Jin L

References (29)

Title : Efgartigimod is a new option for the treatment of thymoma associated myasthenia gravis: A case report - Wang_2024_Int.J.Surg.Case.Rep_115_109241
Author(s) : Wang S , Wang Q , Jin L , Dong J , Ding J
Ref : Int J Surg Case Rep , 115 :109241 , 2024
Abstract : INTRODUCTION: The perioperative efficacy and safety of efgartigimod in patients with thymoma associated myasthenia gravis have not been reported. CASE PRESENTATION: We described the case of a 47-year-old woman who presented thymoma associated myasthenia gravis. Primarily, the patient was treated with acetylcholinesterase inhibitors, immunosuppressive medications, and intravenous immunoglobulin. Unfortunately, the control of symptoms was unsatisfactory. The patient was treated with recommended dosage of efgartigimod (10 mg/kg administered as a 1 h intravenous infusion once weekly for 2 weeks) combined with immunosuppressive therapy. Consequently, improved outcomes and rapid clinical remission were observed. Then, modified subxiphoid thoracoscopic thymectomy was performed smoothly and the patient was discharged from hospital after recovery in short time. DISCUSSION: Administration of efgartigimod could control symptoms significantly and rapidly. Efgartigimod provides the opportunity of thymectomy in short time. Importantly, there was no any perioperative complication or any adverse event related to efgartigimod. CONCLUSION: The improved outcomes of the patient with thymoma associated myasthenia gravis highlight the importance of efgartigimod. Large-scale clinical trials are needed to validate the safety and efficacy of efgartigimod during the perioperative period of thymectomy.
ESTHER : Wang_2024_Int.J.Surg.Case.Rep_115_109241
PubMedSearch : Wang_2024_Int.J.Surg.Case.Rep_115_109241
PubMedID: 38219512

Title : EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25\/Keap1\/Nrf2 axis - Zhang_2023_Redox.Biol_63_102765
Author(s) : Zhang CY , Zhong WJ , Liu YB , Duan JX , Jiang N , Yang HH , Ma SC , Jin L , Hong JR , Zhou Y , Guan CX
Ref : Redox Biol , 63 :102765 , 2023
Abstract : Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and gammaH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.
ESTHER : Zhang_2023_Redox.Biol_63_102765
PubMedSearch : Zhang_2023_Redox.Biol_63_102765
PubMedID: 37269686

Title : Developing an adult stem cell derived microphysiological intestinal system for predicting oral prodrug bioconversion and permeability in humans - Sharma_2023_Lab.Chip__
Author(s) : Sharma A , Jin L , Wang X , Wang YT , Stresser DM
Ref : Lab Chip , : , 2023
Abstract : Microphysiological systems (MPS) incorporating human intestinal organoids have shown the potential to faithfully model intestinal biology with the promise to accelerate development of oral prodrugs. We hypothesized that an MPS model incorporating flow, shear stress, and vasculature could provide more reliable measures of prodrug bioconversion and permeability. Following construction of jejunal and duodenal organoid MPS derived from 3 donors, we determined the area under the concentration-time (AUC) curve for the active drug in the vascular channel and characterized the enzymology of prodrug bioconversion. Fosamprenavir underwent phosphatase mediated hydrolysis to amprenavir while dabigatran etexilate (DABE) exhibited proper CES2- and, as anticipated, not CES1-mediated de-esterification, followed by permeation of amprenavir to the vascular channel. When experiments were conducted in the presence of bio-converting enzyme inhibitors (orthovanadate for alkaline phosphatase; bis(p-nitrophenyl)phosphate for carboxylesterase), the AUC of the active drug decreased accordingly in the vascular channel. In addition to functional analysis, the MPS was characterized through imaging and proteomic analysis. Imaging revealed proper expression and localization of epithelial, endothelial, tight junction and catalytic enzyme markers. Global proteomic analysis was used to analyze the MPS model and 3 comparator sources: an organoid-based transwell model (which was also evaluated for function), Matrigel embedded organoids and finally jejunal and duodenal cadaver tissues collected from 3 donors. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) of global proteomic data demonstrated that all organoid-based models exhibited strong similarity and were distinct from tissues. Intestinal organoids in the MPS model exhibited strong similarity to human tissue for key epithelial markers via HCA. Quantitative proteomic analysis showed higher expression of key prodrug converting and drug metabolizing enzymes in MPS-derived organoids compared to tissues, organoids in Matrigel, and organoids on transwells. When comparing organoids from MPS and transwells, expression of intestinal alkaline phosphatase (ALPI), carboxylesterase (CES)2, cytochrome P450 3A4 (CYP3A4) and sucrase isomaltase (SI) was 2.97-, 1.2-, 11.3-, and 27.7-fold higher for duodenum and 7.7-, 4.6-, 18.1-, and 112.2-fold higher for jejunum organoids in MPS, respectively. The MPS approach can provide a more physiological system than enzymes, organoids, and organoids on transwells for pharmacokinetic analysis of prodrugs that account for 10% of all commercial medicines.
ESTHER : Sharma_2023_Lab.Chip__
PubMedSearch : Sharma_2023_Lab.Chip__
PubMedID: 38099395

Title : Inhibition mechanisms of four ellagitannins from terminalia chebula fruits on acetylcholinesterase by inhibition kinetics, spectroscopy and molecular docking analyses - Li_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123115
Author(s) : Li YJ , Liang CC , Jin L , Chen J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 302 :123115 , 2023
Abstract : Acetylcholinesterase (AChE) is an important therapeutic target for the treatment of Alzheimer's disease (AD), and the development of natural AChE inhibitors as candidates has played a significant role in drug discovery. In this study, the inhibition mechanisms of four ellagitannins, punicalagin, chebulinic acid, geraniin and corilagin, from Terminalia chebula fruits on AChE were investigated systematically by a combination of inhibition kinetics, multi-spectroscopic methods and molecular docking. The kinetic results showed that punicalagin, chebulinic acid and geraniin exhibited strong reversible inhibitory effects on AChE in an uncompetitive manner with the IC(50) values of 0.43, 0.50, and 0.51 mM, respectively, while corilagin inhibited AChE activity in a mixed type with the IC(50) value of 0.72 mM. The results of fluorescence and UV-vis spectra and fluorescence resonance energy transfer (FRET) revealed that four ellagitannins could significantly quenched the intrinsic fluorescence of AChE though a static quenching along with non-radiative energy transfer. Thermodynamic analyses showed that values of deltaG, deltaH and deltaS were negative, indicating that all binding processes were spontaneous, and the hydrogen bonding and Van der Waals forces might make a great contribution to the formation of inhibitor-AChE complexes. The synchronous fluorescence, three-dimensional (3D) fluorescence, UV-vis, and FT-IR spectra studies suggested that four ellagitannins could lead to alterations in the micro-environment and secondary structure of AChE, and thus the conformational change of AChE. Moreover, molecular docking demonstrated that four ellagitannins could interacted with main amino acid residues of AChE with affinity energies ranging from -9.9 to -8.7 kJ/mol, and further confirmed the above experimental results. This study provided valuable findings for the potential application of four ellagitannins as promising candidates in the exploration of natural AChE inhibitors for the treatment of AD.
ESTHER : Li_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123115
PubMedSearch : Li_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123115
PubMedID: 37453379

Title : COX-2\/sEH Dual Inhibitor Alleviates Hepatocyte Senescence in NAFLD Mice by Restoring Autophagy through Sirt1\/PI3K\/AKT\/mTOR - Zhang_2022_Int.J.Mol.Sci_23_8267
Author(s) : Zhang CY , Tan XH , Yang HH , Jin L , Hong JR , Zhou Y , Huang XT
Ref : Int J Mol Sci , 23 :8267 , 2022
Abstract : We previously found that the disorder of soluble epoxide hydrolase (sEH)/cyclooxygenase-2 (COX-2)-mediated arachidonic acid (ARA) metabolism contributes to the pathogenesis of the non-alcoholic fatty liver disease (NAFLD) in mice. However, the exact mechanism has not been elucidated. Accumulating evidence points to the essential role of cellular senescence in NAFLD. Herein, we investigated whether restoring the balance of sEH/COX-2-mediated ARA metabolism attenuated NAFLD via hepatocyte senescence. A promised dual inhibitor of sEH and COX-2, PTUPB, was used in our study to restore the balance of sEH/COX-2-mediated ARA metabolism. In vivo, NAFLD was induced by a high-fat diet (HFD) using C57BL/6J mice. In vitro, mouse hepatocytes (AML12) and mouse hepatic astrocytes (JS1) were used to investigate the effects of PTUPB on palmitic acid (PA)-induced hepatocyte senescence and its mechanism. PTUPB alleviated liver injury, decreased collagen and lipid accumulation, restored glucose tolerance, and reduced hepatic triglyceride levels in HFD-induced NAFLD mice. Importantly, PTUPB significantly reduced the expression of liver senescence-related molecules p16, p53, and p21 in HFD mice. In vitro, the protein levels of gammaH2AX, p53, p21, COX-2, and sEH were increased in AML12 hepatocytes treated with PA, while Ki67 and PCNA were significantly decreased. PTUPB decreased the lipid content, the number of beta-gal positive cells, and the expression of p53, p21, and gammaH2AX proteins in AML12 cells. Meanwhile, PTUPB reduced the activation of hepatic astrocytes JS1 by slowing the senescence of AML12 cells in a co-culture system. It was further observed that PTUPB enhanced the ratio of autophagy-related protein LC3II/I in AML12 cells, up-regulated the expression of Fundc1 protein, reduced p62 protein, and suppressed hepatocyte senescence. In addition, PTUPB enhanced hepatocyte autophagy by inhibiting the PI3K/AKT/mTOR pathway through Sirt1, contributing to the suppression of senescence. PTUPB inhibits the PI3K/AKT/mTOR pathway through Sirt1, improves autophagy, slows down the senescence of hepatocytes, and alleviates NAFLD.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_8267
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_8267
PubMedID: 35897843

Title : Synthesis, Characterization and Biological Evaluation of Benzothiazole-Isoquinoline Derivative - Liu_2022_Molecules_27_9062
Author(s) : Liu W , Zhao D , He Z , Hu Y , Zhu Y , Zhang L , Jin L , Guan L , Wang S
Ref : Molecules , 27 :9062 , 2022
Abstract : Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression.
ESTHER : Liu_2022_Molecules_27_9062
PubMedSearch : Liu_2022_Molecules_27_9062
PubMedID: 36558194

Title : Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial - Shi_2021_Hepatol.Int__
Author(s) : Shi M , Li YY , Xu RN , Meng FP , Yu SJ , Fu JL , Hu JH , Li JX , Wang LF , Jin L , Wang FS
Ref : Hepatol Int , : , 2021
Abstract : BACKGROUND: Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood. METHODS: This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated. RESULTS: During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group. CONCLUSIONS: Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.
ESTHER : Shi_2021_Hepatol.Int__
PubMedSearch : Shi_2021_Hepatol.Int__
PubMedID: 34843069

Title : A facile microfluidic paper-based analytical device for acetylcholinesterase inhibition assay utilizing organic solvent extraction in rapid detection of pesticide residues in food - Jin_2020_Anal.Chim.Acta_1100_215
Author(s) : Jin L , Hao Z , Zheng Q , Chen H , Zhu L , Wang C , Liu X , Lu C
Ref : Anal Chim Acta , 1100 :215 , 2020
Abstract : The incompatibility of most organic solvents with acetylcholinesterase (AChE) inhibition assay normally limits pesticide extraction efficiency in sample pretreatment, which might cause false negatives in real world sample assessment. Herein, a novel method has been developed for an improved AChE inhibition assay via organic solvent extraction combined spontaneous in situ solvent evaporation on microfluidic paper-based analytical devices. Enzyme pre-immobilization procedure was spared and AChE was added to the system after sampling step until a complete in-situ solvent evaporation process was performed on chip. IC50 levels of the six investigated organophosphate and carbamate pesticides indicated a completely eliminated influence of solvents on AChE behavior with the new method. Most importantly, analytical performances were significantly improved in food sample measurements. Reduction in matrix effect was observed when acetonitrile was adopted for lettuce sample pretreatment instead of water. Studies on different pesticides suggested a remarkably decreased discrimination effect on recoveries from sample pretreatment with the new developed method. The recovery level for phoxim spiked head lettuce samples reached (107.5 +/- 14.2) %, in comparison with that of (18.6 +/- 1.4) % from water-based extraction. Spiked water and apple juice samples with carbaryl concentration of as low as 0.02 mg L(-1) were also successfully recognized with the present method by visual detection. This is the first report on direct sampling of organic extracts for AChE inhibition assay on-chip and it might provide a new perspective for real world sample assessments involving bio-reagents.
ESTHER : Jin_2020_Anal.Chim.Acta_1100_215
PubMedSearch : Jin_2020_Anal.Chim.Acta_1100_215
PubMedID: 31987143

Title : Plasma levels of soluble ST2, but not IL-33, correlate with the severity of alcoholic liver disease - Sun_2019_J.Cell.Mol.Med_23_887
Author(s) : Sun Z , Chang B , Huang A , Hao S , Gao M , Sun Y , Shi M , Jin L , Zhang W , Zhao J , Teng G , Han L , Tian H , Liang Q , Zhang JY , Zou Z
Ref : J Cell Mol Med , 23 :887 , 2019
Abstract : Alcoholic liver disease (ALD) is a complication that is a burden on global health and economy. Interleukin-33 (IL-33) is a newly identified member of the IL-1 cytokine family and is released as an "alarmin" during inflammation. Soluble suppression of tumourigenicity 2 (sST2), an IL-33 decoy receptor, has been reported as a new biomarker for the severity of systemic and highly inflammatory diseases. Here, we found the levels of plasma sST2, increased with the disease severity from mild to severe ALD. Importantly, the plasma sST2 levels in ALD patients not only correlated with scores for prognostic models (Maddrey's discriminant function, model for end-stage liver disease and Child-Pugh scores) and indexes for liver function (total bilirubin, international normalized ratio, albumin, and cholinesterase) but also correlated with neutrophil-associated factors as well as some proinflammatory cytokines. In vitro, lipopolysaccharide-activated monocytes down-regulated transmembrane ST2 receptor but up-regulated sST2 mRNA and protein expression and produced higher levels of tumour necrosis factor-alpha (TNF-alpha). By contrast, monocytes pretreated with recombinant sST2 showed decreased TNF-alpha production. In addition, although plasma IL-33 levels were comparable between healthy controls and ALD patients, we found the IL-33 expression in liver tissues from ALD patients was down-regulated at both RNA and protein levels. Immunohistochemical staining further showed that the decreased of IL-33-positive cells were mainly located in liver lobule area. These results suggested that sST2, but not IL-33, is closely related to the severity of ALD. Consequently, sST2 could be used as a potential biomarker for predicting the prognosis of ALD.
ESTHER : Sun_2019_J.Cell.Mol.Med_23_887
PubMedSearch : Sun_2019_J.Cell.Mol.Med_23_887
PubMedID: 30478965

Title : Endoplasmic Reticulum Targeting Ratiometric Fluorescent Probe for Carboxylesterase 2 Detection in Drug-Induced Acute Liver Injury - Tian_2019_Anal.Chem_91_15840
Author(s) : Tian X , Yan F , Zheng J , Cui X , Feng L , Li S , Jin L , James TD , Ma X
Ref : Analytical Chemistry , 91 :15840 , 2019
Abstract : Carboxylesterase 2 (CES2), an endoplasmic reticulum (ER) located phase I enzyme, plays a vital role in the metabolism of various endogenous and exogenous substances, and is regarded as an important target for the design of prodrugs. Unfortunately, superior highly selective ER targeting fluorescent probes for monitoring of CES2 are not currently available. Herein, we report an ER targeting CES2 selective and sensitive ratiometric fluorescent probe ERNB based on the ER localizing group p-toluenesulfonamide. ERNB possessed high specificity, sensitivity, and exhibited excellent subcellular localization when compared to commercial ER tracker, and was used to image CES2 in the ER of living cells. Additionally, using ERNB we evaluated the CES2 regulation under d,l-dithiothreitol and tunicamycin-induced ER stress. Furthermore, we determined the down regulation of CES2 activity and expression in the acetaminophen-induced acute liver injury model. On the basis of these results, we conclude that ERNB is a promising tool for highlighting the role of CES2 in the ER and in exploring the role of CES2 in the development of diseases associated with ER stress.
ESTHER : Tian_2019_Anal.Chem_91_15840
PubMedSearch : Tian_2019_Anal.Chem_91_15840
PubMedID: 31713417
Gene_locus related to this paper: human-CES2

Title : The removal of cyhalofop-butyl in soil by surplus Rhodopseudanonas palustris in wastewater purification - Wu_2019_J.Environ.Manage_245_168
Author(s) : Wu P , Mo W , Chen Z , Wang Y , Cui Y , Zhang Y , Song Y , Jin L , Hou Y , Zhu F , Cao B , Li N
Ref : J Environ Manage , 245 :168 , 2019
Abstract : The biorestoration of cyhalofop-butyl and fertility in soil using Rhodopseudanonas palustris (R. palustris) in the treated wastewater were investigated in this research. Cyhalofop-butyl was not degraded under control group. The treated wastewater containing R. palustris degraded cyhalofop-butyl and remediated fertility. Interestingly, the cyhalofop-butyl-hydrolyzing carboxylesterase gene was expressed after inoculation 24h. Subsequently, the cyhalofop-butyl-hydrolyzing carboxylesterase were synthesized to degrade cyhalofop-butyl. The cyhalofop-butyl started to be degraded after inoculation 24h. The cyhalofop-butyl as stimulus signal induced cyhalofop-butyl-hydrolyzing carboxylesterase gene expression through signal transduction pathway. This process took 24h for R. palustris as they were ancient bacteria. The residual organics in the wastewater provided sufficient carbon sources and energy for R. palustris under three dosage groups. The new method completed the remediation of cyhalofop-butyl pollution, the improvement of soil fertility and soybean processing wastewater treatment simultaneously, and realized the resource reutilization of wastewater and R. palustris as sludge.
ESTHER : Wu_2019_J.Environ.Manage_245_168
PubMedSearch : Wu_2019_J.Environ.Manage_245_168
PubMedID: 31152960

Title : Metabolic Profile of 3-Acetyl-11-Keto-beta-Boswellic Acid and 11-Keto-beta-Boswellic Acid in Human Preparations In Vitro, Species Differences, and Bioactivity Variation - Cui_2016_AAPS.J_18_1273
Author(s) : Cui Y , Tian X , Ning J , Wang C , Yu Z , Wang Y , Huo X , Jin L , Deng S , Zhang B , Ma X
Ref : AAPS J , 18 :1273 , 2016
Abstract : 3-Acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-beta-boswellic acid (KBA) are widely used in the clinic as anti-inflammatory drugs. However, these drugs have the poor bioavailability, which may be caused by their extensive metabolism. In this study, we systemically characterized both phase I and II metabolism of AKBA and KBA in vitro. In total, four major metabolites were firstly biosynthesized and identified using 1D and 2D NMR spectroscopy. Among them, three metabolites were novel. The kinetic parameters (K m , V max , CL int, and K i ) were also analyzed systematically in various biological samples. Finally, the deacetylation of AKBA and hydroxylation of KBA were confirmed to be the major metabolic pathways based on their large CL int and the high amounts of KBA (46.7%) and hydroxylated KBA (50.8%) along with a low amount of AKBA (2.50%) in human primary hepatocytes. Carboxylesterase 2 (CE2) selectively catalyzed the deacetylation of AKBA to form KBA. Although CYP3A4, CYP3A5, and CYP3A7 catalyzed the metabolism of KBA, CYP3A4 played a predominant role in the hydroxylation reaction of KBA in human. Notably, deacetylation and regioselective hydroxylation exhibited considerable species differences. Deacetylation was only observed in human liver microsomes and primary human hepatocytes; 21- and 20-mono-hydroxylation of KBA were primarily observed in human, monkey, and dog; and 16- and 30-mono-hydroxylation were observed in other species. More importantly, all four mono-hydroxylation metabolites exhibited a moderate anti-inflammatory activity. The 21- and 20-hydroxylation metabolites inhibited the expression of iNOS, the LPS-induced activation of IkBalpha and p65 phosphorylation, and suppressed p65 nuclear translocation in RAW264.7 cells.
ESTHER : Cui_2016_AAPS.J_18_1273
PubMedSearch : Cui_2016_AAPS.J_18_1273
PubMedID: 27329304

Title : Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos - Li_2016_Environ.Sci.Pollut.Res.Int_23_8275
Author(s) : Li VW , Tsui MP , Chen X , Hui MN , Jin L , Lam RH , Yu RM , Murphy MB , Cheng J , Lam PK , Cheng SH
Ref : Environ Sci Pollut Res Int , 23 :8275 , 2016
Abstract : The negative effects of overexposure to ultraviolet (UV) radiation in humans, including sunburn and light-induced cellular injury, are of increasing public concern. 4-Methylbenzylidene camphor (4-MBC), an organic chemical UV filter, is an active ingredient in sunscreen products. To date, little information is available about its neurotoxicity during early vertebrate development. Zebrafish embryos were exposed to various concentrations of 4-MBC in embryo medium for 3 days. In this study, a high concentration of 4-MBC, which is not being expected at the current environmental concentrations in the environment, was used for the purpose of phenotypic screening. Embryos exposed to 15 muM of 4-MBC displayed abnormal axial curvature and exhibited impaired motility. Exposure effects were found to be greatest during the segmentation period, when somite formation and innervation occur. Immunostaining of the muscle and axon markers F59, znp1, and zn5 revealed that 4-MBC exposure leads to a disorganized pattern of slow muscle fibers and axon pathfinding errors during the innervation of both primary and secondary motor neurons. Our results also showed reduction in AChE activity upon 4-MBC exposure both in vivo in the embryos (15 muM) and in vitro in mammalian Neuro-2A cells (0.1 muM), providing a possible mechanism for 4-MBC-induced muscular and neuronal defects. Taken together, our results have shown that 4-MBC is a teratogen and influences muscular and neuronal development, which may result in developmental defects.
ESTHER : Li_2016_Environ.Sci.Pollut.Res.Int_23_8275
PubMedSearch : Li_2016_Environ.Sci.Pollut.Res.Int_23_8275
PubMedID: 26888529

Title : Complete Genome Sequence of Paenibacillus polymyxa CF05, a Strain of Plant Growth-Promoting Rhizobacterium with Elicitation of Induced Systemic Resistance - Lei_2015_Genome.Announc_3_e00198
Author(s) : Lei M , Lu P , Jin L , Wang Y , Qin J , Xu X , Zhang L
Ref : Genome Announc , 3 : , 2015
Abstract : Paenibacillus polymyxa CF05 is a Gram-positive rod-shaped bacterium isolated from the interior of an ancient tree, Cryptomeria fortunei, in China. This bacterium displays potent biocontrol effects against certain soil-borne diseases and the elicitation of induced systemic resistance in tomatoes. Here, we report the complete genome sequence of P. polymyxa CF05.
ESTHER : Lei_2015_Genome.Announc_3_e00198
PubMedSearch : Lei_2015_Genome.Announc_3_e00198
PubMedID: 25883277
Gene_locus related to this paper: paepo-a0a0f6ex20 , paepo-a0a0f6em71 , paepo-a0a0f6ezz0

Title : Poly(aryl ether) Dendrons with Monopyrrolotetrathiafulvalene Unit-Based Organogels exhibiting Gel-Induced Enhanced Emission (GIEE) - Liu_2015_Chemistry_21_15235
Author(s) : Liu Y , Lei W , Chen T , Jin L , Sun G , Yin B
Ref : Chemistry , 21 :15235 , 2015
Abstract : A series of poly(aryl ether) dendrons with a monopyrrolo-tetrathiafulvalene unit linked through an acyl hydrazone linkage were designed and synthesized as low molecular mass organogelators (LMOGs). Two of the dendrons could gelate the aromatic solvents and some solvent mixtures, but the others could not gel all solvents tested except for n-pentanol. A subtle change on the molecular structure produces a great influence on the gelation behavior. Note that the dendrons could form the stable gel in the DMSO/water mixture without thermal treatment and could also form the binary gel with fullerene (C60 ) in toluene. The formed gels undergo a reversible gel-sol phase transition upon exposure to external stimuli, such as temperature and chemical oxidation/reduction. A number of experiments (SEM, FTIR spectroscopy, (1) H NMR spectroscopy, and UV/Vis absorption spectroscopy, and XRD) revealed that these dendritic molecules self-assembled into elastically interpenetrating one-dimensional fibrillar aggregates and maintain rectangular molecular-packing mode in organogels. The hydrogen bonding, pi-pi, and donor-acceptor interactions were found to be the main driving forces for formation of the gels. Moreover, the gel system exhibited gel-induced enhanced emission (GIEE) property in the visible region in spite of the absence of a conventional fluorophore unit and the fluorescence was effectively quenched by introduction of C60 .
ESTHER : Liu_2015_Chemistry_21_15235
PubMedSearch : Liu_2015_Chemistry_21_15235
PubMedID: 26471439

Title : Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle - Chen_2014_Nat.Genet_46_253
Author(s) : Chen S , Zhang G , Shao C , Huang Q , Liu G , Zhang P , Song W , An N , Chalopin D , Volff JN , Hong Y , Li Q , Sha Z , Zhou H , Xie M , Yu Q , Liu Y , Xiang H , Wang N , Wu K , Yang C , Zhou Q , Liao X , Yang L , Hu Q , Zhang J , Meng L , Jin L , Tian Y , Lian J , Yang J , Miao G , Liu S , Liang Z , Yan F , Li Y , Sun B , Zhang H , Zhu Y , Du M , Zhao Y , Schartl M , Tang Q , Wang J
Ref : Nat Genet , 46 :253 , 2014
Abstract : Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
ESTHER : Chen_2014_Nat.Genet_46_253
PubMedSearch : Chen_2014_Nat.Genet_46_253
PubMedID: 24487278
Gene_locus related to this paper: cynse-a0a3p8wch2 , cynse-a0a3p8vd14 , cynse-a0a3p8w747 , cynse-a0a3p8wq40 , cynse-a0a3p8wul3 , cynse-a0a3p8vqr4 , cynse-a0a3p8vmz4

Title : The genome of the hydatid tapeworm Echinococcus granulosus - Zheng_2013_Nat.Genet_45_1168
Author(s) : Zheng H , Zhang W , Zhang L , Zhang Z , Li J , Lu G , Zhu Y , Wang Y , Huang Y , Liu J , Kang H , Chen J , Wang L , Chen A , Yu S , Gao Z , Jin L , Gu W , Wang Z , Zhao L , Shi B , Wen H , Lin R , Jones MK , Brejova B , Vinar T , Zhao G , McManus DP , Chen Z , Zhou Y , Wang S
Ref : Nat Genet , 45 :1168 , 2013
Abstract : Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.
ESTHER : Zheng_2013_Nat.Genet_45_1168
PubMedSearch : Zheng_2013_Nat.Genet_45_1168
PubMedID: 24013640
Gene_locus related to this paper: echgr-k4epc5 , echmu-u6hbw4 , echgr-w6ugl0 , echgr-w6u7y4 , echgr-w6vaq5 , echgr-a0a068wxj3 , echgr-a0a068wgw1 , echgr-a0a068wl60

Title : Visible-light-activated photoelectrochemical biosensor for the study of acetylcholinesterase inhibition induced by endogenous neurotoxins - Huang_2013_Biosens.Bioelectron_45C_292
Author(s) : Huang Q , Chen H , Xu L , Lu D , Tang L , Jin L , Xu Z , Zhang W
Ref : Biosensors & Bioelectronics , 45C :292 , 2013
Abstract : In this report, a novel visible-light-activated photoelectrochemical biosensor was fabricated to study the inhibition of acetylcholinesterase (AChE) activity induced by two endogenous neurotoxins, 1(R)-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-Sal] and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline [(R)-NMSal], which have drawn much attention in the study of the pathogenesis of neurodegenerative diseases such as Parkinson's disease. The photoelectrode was prepared by three steps, as follows. At first, nitrogen and fluorine co-doped TiO2 nanotubes (TNs) were obtained by anodic oxidation of a Ti sheet. Secondly, silver nanoparticles (AgNPs) were deposited onto the TNs through a microwave-assisted heating polyol (MAHP) process. At last, AChE was immobilized on the obtained photoelectrode and the biosensor was marked as AChE/Ag/NFTNs. Due to the nitrogen and fluorine co-doping, the photoelectrochemical biosensors can produce high photocurrent under visible light irradiation. Moreover, the presence of AgNPs greatly increased the photocurrent response of the biosensor. AChE/Ag/NFTNs hybrid system was used to study AChE inhibition induced by (R)-Sal and (R)-NMSal. The result proved that both (R)-Sal and (R)-NMSal exhibited mixed and reversible inhibition against AChE. This strategy is of great significance for the development of novel photoelectrochemical biosensors in the future.
ESTHER : Huang_2013_Biosens.Bioelectron_45C_292
PubMedSearch : Huang_2013_Biosens.Bioelectron_45C_292
PubMedID: 23500378

Title : Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients - Shi_2012_Stem.Cells.Transl.Med_1_725
Author(s) : Shi M , Zhang Z , Xu R , Lin H , Fu J , Zou Z , Zhang A , Shi J , Chen L , Lv S , He W , Geng H , Jin L , Liu Z , Wang FS
Ref : Stem Cells Transl Med , 1 :725 , 2012
Abstract : Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients.
ESTHER : Shi_2012_Stem.Cells.Transl.Med_1_725
PubMedSearch : Shi_2012_Stem.Cells.Transl.Med_1_725
PubMedID: 23197664

Title : Three-dimensional ordered macroporous (3DOM) composite for electrochemical study on acetylcholinesterase inhibition induced by endogenous neurotoxin - Teng_2012_J.Phys.Chem.B_116_11180
Author(s) : Teng Y , Fu Y , Xu L , Lin B , Wang Z , Xu Z , Jin L , Zhang W
Ref : J Phys Chem B , 116 :11180 , 2012
Abstract : In this paper, an electrochemical acetylcholinesterase (AChE) inhibition assay based on three-dimensional ordered macroporous (3DOM) composite was conducted. The 3DOM composite was first fabricated on the glassy carbon electrode by electropolymerization of aniline in the presence of ionic liquid (IL) on a sacrificial silica nanospheres template. After the silica nanospheres were etched, an IL-doped polyaniline (IL-PANI) film with 3DOM morphology was formed. Then, gold nanoparticles (AuNPs) were decorated on the IL-PANI film by electrodeposition. The immobilized AChE on the 3DOM composite displayed favorable affinity to substrate acetylthiocholine chloride (ATCh), and the 3DOM composite showed excellent electrocatalytic effect on thiocholine, the hydrolysis product of ATCh. The presence of IL and AuNPs could improve the sensitivity by accelerating the electron transfer. The designed AChE biosensor was successfully applied to evaluate the AChE inhibition induced by endogenous neurotoxin 1(R),2N-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-NMSal]. The results demonstrate that (R)-NMSal exerts a considerable effect on AChE activity, and the inhibition is reversible. The developed method offers a new approach for AChE inhibition assay, which is of great benefit in understanding the mechanism behind neurotoxin-induced neurodegenerative disorders.
ESTHER : Teng_2012_J.Phys.Chem.B_116_11180
PubMedSearch : Teng_2012_J.Phys.Chem.B_116_11180
PubMedID: 22946763

Title : Dexamethasone-mediated transcriptional regulation of rat carboxylesterase 2 gene - Hori_2012_Xenobiotica_42_614
Author(s) : Hori T , Jin L , Fujii A , Furihata T , Nagahara Y , Chiba K , Hosokawa M
Ref : Xenobiotica , 42 :614 , 2012
Abstract : Rat carboxylesterase 2 (rCES2), which was previously identified as a methylprednisolone 21-hemisuccinate hydrolase, is highly inducible by dexamethasone in the liver. In the present study, we investigated the molecular mechanisms by which this induction occurs. Injection of dexamethasone (1 mg/kg weight) into rats resulted in increases in the expression of rCES2 mRNA in a time-dependent manner with a peak at 12 h after injection. In primary rat hepatocytes, the expression level of rCES2 mRNA was increased by treatment with 100 nM dexamethasone, and the increase was completely blocked in the presence of 10 microM mifepristone (RU-486), a potent inhibitor of glucocorticoid receptor (GR), or 10 microg/mL cycloheximide, a translation inhibitor. Luciferase assays revealed that 100 nM dexamethasone increased rCES2 promoter activities, although the effect of dexamethasone on the promoter activity was smaller than that on rCES2 mRNA expression. The increased activities were completely inhibited by treatment of the hepatocytes with 10 microM RU-486. Based on these results, it is concluded that dexamethasone enhances transcription of the rCES2 gene via GR in the rat liver and that the dexamethasone-mediated induction of rCES2 mRNA may be dependent on de novo protein synthesis. Our results provide clues to understanding what compounds induce rCES2.
ESTHER : Hori_2012_Xenobiotica_42_614
PubMedSearch : Hori_2012_Xenobiotica_42_614
PubMedID: 22235919

Title : Layer-by-Layer self-assembled acetylcholinesterase\/PAMAM-Au on CNTs modified electrode for sensing pesticides - Qu_2010_Bioelectrochemistry_77_139
Author(s) : Qu Y , Sun Q , Xiao F , Shi G , Jin L
Ref : Bioelectrochemistry , 77 :139 , 2010
Abstract : In this paper, an acetylcholinesterase (AChE)/dendrimers polyamidoamine (PAMAM)-Au/Carbon nanotubes (CNTs) multilayer modified electrode based on LbL self-assembled technique was employed in the detection of carbofuran in samples. The configuration of the nanostructure on the electrode provided a favorable environment to the immobilization of AChE. The modified films also improved the electrocatalytic characteristics and electron transfer speed between the films and the surface of electrode. The PAMAM-Au nanoparticles were characterized by SEM and UV-VIS methods. A set of experimental conditions were also optimized for the detection of the pesticides. A linear response over carbofuran concentration in the range of 4.8x10(-9)M to 0.9x10(-7)M was exhibited with a detection limit of 4.0x10(-9)M. The biosensor showed high sensitivity, good stability and reproducibility with promising application.
ESTHER : Qu_2010_Bioelectrochemistry_77_139
PubMedSearch : Qu_2010_Bioelectrochemistry_77_139
PubMedID: 19733130

Title : A new microdialysis-electrochemical device for in vivo simultaneous determination of acetylcholine and choline in rat brain treated with N-methyl-(R)-salsolinol - Zhu_2009_Biosens.Bioelectron_24_3594
Author(s) : Zhu W , An Y , Zheng J , Tang L , Zhang W , Jin L , Jiang L
Ref : Biosensors & Bioelectronics , 24 :3594 , 2009
Abstract : Acetylcholine (ACh) and choline (Ch) play a critical role in cholinergic neurotransmission and the abnormalities in their concentrations are related to several neural diseases. Therefore, the in vivo determination of ACh and Ch is important to the research on neurodegenerative disorders. In this work, electrochemical biosensors based on poly(m-(1,3)-phenylenediamine) (pmPD) and polytyramine (PTy) modified enzyme electrodes were fabricated. The electropolymerized pmPD polymer was used to exclude interfering substances and the PTy layer facilitated the immobilization of acetylcholinesterase (AChE) and choline oxidase (ChOx). Then, ACh/Ch sensor and Ch sensor were coupled with microdialysis to produce a novel device, which provides a sensitive and selective method for simultaneous determination of ACh and Ch. This method has detection limits of 63.0+/-3.4 nM for ACh and 25.0+/-1.2 nM for Ch. The integrated device was successfully applied to assessing the impact of endogenous neurotoxin N-methyl-(R)-salsolinol [1(R),2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, (R)-NMSal] on ACh and Ch concentration, which is of great benefit to understand the pathogenesis of Parkinson's disease.
ESTHER : Zhu_2009_Biosens.Bioelectron_24_3594
PubMedSearch : Zhu_2009_Biosens.Bioelectron_24_3594
PubMedID: 19523811

Title : A novel biosensor based on photoelectro-synergistic catalysis for flow-injection analysis system\/amperometric detection of organophosphorous pesticides - Wei_2009_Anal.Chim.Acta_643_13
Author(s) : Wei Y , Li Y , Qu Y , Xiao F , Shi G , Jin L
Ref : Anal Chim Acta , 643 :13 , 2009
Abstract : In this study, a highly sensitive amperometric biosensor based on photoelectro-synergistic catalysis for detecting organophosphorus pesticides (OPs) in flow-injection analysis (FIA) system has been developed. The acetylcholinesterase enzyme (AChE) was immobilized by adsorption into the nanostructured PbO2/TiO2/Ti, which also acted as the working electrode. This strategy was found to catalyze the oxidative reaction of thiocholine effectively, make the AChE/PbO2/TiO2/Ti biosensor detect the substrate at 0.30 V (vs. SCE), hundreds milli-volts lower than others reported. PbO2/TiO2/Ti and TiO2/Ti electrodes were prepared and investigated with atomic force microscope (AFM). Factors influencing the performance were optimized. The resulting flow system offered a fast, sensitive, and stable response. A value of 1.34 mM for the apparent Michaelis-Menten constant (K(M)(app)) was obtained. A wide linear inhibition response for trichlorfon was observed in the range of 0.01-20 microM with the detection limit of 0.1 nM. The results using this biosensor agreed very well with chromatographic method and we also examined the real samples successfully in this work.
ESTHER : Wei_2009_Anal.Chim.Acta_643_13
PubMedSearch : Wei_2009_Anal.Chim.Acta_643_13
PubMedID: 19446058

Title : Effect of (R)-salsolinol and N-methyl-(R)-salsolinol on the balance impairment between dopamine and acetylcholine in rat brain: involvement in pathogenesis of Parkinson disease - Zhu_2008_Clin.Chem_54_705
Author(s) : Zhu W , Wang D , Zheng J , An Y , Wang Q , Zhang W , Jin L , Gao H , Lin L
Ref : Clinical Chemistry , 54 :705 , 2008
Abstract : BACKGROUND: Parkinson disease (PD), a progressive neurodegenerative disease, affects at least 1% of population above the age of 65. Although the specific etiology of PD remains unclear, recently the endogenous neurotoxins such as (R)-salsolinol [(R)-Sal] and N-methyl-(R)-salsolinol [(R)-NMSal] have been thought to play a major role in PD. Much interest is focused on the degeneration of dopamine neurons induced by these neurotoxins. However, little literature is available on the impact of endogenous neurotoxins on the balance between dopamine (DA) and acetylcholine (ACh). METHODS: After injection of (R)-Sal or (R)-NMSal into the rat brain striatum, the concentrations of DA and its metabolites were detected by HPLC with electrochemical detection. We assessed the influence of neurotoxins on acetylcholinesterase (AChE) activity and developed a microdialysis-electrochemical device to measure ACh concentrations with enzyme-modified electrodes. RESULTS: (R)-Sal and (R)-NMSal led to concentration-dependent decreases in the activity of AChE. ACh concentrations in striatum treated with (R)-Sal or (R)-NMSal were increased to 131.7% and 239.8% of control, respectively. As to the dopaminergic system, (R)-NMSal caused a significant decrease in DA concentrations and (R)-Sal reduced the concentrations of DA metabolites in the striatum. CONCLUSIONS: (R)-Sal and (R)-NMSal exerted a considerable effect on the balance between DA and ACh by impairing the cholinergic system as well as the dopaminergic system. It is likely that the disruption of balance between DA and ACh plays a critical role in the pathogenesis of neurotoxin-induced PD.
ESTHER : Zhu_2008_Clin.Chem_54_705
PubMedSearch : Zhu_2008_Clin.Chem_54_705
PubMedID: 18238832

Title : In vitro metabolism of indiplon and an assessment of its drug interaction potential - Madan_2007_Xenobiotica_37_736
Author(s) : Madan A , Fisher A , Jin L , Chapman D , Bozigian HP
Ref : Xenobiotica , 37 :736 , 2007
Abstract : This study was designed to study the in vitro metabolism of indiplon, a novel hypnotic agent, and to assess its potential to cause drug interactions. In incubations with pooled human liver microsomes, indiplon was converted to two major, pharmacologically inactive metabolites, N-desmethyl-indiplon and N-desacetyl-indiplon. The N-deacetylation reaction did not require NADPH, and appeared to be catalyzed by organophosphate-sensitive microsomal carboxylesterases. The N-demethylation of indiplon was catalyzed by CYP3A4/5 based on the following observations: (1) the sample-to-sample variation in N-demethylation of indiplon ([S] = 100 microM) in a bank of human liver microsomes was strongly correlated with testosterone 6beta-hydroxylase (CYP3A4/5) activity (r(2) = 0.98), but not with any other CYP enzyme; (2) recombinant CYP1A1, CYP1A2, CYP3A4, CYP3A5 and CYP3A7 had the ability to catalyze this reaction; (3) the N-demethylation of indiplon was inhibited by CYP3A4/5 inhibitors (ketoconazole and troleandomycin), but not by a CYP1A2 inhibitor (furafylline). In pooled human liver microsomes, indiplon exhibited a weak capacity to inhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP3A4/5 and carboxylesterase (p-nitrophenylacetate hydrolysis) activities (IC50 >/= 20 microM). Clinical data available on indiplon support the conclusions of this paper that the in vitro metabolism of indiplon is catalyzed by multiple enzymes, and indiplon is a weak inhibitor of human CYP enzymes.
ESTHER : Madan_2007_Xenobiotica_37_736
PubMedSearch : Madan_2007_Xenobiotica_37_736
PubMedID: 17620220

Title : Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats - Zhao_2005_Am.J.Physiol.Regul.Integr.Comp.Physiol_288_R188
Author(s) : Zhao X , Dey A , Romanko OP , Stepp DW , Wang MH , Zhou Y , Jin L , Pollock JS , Webb RC , Imig JD
Ref : American Journal of Physiology Regul Integr Comp Physiol , 288 :R188 , 2005
Abstract : Previous studies suggest that epoxyeicosatrienoic acids (EETs) are vasodilators of the mesenteric artery; however, the production and regulation of EETs in the mesenteric artery remain unclear. The present study was designed 1) to determine which epoxygenase isoform may contribute to formation of EETs in mesenteric arteries and 2) to determine the regulation of mesenteric artery cytochrome P-450 (CYP) enzymes in obese Zucker rats. Microvessels were incubated with arachidonic acid, and CYP enzyme activity was determined. Mesenteric arteries demonstrate detectable epoxygenase and hydroxylase activities. Next, protein and mRNA expressions were determined in microvessels. Although renal microvessels express CYP2C23 mRNA and protein, mesenteric arteries lacked CYP2C23 expression. CYP2C11 and CYP2J mRNA and protein were expressed in mesenteric arteries and renal microvessels. In addition, mesenteric artery protein expression was evaluated in lean and obese Zucker rats. Compared with lean Zucker rats, mesenteric arterial CYP2C11 and CYP2J proteins were decreased by 38 and 43%, respectively, in obese Zucker rats. In contrast, soluble epoxide hydrolase mRNA and protein expressions were significantly increased in obese Zucker rat mesenteric arteries. In addition, nitric oxide-independent dilation evoked by acetylcholine was significantly attenuated in mesenteric arteries of obese Zucker rats. These data suggest that the main epoxygenase isoforms expressed in mesenteric arteries are different from those expressed in renal microvessels and that decreased epoxygenases and increased soluble epoxide hydrolase are associated with impaired mesenteric artery dilator function in obese Zucker rats.
ESTHER : Zhao_2005_Am.J.Physiol.Regul.Integr.Comp.Physiol_288_R188
PubMedSearch : Zhao_2005_Am.J.Physiol.Regul.Integr.Comp.Physiol_288_R188
PubMedID: 15345471

Title : Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans - Song_2004_DNA.Res_11_179
Author(s) : Song Y , Tong Z , Wang J , Wang L , Guo Z , Han Y , Zhang J , Pei D , Zhou D , Qin H , Pang X , Zhai J , Li M , Cui B , Qi Z , Jin L , Dai R , Chen F , Li S , Ye C , Du Z , Lin W , Yu J , Yang H , Huang P , Yang R
Ref : DNA Research , 11 :179 , 2004
Abstract : Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity.
ESTHER : Song_2004_DNA.Res_11_179
PubMedSearch : Song_2004_DNA.Res_11_179
PubMedID: 15368893
Gene_locus related to this paper: yerpe-BIOH , yerpe-IRP1 , yerpe-PIP , yerpe-PLDB , yerpe-PTRB , yerpe-q8zey9 , yerpe-Y0644 , yerpe-y1616 , yerpe-y3224 , yerpe-YPLA , yerpe-YPO0180 , yerpe-YPO0667 , yerpe-YPO0773 , yerpe-YPO0776 , yerpe-YPO0986 , yerpe-YPO1501 , yerpe-YPO1997 , yerpe-YPO2002 , yerpe-YPO2336 , yerpe-YPO2526 , yerpe-YPO2638 , yerpe-YPO2814

Title : Genetics of metabolic variations between Yersinia pestis biovars and the proposal of a new biovar, microtus - Zhou_2004_J.Bacteriol_186_5147
Author(s) : Zhou D , Tong Z , Song Y , Han Y , Pei D , Pang X , Zhai J , Li M , Cui B , Qi Z , Jin L , Dai R , Du Z , Wang J , Guo Z , Huang P , Yang R
Ref : Journal of Bacteriology , 186 :5147 , 2004
Abstract : Yersinia pestis has been historically divided into three biovars: antiqua, mediaevalis, and orientalis. On the basis of this study, strains from Microtus-related plague foci are proposed to constitute a new biovar, microtus. Based on the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis strains can be assigned to one of four biovars: antiqua (glycerol positive, arabinose positive, and nitrate positive), mediaevalis (glycerol positive, arabinose positive, and nitrate negative), orientalis (glycerol negative, arabinose positive, and nitrate positive), and microtus (glycerol positive, arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene results in the glycerol-negative characteristic of biovar orientalis strains. Two kinds of point mutations in the napA gene may cause the nitrate reduction-negative characteristic in biovars mediaevalis and microtus, respectively. A 122-bp frameshift deletion in the araC gene may lead to the arabinose-negative phenotype of biovar microtus strains. Biovar microtus strains have a unique genomic profile of gene loss and pseudogene distribution, which most likely accounts for the human attenuation of this new biovar. Focused, hypothesis-based investigations on these specific genes will help delineate the determinants that enable this deadly pathogen to be virulent to humans and give insight into the evolution of Y. pestis and plague pathogenesis. Moreover, there may be the implications for development of biovar microtus strains as a potential vaccine.
ESTHER : Zhou_2004_J.Bacteriol_186_5147
PubMedSearch : Zhou_2004_J.Bacteriol_186_5147
PubMedID: 15262951
Gene_locus related to this paper: yerpe-YPLA