Author Report for: Hu GNo contact information in database for Hu G
Tian Y, Li S, Yang P, Su X, Liu J, Lv X, Dong K, Yang T, Duan M and Zhao Y <9 more author(s)> Tian Y, Li S, Yang P, Su X, Liu J, Lv X, Dong K, Yang T, Duan M, Hu G, Yue H, Sun Y, Zhang H, Du Z, Miao Z, Tong M, Hou Y, Gao Z, Zhao Y (- 9) Ref: Bioorganic & Medicinal Chemistry Lett, 70:128805, 2022 : PubMed ESTHER: Tian_2022_Bioorg.Med.Chem.Lett_70_128805 PubMedSearch: Tian 2022 Bioorg.Med.Chem.Lett 70 128805 PubMedID: 35598794 Abstract The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC(50) value of 0.03 +/- 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief. Title: Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors Tian Y, Li S, Dong K, Su X, Fu S, Lv X, Duan M, Yang T, Han Y and Zhao Y <13 more author(s)> Tian Y, Li S, Dong K, Su X, Fu S, Lv X, Duan M, Yang T, Han Y, Hu G, Liu J, Sun Y, Yue H, Zhang H, Du Z, Miao Z, Tong M, Liu Y, Qin M, Gong P, Hou Y, Gao Z, Zhao Y (- 13) Ref: Bioorg Chem, 127:105898, 2022 : PubMed ESTHER: Tian_2022_Bioorg.Chem_127_105898 PubMedSearch: Tian 2022 Bioorg.Chem 127 105898 PubMedID: 35792317 Abstract The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC(50) value of 0.04 +/- 0.01 nM and a K(i) value of 0.2 +/- 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors. Title: HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture Hu G, Niu F, Liao K, Periyasamy P, Sil S, Liu J, Dravid SM, Buch S Ref: J Neuroimmune Pharmacol, 15:538, 2020 : PubMed ESTHER: Hu_2020_J.Neuroimmune.Pharmacol_15_538 PubMedSearch: Hu 2020 J.Neuroimmune.Pharmacol 15 538 PubMedID: 31401755 Abstract Although combination antiretroviral therapy (cART) has improved the health of millions of those living with HIV-1 (Human Immunodeficiency Virus, Type 1), the penetration into the central nervous system (CNS) of many such therapies is limited, thereby resulting in residual neurocognitive impairment commonly referred to as NeuroHIV. Additionally, while cART has successfully suppressed peripheral viremia, cytotoxicity associated with the presence of viral Transactivator of transcription (Tat) protein in tissues such as the brain, remains a significant concern. Our previous study has demonstrated that both HIV-1 Tat as well as opiates such as morphine, can directly induce synaptic alterations via independent pathways. Herein, we demonstrate that exposure of astrocytes to HIV-1 protein Tat mediates the induction and release of extracellular vesicle (EV) microRNA-7 (miR-7) that is taken up by neurons, leading in turn, to downregulation of neuronal neuroligin 2 (NLGN2) and ultimately to synaptic alterations. More importantly, we report that these impairments could be reversed by pretreatment of neurons with a neurotrophic factor platelet-derived growth factor-CC (PDGF-CC). Graphical Abstract. Title: Lipoprotein-Associated Phospholipase A2 Activity and Mass as Independent Risk Factor of Stroke: A Meta-Analysis Hu G, Liu D, Tong H, Huang W, Hu Y, Huang Y Ref: Biomed Res Int, 2019:8642784, 2019 : PubMed ESTHER: Hu_2019_Biomed.Res.Int_2019_8642784 PubMedSearch: Hu 2019 Biomed.Res.Int 2019 8642784 PubMedID: 31236414 Gene_locus related to this paper: human-PLA2G7 Abstract BACKGROUND: The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and stroke risk is inconsistent. We conducted a meta-analysis to determine whether elevated Lp-PLA2 is a risk factor for stroke. METHODS: Studies were included if they reported Lp-PLA2 mass and/or activity levels and adjusted risk estimates of stroke. The primary outcome was overall stroke incidence. The combined results were shown as relative risks (RRs) with 95% confidence intervals (CI) for per 1 standard deviation (SD) higher value of Lp-PLA2 and the highest versus lowest Lp-PLA2 category. RESULTS: Twenty-two studies involving 157,693 participants were included for analysis. After adjusting for conventional risk factors, the RRs for overall stroke with 1 SD higher Lp-PLA2 activity and mass were 1.07 (95% CI 1.02-1.13) and 1.11 (95% CI 1.04-1.19), respectively. The RRs of ischemic stroke with 1 SD higher Lp-PLA2 activity and mass were 1.08 (95% CI 1.01-1.15) and 1.11 (95% CI 1.02-1.22), respectively. When comparing the highest and lowest levels of Lp-PLA2, the RRs of stroke for Lp-PLA2 activity and mass were 1.26 (95% CI 1.03-1.54) and 1.56 (95% CI 1.21-2.00), respectively. Finally, when comparing the highest and lowest levels of Lp-PLA2, the pooled RRs of ischemic stroke for Lp-PLA2 activity and mass were 1.29 (95% CI 1.07-1.56) and 1.68 (95% CI 1.12-2.53), respectively. CONCLUSIONS: Elevated baseline Lp-PLA2 levels, detected either by activity or mass, are associated with increased stroke risk. Title: Degradation of methomyl by the combination of Aminobacter sp. MDW-2 and Afipia sp. MDW-3 Zhang C, Yang Z, Jin W, Wang X, Zhang Y, Zhu S, Yu X, Hu G, Hong Q Ref: Lett Appl Microbiol, 64:289, 2017 : PubMed ESTHER: Zhang_2017_Lett.Appl.Microbiol_64_289 PubMedSearch: Zhang 2017 Lett.Appl.Microbiol 64 289 PubMedID: 28083911 Abstract Methomyl (S-methyl N-(methylcarbamoyloxy) thioacetimidate) is a kind of oxime carbamate insecticide. It is considered to be extremely toxic to nontarget organism. To date, no pure culture or consortium has been reported to have the ability to degrade methomyl completely. In this study, a methomyl-degrading enrichment E1 was obtained by using the sludge from the wastewater-treating system of a pesticide manufacturer as the original inoculant. Two bacterial strains named MDW-2 and MDW-3 were isolated from this enrichment, and they were preliminarily identified as Aminobacter sp. and Afipia sp. respectively. Strains MDW-2 and MDW-3 could coexist and degrade 50smgsl(-1) methomyl completely within 3sdays by the cooperative metabolism. Methomyl was first converted to methomyl oxime and methylcarbamic acid by strain MDW-2, and the latter could be used as the carbon source for the growth of strain MDW-2. But methomyl oxime could not be sequentially degraded by strain MDW-2. However, it could be degraded and used as the carbon source by strain MDW-3. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a bacterial combination of Aminobacter sp. MDW-2 and Afipia sp. MDW-3, which could degrade methomyl completely by biochemical cooperation. This study also proposes the biodegradation pathway of methomyl for the first time and highlights the application potential of a bacterial combination in the remediation of methomyl-contaminated environments. Title: Gambogic acid potentiates clopidogrel-induced apoptosis and attenuates irinotecan-induced apoptosis through down-regulating human carboxylesterase 1 and -2 Ning R, Wang XP, Zhan YR, Qi Q, Huang XF, Hu G, Guo QL, Liu W, Yang J Ref: Xenobiotica, :1, 2016 : PubMed ESTHER: Ning_2016_Xenobiotica__1 PubMedSearch: Ning 2016 Xenobiotica 1 PubMedID: 26750665 Abstract 1. In this study, we report that gambogic acid (GA), a promising anticancer agent, potentiates clopidogrel-induced apoptosis and attenuates CPT-11-induced apoptosis by down-regulating human carboxylesterase (CES) 1 and -2 via ERK and p38 MAPK pathway activation, which provides a molecular explanation linking the effect of drug combination directly to the decreased capacity of hydrolytic biotransformation. 2. The expression levels of CES1 and CES2 decreased significantly in a concentration- and time-dependent manner in response to GA in Huh7 and HepG2 cells; hydrolytic activity was also reduced. 3. The results showed that pretreatment with GA potentiated clopidogrel-induced apoptosis by down-regulating CES1. Moreover, the GA-mediated repression of CES2 attenuated CPT-11-induced apoptosis. 4. Furthermore, the ERK and p38 MAPK pathways were involved in the GA-mediated down-regulation of CES1 and CES2. 5. Taken together, our data suggest that GA is a potent repressor of CES1 and CES2 and that combination with GA will affect the metabolism of drugs containing ester bonds. Title: Fluoxetine reduces CES1, CES2, and CYP3A4 expression through decreasing PXR and increasing DEC1 in HepG2 cells Shang W, Liu J, Chen R, Ning R, Xiong J, Liu W, Mao Z, Hu G, Yang J Ref: Xenobiotica, 46:393, 2016 : PubMed ESTHER: Shang_2016_Xenobiotica_46_393 PubMedSearch: Shang 2016 Xenobiotica 46 393 PubMedID: 26340669 Gene_locus related to this paper: human-CES1 Abstract 1. This study investigated the mechanisms of the decreases of carboxylesterases (CES) and cytochrome P4503A4 (CYP3A4) and the enzymatic activities induced by fluoxetine (FLX) in HepG2 cells. We found that FLX decreased the carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) expression and the hydrolytic activity. 2. FLX decreased the pregnane X receptor (PXR) expression which regulated the target genes such as CYP3A4, whereas increased the differentiated embryonic chondrocyte-expressed gene 1 (DEC1) expression. 3. FLX repressed the PXR at transcriptional level. 4. Overexpression of PXR alone increased the expression of CES1, CES2, and CYP3A4 and attenuated the decreases of CES1, CES2, and CYP3A4 induced by FLX. On the contrary, knockdown of PXR alone decreased the expression of CES1, CES2, and CYP3A4 and almost abolished the decreases of CES1, CES2, and CYP3A4 induced by FLX. 5. Knockdown of DEC1 alone increased the expression of PXR and CYP3A4 and almost abolished the decreases of CES1, CES2, and CYP3A4 induced by FLX. 6. Taken together, the decreases of CES and CYP3A4 expression and enzymatic activities induced by FLX are through decreasing PXR and increasing DEC1 in HepG2 cells. Title: Decreased carboxylesterases expression and hydrolytic activity in type 2 diabetic mice through Akt/mTOR/HIF-1alpha/Stra13 pathway Chen R, Wang Y, Ning R, Hu J, Liu W, Xiong J, Wu L, Liu J, Hu G, Yang J Ref: Xenobiotica, 45:782, 2015 : PubMed ESTHER: Chen_2015_Xenobiotica_45_782 PubMedSearch: Chen 2015 Xenobiotica 45 782 PubMedID: 25801056 Abstract 1. This study investigated the alteration of carboxylesterases in type 2 diabetes. We found that the carboxylesterase 1d (Ces1d) and carboxylesterase 1e (Ces1e) expression and the capacity of hydrolytic activity of liver and intestine decreased, whereas the Akt/mTOR/HIF-1alpha/ Stra13 (DEC1) signaling was activated in T2D mice. Consistently, high insulin could give rise to the same results in the high-glucose DMEM condition, which mimicked T2D, in primary mouse hepatocytes. 2. Perifosine or rapamycin almost abolished the decrease of the Ces1d and Ces1e expression and the hydrolytic activity induced by the insulin in the primary mouse hepatocytes. 3. The responsiveness of human hepatoma (HepG2) cells to high insulin in high-glucose condition was similar to that of primary mouse hepatocytes in terms of the altered expression of carboxylesterases. 4. The knockdown of HIF-1alpha or DEC1 with shRNA construct abrogated the decrease of the CES1 and CES2 expression induced by the insulin in high glucose condition in HepG2 cells. 5. Taken together, the decreased carboxylesterases expression and hydrolytic activity in T2D mice are through the Akt/mTOR/HIF-1alpha/Stra13 (DEC1) pathway. Title: The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y and He Y <14 more author(s)> Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y, Chen M, Xu Y, Jin H, Xiao X, Hu G, Bao F, Hu Y, Wan P, Li L, Deng X, Kuang T, Xiang C, Zhu JK, Oliver MJ, He Y (- 14) Ref: Proc Natl Acad Sci U S A, 112:5833, 2015 : PubMed ESTHER: Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833 PubMedSearch: Xiao 2015 Proc.Natl.Acad.Sci.U.S.A 112 5833 PubMedID: 25902549 Gene_locus related to this paper: 9lami-a0a2z7c6k4, 9lami-a0a2z7bgj4 Abstract "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes. Title: Glucose dominates the regulation of carboxylesterases induced by lipopolysaccharide or interleukin-6 in primary mouse hepatocytes Xiong J, Shang W, Wu L, Chen R, Liu W, Ning R, Hu G, Yang J Ref: Life Sciences, 112:41, 2014 : PubMed ESTHER: Xiong_2014_Life.Sci_112_41 PubMedSearch: Xiong 2014 Life.Sci 112 41 PubMedID: 25066929 Abstract AIMS: Altered drug disposition has been associated with inflammation and diabetes, leading to the alteration of drug efficacy and toxicity. Carboxylesterases are major hydrolytic enzymes in the liver, catalyzing the hydrolytic biotransformation of numerous therapeutic agents. Therefore, how glucose affects the regulation of carboxylesterases by interleukin-6 (IL-6) and lipopolysaccharide (LPS) were investigated. MAIN Title: Fluoxetine Induces Hepatic Lipid Accumulation Via Both Promotion of the SREBP1c-Related Lipogenesis and Reduction of Lipolysis in Primary Mouse Hepatocytes Feng XM, Xiong J, Qin H, Liu W, Chen RN, Shang W, Ning R, Hu G, Yang J Ref: CNS Neurosci Ther, 18:974, 2012 : PubMed ESTHER: Feng_2012_CNS.Neurosci.Ther_18_974 PubMedSearch: Feng 2012 CNS.Neurosci.Ther 18 974 PubMedID: 23137031 Abstract AIMS: In this study, we investigated the peripheral mechanisms underlying the metabolic side effects of fluoxetine (FLX) by focusing on hepatic lipid metabolism. Title: Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres Paterson AH, Wendel JF, Gundlach H, Guo H, Jenkins J, Jin D, Llewellyn D, Showmaker KC, Shu S and Schmutz J <64 more author(s)> Paterson AH, Wendel JF, Gundlach H, Guo H, Jenkins J, Jin D, Llewellyn D, Showmaker KC, Shu S, Udall J, Yoo MJ, Byers R, Chen W, Doron-Faigenboim A, Duke MV, Gong L, Grimwood J, Grover C, Grupp K, Hu G, Lee TH, Li J, Lin L, Liu T, Marler BS, Page JT, Roberts AW, Romanel E, Sanders WS, Szadkowski E, Tan X, Tang H, Xu C, Wang J, Wang Z, Zhang D, Zhang L, Ashrafi H, Bedon F, Bowers JE, Brubaker CL, Chee PW, Das S, Gingle AR, Haigler CH, Harker D, Hoffmann LV, Hovav R, Jones DC, Lemke C, Mansoor S, ur Rahman M, Rainville LN, Rambani A, Reddy UK, Rong JK, Saranga Y, Scheffler BE, Scheffler JA, Stelly DM, Triplett BA, Van Deynze A, Vaslin MF, Waghmare VN, Walford SA, Wright RJ, Zaki EA, Zhang T, Dennis ES, Mayer KF, Peterson DG, Rokhsar DS, Wang X, Schmutz J (- 64) Ref: Nature, 492:423, 2012 : PubMed ESTHER: Paterson_2012_Nature_492_423 PubMedSearch: Paterson 2012 Nature 492 423 PubMedID: 23257886 Gene_locus related to this paper: gosra-a0a0d2qg22, gosra-a0a0d2w3z1, gosra-a0a0d2uuz7, gosra-a0a0d2rxs2, gosra-a0a0d2sdk0, gosra-a0a0d2tng2, gosra-a0a0d2twz7, gosra-a0a0d2vdc5, gosra-a0a0d2vj24, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8kis4, gosra-a0a0d2pul0, gosra-a0a0d2p3f2, gosra-a0a0d2ril5, gosra-a0a0d2s7d5, gosra-a0a0d2t9b3, gosra-a0a0d2tw88, gosra-a0a0d2umz5, gosra-a0a0d2pzd7 Abstract Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups. Title: Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts D'Souza CA, Kronstad JW, Taylor G, Warren R, Yuen M, Hu G, Jung WH, Sham A, Kidd SE and Cuomo CA <31 more author(s)> D'Souza CA, Kronstad JW, Taylor G, Warren R, Yuen M, Hu G, Jung WH, Sham A, Kidd SE, Tangen K, Lee N, Zeilmaker T, Sawkins J, McVicker G, Shah S, Gnerre S, Griggs A, Zeng Q, Bartlett K, Li W, Wang X, Heitman J, Stajich JE, Fraser JA, Meyer W, Carter D, Schein J, Krzywinski M, Kwon-Chung KJ, Varma A, Wang J, Brunham R, Fyfe M, Ouellette BF, Siddiqui A, Marra M, Jones S, Holt R, Birren BW, Galagan JE, Cuomo CA (- 31) Ref: MBio, 2:e00342, 2011 : PubMed ESTHER: D'Souza_2011_MBio_2_e00342 PubMedSearch: D'Souza 2011 MBio 2 e00342 PubMedID: 21304167 Gene_locus related to this paper: crygw-e6qy09, crygw-e6r2n3, crygw-e6r7g6, crygw-e6rbd6, crygw-e6rcm3, crygw-e6rg44, cryne-q5ka03, cryne-q5km63, cryne-q5knq0, cryne-q55va3, crynj-q5kpe0, crygr-a0a095cfy5, crygw-kex1 Abstract Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the genetics of virulence in this pathogen, we sequenced the genomes of a strain (WM276) representing the predominant global molecular type (VGI) and a clinical strain (R265) of the major genotype (VGIIa) causing disease in North America. We compared these C. gattii genomes with each other and with the genomes of representative strains of the two varieties of Cryptococcus neoformans that generally cause disease in immunocompromised people. Our comparisons included chromosome alignments, analysis of gene content and gene family evolution, and comparative genome hybridization (CGH). These studies revealed that the genomes of the two representative C. gattii strains (genotypes VGI and VGIIa) are colinear for the majority of chromosomes, with some minor rearrangements. However, multiortholog phylogenetic analysis and an evaluation of gene/sequence conservation support the existence of speciation within the C. gattii complex. More extensive chromosome rearrangements were observed upon comparison of the C. gattii and the C. neoformans genomes. Finally, CGH revealed considerable variation in clinical and environmental isolates as well as changes in chromosome copy numbers in C. gattii isolates displaying fluconazole heteroresistance. Title: Lipopolysaccharide down-regulates carbolesterases 1 and 2 and reduces hydrolysis activity in vitro and in vivo via p38MAPK-NF-kappaB pathway Mao Z, Li Y, Peng Y, Luan X, Gui H, Feng X, Hu G, Shen J, Yan B, Yang J Ref: Toxicol Lett, 201:213, 2011 : PubMed ESTHER: Mao_2011_Toxicol.Lett_201_213 PubMedSearch: Mao 2011 Toxicol.Lett 201 213 PubMedID: 21237253 Abstract Carboxylesterases constitute a class of enzymes that hydrolyze drugs containing such functional groups as carboxylic acid ester, amide, and thioester. Hydrolysis of many drugs is reduced in liver diseases such as hepatitis and cirrhosis. In this study, we have demonstrated, in vitro and in vivo, treatment with LPS decreased the expression of HCE1 and HCE2 and the capacity of hydrolytic activity. In HepG2 cells, the decreased expression by LPS occurred at both mRNA and protein levels. Both HCE1 and HCE2 promoters were significantly repressed by LPS, and the repression was comparable with the decrease in HCE1 and HCE2 mRNA, suggesting the transrepression is responsible for suppressed expression. Further study showed that both PDTC, a NF-B inhibitor, and SB203580, a p38MAPK inhibitor, could abolish the repression of HCE1 and HCE2 mediated by LPS, but U0126, a selective ERK1/2 inhibitor, could not do so, suggesting the repression of HCE1 and HCE2 by LPS through the p38MAPK-NF-B pathway. In addition, being pretreated with LPS, HepG2 cells altered the cellular responsiveness to ester therapeutic agents, including clopidogrel (hydrolyzed by HCE1) and irinotecan (hydrolyzed by HCE2). The altered cellular responsiveness occurred at low micromolar concentrations, suggesting that suppressed expression of carboxylesterases by LPS has profound pharmacological and toxicological consequences, particularly with those that are hydrolyzed in an isoform-specific manner. This study provides new insight into the understanding of the pharmacological and toxicological effects and the mechanisms for repressing drug metabolism enzymes in inflammation. Title: A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides Liu Q, Huang Y, Xue F, Simard AR, DeChon J, Li G, Zhang J, Lucero L, Wang M and Wu J <4 more author(s)> Liu Q, Huang Y, Xue F, Simard AR, DeChon J, Li G, Zhang J, Lucero L, Wang M, Sierks M, Hu G, Chang Y, Lukas RJ, Wu J (- 4) Ref: Journal of Neuroscience, 29:918, 2009 : PubMed ESTHER: Liu_2009_J.Neurosci_29_918 PubMedSearch: Liu 2009 J.Neurosci 29 918 PubMedID: 19176801 Abstract Nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunits are thought to assemble as homomers. alpha7-nAChR function has been implicated in learning and memory, and alterations of alpha7-nAChR have been found in patients with Alzheimer's disease (AD). Here we report findings consistent with a novel, naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons. In these cells, alpha7 subunits are coexpressed, colocalize, and coassemble with beta2 subunit(s). Compared with homomeric alpha7-nAChRs from ventral tegmental area neurons, functional, presumably heteromeric alpha7beta2-nAChRs on cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB) exhibit relatively slow kinetics of whole-cell current responses to nicotinic agonists and are more sensitive to the beta2 subunit-containing nAChR-selective antagonist, dihydro-beta-erythroidine (DHbetaE). Interestingly, presumed, heteromeric alpha7beta2-nAChRs are highly sensitive to functional inhibition by pathologically relevant concentrations of oligomeric, but not monomeric or fibrillar, forms of amyloid beta(1-42) (Abeta(1-42)). Slow whole-cell current kinetics, sensitivity to DHbetaE, and specific antagonism by oligomeric Abeta(1-42) also are characteristics of heteromeric alpha7beta2-nAChRs, but not of homomeric alpha7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover, choline-induced currents have faster kinetics and less sensitivity to Abeta when elicited from MS/DB neurons derived from nAChR beta2 subunit knock-out mice rather than from wild-type mice. The presence of novel, functional, heteromeric alpha7beta2-nAChRs on basal forebrain cholinergic neurons and their high sensitivity to blockade by low concentrations of oligomeric Abeta(1-42) suggests possible mechanisms for deficits in cholinergic signaling that could occur early in the etiopathogenesis of AD and might be targeted by disease therapies. Title: Identification and characterization of HTD2: a novel gene negatively regulating tiller bud outgrowth in rice Liu W, Wu C, Fu Y, Hu G, Si H, Zhu L, Luan W, He Z, Sun Z Ref: Planta, 230:649, 2009 : PubMed ESTHER: Liu_2009_Planta_230_649 PubMedSearch: Liu 2009 Planta 230 649 PubMedID: 19579033 Gene_locus related to this paper: orysj-Q10QA5 Abstract Tiller number is highly regulated by controlling the formation of tiller bud and its subsequent outgrowth in response to endogenous and environmental signals. Here, we identified a rice mutant htd2 from one of the 15,000 transgenic rice lines, which is characterized by a high tillering and dwarf phenotype. Phenotypic analysis of the mutant showed that the mutation did not affect formation of tiller bud, but promoted the subsequent outgrowth of tiller bud. To isolate the htd2 gene, a map-based cloning strategy was employed and 17 new insertions-deletions (InDels) markers were developed. A high-resolution physical map of the chromosomal region around the htd2 gene was made using the F(2) and F(3) population. Finally, the gene was mapped in 12.8 kb region between marker HT41 and marker HT52 within the BAC clone OSJNBa0009J13. Cloning and sequencing of the target region from the mutant showed that the T-DNA insertion caused a 463 bp deletion between the promoter and first exon of an esterase/lipase/thioesterase family gene in the 12.8 kb region. Furthermore, transgenic rice with reduced expression level of the gene exhibited an enhanced tillering and dwarf phenotype. Accordingly, the esterase/lipase/thioesterase family gene (TIGR locus Os03g10620) was identified as the HTD2 gene. HTD2 transcripts were expressed mainly in leaf. Loss of function of HTD2 resulted in a significantly increased expression of HTD1, D10 and D3, which were involved in the strigolactone biosynthetic pathway. The results suggest that the HTD2 gene could negatively regulate tiller bud outgrowth by the strigolactone pathway. Title: Association between polymorphisms of microsomal epoxide hydrolase and COPD: results from meta-analyses Hu G, Shi Z, Hu J, Zou G, Peng G, Ran P Ref: Respirology, 13:837, 2008 : PubMed ESTHER: Hu_2008_Respirology_13_837 PubMedSearch: Hu 2008 Respirology 13 837 PubMedID: 18811882 Abstract BACKGROUND AND OBJECTIVE: COPD is a complex polygenic disease in which gene-environment interactions are very important. The gene encoding microsomal epoxide hydrolase (EPHX1) is one of several candidate loci for COPD pathogenesis and is highly polymorphic. Based chi on the polymorphisms of EPHX1 gene (tyrosine/histidine 113, histidine/arginine 139), the population can be classified into four groups of putative EPHX1 phenotypes (fast, normal, slow and very slow). A number of studies have investigated the association between the genotypes and phenotypes of EPHX1 and COPD susceptibility in different populations, with inconsistent results. A systematic review and meta-analysis of the published data was performed to gain a clearer understanding of this association. METHODS: The MEDLINE database was searched for case-control studies published from 1966 to August 2007. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Sixteen eligible studies, comprising 1847 patients with COPD and 2455 controls, were included in the meta-analysis. The pooled result showed that the EPHX1 113 mutant homozygote was significantly associated with an increased risk of COPD (OR 1.59, 95% CI: 1.14-2.21). Subgroup analysis supported the result in the Asian population, but not in the Caucasian population. When the analysis was limited to only the larger-sample-size studies, studies in which controls were in Hardy-Weinberg equilibrium and studies in which controls were smokers/ex-smokers, the pooled results supported the conclusion. The EPHX1 139 heterozygote protected against the development of COPD in the Asian population, but not in the Caucasian population. The other gene types of EPHX1 113 and EPHX1 139 were not associated with an increased risk of COPD. The slow activity phenotype of EPHX1 was associated with an increased risk of COPD. The fast activity phenotype of EPHX1 was a protective factor for developing COPD in the Asian population, but not in the Caucasian population. However, the very slow activity phenotype of EPHX1 was a risk for developing COPD in the Caucasian population, but not in the Asian population. CONCLUSIONS: The polymorphisms of EPHX1 113 and EPHX1 139 are genetic contributors to COPD susceptibility in Asian populations. The phenotypes of EPHX1 were contributors to overall COPD susceptibility. Title: Mating factor linkage and genome evolution in basidiomycetous pathogens of cereals Bakkeren G, Jiang G, Warren RL, Butterfield Y, Shin H, Chiu R, Linning R, Schein J, Lee N and Kronstad JW <6 more author(s)> Bakkeren G, Jiang G, Warren RL, Butterfield Y, Shin H, Chiu R, Linning R, Schein J, Lee N, Hu G, Kupfer DM, Tang Y, Roe BA, Jones S, Marra M, Kronstad JW (- 6) Ref: Fungal Genet Biol, 43:655, 2006 : PubMed ESTHER: Bakkeren_2006_Fungal.Genet.Biol_43_655 PubMedSearch: Bakkeren 2006 Fungal.Genet.Biol 43 655 PubMedID: 16793293 Gene_locus related to this paper: ustho-q2a721 Abstract Sex in basidiomycete fungi is controlled by tetrapolar mating systems in which two unlinked gene complexes determine up to thousands of mating specificities, or by bipolar systems in which a single locus (MAT) specifies different sexes. The genus Ustilago contains bipolar (Ustilago hordei) and tetrapolar (Ustilago maydis) species and sexual development is associated with infection of cereal hosts. The U. hordei MAT-1 locus is unusually large (approximately 500 kb) and recombination is suppressed in this region. We mapped the genome of U. hordei and sequenced the MAT-1 region to allow a comparison with mating-type regions in U. maydis. Additionally the rDNA cluster in the U. hordei genome was identified and characterized. At MAT-1, we found 47 genes along with a striking accumulation of retrotransposons and repetitive DNA; the latter features were notably absent from the corresponding U. maydis regions. The tetrapolar mating system may be ancestral and differences in pathogenic life style and potential for inbreeding may have contributed to genome evolution. Title: Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats Liu Q, Li Z, Ding JH, Liu SY, Wu J, Hu G Ref: Brain Research, 1085:138, 2006 : PubMed ESTHER: Liu_2006_Brain.Res_1085_138 PubMedSearch: Liu 2006 Brain.Res 1085 138 PubMedID: 16647046 Abstract Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons. In the present study, we examined whether Ipt prevents nicotine-induced neurotransmitter release in the nucleus accumbens (NAc) using in vivo microdialysis methods in awake, freely moving rats. Ipt was administered through a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg, s.c.). The results show that acute nicotine treatment induced an increase of both dopamine and glutamate levels in the rat NAc, and that Ipt significantly attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt may serve as a novel compound to block nicotine-induced dopamine and glutamate release in the brain reward center, in turn decreasing nicotine reinforcement and dependence. Title: EDS1 in tomato is required for resistance mediated by TIR-class R genes and the receptor-like R gene Ve Hu G, deHart AK, Li Y, Ustach C, Handley V, Navarre R, Hwang CF, Aegerter BJ, Williamson VM, Baker B Ref: Plant J, 42:376, 2005 : PubMed ESTHER: Hu_2005_Plant.J_42_376 PubMedSearch: Hu 2005 Plant.J 42 376 PubMedID: 15842623 Gene_locus related to this paper: lyces-q56r03 Abstract In tobacco and other Solanaceae species, the tobacco N gene confers resistance to tobacco mosaic virus (TMV), and leads to induction of standard defense and resistance responses. Here, we report the use of N-transgenic tomato to identify a fast-neutron mutant, sun1-1 (suppressor of N), that is defective in N-mediated resistance. Induction of salicylic acid (SA) and expression of pathogenesis-related (PR) genes, each signatures of systemic acquired resistance, are both dramatically suppressed in sun1-1 plants after TMV treatment compared to wild-type plants. Application of exogenous SA restores PR gene expression, indicating that SUN1 acts upstream of SA. Upon challenge with additional pathogens, we found that the sun1-1 mutation impairs resistance mediated by certain resistance (R) genes, (Bs4, I, and Ve), but not others (Mi-1). In addition, sun1-1 plants exhibit enhanced susceptibility to TMV, as well as to virulent pathogens. sun1-1 has been identified as an EDS1 homolog present on chromosome 6 of tomato. The discovery of enhanced susceptibility in the sun1-1 (Le_eds1-1) mutant plant, which contrasts to reports in Nicotiana benthamiana using virus-induced gene silencing, provides evidence that the intersection of R gene-mediated pathways with general resistance pathways is conserved in a Solanaceous species. In tomato, EDS1 is important for mediating resistance to a broad range of pathogens (viral, bacterial, and fungal pathogens), yet shows specificity in the class of R genes that it affects (TIR-NBS-LRR as opposed to CC-NBS-LRR). In addition, a requirement for EDS1 for Ve-mediated resistance in tomato exposes that the receptor-like R gene class may also require EDS1. Title: Huperzine A, a nootropic alkaloid, inhibits N-methyl-D-aspartate-induced current in rat dissociated hippocampal neurons Zhang J, Hu G Ref: Neuroscience, 105:663, 2001 : PubMed ESTHER: Zhang_2001_Neurosci_105_663 PubMedSearch: Zhang 2001 Neurosci 105 663 PubMedID: 11516831 Abstract Huperzine A, a nootropic alkaloid isolated from a Chinese herb, has been proposed as one of the most promising agents to treat Alzheimer's disease. Recently, the agent was found to inhibit the N-methyl-D-aspartate (NMDA) receptors in rat cerebral cortex in addition to causing an inhibitory effect on acetylcholinesterase. In the present study, the mechanisms underlying NMDA receptor inhibition were investigated using whole-cell voltage-clamp recording in CA1 pyramidal neurons acutely dissociated from rat hippocampus. Huperzine A reversibly inhibited the NMDA-induced current (IC(50)=126 microM, Hill coefficient=0.92), whereas it had no effect on the current induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate or kainate. The effect was non-competitive, and showed neither 'voltage-dependency', nor 'use-dependency'. The IC(50) values of huperzine A were neither altered by changing the concentrations of glycine (2-0.2 microM) and pH (7.4-6.7) in the external solution, nor by addition of Zn(2+) (5 microM) and dithiothreitol (5 mM) to the external solution. However, addition of spermine (200 microM) to the external solution caused a parallel shift to the right of the huperzine A concentration-response curve. From these we suggest that huperzine A acts as a non-competitive antagonist of the NMDA receptors, via a competitive interaction with one of the polyamine binding sites. The potential relevance of NMDA receptor antagonist activity of huperzine A to the treatment of Alzheimer's disease is discussed. | |||||||
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