti larvae. Title: Gold nanoclusters-Cu ensemble-based fluorescence turn-on and real-time assay for acetylcholinesterase activity and inhibitor screening Sun J, Yang X Ref: Biosensors & Bioelectronics, 74:177, 2015 : PubMed ESTHER: Sun_2015_Biosens.Bioelectron_74_177 PubMedSearch: Sun 2015 Biosens.Bioelectron 74 177 PubMedID: 26141104 Abstract Based on the specific binding of Cu2+ ions to the 11-mercaptoundecanoic acid (11-MUA)-protected AuNCs with intense orange-red emission, we have proposed and constructed a novel fluorescent nanomaterials-metal ions ensemble at a nonfluorescence off-state. Subsequently, an AuNCs@11-MUA-Cu2+ ensemble-based fluorescent chemosensor, which is amenable to convenient, sensitive, selective, turn-on and real-time assay of acetylcholinesterase (AChE), could be developed by using acetylthiocholine (ATCh) as the substrate. Herein, the sensing ensemble solution exhibits a marvelous fluorescent enhancement in the presence of AChE and ATCh, where AChE hydrolyzes its active substrate ATCh into thiocholine (TCh), and then TCh captures Cu2+ from the ensemble, accompanied by the conversion from fluorescence off-state to on-state of the AuNCs. The AChE activity could be detected less than 0.05mU/mL within a good linear range from 0.05 to 2.5mU/mL. Our proposed fluorescence assay can be utilized to evaluate the AChE activity quantitatively in real biological sample, and furthermore to screen the inhibitor of AChE. As far as we know, the present study has reported the first analytical proposal for sensing AChE activity in real time by using a fluorescent nanomaterials-Cu2+ ensemble or focusing on the Cu2+-triggered fluorescence quenching/recovery. This strategy paves a new avenue for exploring the biosensing applications of fluorescent AuNCs, and presents the prospect of AuNCs@11-MUA-Cu2+ ensemble as versatile enzyme activity assay platforms by means of other appropriate substrates/analytes. Title: Colorimetric and Phosphorimetric Dual-Signaling Strategy Mediated by Inner Filter Effect for Highly Sensitive Assay of Organophosphorus Pesticides Zhang R, Li N, Sun J, Gao F Ref: Journal of Agricultural and Food Chemistry, 63:8947, 2015 : PubMed ESTHER: Zhang_2015_J.Agric.Food.Chem_63_8947 PubMedSearch: Zhang 2015 J.Agric.Food.Chem 63 8947 PubMedID: 26411607 Abstract We describe here a colorimetric and phosphorimetric dual-signaling strategy for sensitive assay of organophosphorus pesticides (OPPs). The principle for assay depends on the phenomenon that the phosphorescence of Mn-ZnS quantum dots (QDs) can be dramatically quenched by Au nanoparticles (AuNPs) through the inner filter effect (IFE) and the activity of acetylcholinesterase (AChE), an enzyme that catalytically hydrolyzes acetylthiocholine to thiocholine that can be inhibited by OPPs. By virtue of the variations of absorbance and phosphorescence of the analytical system, a dual-readout assay for OPPs has been proposed. The limits of detection for different OPPs including paraoxon, parathion, omethoate, and dimethyl dichlorovinyl phosphate (DDVP) are found to be 0.29, 0.59, 0.67, and 0.44 ng/L, respectively. The proposed assay was allowed to detect pesticides in real spiked samples and authentic contaminated apples with satisfactory results, suggesting its potential applications to detect pesticides in complicated samples. Title: Molecular Cloning and Characterization of a Novel Cold-Adapted Family VIII Esterase from a Biogas Slurry Metagenomic Library Cheng X, Wang X, Qiu T, Yuan M, Sun J, Gao J Ref: J Microbiol Biotechnol, 24:1484, 2014 : PubMed ESTHER: Cheng_2014_J.Microbiol.Biotechnol_24_1484 PubMedSearch: Cheng 2014 J.Microbiol.Biotechnol 24 1484 PubMedID: 25394508 Abstract A novel esterase gene, est01, was successfully unearthed from a biogas digester microbiota metagenomic library. The 1,194 bp est01 gene encodes a protein of 44,804 Da (designated Est01). The amino acid sequence of Est01 shows only moderate (33%) identity to a lipase/ esterase. Phylogenetic analysis and biochemical characterization confirmed that Est01 is a new member of family VIII esterases. The purified Est01 from recombinant Escherichia coli BL21 (DE3) showed high hydrolytic activity against short-chain fatty acid esters, suggesting that it is a typical carboxylesterase rather than a lipase. Furthermore, the Est01 was even active at 10 degrees C (43% activity remained), with the optimal temperature at 20 degrees C, and had a broad pH range from 5.0 to 10.0, with the optimal pH of 8.0. These properties suggest that Est01 is a cold-adaptive esterase and could have good potential for low-temperature hydrolysis application. Title: Synthesis and evaluation of odour-active methionyl esters of fatty acids via esterification and transesterification of butter oil Li C, Sun J, Fu C, Yu B, Liu SQ, Li T, Huang D Ref: Food Chem, 145:796, 2014 : PubMed ESTHER: Li_2014_Food.Chem_145_796 PubMedSearch: Li 2014 Food.Chem 145 796 PubMedID: 24128547 Abstract Methionol-derived fatty acid esters were synthesised by both chemical and lipase catalysed esterification between fatty acids and methionol. Beneficial effects of both methods were compared qualitatively and quantitatively by GC-MS/GC-FID results. And the high acid and heat stability of our designed methionyl esters meet the requirement of the food industry. Most importantly, the sensory test showed that fatty acid carbon-chain length had an important effect on the flavour attributes of methionyl esters. Moreover, through Lipozyme TL IM-mediated transesterification, valuable methionol-derived esters were synthesised from the readily available natural material butter oil as the fatty acid source. The conversion of methionol and yield of each methionyl ester were also elucidated by GC-MS-FID. Title: Chemical and enzymatic synthesis of a library of 2-phenethyl esters and their sensory attributes Li C, Sun J, Li T, Liu SQ, Huang D Ref: Food Chem, 154:205, 2014 : PubMed ESTHER: Li_2014_Food.Chem_154_205 PubMedSearch: Li 2014 Food.Chem 154 205 PubMedID: 24518334 Abstract We report a simple enzymatic approach to synthesise phenethyl esters as natural flavouring materials. Chemical and lipase-catalysed esterification reactions between fatty acids of C4-C18 and 2-phenethyl alcohol were studied. Both methods were compared qualitatively and quantitatively by GC-MS/FID. The acid and thermal stabilities of 2-phenethyl esters were excellent and can meet the requirements of food matrices under most processing conditions. Sensory evaluation showed that each 2-phenethyl ester with a different carbon-chain-length fatty acid had unique sensory notes. Moreover, through Lipozyme TL IM-mediated transesterification, valuable 2-phenethyl alcohol-derived esters were synthesised from butter oil and 2-phenethyl alcohol. The influence of several physicochemical parameters (temperature, substrate molar ratio, enzyme loading, shaking speed and time) on the transesterification reaction was investigated to give optimal reaction conditions, leading to a high yield of 80.0%. Title: Meserine, a Novel Carbamate AChE Inhibitor, Ameliorates Scopolamine-Induced Dementia and Alleviates Amyloidogenesis of APP/PS1 Transgenic Mice Shao BY, Xia Z, Xie Q, Ge XX, Zhang WW, Sun J, Jiang P, Wang H, Le WD and Chen HZ <2 more author(s)> Shao BY, Xia Z, Xie Q, Ge XX, Zhang WW, Sun J, Jiang P, Wang H, Le WD, Qiu ZB, Lu Y, Chen HZ (- 2) Ref: CNS Neurosci Ther, 20:165, 2014 : PubMed ESTHER: Shao_2014_CNS.Neurosci.Ther_20_165 PubMedSearch: Shao 2014 CNS.Neurosci.Ther 20 165 PubMedID: 24279603 Abstract AIMS: To investigate whether Meserine, a novel phenylcarbamate derivative of (-)-meptazinol, possesses beneficial activities against cholinergic deficiency and amyloidogenesis, the two major pathological characteristics of Alzheimer's disease (AD). Title: Enantioselective Interaction of Acid alpha-Naphthyl Acetate Esterase with Chiral Organophosphorus Insecticides Zhang A, Sun J, Lin C, Hu X, Liu W Ref: Journal of Agricultural and Food Chemistry, 62:1477, 2014 : PubMed ESTHER: Zhang_2014_J.Agric.Food.Chem_62_1477 PubMedSearch: Zhang 2014 J.Agric.Food.Chem 62 1477 PubMedID: 24475784 Abstract Many previous works have demonstrated that acetylcholinesterase (AChE) was enantioselectively inhibited by chiral organophosphorus insecticides (OPs) and that a significant difference in reactivation existed for AChE inactivated by (1R)- versus (1S,3S)-stereoisomers of isomalathion. It had been known that alpha-naphthyl acetate esterase (ANAE), an enzyme which might play an essential role in the growth of plants and the defense of plants against environmental stress by regulating the concentration of hormones in plants, can be inhibited by OPs. However, it was unknown whether interaction of ANAE with chiral OPs was enantioselective. The present work investigated the inhibition kinetics and spontaneous reactivation of ANAE inactivated by enantiomers of malaoxon, isomalathion, and methamidophos. The order of inhibition potency is (R) > (S) for malaoxon, (1R,3R) > (1R,3S) > (1S,3R) > (1S,3S) for isomalathion, and (S) > (R) for methamidophos according to bimolecular rate constants of inhibition (ki), which is consistent with the order observed in the enantioselective inhibition of AChE by malaoxon, isomalathion, and methamidophos. The difference in spontaneous reactivation of AChE inactivated between (1R)- and (1S,3S)-isomers of isomalathion is conserved for ANAE. The observations indicated ANAE and AChE have similar selective inhibition kinetics and postinhibitory reactions in reaction with chiral OPs. Title: Bacillus ligniniphilus sp. nov., an alkaliphilic and halotolerant bacterium isolated from sediments of the South China Sea Zhu D, Tanabe SH, Xie C, Honda D, Sun J, Ai L Ref: Int J Syst Evol Microbiol, 64:1712, 2014 : PubMed ESTHER: Zhu_2014_Int.J.Syst.Evol.Microbiol_64_1712 PubMedSearch: Zhu 2014 Int.J.Syst.Evol.Microbiol 64 1712 PubMedID: 24554634 Abstract An alkaliphilic and halotolerant Gram-stain-positive bacterium, which was isolated from sediment samples from the South China Sea, was subjected to a taxonomic study. The isolate, strain L1T, grew well at a wide range of temperatures and pH values, 10.0-45.0 degrees C and pH 6-11, with optima at 30 degrees C and pH 9.0, respectively. The growth of strain L1T occurred at total salt concentrations of 0-10% (w/v) with an optimum at 2% (w/v). Phylogenetic analysis based on 16S rRNA sequence comparison indicated that the isolate represented a member of the genus Bacillus. The strains most closely related to strain L1T were Bacillus nanhaiisediminis JCM 16507T, Bacillus halodurans DSM 497T and Bacillus pseudofirmus DSM 8715T, with 16S rRNA similarities of 96.5%, 95.9% and 95.7%, respectively. DNA-DNA hybridization of strain L1T with the type strains of the most closely related species, B. nanhaiisediminis JCM 16507T, B. halodurans DSM 497T and B. pseudofirmus DSM 8715T, showed reassociation values of about 21.7%, 14.3% and 13.9%, respectively. The DNA G+C content of strain L1T was 40.76 mol%. The predominant isoprenoid quinone was menaquinone 7 (MK-7). The cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant cellular fatty acids of strain L1T were iso-C14 : 0 and anteiso-C15:0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Based on the phenotypic and phylogenetic characteristics, it is proposed that strain L1T (=JCM 18543T=DSM 26145T) should be classified as the type strain of Bacillus ligniniphilus sp. nov. Title: NO-donating tacrine derivatives as potential butyrylcholinesterase inhibitors with vasorelaxation activity Chen Y, Sun J, Huang Z, Liao H, Peng S, Lehmann J, Zhang Y Ref: Bioorganic & Medicinal Chemistry Lett, 23:3162, 2013 : PubMed ESTHER: Chen_2013_Bioorg.Med.Chem.Lett_23_3162 PubMedSearch: Chen 2013 Bioorg.Med.Chem.Lett 23 3162 PubMedID: 23639542 Abstract To search for potent anti-Alzheimer's disease (AD) agents with multifunctional effects, 12 NO-donating tacrine-flurbiprofen hybrid compounds (2a-l) were synthesized and biologically evaluated. It was found that all the new target compounds showed selective butyrylcholinesterase (BCHE) inhibitory activity in vitro comparable or higher than tacrine and the tacrine-flurbiprofen hybrid compounds 1a-c, and released moderate amount of NO in vitro. The kinetic study suggests that one of the most active and highest BCHE selective compounds 2d may not only compete with the substrate for the same catalytic active site (CAS) but also interact with a second binding site. Furthermore, 2d and 2l exhibited significant vascular relaxation effect, which is beneficial for the treatment of AD. All the results suggest that 2d and 2l might be promising lead compounds for further research. Title: Tacrine-flurbiprofen hybrids as multifunctional drug candidates for the treatment of Alzheimer's disease Chen Y, Sun J, Peng S, Liao H, Zhang Y, Lehmann J Ref: Arch Pharm (Weinheim), 346:865, 2013 : PubMed ESTHER: Chen_2013_Arch.Pharm.(Weinheim)_346_865 PubMedSearch: Chen 2013 Arch.Pharm.(Weinheim) 346 865 PubMedID: 24203864 Abstract Five tacrine-flurbiprofen hybrid compounds (3a-e) were synthesized as multi-target-directed compounds for the treatment of Alzheimer's disease. Compared to tacrine, two compounds (3d and 3e) showed better acetylcholinesterase (AChE) inhibitory activity and others (3b-e) better or the same butyrylcholinesterase (BCHE) inhibitory activity. Notably, 3d showed a mixed-type inhibitory action for AChE, indicating a "dual-binding site action" of both toward the catalytic active site (CAS) and the peripheral anionic site (PAS), whereas for BCHE, a competitive inhibitory action was observed. Furthermore, a cell-based assay on amyloid-beta inhibition demonstrated that the selected target compound 3d effectively inhibits the formation of amyloid-beta in vitro. 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: Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H and Ehringer MA <116 more author(s)> Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Han Y, Hansel NN, Jiang C, Korhonen T, Lind PA, Liu J, Lyytikainen LP, Michel M, Shaffer JR, Short SE, Sun J, Teumer A, Thompson JR, Vogelzangs N, Vink JM, Wenzlaff A, Wheeler W, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty TH, Benjamin DJ, Bergen AW, Broms U, Cesarini D, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick D, Foroud T, Furberg H, Giegling I, Gillespie NA, Gu F, Hall AS, Hallfors J, Han S, Hartmann AM, Heikkila K, Hickie IB, Hottenga JJ, Jousilahti P, Kaakinen M, Kahonen M, Koellinger PD, Kittner S, Konte B, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Murray T, Nauck M, North KE, Pare PD, Pergadia M, Ruczinski I, Salomaa V, Viikari J, Willemsen G, Barnes KC, Boerwinkle E, Boomsma DI, Caporaso N, Edenberg HJ, Francks C, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Johannesson M, Kendler KS, Lehtimaki T, Magnusson PK, Marazita ML, Marchini J, Mitchell BD, Nothen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Schwartz AG, Shete S, Spitz M, Swan GE, Volzke H, Veijola J, Wei Q, Amos C, Cannon DS, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Weiss RB, Kraft P, Bierut LJ, Ehringer MA (- 116) Ref: Genet Epidemiol, 37:846, 2013 : PubMed ESTHER: Stephens_2013_Genet.Epidemiol_37_846 PubMedSearch: Stephens 2013 Genet.Epidemiol 37 846 PubMedID: 24186853 Abstract Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype. Title: Targeting the Metastasis Suppressor, NDRG1, Using Novel Iron Chelators: Regulation of Stress Fiber-Mediated Tumor Cell Migration via Modulation of the ROCK1/pMLC2 Signaling Pathway Sun J, Zhang D, Zheng Y, Zhao Q, Zheng M, Kovacevic Z, Richardson DR Ref: Molecular Pharmacology, 83:454, 2013 : PubMed ESTHER: Sun_2013_Mol.Pharmacol_83_454 PubMedSearch: Sun 2013 Mol.Pharmacol 83 454 PubMedID: 23188716 Abstract The iron-regulated metastasis suppressor, N-myc downstream-regulated gene 1 (NDRG1), is up-regulated by cellular iron depletion mediated by iron chelators and can inhibit cancer cell migration. However, the mechanism of how NDRG1 achieves this effect remains unclear. In this study, we implemented established and newly constructed NDRG1 overexpression and knockdown models using the DU145, HT29, and HCT116 cancer cell lines to investigate the molecular basis by which NDRG1 exerts its inhibitory effect on cell migration. Using these models, we demonstrated that NDRG1 overexpression inhibits cell migration by preventing actin-filament polymerization, stress fiber assembly and formation. In contrast, NDRG1 knockdown had the opposite effect. Moreover, we identified that NDRG1 inhibited an important regulatory pathway mediated by the Rho-associated, coiled-coil containing protein kinase 1 (ROCK1)/phosphorylated myosin light chain 2 (pMLC2) pathway that modulates stress fiber assembly. The phosphorylation of MLC2 is a key process in inducing stress fiber contraction, and this was shown to be markedly decreased or increased by NDRG1 overexpression or knockdown, respectively. The mechanism involved in the inhibition of MLC2 phosphorylation by NDRG1 was mediated by a significant (P < 0.001) decrease in ROCK1 expression that is a key kinase involved in MLC2 phosphorylation. Considering that NDRG1 is up-regulated after cellular iron depletion, novel thiosemicarbazone iron chelators (e.g., di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone) were demonstrated to inhibit ROCK1/pMLC2-modulated actin-filament polymerization, stress fiber assembly, and formation via a mechanism involving NDRG1. These results highlight the role of the ROCK1/pMLC2 pathway in the NDRG1-mediated antimetastatic signaling network and the therapeutic potential of iron chelators at inhibiting metastasis. Title: Basic fibroblast growth factor attenuates the degeneration of injured spinal cord motor endplates Wang J, Sun J, Tang Y, Guo G, Zhou X, Chen Y, Shen M Ref: Neural Regen Res, 8:2213, 2013 : PubMed ESTHER: Wang_2013_Neural.Regen.Res_8_2213 PubMedSearch: Wang 2013 Neural.Regen.Res 8 2213 PubMedID: 25206531 Abstract The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen's method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through attenuating the decreased expression of calcitonin gene related peptide and acetylcholinesterase in anterior horn motor neurons of the injured spinal cord. Title: Tacrine-ferulic acid-nitric oxide (NO) donor trihybrids as potent, multifunctional acetyl- and butyrylcholinesterase inhibitors Chen Y, Sun J, Fang L, Liu M, Peng S, Liao H, Lehmann J, Zhang Y Ref: Journal of Medicinal Chemistry, 55:4309, 2012 : PubMed ESTHER: Chen_2012_J.Med.Chem_55_4309 PubMedSearch: Chen 2012 J.Med.Chem 55 4309 PubMedID: 22512543 Abstract In search of multifunctional cholinesterase inhibitors as potential anti-Alzheimer drug candidates, tacrine-ferulic acid-NO donor trihybrids were synthesized and tested for their cholinesterase inhibitory activities, release of nitric oxide, vasodilator properties, cognition improving potency, and hepatotoxicity. All of the novel target compounds show higher in vitro cholinesterase inhibitory activity than tacrine. Three selected compounds (3a, 3f, and 3k) produce moderate vasorelaxation in vitro, which correlates with the release of nitric oxide. Compared to its non-nitrate dihybrid analogue (3u), the trihybrid 3f exhibits better performance in improving the scopolamine-induced cognition impairment (mice) and, furthermore, less hepatotoxicity than tacrine. Title: Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH and Bierut LJ <142 more author(s)> Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH, Sun J, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Geller F, Gubjartsson D, Hansel NN, Jiang C, Keskitalo-Vuokko K, Liu Z, Lyytikainen LP, Michel M, Rawal R, Rosenberger A, Scheet P, Shaffer JR, Teumer A, Thompson JR, Vink JM, Vogelzangs N, Wenzlaff AS, Wheeler W, Xiao X, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty T, Bennett S, Bergen AW, Boyd HA, Broms U, Campbell H, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick DM, Foroud T, Furberg H, Giegling I, Gu F, Hall AS, Hallfors J, Han S, Hartmann AM, Hayward C, Heikkila K, Hewitt JK, Hottenga JJ, Jensen MK, Jousilahti P, Kaakinen M, Kittner SJ, Konte B, Korhonen T, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Muley T, Murray T, Nauck M, North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Ruczinski I, Rudan I, Salomaa V, Schlessinger D, Styrkarsdottir U, Terracciano A, Uda M, Willemsen G, Wu X, Abecasis G, Barnes K, Bickeboller H, Boerwinkle E, Boomsma DI, Caporaso N, Duan J, Edenberg HJ, Francks C, Gejman PV, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Viikari J, Kahonen M, Kendler KS, Lehtimaki T, Levinson DF, Marazita ML, Marchini J, Melbye M, Mitchell BD, Murray JC, Nothen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Sanders AR, Schwartz AG, Shete S, Shi J, Spitz M, Stefansson K, Swan GE, Thorgeirsson T, Volzke H, Wei Q, Wichmann HE, Amos CI, Breslau N, Cannon DS, Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Stitzel JA, Weiss RB, Kraft P, Bierut LJ (- 142) Ref: Arch Gen Psychiatry, 69:854, 2012 : PubMed ESTHER: Hartz_2012_Arch.Gen.Psychiatry_69_854 PubMedSearch: Hartz 2012 Arch.Gen.Psychiatry 69 854 PubMedID: 22868939 Abstract CONTEXT: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY SELECTION: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION: Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD </=10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset </=16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. DATA SYNTHESIS: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). CONCLUSION: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. Title: A highly sensitive gold-nanoparticle-based assay for acetylcholinesterase in cerebrospinal fluid of transgenic mice with Alzheimer's disease Liu D, Chen W, Tian Y, He S, Zheng W, Sun J, Wang Z, Jiang X Ref: Adv Healthc Mater, 1:90, 2012 : PubMed ESTHER: Liu_2012_Adv.Healthc.Mater_1_90 PubMedSearch: Liu 2012 Adv.Healthc.Mater 1 90 PubMedID: 23184691 Abstract A highly sensitive, selective, and dual-readout (colorimetric and fluorometric) assay for acetylcholinesterase (AChE) based on Rhodamine B-modified gold nanoparticle is reported. Due to its good sensitivity and selectivity, the assay can be used for monitoring AChE levels in the cerebrospinal fluid of transgenic mice with Alzheimer's disease. Title: Dipeptidyl peptidases as survival factors in Ewing sarcoma family of tumors: implications for tumor biology and therapy Lu C, Tilan JU, Everhart L, Czarnecka M, Soldin SJ, Mendu DR, Jeha D, Hanafy J, Lee CK and Kitlinska J <3 more author(s)> Lu C, Tilan JU, Everhart L, Czarnecka M, Soldin SJ, Mendu DR, Jeha D, Hanafy J, Lee CK, Sun J, Izycka-Swieszewska E, Toretsky JA, Kitlinska J (- 3) Ref: Journal of Biological Chemistry, 286:27494, 2011 : PubMed ESTHER: Lu_2011_J.Biol.Chem_286_27494 PubMedSearch: Lu 2011 J.Biol.Chem 286 27494 PubMedID: 21680731 Abstract Ewing sarcoma family of tumors (ESFT) is a group of aggressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription factor up-regulating specific target genes, such as neuropeptide Y (NPY) and its Y1 and Y5 receptors (Y5Rs). Previously, we have shown that both exogenous NPY and endogenous NPY stimulate ESFT cell death via its Y1 and Y5Rs. Here, we demonstrate that this effect is prevented by dipeptidyl peptidases (DPPs), which cleave NPY to its shorter form, NPY(3-36), not active at Y1Rs. We have shown that NPY-induced cell death can be abolished by overexpression of DPPs and enhanced by their down-regulation. Both NPY treatment and DPP blockade activated the same cell death pathway mediated by poly(ADP-ribose) polymerase (PARP-1) and apoptosis-inducing factor (AIF). Moreover, the decrease in cell survival induced by DPP inhibition was blocked by Y1 and Y5R antagonists, confirming its dependence on endogenous NPY. Interestingly, similar levels of NPY-driven cell death were achieved by blocking membrane DPPIV and cytosolic DPP8 and DPP9. Thus, this is the first evidence of these intracellular DPPs cleaving releasable peptides, such as NPY, in live cells. In contrast, another membrane DPP, fibroblast activation protein (FAP), did not affect NPY actions. In conclusion, DPPs act as survival factors for ESFT cells and protect them from cell death induced by endogenous NPY. This is the first demonstration that intracellular DPPs are involved in regulation of ESFT growth and may become potential therapeutic targets for these tumors. Title: Genome sequence of the thermophilic strain Bacillus coagulans 2-6, an efficient producer of high-optical-purity L-lactic acid Su F, Yu B, Sun J, Ou HY, Zhao B, Wang L, Qin J, Tang H, Tao F and Xu P <4 more author(s)> Su F, Yu B, Sun J, Ou HY, Zhao B, Wang L, Qin J, Tang H, Tao F, Jarek M, Scharfe M, Ma C, Ma Y, Xu P (- 4) Ref: Journal of Bacteriology, 193:4563, 2011 : PubMed ESTHER: Su_2011_J.Bacteriol_193_4563 PubMedSearch: Su 2011 J.Bacteriol 193 4563 PubMedID: 21705584 Gene_locus related to this paper: bacc6-f7z0w1, bacco-c1p801, bacco-g2tqg6 Abstract Bacillus coagulans 2-6 is an efficient producer of lactic acid. The genome of B. coagulans 2-6 has the smallest genome among the members of the genus Bacillus known to date. The frameshift mutation at the start of the d-lactate dehydrogenase sequence might be responsible for the production of high-optical-purity l-lactic acid. Title: [Correlation research of isolated liver tissue pathology and clinical diagnosis in patients with chronic severe hepatitis B] Sun J, Yu HW, Liu Z, Liu H, Zhang Q, Yao QW, Feng YM, Li J, Meng QH Ref: Zhonghua Gan Zang Bing Za Zhi, 19:603, 2011 : PubMed ESTHER: Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603 PubMedSearch: Sun 2011 Zhonghua.Gan.Zang.Bing.Za.Zhi 19 603 PubMedID: 22152318 Abstract To study the coincidence rate of clinical diagonisis with pathological diagnosis for chronic severe hepatitis, and to screen out clinical indicators consistent with pathological diagnosis. Fifty-one patients diagnosed as chronic severe hepatitis and underwent liver transplantation in Beijing You'an hospital from November 2004 to June 2009 participated in this study. The clinical data were selected as following: ALT, AST, urea nitrogen, creatinine, glucose, cholinesterase, total cholesterol, Glutamyl endopeptidase, alkaline phosphatase, serum potassium, serum sodium, prothrombin activity and blood ammonia level. The width of the portal vein and splenic vein thickness were measured by color Doppler ultrasound and were compared in different groups. Data were ananlyzed with independent sample t test and F test. The coincidence rate between clinical and pathological diagnoses in this study was 64.7%. ALT and AST levels for Chronic severe hepatitis and decompensated cirrhosis were 675.0+/-510.0 U/L, 67.00+/-45.0 U/L ( P is less than to 0.01) and 392.0 +/-370.0 U/L, 103.0+/-59.0 U/L (P is less than to 0.01) respectively, with statistically significant difference existed. The mean level of ALT in Chronic severe hepatitis group was significantly different in the situations of onset less than 30 days or more than 30 days (means were 761.0+/-743.0 U/L and 117.0+/-112.0 U/L, P is less than to 0.01). The rate of the phenomenon of enzyme isolated bile in the chronic severe hepatitis and decompensated cirrhosis group were 78.9% and 0 respectively. The coincidence rate of clinical with pathological diagnoses for Chronic Severe Hepatitis was low, increased ALT and AST levels would help improve the diagnostic accuracy. Title: Inheritance of resistance to a new non-steroidal ecdysone agonist, fufenozide, in the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae) Sun J, Liang P, Gao X Ref: Pest Manag Sci, 66:406, 2010 : PubMed ESTHER: Sun_2010_Pest.Manag.Sci_66_406 PubMedSearch: Sun 2010 Pest.Manag.Sci 66 406 PubMedID: 19960491 Abstract BACKGROUND: The diamondback moth (DBM), Plutella xylostella (L.), is a cosmopolitan pest of cruciferous crops. Fufenozide, a novel non-steroidal ecdysone agonist, exhibits good efficacy and plays an increasingly important role in the control of Lepidopterous pests in China. A laboratory strain of DBM was selected for resistance to fufenozide, and the genetic basis of resistance was studied. RESULTS: The resistant strain, selected under laboratory conditions, exhibited a higher level of resistance to fufenozide (302.8-fold based on LC(50)s) than the laboratory susceptible strain. Mortality data from the testing of F(1) progeny of reciprocal crosses of resistant and susceptible DBM indicated that resistance was autosomal and incompletely recessive with a degree of dominance of -0.664. Chi-square analysis from responses of a backcross of crossed F(1) progeny and the resistant strain and F(2) progeny were highly significant, suggesting that the resistance was probably controlled by more than one gene. The estimated realised heritability (h(2)) of fufenozide resistance was 0.08, indicating that diamondback moth may have a lower chance of developing resistance to fufenozide than other kinds of insecticide. CONCLUSION: The resistance of DBM to fufenozide might be autosomal and incompletely recessive, and the resistance is probably controlled by more than one gene. These results provide the basic information for pest management programmes. Title: Immobilization of Candida antarctica lipase B by adsorption in organic medium Sun J, Jiang Y, Zhou L, Gao J Ref: N Biotechnol, 27:53, 2010 : PubMed ESTHER: Sun_2010_N.Biotechnol_27_53 PubMedSearch: Sun 2010 N.Biotechnol 27 53 PubMedID: 20004754 Abstract Candida antarctica lipase B (CALB) was immobilized on the macroporous resin by physical adsorption in organic medium. The immobilization was performed in 5 mL isooctane, and the immobilization conditions were optimized. The results were achieved with the mass ratio of lipase to support 1:80, the buffer of pH 6.0, initial addition of PBS 75 microL, and immobilization time of two hours at 30 degrees C. Under the optimal conditions, the activity recovery was 83.3%. IM-CALB presented enhanced pH and thermal stability compared to the free lipase, and showed comparable stability with the commercial Novozym 435, after 7 times repeated use for catalyzing the synthesis of ethyl lactate, 56.9% of its initial activity was retained, and only 24.7% was retained when used for catalyzing the hydrolysis of olive oil. Title: Specificity of a prodrug-activating enzyme hVACVase: the leaving group effect Sun J, Dahan A, Walls ZF, Lai L, Lee KD, Amidon GL Ref: Mol Pharm, 7:2362, 2010 : PubMed ESTHER: Sun_2010_Mol.Pharm_7_2362 PubMedSearch: Sun 2010 Mol.Pharm 7 2362 PubMedID: 21028903 Gene_locus related to this paper: human-BPHL Abstract Human valacyclovirase (hVACVase) is a prodrug-activating enzyme for amino acid prodrugs including the antiviral drugs valacyclovir and valganciclovir. In hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, making the leaving group effect essential for the rational design of new prodrugs targeting hVACVase activation. In this study, a series of valine esters, phenylalanine esters, and a valine amide were characterized for the effect of the leaving group on the efficiency of hVACVase-mediated prodrug activation. Except for phenylalanine methyl and ethyl esters, all of the ester substrates exhibited a relatively high specificity constant (k(cat)/K(m)), ranging from 850 to 9490 mM(-1).s(-1). The valine amide Val-3-APG exhibited significantly higher K(m) and lower k(cat) values compared to the corresponding ester Val-3-HPG, indicating poor specificity for hVACVase. In conclusion, the substrate leaving group has been shown to affect both binding and specific activity of hVACVase-catalyzed activation. It is proposed that hVACVase is an ideal target for alpha-amino acid ester prodrugs with relatively labile leaving groups while it is relatively inactivate toward amide prodrugs. Title: Study of paraoxonase-1 function on tissue damage of dichlorvos Wang NN, Dai H, Yuan L, Han ZK, Sun J, Zhang Z, Zhao M Ref: Toxicol Lett, 196:125, 2010 : PubMed ESTHER: Wang_2010_Toxicol.Lett_196_125 PubMedSearch: Wang 2010 Toxicol.Lett 196 125 PubMedID: 20412842 Abstract To examine the protective efficacy of paraoxonase-1 (PON1) against tissue damage caused by dichlorvos, purified rabbit PON1 was injected intravenously into rats 30min before they were given dichlorvos, while dichlorvos administration group and corn coil administration group were conducted to compare. Blood was collected at different time points after dichlorvos administration to examine the acetyl cholinesterase (AChE) inhibition level and clinical signs were observed after poisoning. 72h later, animals were anesthetized and the hippocampus, liver, lung and kidney were removed for observation of ultrastructure. AChE activities in PON1 pretreament group were statistically significant from dichlorvos administration group (P<0.01). The clinical signs were alleviated by PON1 significantly (P<0.05). The most common change of organophosphorus poisoning damage to liver was small lipid-like structures could be seen throughout the liver structure. In kidney, dense bodies were seen. The most significant changes in lung were lost of lamellar structure of lamellar bodies in type II alveolar epithelial cell. As for changes of hippocampus, demyaliation takes place after acute organophosphorus, but neural edema was not improved significantly in our study. In conclusion, PON1 can decrease the AChE inhibition, and alleviated clinical signs and tissue damage caused by dichlorvos. Title: lip2, a novel lipase gene cloned from Aspergillus niger exhibits enzymatic characteristics distinct from its previously identified family member Yang J, Sun J, Yan Y Ref: Biotechnol Lett, 32:951, 2010 : PubMed ESTHER: Yang_2010_Biotechnol.Lett_32_951 PubMedSearch: Yang 2010 Biotechnol.Lett 32 951 PubMedID: 20213520 Abstract We have cloned a novel lipase gene, lip2, from Aspergillus niger and expressed it in Escherichia coli. Upon purification of the recombinant Lip2 protein, its properties were characterized. In comparison with a previously identified lipase Lip1, both enzymes are acid lipases (optimal pH <6.5), Ca(2+)-dependent and PMSF-sensitive, but have different molecular weights (35 and 43 kDa), optimal substrate spectra (C10 and C8), optimal reaction temperatures (45 and 50 degrees C) and thermal stability. Circular dichroism spectroscopy revealed that Lip2 contains a typical Ca(2+)-active site. This first report on the cloning of the Lip2 gene and its enzymatic characteristics may greatly facilitate its potential industrial application. Title: Genome sequence of Azotobacter vinelandii, an obligate aerobe specialized to support diverse anaerobic metabolic processes Setubal JC, dos Santos P, Goldman BS, Ertesvag H, Espin G, Rubio LM, Valla S, Almeida NF, Balasubramanian D and Wood D <34 more author(s)> Setubal JC, dos Santos P, Goldman BS, Ertesvag H, Espin G, Rubio LM, Valla S, Almeida NF, Balasubramanian D, Cromes L, Curatti L, Du Z, Godsy E, Goodner B, Hellner-Burris K, Hernandez JA, Houmiel K, Imperial J, Kennedy C, Larson TJ, Latreille P, Ligon LS, Lu J, Maerk M, Miller NM, Norton S, O'Carroll IP, Paulsen I, Raulfs EC, Roemer R, Rosser J, Segura D, Slater S, Stricklin SL, Studholme DJ, Sun J, Viana CJ, Wallin E, Wang B, Wheeler C, Zhu H, Dean DR, Dixon R, Wood D (- 34) Ref: Journal of Bacteriology, 191:4534, 2009 : PubMed ESTHER: Setubal_2009_J.Bacteriol_191_4534 PubMedSearch: Setubal 2009 J.Bacteriol 191 4534 PubMedID: 19429624 Gene_locus related to this paper: azovd-c1dex6, azovd-c1df21, azovd-c1dfb5, azovd-c1dg75, azovd-c1dgm6, azovd-c1dh91, azovd-c1di03, azovd-c1dib3, azovd-c1dif2, azovd-c1dIq5, azovd-c1dir1, azovd-c1dis2, azovd-c1djq5, azovd-c1djw3, azovd-c1dk37, azovd-c1dkb2, azovd-c1dkj0, azovd-c1dli6, azovd-c1dng8, azovd-c1dni5, azovd-c1dpr0, azovd-c1dqu3, azovd-c1dri5, azovd-c1drx0, azovd-c1dsl7, azovd-c1dsq7, azovd-c1dss1, azovd-metx, azovi-PHBC, azovd-c1dem4 Abstract Azotobacter vinelandii is a soil bacterium related to the Pseudomonas genus that fixes nitrogen under aerobic conditions while simultaneously protecting nitrogenase from oxygen damage. In response to carbon availability, this organism undergoes a simple differentiation process to form cysts that are resistant to drought and other physical and chemical agents. Here we report the complete genome sequence of A. vinelandii DJ, which has a single circular genome of 5,365,318 bp. In order to reconcile an obligate aerobic lifestyle with exquisitely oxygen-sensitive processes, A. vinelandii is specialized in terms of its complement of respiratory proteins. It is able to produce alginate, a polymer that further protects the organism from excess exogenous oxygen, and it has multiple duplications of alginate modification genes, which may alter alginate composition in response to oxygen availability. The genome analysis identified the chromosomal locations of the genes coding for the three known oxygen-sensitive nitrogenases, as well as genes coding for other oxygen-sensitive enzymes, such as carbon monoxide dehydrogenase and formate dehydrogenase. These findings offer new prospects for the wider application of A. vinelandii as a host for the production and characterization of oxygen-sensitive proteins. Title: Genome sequences of three agrobacterium biovars help elucidate the evolution of multichromosome genomes in bacteria Slater SC, Goldman BS, Goodner B, Setubal JC, Farrand SK, Nester EW, Burr TJ, Banta L, Dickerman AW and Wood DW <26 more author(s)> Slater SC, Goldman BS, Goodner B, Setubal JC, Farrand SK, Nester EW, Burr TJ, Banta L, Dickerman AW, Paulsen I, Otten L, Suen G, Welch R, Almeida NF, Arnold F, Burton OT, Du Z, Ewing A, Godsy E, Heisel S, Houmiel KL, Jhaveri J, Lu J, Miller NM, Norton S, Chen Q, Phoolcharoen W, Ohlin V, Ondrusek D, Pride N, Stricklin SL, Sun J, Wheeler C, Wilson L, Zhu H, Wood DW (- 26) Ref: J. Bacteriol, 191:2501, 2009 : PubMed ESTHER: Slater_2009_J.Bacteriol_191_2501 PubMedSearch: Slater 2009 J.Bacteriol 191 2501 PubMedID: 19251847 Gene_locus related to this paper: agrrk-b9j7k2, agrrk-b9j8e4, agrrk-b9j8g5, agrrk-b9j9n4, agrrk-b9j9p4, agrrk-b9ja88, agrrk-b9jbs5, agrrk-b9jd67, agrrk-b9jd85, agrrk-b9jfh5, agrrk-b9jfj6, agrrk-b9jfu6, agrrk-b9jfy6, agrrk-b9jh78, agrrk-b9ji04, agrrk-b9jih5, agrrk-b9jih7, agrrk-b9jj14, agrrk-b9jjt5, agrrk-b9jjt6, agrrk-b9jk42, agrrk-b9jki6, agrrk-b9jkt4, agrrk-b9jla0, agrrk-b9jlc3, agrrk-b9jlj1, agrrk-b9jlj2, agrrk-b9jlr1, agrrk-b9jmj9, agrrk-b9jml0, agrrk-b9jmn1, agrrk-b9jnw6, agrrk-b9jq01, agrrk-b9jq11, agrrk-b9jq35, agrtu-DHAA, agrvs-b9jqv2, agrvs-b9jr09, agrvs-b9js24, agrvs-b9js61, agrvs-b9ju03, agrvs-b9jw40, agrvs-b9jx20, agrvs-b9jy84, agrvs-b9k1h8, agrvs-b9k2m9, agrvs-b9k3r6, agrvs-b9k5p9, agrvs-b9k093, agrvs-b9k188, agrvs-b9k312, agrrk-b9jls9, agrrk-b9jca1, agrvs-b9jur1, agrrk-rutd Abstract The family Rhizobiaceae contains plant-associated bacteria with critical roles in ecology and agriculture. Within this family, many Rhizobium and Sinorhizobium strains are nitrogen-fixing plant mutualists, while many strains designated as Agrobacterium are plant pathogens. These contrasting lifestyles are primarily dependent on the transmissible plasmids each strain harbors. Members of the Rhizobiaceae also have diverse genome architectures that include single chromosomes, multiple chromosomes, and plasmids of various sizes. Agrobacterium strains have been divided into three biovars, based on physiological and biochemical properties. The genome of a biovar I strain, A. tumefaciens C58, has been previously sequenced. In this study, the genomes of the biovar II strain A. radiobacter K84, a commercially available biological control strain that inhibits certain pathogenic agrobacteria, and the biovar III strain A. vitis S4, a narrow-host-range strain that infects grapes and invokes a hypersensitive response on nonhost plants, were fully sequenced and annotated. Comparison with other sequenced members of the Alphaproteobacteria provides new data on the evolution of multipartite bacterial genomes. Primary chromosomes show extensive conservation of both gene content and order. In contrast, secondary chromosomes share smaller percentages of genes, and conserved gene order is restricted to short blocks. We propose that secondary chromosomes originated from an ancestral plasmid to which genes have been transferred from a progenitor primary chromosome. Similar patterns are observed in select Beta- and Gammaproteobacteria species. Together, these results define the evolution of chromosome architecture and gene content among the Rhizobiaceae and support a generalized mechanism for second-chromosome formation among bacteria. Title: Development of a LC/MS/MS method to analyze butyrylcholinesterase inhibition resulting from multiple pesticide exposure Sun J, Lynn BC Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 877:3681, 2009 : PubMed ESTHER: Sun_2009_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_877_3681 PubMedSearch: Sun 2009 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 877 3681 PubMedID: 19783488 Abstract A hybrid LC/MS/MS and proteomics method was developed for the assessment of multiple pesticide exposure. The methodology was based on the analysis of tryptic peptides resulting from inhibited butyrylcholinesterase (BChE) after exposure to pesticides including organophosphates (OPs) and carbamates (CBs). The primary advantage of the assay was its ability to simultaneously examine multiple pesticide exposures in a single analytical experiment. Application of tandem and MS(3) techniques provided identities of the inhibiting pesticide, confirmation and localization of the site of inhibition and relative quantification of phosphorylated peptides present in tryptic digests of equine BChE (eBChE). Title: The 2008 update of the Aspergillus nidulans genome annotation: a community effort Wortman JR, Gilsenan JM, Joardar V, Deegan J, Clutterbuck J, Andersen MR, Archer D, Bencina M, Braus G and Turner G <76 more author(s)> Wortman JR, Gilsenan JM, Joardar V, Deegan J, Clutterbuck J, Andersen MR, Archer D, Bencina M, Braus G, Coutinho P, von Dohren H, Doonan J, Driessen AJ, Durek P, Espeso E, Fekete E, Flipphi M, Estrada CG, Geysens S, Goldman G, de Groot PW, Hansen K, Harris SD, Heinekamp T, Helmstaedt K, Henrissat B, Hofmann G, Homan T, Horio T, Horiuchi H, James S, Jones M, Karaffa L, Karanyi Z, Kato M, Keller N, Kelly DE, Kiel JA, Kim JM, van der Klei IJ, Klis FM, Kovalchuk A, Krasevec N, Kubicek CP, Liu B, Maccabe A, Meyer V, Mirabito P, Miskei M, Mos M, Mullins J, Nelson DR, Nielsen J, Oakley BR, Osmani SA, Pakula T, Paszewski A, Paulsen I, Pilsyk S, Pocsi I, Punt PJ, Ram AF, Ren Q, Robellet X, Robson G, Seiboth B, van Solingen P, Specht T, Sun J, Taheri-Talesh N, Takeshita N, Ussery D, vanKuyk PA, Visser H, van de Vondervoort PJ, de Vries RP, Walton J, Xiang X, Xiong Y, Zeng AP, Brandt BW, Cornell MJ, van den Hondel CA, Visser J, Oliver SG, Turner G (- 76) Ref: Fungal Genet Biol, 46 Suppl 1:S2, 2009 : PubMed ESTHER: Wortman_2009_Fungal.Genet.Biol_46 Suppl 1_S2 PubMedSearch: Wortman 2009 Fungal.Genet.Biol 46 Suppl 1 S2 PubMedID: 19146970 Gene_locus related to this paper: emeni-axe1, emeni-c8v4m7, emeni-faec, emeni-ppme1, emeni-q5ara9, emeni-q5arf0, emeni-q5as30, emeni-q5ase8, emeni-q5av79, emeni-q5aw09, emeni-q5awc3, emeni-q5awc7, emeni-q5awu9, emeni-q5aww4, emeni-q5ax50, emeni-q5ay37, emeni-q5ay57, emeni-q5ay59, emeni-q5ayk9, emeni-q5ays5, emeni-q5az32, emeni-q5az91, emeni-q5az97, emeni-q5azp1, emeni-q5b0i6, emeni-q5b1h2, emeni-q5b2a9, emeni-q5b2p7, emeni-q5b3d2, emeni-q5b4q7, emeni-q5b5u7, emeni-q5b5y4, emeni-q5b9e7, emeni-q5b9i0, emeni-q5b364, emeni-q5b446, emeni-q5b938, emeni-q5ba78, emeni-q5bcd1, emeni-q5bcd2, emeni-q5bde7, emeni-q5bdr0, emeni-q5bf92, emeni-q7si80, emeni-q5bdv9, emeni-c8vu15, 9euro-a0a3d8t644, emeni-q5b719, emeni-q5ax97, emeni-tdia, emeni-afoc, emeni-dbae Abstract The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. Title: Complete genome of Phenylobacterium zucineum--a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562 Luo Y, Xu X, Ding Z, Liu Z, Zhang B, Yan Z, Sun J, Hu S, Hu X Ref: BMC Genomics, 9:386, 2008 : PubMed ESTHER: Luo_2008_BMC.Genomics_9_386 PubMedSearch: Luo 2008 BMC.Genomics 9 386 PubMedID: 18700039 Gene_locus related to this paper: phezh-b4r8z3, phezh-b4r801, phezh-b4r876, phezh-b4ras1, phezh-b4ras4, phezh-b4ray3, phezh-b4rb44, phezh-b4rd51, phezh-b4re02, phezh-b4rfb7, phezh-b4rfk3, phezh-b4rfq9, phezh-b4rfw5, phezh-b4rgf2, phezh-b4rh78, phezh-b4rh88, phezh-b4rhb1, phezh-b4rhb2, phezh-dhma, phezh-b4r875, phezh-b4rfb8, phezh-b4rbt7 Abstract BACKGROUND: Phenylobacterium zucineum is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, P. zucineum maintains a stable association with its host cell without affecting the growth and morphology of the latter. RESULTS: Here, we report the whole genome sequence of the type strain HLK1T. The genome consists of a circular chromosome (3,996,255 bp) and a circular plasmid (382,976 bp). It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to Caulobacter crescentus, a model species for cell cycle research. Notably, P. zucineum has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of C. crescentus, and most of the genes directly regulated by CtrA in the latter have orthologs in the former. CONCLUSION: This work presents the first complete bacterial genome in the genus Phenylobacterium. Comparative genomic analysis indicated that the CtrA regulon is well conserved between C. crescentus and P. zucineum. Title: Controlled release of huperzine A from biodegradable microspheres: In vitro and in vivo studies Gao P, Xu H, Ding P, Gao Q, Sun J, Chen D Ref: Int J Pharm, 330:1, 2007 : PubMed ESTHER: Gao_2007_Int.J.Pharm_330_1 PubMedSearch: Gao 2007 Int.J.Pharm 330 1 PubMedID: 16987624 Abstract The objective of the present work was to further study the in vitro characteristics, in vivo pharmacokinetics and pharmacodynamics of huperzine A (HupA) loaded biodegradable microspheres designed for sustained release of HupA over several weeks. A conventional o/w emulsion-solvent evaporation method was used to incorporate HupA, which is of interest in the palliative treatment of Alzheimer's disease (AD), into end-group uncapped poly(D,L-lactide-co-glycolide) (PLG-H). A prolonged in vitro drug release profile was observed, with a complete release of the incorporated drug within 5-6 weeks. The in vivo pharmacokinetics study of HupA loaded microspheres showed sustained plasma HupA concentration-time profile after subcutaneous injection into rats. The pharmacodynamics evaluated by determination of the activity of acetylcholinesterase in the rat cortex also showed a prolonged pharmacological response. Both the in vitro release and in vivo pharmacological responses correlated well with the in vivo pharmacokinetics profile. The results suggest the potential use of HupA-loaded biodegradable microspheres for treatment of AD over long periods. Title: Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88 Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, Schaap PJ, Turner G, de Vries RP, Albang R and Stam H <59 more author(s)> Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, Schaap PJ, Turner G, de Vries RP, Albang R, Albermann K, Andersen MR, Bendtsen JD, Benen JA, van den Berg M, Breestraat S, Caddick MX, Contreras R, Cornell M, Coutinho PM, Danchin EG, Debets AJ, Dekker P, van Dijck PW, van Dijk A, Dijkhuizen L, Driessen AJ, d'Enfert C, Geysens S, Goosen C, Groot GS, de Groot PW, Guillemette T, Henrissat B, Herweijer M, van den Hombergh JP, van den Hondel CA, van der Heijden RT, van der Kaaij RM, Klis FM, Kools HJ, Kubicek CP, van Kuyk PA, Lauber J, Lu X, van der Maarel MJ, Meulenberg R, Menke H, Mortimer MA, Nielsen J, Oliver SG, Olsthoorn M, Pal K, van Peij NN, Ram AF, Rinas U, Roubos JA, Sagt CM, Schmoll M, Sun J, Ussery D, Varga J, Vervecken W, van de Vondervoort PJ, Wedler H, Wosten HA, Zeng AP, van Ooyen AJ, Visser J, Stam H (- 59) Ref: Nat Biotechnol, 25:221, 2007 : PubMed ESTHER: Pel_2007_Nat.Biotechnol_25_221 PubMedSearch: Pel 2007 Nat.Biotechnol 25 221 PubMedID: 17259976 Gene_locus related to this paper: aspna-g3yal2, aspnc-a2q8r7, aspnc-a2q814, aspnc-a2qb93, aspnc-a2qbd3, aspnc-a2qbh3, aspnc-a2qbx7, aspnc-a2qdj6, aspnc-a2qe77, aspnc-a2qf54, aspnc-a2qfe9, aspnc-a2qg33, aspnc-a2qgj6, aspnc-a2qgm6, aspnc-a2qh52, aspnc-a2qh76, aspnc-a2qh85, aspnc-a2qhe2, aspnc-a2qi32, aspnc-a2qib2, aspnc-a2qk14, aspnc-a2ql23, aspnc-a2ql89, aspnc-a2ql90, aspnc-a2qla0, aspnc-a2qlz0, aspnc-a2qm14, aspnc-a2qmk5, aspnc-a2qms0, aspnc-a2qn29, aspnc-a2qn56, aspnc-a2qn70, aspnc-a2qnw9, aspnc-a2qr21, aspnc-a2qs22, aspnc-a2qt50, aspnc-a2qti9, aspnc-a2qtz0, aspnc-a2quc1, aspnc-a2qw06, aspnc-a2qwz6, aspnc-a2qx92, aspnc-a2qyf0, aspnc-a2qys7, aspnc-a2qz72, aspnc-a2qzn6, aspnc-a2qzr0, aspnc-a2qzs1, aspnc-a2qzx0, aspnc-a2qzx4, aspnc-a2r0p4, aspnc-a2r0u0, aspnc-a2r1p3, aspnc-a2r1r5, aspnc-a2r2i5, aspnc-a2r2l0, aspnc-a2r3s8, aspnc-a2r4c0, aspnc-a2r4j8, aspnc-a2r5r4, aspnc-a2r6g3, aspnc-a2r6h5, aspnc-a2r6h8, aspnc-a2r7q1, aspnc-a2r8r3, aspnc-a2r8z3, aspnc-a2r9y8, aspnc-a2r032, aspnc-a2r040, aspnc-a2r273, aspnc-a2r496, aspnc-a2r502, aspnc-a2ra07, aspnc-a2rap4, aspnc-a2raq2, aspnc-a2rav1, aspnc-a5aaf4, aspnc-a5ab63, aspnc-a5abc6, aspnc-a5abe5, aspnc-a5abe8, aspnc-a5abf0, aspnc-a5abh9, aspnc-a5abk1, aspnc-a5abt2, aspnc-a5abz1, aspnc-atg15, aspnc-axe1, aspnc-cuti1, aspnc-cuti2, aspnc-faec, aspng-a2q8w0, aspng-a2qs46, aspng-a2qst4, aspng-a2qv27, aspng-a2qzk9, aspng-a2r0p8, aspng-a2r225, aspng-DAPB, aspng-DPP5, aspng-faeb, aspni-APSC, aspni-EstA, aspni-FAEA, aspni-PAPA, aspkw-g7y0v7, aspnc-a2qt47, aspnc-a2qt66, aspnc-a2r199, aspnc-a2r871, aspnc-a2qbp6, aspnc-a2qqa1, aspnc-a2qt70, aspna-g3y5a6, aspna-g3xpw9, aspnc-a2qw57, aspaw-a0a401kcz4, aspna-alba, aspnc-kex1, aspnc-cbpya, aspnc-a2qbg8 Abstract The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis. Title: Development of a MALDI-TOF-MS method to identify and quantify butyrylcholinesterase inhibition resulting from exposure to organophosphate and carbamate pesticides Sun J, Lynn BC Ref: J Am Soc Mass Spectrom, 18:698, 2007 : PubMed ESTHER: Sun_2007_J.Am.Soc.Mass.Spectrom_18_698 PubMedSearch: Sun 2007 J.Am.Soc.Mass.Spectrom 18 698 PubMedID: 17223355 Abstract A novel, proteomics based method was developed for the detection, quantification, and categorization of serum butyrylcholinesterase (BChE) inhibitors, including organophosphates (OPs) and carbamates (CBs). This method was based on the MALDI-TOF-MS analysis of the trypsin generated BChE active site peptide (191-SVTLFGESAGAASVSLHLLSPR-212) previously modified by reaction with an OP or CB. The ionization efficiency of OP modified active site peptides by MALDI was greatly improved by adding diammonium citrate to the MALDI matrix, which made the quantification of OP exposure feasible. Excellent linearity (r2 > 0.98) between the normalized abundance ratios (NARs) and OP concentrations or logarithm of carbaryl concentration was obtained. The accuracy of the developed assay was evaluated by comparison of IC50 and IC100 values from the assay with those determined by the Ellman method. Results from this method were comparable with those from the Ellman method. The advantage of the assay was that both the origin and the extent of pesticide exposure can be determined in one analysis. Our MALDI method can provide critical evidence for the pesticide exposure at low BChE inhibition levels even down to 3%, not available with the Ellman method. Title: Loss of lipoprotein lipase-derived fatty acids leads to increased cardiac glucose metabolism and heart dysfunction Augustus AS, Buchanan J, Park TS, Hirata K, Noh HL, Sun J, Homma S, D'Armiento J, Abel ED, Goldberg IJ Ref: Journal of Biological Chemistry, 281:8716, 2006 : PubMed ESTHER: Augustus_2006_J.Biol.Chem_281_8716 PubMedSearch: Augustus 2006 J.Biol.Chem 281 8716 PubMedID: 16410253 Abstract Long-chain fatty acids (FAs) are the predominant energy substrate utilized by the adult heart. The heart can utilize unesterified FA bound to albumin or FA obtained from lipolysis of lipoprotein-bound triglyceride (TG). We used heart-specific lipoprotein lipase knock-out mice (hLpL0) to test whether these two sources of FA are interchangeable and necessary for optimal heart function. Hearts unable to obtain FA from lipoprotein TG were able to compensate by increasing glucose uptake, glycolysis, and glucose oxidation. HLpL0 hearts had decreased expression of pyruvate dehydrogenase kinase 4 and increased cardiomyocyte expression of glucose transporter 4. Conversely, FA oxidation rates were reduced in isolated perfused hLpL0 hearts. Following abdominal aortic constriction expression levels of genes regulating FA and glucose metabolism were acutely up-regulated in control and hLpL0 mice, yet all hLpL0 mice died within 48 h of abdominal aortic constriction. Older hLpL0 mice developed cardiac dysfunction characterized by decreased fractional shortening and interstitial and perivascular fibrosis. HLpL0 hearts had increased expression of several genes associated with transforming growth factor-beta signaling. Thus, long term reduction of lipoprotein FA uptake is associated with impaired cardiac function despite a compensatory increase in glucose utilization. Title: The genome sequence of the malaria mosquito Anopheles gambiae Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM and Hoffman SL <113 more author(s)> Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chaturverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O'Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, Hoffman SL (- 113) Ref: Science, 298:129, 2002 : PubMed ESTHER: Holt_2002_Science_298_129 PubMedSearch: Holt 2002 Science 298 129 PubMedID: 12364791 Gene_locus related to this paper: anoga-a0nb77, anoga-a0nbp6, anoga-a0neb7, anoga-a0nei9, anoga-a0nej0, anoga-a0ngj1, anoga-a7ut12, anoga-a7uuz9, anoga-ACHE1, anoga-ACHE2, anoga-agCG44620, anoga-agCG44666, anoga-agCG45273, anoga-agCG45279, anoga-agCG45511, anoga-agCG46741, anoga-agCG47651, anoga-agCG47655, anoga-agCG47661, anoga-agCG47690, anoga-agCG48797, anoga-AGCG49362, anoga-agCG49462, anoga-agCG49870, anoga-agCG49872, anoga-agCG49876, anoga-agCG50851, anoga-agCG51879, anoga-agCG52383, anoga-agCG54954, anoga-AGCG55021, anoga-agCG55401, anoga-agCG55408, anoga-agCG56978, anoga-ebiG239, anoga-ebiG2660, anoga-ebiG5718, anoga-ebiG5974, anoga-ebiG8504, anoga-ebiG8742, anoga-glita, anoga-nrtac, anoga-q5tpv0, anoga-Q5TVS6, anoga-q7pm39, anoga-q7ppw9, anoga-q7pq17, anoga-Q7PQT0, anoga-q7q8m4, anoga-q7q626, anoga-q7qa14, anoga-q7qa52, anoga-q7qal7, anoga-q7qbj0, anoga-f5hl20, anoga-q7qkh2, anoga-a0a1s4h1y7, anoga-q7q887 Abstract Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect. Title: [The neuromuscular transmission effects induced by pralidoxine chloride on rats with acute isocarbophos poisoning] Ju Z, Sun J Ref: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 20:425, 2002 : PubMed ESTHER: Ju_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_425 PubMedSearch: Ju 2002 Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi 20 425 PubMedID: 14694590 Inhibitor(s) related to this paper: Isocarbophos Abstract OBJECTIVE: To study the effects of improving the neuromuscular transmission (NMT), "non-AChE-reactivating effects", by oximes in treating acute isocarbophos poisoning. Title: A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG and Stephenson LD <169 more author(s)> Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG, Nadeau J, Salzberg SL, Holt RA, Kodira CD, Lu F, Chen L, Deng Z, Evangelista CC, Gan W, Heiman TJ, Li J, Li Z, Merkulov GV, Milshina NV, Naik AK, Qi R, Shue BC, Wang A, Wang J, Wang X, Yan X, Ye J, Yooseph S, Zhao Q, Zheng L, Zhu SC, Biddick K, Bolanos R, Delcher AL, Dew IM, Fasulo D, Flanigan MJ, Huson DH, Kravitz SA, Miller JR, Mobarry CM, Reinert K, Remington KA, Zhang Q, Zheng XH, Nusskern DR, Lai Z, Lei Y, Zhong W, Yao A, Guan P, Ji RR, Gu Z, Wang ZY, Zhong F, Xiao C, Chiang CC, Yandell M, Wortman JR, Amanatides PG, Hladun SL, Pratts EC, Johnson JE, Dodson KL, Woodford KJ, Evans CA, Gropman B, Rusch DB, Venter E, Wang M, Smith TJ, Houck JT, Tompkins DE, Haynes C, Jacob D, Chin SH, Allen DR, Dahlke CE, Sanders R, Li K, Liu X, Levitsky AA, Majoros WH, Chen Q, Xia AC, Lopez JR, Donnelly MT, Newman MH, Glodek A, Kraft CL, Nodell M, Ali F, An HJ, Baldwin-Pitts D, Beeson KY, Cai S, Carnes M, Carver A, Caulk PM, Center A, Chen YH, Cheng ML, Coyne MD, Crowder M, Danaher S, Davenport LB, Desilets R, Dietz SM, Doup L, Dullaghan P, Ferriera S, Fosler CR, Gire HC, Gluecksmann A, Gocayne JD, Gray J, Hart B, Haynes J, Hoover J, Howland T, Ibegwam C, Jalali M, Johns D, Kline L, Ma DS, MacCawley S, Magoon A, Mann F, May D, McIntosh TC, Mehta S, Moy L, Moy MC, Murphy BJ, Murphy SD, Nelson KA, Nuri Z, Parker KA, Prudhomme AC, Puri VN, Qureshi H, Raley JC, Reardon MS, Regier MA, Rogers YH, Romblad DL, Schutz J, Scott JL, Scott R, Sitter CD, Smallwood M, Sprague AC, Stewart E, Strong RV, Suh E, Sylvester K, Thomas R, Tint NN, Tsonis C, Wang G, Williams MS, Williams SM, Windsor SM, Wolfe K, Wu MM, Zaveri J, Chaturvedi K, Gabrielian AE, Ke Z, Sun J, Subramanian G, Venter JC, Pfannkoch CM, Barnstead M, Stephenson LD (- 169) Ref: Science, 296:1661, 2002 : PubMed ESTHER: Mural_2002_Science_296_1661 PubMedSearch: Mural 2002 Science 296 1661 PubMedID: 12040188 Gene_locus related to this paper: mouse-ABH15, mouse-Ces3b, mouse-Ces4a, mouse-dpp4, mouse-FAP, mouse-Lipg, mouse-Q8C1A9, mouse-rbbp9, mouse-SERHL, mouse-SPG21, mouse-w4vsp6 Abstract The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart. Title: The sequence of the human genome Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264) Ref: Science, 291:1304, 2001 : PubMed ESTHER: Venter_2001_Science_291_1304 PubMedSearch: Venter 2001 Science 291 1304 PubMedID: 11181995 Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21 Abstract A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. Title: Ozone-induced airway hyperresponsiveness: role of superoxide anions, NEP, and BK receptors Tsukagoshi H, Haddad EB, Sun J, Barnes PJ, Chung KF Ref: J Appl Physiol (1985), 78:1015, 1995 : PubMed ESTHER: Tsukagoshi_1995_J.Appl.Physiol.(1985)_78_1015 PubMedSearch: Tsukagoshi 1995 J.Appl.Physiol.(1985) 78 1015 PubMedID: 7775293 Abstract We investigated the role of reactive oxygen species in ozone-induced airway hyperresponsiveness (AHR) in Brown Norway rats. Airway responsiveness to inhaled acetylcholine (ACh) and bradykinin (BK) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were measured in vivo. Neutral endopeptidase (NEP) activity assay and measurement of BK-receptor binding sites in Brown Norway rat lungs were carried out in vitro. Apocynin (5 mg/kg), an inhibitor of superoxide anion-generating NADPH oxidase, was administered perorally 30 min before a 3- or 6-h exposure to 3 ppm of ozone, and the animals were studied 18-24 h postexposure. Ozone induced increases in airway responsiveness to ACh and BK and in neutrophil counts in BALF. Apocynin inhibited the increase in airway responsiveness to BK but not to ACh without affecting the neutrophil counts in BALF. The antioxidants allopurinol and deferoxamine prevented ozone-induced AHR to both ACh and BK but did not reduce neutrophil counts. To further examine the mechanisms of ozone-induced AHR to BK, we measured NEP activity and the density of BK receptors in vitro after ozone exposure. Ozone exposure had no significant effect either on NEP activity or on the affinity and the number of BK receptors in lungs from rats treated with or without apocynin. We conclude that superoxide anions released from inflammatory cells in the airway may be involved in ozone-induced AHR. Inactivation of NEP or upregulation of BK receptors do not appear to be involved, but the possibility of localized changes cannot be excluded. Title: Cloning and sequencing of a cDNA encoding the murine vitamin K-dependent protein S Chu MD, Sun J, Bird P Ref: Biochimica & Biophysica Acta, 6:325, 1994 : PubMed ESTHER: Chu_1994_Biochim.Biophys.Acta_6_325 PubMedSearch: Chu 1994 Biochim.Biophys.Acta 6 325 PubMedID: 8148380 Abstract A cDNA clone encoding the vitamin K-dependent protein S was isolated from a murine liver cDNA library. Sequencing revealed an open reading frame encoding a 634 amino acid mature protein. Comparison to human and bovine sequences showed a high degree of similarity and the conservation of key residues between the species. Title: Effects of prolonged repeated exposure to ovalbumin in sensitized brown Norway rats Haczku A, Moqbel R, Elwood W, Sun J, Kay AB, Barnes PJ, Chung KF Ref: American Journal of Respiratory & Critical Care Medicine, 150:23, 1994 : PubMed ESTHER: Haczku_1994_Am.J.Respir.Crit.Care.Med_150_23 PubMedSearch: Haczku 1994 Am.J.Respir.Crit.Care.Med 150 23 PubMedID: 8025754 Abstract The effects of chronic exposure to ovalbumin (OA) aerosol were studied in Brown Norway rats following intraperitoneal injections with OA and AI(OH)3 and exposure to OA or saline aerosols, once or every third day for 3 to 8 wk. Measurements of airway responsiveness to acetylcholine (ACh) aerosol at 18 to 24 h after allergen exposure showed a significant increase in -logPC150, the concentration of ACh needed to cause a 150% increase in baseline lung resistance, in animals single-exposed or chronic OA-exposed for 3 wk, compared with saline-exposed control animals. The group receiving 8 wk of OA exposure demonstrated no difference from the control animals with -logPC150 lower than that of the two previous groups (p < 0.001). In all three groups, BAL fluid showed a significant increase in neutrophils, but a significant increase in eosinophils (p < 0.01) was only observed in the single-exposed group when compared with saline-exposed control animals. In the 8-wk exposed rats, there was a higher recovery of macrophages and lymphocytes (p < 0.01) compared with control animals and the other two groups. AHR, present after single or 3-wk repeated exposure, disappears by 8 wk of continuous allergen exposure. Both the enhancement and suppression of AHR may be linked to OA-induced immune and inflammatory mechanisms. Title: [The changes in the summating potential and morphology in the cochlea of guinea pigs with anoxia]. [Chinese] Li X, Sun J, Sun W Ref: Chinese Journal of Otorhinolaryngology, 29:74, 1994 : PubMed ESTHER: Li_1994_Chung.Hua.Erh.Pi.Yen.Hou.Ko.Tsa.Chih_29_74 PubMedSearch: Li 1994 Chung.Hua.Erh.Pi.Yen.Hou.Ko.Tsa.Chih 29 74 PubMedID: 7803093 Abstract The dynamic changes in the CAP, SP and EP in the scale media were examined with single micropipet during anoxia and reventilation with oxygen. Also, the morphologic changes in the IHC, OHC and synapse were observed in this experiment. It was found that the amplitude of the SP and EP values declined with alteration in polarity of these value. The changes in polarity and amplitude of the SP followed the changes of CAP threshold induced by anoxia. The histologic examinations revealed no evidence of acetylcholinesterase (AChE) alteration in the synapse and no succinic dehydrogenase (SDH) changes in IHC appeared. However, the activity of SDH in the OHC decreased. The results suggest that the polarity and amplitude of SP were influenced passively by the changes of EP value. In addition, the changes of SP polarity from positive to negative during anoxia is due to the loss of modulation process of OHC to IHC, while the SP polarity from negative to positive during the supply of oxygen is caused by regain of the modulation process of OHC. Title: Effect of thiazide diuretics against neurally mediated contraction of guinea pig airways. Contribution of carbonic anhydrase Sun J, Elwood W, Barnes PJ, Chung KF Ref: Am Rev Respir Dis, 148:902, 1993 : PubMed ESTHER: Sun_1993_Am.Rev.Respir.Dis_148_902 PubMedSearch: Sun 1993 Am.Rev.Respir.Dis 148 902 PubMedID: 7692774 Abstract The effect of thiazide diuretics on neurally and agonist-induced contractile responses of guinea pig airways in vitro were investigated. Tracheal or bronchial strips were suspended in organ baths and isometric tension recorded. Chlorothiazide (CTZ, 10(-4) to 3 x 10(-3) M), hydrochlorothiazide (HCTZ, 10(-3) M), and dichlorphenamide (DCPM, 10(-3) M) significantly potentiated contraction of tracheal strips induced by electrical field stimulation (EFS). They also increased acetylcholine (ACh)- but not carbachol-induced tracheal contraction. In the presence of atropine and propranolol, on the other hand, CTZ and DCPM but not HCTZ significantly inhibited EFS-induced contraction in bronchial strips. We determined whether carbonic anhydrase inhibition could mimic the effects of CTZ and DCPM. Acetazolamide (ATZ), an inhibitor of carbonic anhydrase, had no effect on either EFS- or ACh-induced contraction in tracheal strips but significantly inhibited nonadrenergic, noncholinergic (NANC) contractile responses induced by EFS in bronchial strips. CTZ, DCPM, and ATZ did not affect substance P-induced contractile responses in the bronchi. We conclude that CTZ, DCPM, and ATZ attenuate NANC neurally mediated bronchial contraction by preventing the release of contractile neuropeptides from sensory nerve endings. This effect may occur through inhibition of carbonic anhydrase activity. In addition, thiazide diuretics potentiate contractile responses to ACh in the trachea, probably through inhibition of acetylcholinesterase activity. | |||||||
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