Li N

References (74)

Title : Ultrasensitive Quantification Method for Understanding Biologically Relevant Concentrations of Host Cell Proteins in Therapeutics - Zhang_2023_Anal.Chem__
Author(s) : Zhang S , Zhao B , Adaniya S , Xiao H , Li N
Ref : Analytical Chemistry , : , 2023
Abstract : Certain host cell proteins (HCPs) in biotherapeutic drugs may be detrimental to drug product quality even when they are present at the subppm level. Therefore, an analytical method that can reliably quantify trace amounts of HCPs is desirable. This study demonstrates a novel strategy to quantify HCPs present at subppm levels with ProteoMiner enrichment coupled with limited digestion followed by targeted analysis with nano-liquid chromatography-parallel reaction monitoring. The method can achieve LLOQ values as low as 0.06 ppm, with an accuracy of 85%-111% of the theoretical value, and inter-run and intrarun precision within 12% and 25%, respectively. The approach was applied to the quantification of five high-risk HCPs in drug products. The results indicated that 2.5 ppm lysosomal acid lipase, 0.14 ppm liver carboxylesterase, 1.8 ppm palmitoyl-protein thioesterase 1, and 1 ppm cathepsin D affected the stability of drug products, whereas drug products could safely contain 1.5 ppm lipoprotein lipase, 0.1 ppm lysosomal acid lipase, or 0.3 ppm cathepsin D. In combination with lipase activity analysis, the accurate quantification of lipases/esterases in drug products enables better understanding and comparison of the enzymatic activity of polysorbate degradation from endogenous proteins.
ESTHER : Zhang_2023_Anal.Chem__
PubMedSearch : Zhang_2023_Anal.Chem__
PubMedID: 36977129

Title : Flexible changes to the Heliothis virescens ascovirus 3h (HvAV-3h) virion components affect pathogenicity against different host larvae species - Yu_2023_Microbiol.Spectr__e0248823
Author(s) : Yu H , Chen H , Li N , Yang CJ , Xiao HY , Chen G , Huang GH
Ref : Microbiol Spectr , :e0248823 , 2023
Abstract : The pathogenicity of a virus to a specific host species is an inerratic and describable ability of a virus to cause infection but is generally shaped by a variety of abiotic and biotic factors. In this investigation, the variations in pathogenicity of Heliothis virescens ascovirus 3h (HvAV-3h) to five noctuid pests were assessed based on mass spectrometry analysis on the virion compositions. Twenty-nine common HvAV-3h proteins were shared across all hosts, and different flexible proteins were identified in the virions of each specific host. Different host proteins were identified as HvAV-3h virion-associated proteins, including different detoxification enzyme proteins. Furthermore, a relatively fixed relationship between viral replication and changes in host detoxification enzyme activity caused by deficiencies in various viral structural proteins was found in the host larvae using a correlation matrix analysis: the host larval carboxylesterase and cytochrome P450 monooxygenases generally had highly similar responses to the viruses blocked by different structural proteins' antisera and their effects on viral DNA replication. Different interaction patterns for the virion structural proteins were found in different host larvae-produced virions, and the interactions between Spodoptera litura glutathione S-transferases and viral structural proteins were confirmed. The different host responses after viral infection could be the reason for the changes in viral pathogenicity, while the virus responses gradually adapted to the different hosts and there were flexible changes in the virion structures.IMPORTANCEDifferent pathogenic processes of a virus in different hosts are related to the host individual differences, which makes the virus undergoes different survival pressures. Here, we found that the virions of an insect virus, Heliothis virescens ascovirus 3h (HvAV-3h), had different protein composition when they were purified from different host larval species. These "adaptive changes" of the virions were analyzed in detail in this study, which mainly included the differences of the protein composition of virions and the differences in affinity between virions and different host proteins. The results of this study revealed the flexible changes of viruses to help themselves adapt to different hosts. Also, these interesting findings can provide new insights to improve our understanding of virus adaptability and virulence differentiation caused by the adaptation process.
ESTHER : Yu_2023_Microbiol.Spectr__e0248823
PubMedSearch : Yu_2023_Microbiol.Spectr__e0248823
PubMedID: 37943038

Title : Polyphenols: Natural food grade biomolecules for treating neurodegenerative diseases from a multi-target perspective - Li_2023_Front.Nutr_10_1139558
Author(s) : Li Z , Zhao T , Shi M , Wei Y , Huang X , Shen J , Zhang X , Xie Z , Huang P , Yuan K , Li N , Qin D
Ref : Front Nutr , 10 :1139558 , 2023
Abstract : As natural functional bioactive ingredients found in foods and plants, polyphenols play various antioxidant and anti-inflammatory roles to prevent the development of disease and restore human health. The multi-target modulation of polyphenols provides a novel practical therapeutic strategy for neurodegenerative diseases that are difficult to treat with traditional drugs like glutathione and cholinesterase inhibitors. This review mainly focuses on the efficacy of polyphenols on ischemic stroke, Parkinson's disease and Alzheimer's disease, including in vivo and in vitro experimental studies. It is further emphasized that polyphenols exert neuroprotective effects primarily through inhibiting production of oxidative stress and inflammatory cytokines, which may be the underlying mechanism. However, polyphenols are still rarely used as medicines to treat neurodegenerative diseases. Due to the lack of clinical trials, the mechanism of polyphenols is still in the stage of insufficient exploration. Future large-scale multi-center randomized controlled trials and in-depth mechanism studies are still needed to fully assess the safety, efficacy and side effects of polyphenols.
ESTHER : Li_2023_Front.Nutr_10_1139558
PubMedSearch : Li_2023_Front.Nutr_10_1139558
PubMedID: 36925964

Title : Hydrolytic Metabolism of Withangulatin A Mediated by Serum Albumin Instead of Common Esterases in Plasma - Zhuang_2023_Eur.J.Drug.Metab.Pharmacokinet__
Author(s) : Zhuang Y , Wang Y , Li N , Meng H , Li Z , Luo J , Qiu Z
Ref : Eur J Drug Metab Pharmacokinet , : , 2023
Abstract : BACKGROUND AND OBJECTIVES: The oral bioavailability of withangulatin A (WA) is low and may undergo first-pass metabolism because of the presence of two esters bonds. This study aimed to identify the hydrolysis behavior and mechanism of WA, thus enriching its structure-pharmacokinetic relationship. METHODS: The in vivo pharmacokinetic studies of WA in rats were first investigated, followed by in vitro assays including metabolic stability, phenotyping identification and metabolic kinetics assays. After screening out the responsible enzymes with higher catalytic capacity, molecular docking study was performed to demonstrate the interaction mode between WA and metabolic enzymes. Then, metabolites in human serum albumin (HSA) were identified by LC-TOF-MS/MS. RESULTS: In rats, the oral bioavailability of WA was only 2.83%. In vitro, WA was hydrolyzed in both rat and human plasma and could not be inhibited by selective esterase inhibitors. Physiologic concentration of HSA not recombinant human carboxylesterases (rhCES) could significantly hydrolyze WA, and it had a similar hydrolytic capacity with human plasma to WA. Furthermore, WA could stably bind to HSA by forming hydrogen bonds with Lys199 and Arg410, accompanied by the metabolic reaction of the lactone ring opening. CONCLUSION: The study showed that WA underwent obvious hydrolysis in rat and human plasma, which implied a strong first-pass effect. Serum albumin rather than common esterases primarily contributed to the hydrolytic metabolism of WA in plasma.
ESTHER : Zhuang_2023_Eur.J.Drug.Metab.Pharmacokinet__
PubMedSearch : Zhuang_2023_Eur.J.Drug.Metab.Pharmacokinet__
PubMedID: 37344636

Title : APC and P53 mutations synergise to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer - Tian_2023_Gut__
Author(s) : Tian Y , Wang X , Cramer Z , Rhoades J , Estep KN , Ma X , Adams-Tzivelekidis S , Katona BW , Johnson FB , Yu Z , Blanco MA , Lengner CJ , Li N
Ref : Gut , : , 2023
Abstract : OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with the majority of cases initiated by inactivation of the APC tumour suppressor. This results in the constitutive activation of canonical WNT pathway transcriptional effector -catenin, along with induction of WNT feedback inhibitors, including the extracellular palmitoleoyl-protein carboxylesterase NOTUM which antagonises WNT-FZD receptor-ligand interactions. Here, we sought to evaluate the effects of NOTUM activity on CRC as a function of driver mutation landscape. DESIGN: Mouse and human colon organoids engineered with combinations of CRC driver mutations were used for Notum genetic gain-of-function and loss-of-function studies. In vitro assays, in vivo endoscope-guided orthotopic organoid implantation assays and transcriptomic profiling were employed to characterise the effects of Notum activity. Small molecule inhibitors of Notum activity were used in preclinical therapeutic proof-of-principle studies targeting oncogenic Notum activity. RESULTS: NOTUM retains tumour suppressive activity in APC-null adenomas despite constitutive -catenin activity. Strikingly, on progression to adenocarcinoma with P53 loss, NOTUM becomes an obligate oncogene. These phenotypes are Wnt-independent, resulting from differential activity of NOTUM on glypican 1 and 4 in early-stage versus late-stage disease, respectively. Ultimately, preclinical mouse models and human organoid cultures demonstrate that pharmacological inhibition of NOTUM is highly effective in arresting primary adenocarcinoma growth and inhibiting metastatic colonisation of distal organs. CONCLUSIONS: Our findings that a single agent targeting the extracellular enzyme NOTUM is effective in treating highly aggressive, metastatic adenocarcinomas in preclinical mouse models and human organoids make NOTUM and its glypican targets therapeutic vulnerabilities in advanced CRC.
ESTHER : Tian_2023_Gut__
PubMedSearch : Tian_2023_Gut__
PubMedID: 37591698

Title : Hydrolysis enabled specific colorimetric assay of carbosulfan with sensitivity manipulation via metal-doped or metal-free carbon nanozyme - Zhu_2023_Biosens.Bioelectron_243_115786
Author(s) : Zhu D , Li N , Zhang M , Wang Y , Li F , Hou T
Ref : Biosensors & Bioelectronics , 243 :115786 , 2023
Abstract : Precise determination of the carbamate pesticide carbosulfan is crucial for assessing the associated risks in food and environment. Due to the strong interaction between carbosulfan and target enzyme, current methods primarily depend on the acetylcholinesterase (AChE) inhibition strategy, which generally lacks selectivity. In this study, we propose a nanozyme colorimetric sensor for the specific carbosulfan detection, based on its distinctive hydrolysis property. In contrast to other pesticides, carbosulfan can be hydrolyzed to produce the reductive sulfide compound by the cleavage of N-S bond under acidic condition, thereby significantly hindering the nanozyme-mediated chromogenic reaction. Consequently, the absorbance is significantly correlated with carbosulfan concentration. Furthermore, the influence of nanozyme type is disclosed, and two oxidase-like carbon nanozymes were formulated, namely metal-free NC and metal-based CeO(2)@NC. However, the distinct active sites significantly impact the proposed sensor. For CeO(2)@NC-based sensor, the produced sulfide compounds not only poison Ce active site, but also consume the reactive oxygen species, thereby, exhibiting high sensitivity with low detection limit of 3.3 nM. By contrast, the metal-free nature of NC allows the assay to remain unaffected by coordination effects, exhibiting superior anti-interference capability. This work not only offers an efficient alternative to the conventional method for detecting carbosulfan specifically, but also shed light on the role of metal-based or metal-free nanozyme among analytical applications.
ESTHER : Zhu_2023_Biosens.Bioelectron_243_115786
PubMedSearch : Zhu_2023_Biosens.Bioelectron_243_115786
PubMedID: 37883845

Title : Activity-Based Protein Profiling Probe for the Detection of Enzymes Catalyzing Polysorbate Degradation - Liu_2022_Anal.Chem_94_8625
Author(s) : Liu GY , Nie S , Zheng X , Li N
Ref : Analytical Chemistry , 94 :8625 , 2022
Abstract : Polysorbates are nonionic surfactants that have been widely used in biotherapeutic formulations to prevent protein aggregation and denaturation. However, polysorbates are subject to degradation after prolonged storage if certain lipases are present in the biotherapeutic product. Because the degradation of polysorbates compromises the shelf life of biotherapeutics and leads to the formation of undesirable products such as protein aggregates and subvisible particles, it is important to identify the active enzymes that catalyze polysorbate hydrolysis. In this study, we developed a novel fluorophosphonate activity-based protein profiling (ABPP) probe (termed the REGN probe), which mimics the structure of polysorbate and targets lipases catalyzing polysorbate degradation. We demonstrated that the REGN probe could enrich certain lipases from Chinese hamster ovary (CHO) cell lysate by more than 100-fold compared with direct tryptic digestion. Furthermore, we found that the REGN probe had higher lipase enrichment efficiency than commercially available ABPP probes including fluorophosphonate-biotin (FP-biotin) and FP-desthiobiotin. Remarkably, the REGN probe can enrich several lipases that cannot be labeled by commercial probes, such as lysosomal acid lipase and cytosolic phospholipase A2. Additionally, we showed that lipases with abundances as low as 0.08 ppm in drug substances were detected by the REGN probe enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Collectively, we have developed a novel ABPP probe with higher enrichment efficiency and broader coverage for lipases compared with commercial probes, and this probe can be used to detect the trace level of lipases in biotherapeutic products and to facilitate their development and manufacturing.
ESTHER : Liu_2022_Anal.Chem_94_8625
PubMedSearch : Liu_2022_Anal.Chem_94_8625
PubMedID: 35679579

Title : Organophosphate esters cause thyroid dysfunction via multiple signaling pathways in zebrafish brain - Yan_2022_Environ.Sci.Ecotechnol_12_100198
Author(s) : Yan Z , Feng C , Jin X , Wang F , Liu C , Li N , Qiao Y , Bai Y , Wu F , Giesy JP
Ref : Environ Sci Ecotechnol , 12 :100198 , 2022
Abstract : Organophosphate esters (OPEs) are widespread in various environmental media, and can disrupt thyroid endocrine signaling pathways. Mechanisms by which OPEs disrupt thyroid hormone (TH) signal transduction are not fully understood. Here, we present in vivo-in vitro-in silico evidence establishing OPEs as environmental THs competitively entering the brain to inhibit growth of zebrafish via multiple signaling pathways. OPEs can bind to transthyretin (TTR) and thyroxine-binding globulin, thereby affecting the transport of TH in the blood, and to the brain by TTR through the blood-brain barrier. When GH3 cells were exposed to OPEs, cell proliferation was significantly inhibited given that OPEs are competitive inhibitors of TH. Cresyl diphenyl phosphate was shown to be an effective antagonist of TH. Chronic exposure to OPEs significantly inhibited the growth of zebrafish by interfering with thyroperoxidase and thyroglobulin to inhibit TH synthesis. Based on comparisons of modulations of gene expression with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, signaling pathways related to thyroid endocrine functions, such as receptor-ligand binding and regulation of hormone levels, were identified as being affected by exposure to OPEs. Effects were also associated with the biosynthesis and metabolism of lipids, and neuroactive ligand-receptor interactions. These findings provide a comprehensive understanding of the mechanisms by which OPEs disrupt thyroid pathways in zebrafish.
ESTHER : Yan_2022_Environ.Sci.Ecotechnol_12_100198
PubMedSearch : Yan_2022_Environ.Sci.Ecotechnol_12_100198
PubMedID: 36157343

Title : Development of esterase-resistant and highly active ghrelin analogs via thiol-ene click chemistry - Li_2022_Biorxiv__
Author(s) : Li H-Z , Shao X-X , Shou L-L , Li N , Liu Y-L , Xu Z-G , Guo Z-Y
Ref : Biorxiv , : , 2022
Abstract : The orexigenic peptide ghrelin exerts important functions in energy metabolism and cellular homeostasis by activating the growth hormone secretagogue receptor type 1a (GHSR1a), and thus has therapeutic potential to treat certain diseases. Native ghrelin carries an essential O-fatty acyl moiety at the side-chain of its third Ser residue; however, this posttranslational modification is susceptible to hydrolysis by certain esterases in circulation, representing a major route of in vivo inactivation of ghrelin. In the present study, we developed a novel approach to prepare various esterase-resistant ghrelin analogs via photo-induced thiol-ene click chemistry. A recombinant unacylated human ghrelin mutant carrying a unique Cys residue at the third position was reacted with commercially available end alkenes, thus various alkyl moieties were introduced to the side-chain of its unique Cys residue via a thioether bond. Among eleven S-alkylated ghrelin analogs, analog 11, generated by reacting with 2-methyl-1-octene, not only acquired much higher stability in human serum and fetal bovine serum, but also acquired moderately higher activity compared with native human ghrelin. Thus, the present study not only provided an efficient approach to prepare various esterase-resistant ghrelin analogs, but also produced a novel highly stable and highly active ghrelin analog with therapeutic potential.Competing Interest StatementThe authors have declared no competing interest.BSAbovine serum albuminCREcAMP-response elementDAGdes-acyl ghrelinGHSR1agrowth hormone secretagogue receptor type 1aDMEMDulbecco's Modified Eagle MediumGOATghrelin O-acyltransferaseHEKhuman embryonic kidneyHPLChigh performance liquid chromatographyLEAP2liver-expressed antimicrobial peptide 2LEDlight emitting diodeMBOAT4membrane-bound O-acyltransferase domain containing 4NanoBiTNanoLuc Binary TechnologyPBSphosphate-buffered salineSDstandard deviationsLgBiTsecretory large NanoLuc fragment for NanoBiTSmBiTlow-affinity complementation tag for NanoBiTTFAtrifluoroacetic acidUAGunacylated ghrelinUVultra-violet
ESTHER : Li_2022_Biorxiv__
PubMedSearch : Li_2022_Biorxiv__
PubMedID:

Title : Identification and quantification of a problematic host cell protein to support therapeutic protein development - E_2022_J.Pharm.Sci__
Author(s) : E SY , Hu Y , Molden R , Qiu H , Li N
Ref : J Pharm Sci , : , 2022
Abstract : Monitoring of residual host cell proteins (HCPs) in therapeutic protein is essential to ensure product quality, safety and efficacy. Despite the development of advanced mass spectrometry techniques and optimized workflows, identifying and quantifying all problematic HCPs present at low levels remain challenging. Here, we developed a practical, effective strategy for the identification and quantification of low abundance HCPs, which facilitates the improvement of downstream purification process to eliminate potentially problematic HCPs. A case study of using this strategy to investigate a problematic HCP is presented. Initially, a commonly used native digestion approach coupled with UPLC-MS/MS was applied for HCP profiling, wherein several lipases and proteases were identified in a monoclonal antibody named mAb1 in early stages of purification process development. A highly active lipase, liver carboxylesterase (CES), was found to be responsible for polysorbate 80 degradation. To facilitate process improvement, after the identification of CES, we developed a highly sensitive LC-MS/MS-MRM assay with a lower limit of quantification of 0.05 ppm for routine monitoring of the CES in mAb1 produced through the different processes. This workflow was applied in low-level lipase identification and absolute quantification, which facilitated the investigation of polysorbate degradation and downstream purification improvement to further remove the problematic HCP. The current MRM method increased the sensitivity of HCP quantification by over 10-fold that in previously published studies, thus meeting the needs for quantification of problematic HCPs at sub-ppm to ppb levels during drug development. This workflow could be readily adapted to the detection and quantification of other problematic HCPs present at extremely low levels in therapeutic protein drug candidates.
ESTHER : E_2022_J.Pharm.Sci__
PubMedSearch : E_2022_J.Pharm.Sci__
PubMedID: 36220394

Title : Identification of the specific causes of polysorbate 20 degradation in monoclonal antibody formulations containing multiple lipases - Zhang_2022_Pharm.Res_39_75
Author(s) : Zhang S , Riccardi C , Kamen D , Reilly J , Mattila J , Bak H , Xiao H , Li N
Ref : Pharm Res , 39 :75 , 2022
Abstract : PURPOSE: Polysorbates (PS) are excipients used in the biotech industry to stabilize monoclonal antibody (mAb) protein products. However, PS in drug product formulations can be degraded during storage and lead to particle formation because of the limited solubility of the free fatty acids released through the enzymatic hydrolysis of PS-a process driven by residual host cell proteins, especially lipases, that are co-purified with the drugs. When multiple lipases are present, it is very difficult to know the cause for PS degradation. In this study, we aim to determine the cause of PS degradation from two lipases, lysosomal acid lipase (LAL) and lipoprotein lipase (LPL). METHODS: PS degradation pattern of the drug product was compared with those induced by recombinant lipases. Correlations between the concentration of LPL or LAL and PS20 loss were compared. Specific inhibitors, LAL inhibitor lalistat2 and LPL inhibitor GSK264220A, were used to differentiate their degradation of PS in the drug products. RESULTS: The complete inhibition of PS20 degradation by lalistat2 suggested that LAL, rather than LPL, was responsible for the PS20 degradation. In addition, LAL was more strongly correlated than LPL with the percentage of PS20 degradation. No PS20 degradation was observed for several mAbs containing similar levels of LPL (0.5-1.5 ppm) in the absence of LAL, suggesting that LPL concentrations below 1.5 ppm does not degrade PS20 in drug products. CONCLUSIONS: LAL was determined to be the cause of the PS20 degradation. This study provides a practical strategy to determine the root cause of PS degradation.
ESTHER : Zhang_2022_Pharm.Res_39_75
PubMedSearch : Zhang_2022_Pharm.Res_39_75
PubMedID: 34981317

Title : Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics - Yang_2022_Nat.Genet_54_1553
Author(s) : Yang T , Liu R , Luo Y , Hu S , Wang D , Wang C , Pandey MK , Ge S , Xu Q , Li N , Li G , Huang Y , Saxena RK , Ji Y , Li M , Yan X , He Y , Liu Y , Wang X , Xiang C , Varshney RK , Ding H , Gao S , Zong X
Ref : Nat Genet , 54 :1553 , 2022
Abstract : Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
ESTHER : Yang_2022_Nat.Genet_54_1553
PubMedSearch : Yang_2022_Nat.Genet_54_1553
PubMedID: 36138232
Gene_locus related to this paper: pea-a0a9d4zt76

Title : Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy - Zou_2021_J.Proteomics__104124
Author(s) : Zou S , Dong R , Wang J , Liang B , Zhu T , Zhao S , Zhang Y , Wang T , Zou P , Li N , Wang Y , Chen M , Zhou C , Zhang T , Luo L
Ref : J Proteomics , :104124 , 2021
Abstract : We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SIGNIFICANCE: This preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP.
ESTHER : Zou_2021_J.Proteomics__104124
PubMedSearch : Zou_2021_J.Proteomics__104124
PubMedID: 33545297

Title : Bioactive phenylpropanoid derivatives from the fruits of Lycium ruthenicum Murr - Zhao_2021_Bioorg.Chem_116_105307
Author(s) : Zhao SS , Li S , Luo ZH , Zhou ZQ , Li N , Wang Y , Yao XS , Gao H
Ref : Bioorg Chem , 116 :105307 , 2021
Abstract : Eight new (1-7 and 15) and 18 known (8-14 and 16-26) phenylpropanoid derivatives were isolated from the fruits of Lycium ruthenicum Murr. (black wolfberry). Their structures were determined by comprehensive spectroscopic analyses, chemical methods, and comparisons of spectroscopic data. Four known compounds (16, 17, 24, and 26) were firstly isolated from the genus Lycium. Interestingly, compounds 1/2 and 4/5 were isolated as two pairs of inseparable anomers owing to the tautomerism of the free hemiacetal at C-1'' in solution. The antioxidant, alpha-glucosidase inhibitory, and acetylcholinesterase (AChE) inhibitory activities of compounds 1-26 were evaluated. Some compounds possessed DPPH radical scavenging activity, and all compounds (1-26) exhibited different levels of oxygen radical absorbance capacity (ORAC). One compound displayed alpha-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).
ESTHER : Zhao_2021_Bioorg.Chem_116_105307
PubMedSearch : Zhao_2021_Bioorg.Chem_116_105307
PubMedID: 34482167

Title : Esterase D stabilizes FKBP25 to suppress mTORC1 - Yang_2021_Cell.Mol.Biol.Lett_26_50
Author(s) : Yang Y , Chen X , Yao W , Cui X , Li N , Lin Z , Zhao B , Miao J
Ref : Cellular & Molecular Biology Lett , 26 :50 , 2021
Abstract : BACKGROUND: Esterase D (ESD) is a nonspecific esterase that detoxifies formaldehyde. Many reports have stated that ESD activity is associated with a variety of physiological and pathological processes. However, the detailed signaling pathway of ESD remains poorly understood. METHODS: Considering the advantages of the small chemical molecule, our recent work demonstrated that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) activates ESD, and will be a good tool for studying ESD further. Firstly, we determined the interaction between ESD and FK506 binding protein 25 (FKBP25) by yeast two-hybrid assay and co-immunoprecipitation (CO-IP) and analyzed the phosphorylation levels of mTORC1, P70S6K and 4EBP1 by western blot. Furthermore, we used the sulforhodamine B (SRB) and chick chorioallantoic membrane (CAM) assay to analyze cell viability in vitro and in vivo after treatment with ESD activator FPD5. RESULTS: We screened FKBP25 as a candidate protein to interact with ESD by yeast two-hybrid assay. Then we verified the interaction between ESD and endogenous FKBP25 or ectopically expressed GFP-FKBP25 by CO-IP. Moreover, the N-terminus (1-90 aa) domain of FKBP25 served as the crucial element for their interaction. More importantly, ESD reduced the K48-linked poly-ubiquitin chains of FKBP25 and thus stabilized cytoplasmic FKBP25. ESD also promoted FKBP25 to bind more mTORC1, suppressing the activity of mTORC1. In addition, ESD suppressed tumor cell growth in vitro and in vivo through autophagy. CONCLUSIONS: These findings provide novel evidence for elucidating the molecular mechanism of ESD and ubiquitination of FKBP25 to regulate autophagy and cancer cell growth. The ESD/FKBP25/mTORC1 signaling pathway is involved in inhibiting tumor cell growth via regulating autophagy.
ESTHER : Yang_2021_Cell.Mol.Biol.Lett_26_50
PubMedSearch : Yang_2021_Cell.Mol.Biol.Lett_26_50
PubMedID: 34875997

Title : Avobenzone and nanoplastics affect the development of zebrafish nervous system and retinal system and inhibit their locomotor behavior - Liu_2021_Sci.Total.Environ__150681
Author(s) : Liu Y , Wang Y , Li N , Jiang S
Ref : Sci Total Environ , :150681 , 2021
Abstract : The use of cosmetics is growing with each passing day, arousing widespread attention to their ingredients. Avobenzone (AVO) and nanoplastics (NPs) are typical ingredients in cosmetics, which coexist in the aquatic environment and have a combined effect on aquatic organisms. In this study, the accumulation of AVO and NPs in zebrafish larvae and effects on gene expression and enzymatic activity related to nervous functions, and locomotor behavior were investigated. AVO and NPs accumulated continuously in zebrafish, and the combined exposure enhanced AVO accumulation. After recovery, the accumulated concentrations of AVO and NPs in zebrafish remained unchanged, suggesting that AVO and NPs could not be eliminated in 72 h. The genes regulated nervous system development were affected mainly by AVO exposure, while the genes regulated retinal system development were affected by NPs exposure. Single and combined exposures of AVO and NPs affected the activities of acetylcholinesterase and antioxidant enzymes in zebrafish, and superoxide dismutase activity could not return to normal level after 72 h of recovery period. The locomotor activity of zebrafish larvae was significantly inhibited by AVO and NPs, which might be related to the alterations in functions of nervous system development and retinal system development as well as the interference of neurotransmitter system and antioxidant system.
ESTHER : Liu_2021_Sci.Total.Environ__150681
PubMedSearch : Liu_2021_Sci.Total.Environ__150681
PubMedID: 34599957

Title : Molecular response uncovers neurotoxicity of Pardosa pseudoannulata exposed to cadmium pressure - Lv_2021_Environ.Pollut_280_117000
Author(s) : Lv B , Wang J , He Y , Zeng Z , Tang YE , Li N , Chen LJ , Wang Z , Song QS
Ref : Environ Pollut , 280 :117000 , 2021
Abstract : Cadmium (Cd) is a widely distributed heavy metal in south of China. Growing evidence indicates that systemic exposure to Cd, particularly the long-term exposure, may cause neurotoxic effects. Nevertheless, mechanisms underlying Cd neurotoxicity remain not completely understood. In this report, we investigated the neural alterations in the spider Pardosa pseudoannulata (Bosenberg and Strand, 1906) exposed to long-term Cd (LCd) and short-term Cd (SCd) pressure. Cd stress lowered foraging ability and prey consuming time in the spiders. In addition, enzymatic analysis results indicated that Cd exposure reduced the level of acetylcholinesterase at subcellular level. We then identified differentially expressed genes (DEGs) in the Cd exposed spiders using pairwise comparisons and found that a large number of DEGs were related to neurotransmitter receptors and ion transport and binding proteins. Notably, LCd exposure harbored more altered genes in ion transporter activity comparing with SCd exposure. From six K-means clusters, 53 putative transcriptional factors (TFs) belonging to 21 families were characterized, and ZBTB subfamily displayed the most distinctive alterations in the characterized genes, which is assumed to play a key role in the regulation of ion transmembrane process under Cd stress. A protein-to-protein interaction network constructed by the yielded DEGs also showed that ion and receptor binding activities were affected under long-term Cd exposure. Four key modules from the network indicated that Cd may further down-regulate energy metabolism pathway in spiders. Collectively, this comprehensive analysis provides multi-dimensional insights to understand the molecular response of spiders to Cd exposure.
ESTHER : Lv_2021_Environ.Pollut_280_117000
PubMedSearch : Lv_2021_Environ.Pollut_280_117000
PubMedID: 33784568

Title : JZL184 protects hippocampal neurons from oxygen-glucose deprivation-induced injury via activating Nrf2\/ARE signaling pathway - Xu_2020_Hum.Exp.Toxicol__960327120984220
Author(s) : Xu J , Guo Q , Huo K , Song Y , Li N , Du J
Ref : Hum Exp Toxicol , :960327120984220 , 2020
Abstract : JZL184 is a selective inhibitor of monoacylglycerol lipase (MAGL) that has neuroprotective effect. However, the role of JZL184 in cerebral ischemia/reperfusion (I/R) injury and the exact mechanism have not been fully understood. This study was designed to elucidate the role of JZL184 in cerebral I/R injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons. Hippocampal neurons were pretreated with various concentrations of JZL184 for 2 h, followed by OGD for 3 h and reoxygen for 24 h. Our results showed that JZL184 improved cell viability in hippocampal neurons in response to OGD/R. JZL184 treatment significantly inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in OGD/R-induced hippocampal neurons. The increased TNF-alpha, IL-1beta, and IL-6 productions in OGD/R-induced hippocampal neurons were decreased after treatment with JZL184. Moreover, the OGD/R-caused intense TUNEL staining in hippocampal neurons was attenuated by JZL184. JZL184 treatment prevented OGD/R-caused increases in bax and cleaved caspase-3 expression and a decrease in bcl-2 expression. Furthermore, JZL184 treatment significantly promoted the activation of Nrf2/ARE signaling pathway in OGD/R-induced hippocampal neurons. Additionally, silencing of Nrf2 reversed the protective effect of JZL184 on hippocampal neurons under OGD/R condition. Taken together, these findings suggested that JZL184 exerted protective effect against OGD/R-induced injury in hippocampal neurons via activating Nrf2/ARE signaling pathway, which provided in vitro experimental support for the therapeutic benefit of JZL184 in cerebral ischemia.
ESTHER : Xu_2020_Hum.Exp.Toxicol__960327120984220
PubMedSearch : Xu_2020_Hum.Exp.Toxicol__960327120984220
PubMedID: 33375871

Title : Rapid Polysorbate 80 Degradation by Liver Carboxylesterase in a Monoclonal Antibody Formulated Drug Substance at Early Stage Development - Zhang_2020_J.Pharm.Sci_109_3300
Author(s) : Zhang S , Xiao H , Molden R , Qiu H , Li N
Ref : J Pharm Sci , 109 :3300 , 2020
Abstract : Polysorbates (PS) are surfactants commonly added in a therapeutic protein drug product to protect proteins from denaturation and aggregation during storage, transportation, and delivery. Significant degradation of PS in drug products could lead to particulate formation with shortened drug shelf life, and one of the major root causes of PS degradation is the host cell protein (HCP) derived lipase/esterase, which belong to the serine hydrolase family. Typically, PS degradation can only be observed in drug products after a long time of storage if very low levels of host cell protein impurity with PS degradation activities are present. In this study, PS80 degradation was observed in a monoclonal antibody (mAb) within 18 h at 5 degreesC with a low level of HCP presented (<20 ppm) based on ELISA quantitation. This observation suggested that a trace amount of unknown host cell protein(s) with strong enzymatic activity on polysorbate degradation was present in this drug substance. The activity-based protein profiling (ABPP) method with the ActivX FP serine hydrolase probe was employed to identify host cell proteins that can hydrolyze PS. Two hydrolases, liver carboxylesterase B-1-like protein (CES-B1L, A0A061I7X9) and liver carboxylesterase 1-like protein (CES-1L, A0A061IFE2) were identified with high confidence using the ABPP approach for the first time in a mAb drug substance during early stage development. PS80 became stable in the drug substance sample after the two hydrolases were depleted using the immobilized ActivX FP probe, confirming these two hydrolases were responsible for the rapid PS80 degradation. In addition, the PS80 degradation pattern was found to be equivalent to that generated by their human analog, human liver carboxylesterase-1 (hCES-1) and rabbit liver esterase (rLES). Overall, these results suggest that CES-B1L and CES-1L are the primary cause of PS80 degradation in this mAb drug.
ESTHER : Zhang_2020_J.Pharm.Sci_109_3300
PubMedSearch : Zhang_2020_J.Pharm.Sci_109_3300
PubMedID: 32721471
Gene_locus related to this paper: crigr-g3i7x7 , crigr-a0a061i7x9

Title : New Flavoalkaloids with Potent alpha-Glucosidase and Acetylcholinesterase Inhibitory Activities from Yunnan Black Tea 'Jin-Ya' - Li_2020_J.Agric.Food.Chem_68_7955
Author(s) : Li N , Zhu HT , Wang D , Zhang M , Yang CR , Zhang YJ
Ref : Journal of Agricultural and Food Chemistry , 68 :7955 , 2020
Abstract : As the subgroup of flavoalkaloids, N-ethyl-2-pyrrolidinone substituted flavan-3-ols are reported to possess various biological activities that may play important roles in the beneficial healthcare functions of tea. The HPLC and LC-MS analyses showed the existence of N-ethyl-2-pyrrolidinone substituted flavan-3-ols in 'Jin-Ya', which is a Yunnan black tea produced only from buds of tea plant, Camellia sinensis var. assamica. Further phytochemical study on this precious black tea led to the identification of eight flavoalkaloids, 1-8, along with 11 known flavan-3-ols (9-14) and flavonol glycosides (15-19). The new compounds, (-)-6-(5''S)-N-ethyl-2-pyrrolidinone-epiafzelechin (1), (-)-8-(5''R)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2a) and (-)-8-(5''S)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2b), were identified based on extensive spectroscopic analysis. Flavoalkaloids 2-6 showed inhibitory activity on alpha-glucosidase with IC50 values ranging from 2.09 to 8.47 muM, comparing to those of quercetin and acarbose (IC50 = 6.87 and 228.9 muM, resp.). Moreover, compounds 2, 3 and 6 displayed inhibitory effect on acetyl-cholinesterase with IC50 values of 14.23, 33.79 and 34.82 muM, respectively, comparing to tacrine (IC50 = 0.223 muM).
ESTHER : Li_2020_J.Agric.Food.Chem_68_7955
PubMedSearch : Li_2020_J.Agric.Food.Chem_68_7955
PubMedID: 32628847

Title : Effects of ammonia exposure on antioxidant function, immune response and NF-kappaB pathway in Chinese Strip-necked Turtle (Mauremys sinensis) - Liang_2020_Aquat.Toxicol__105621
Author(s) : Liang L , Huang Z , Li N , Wang D , Ding L , Shi H , Hong M
Ref : Aquat Toxicol , :105621 , 2020
Abstract : As one of the main toxic substances in aquaculture water, ammonia causes seriously physiological harm to aquatic animals. In order to investigate the effects of ammonia exposure on the antioxidant defense, immune response, and NF-kappaB signaling pathway in Chinese Strip-necked Turtle (Mauremys sinensis), we designed two experimental groups (control and 6.45 mM ammonia), and sampled at 6 h, 24 h, 48 h, re 24 h (recover 24 h), and re 48 h. The results showed that the blood ammonia (BA) content was significantly increased when the turtles were subjected to ammonia, and the activities of cholinesterase (CHE) and aspartate aminotransferase (AST) in the serum also showed a significant upward trend. The malondialdehyde (MDA) content continuously increased during ammonia exposure, and more than doubled at 48 h compared with the control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and their corresponding relative mRNA expression levels in the liver during ammonia exposure were obviously increased when compared to the control group, but most decreased to the normal levels at re 48 h. In addition, the relative mRNA and protein expression levels of NF-E2 related factor 2 (Nrf2) showed similar up-regulation patterns to antioxidase during ammonia exposed periods; whereas kelch-like ECH-binding protein 1 (Keap1), as Nrf2 negative regulator, showed opposite patterns. Moreover, the relative mRNA expression levels of heat shock proteins (HSP70, HSP90) significantly elevated upon the exposure of ammonia. Furthermore, ammonia increased the relative mRNA and protein expression levels of p50 and p65 at different exposed times. The reative mRNA expression levels of immune cytokines (BAFF and IL-6) were upregulated during ammonia exposured time, while there was a decline but did not return to normal levels, in the recovery periods. Taken together, these results indicated that antioxidation, immunity, and NF-kappaB signaling played a certain protective role for Mauremys sinensis under ammonia exposure. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in turtles.
ESTHER : Liang_2020_Aquat.Toxicol__105621
PubMedSearch : Liang_2020_Aquat.Toxicol__105621
PubMedID: 33129562

Title : Cadmium exposure alters expression of protective enzymes and protein processing genes in venom glands of the wolf spider Pardosa pseudoannulata - Lv_2020_Environ.Pollut_268_115847
Author(s) : Lv B , Yang HL , Peng YD , Wang J , Zeng Z , Li N , Tang YE , Wang Z , Song QS
Ref : Environ Pollut , 268 :115847 , 2020
Abstract : Cadmium (Cd) pollution is currently the most serious type of heavy metal pollution throughout the world. Previous studies have shown that Cd elevates the mortality of paddy field spiders, but the lethal mechanism remains to be explored profoundly. In the present study, we measured the activities of protective enzymes (acetylcholinesterase, glutathione peroxidase, phenol oxidase) and a heavy metal chelating protein (metallothionein) in the pond wolf spider Pardosa pseudoannulata after Cd exposure. The results indicated that Cd initially increased the enzyme activities and protein concentration of the spider after 10- and 20-day exposure before inhibiting them at 30-day exposure. Further analysis showed that the enzyme activities in the cephalothorax were inhibited to some extent. Since the cephalothorax region contains important venom glands, we performed transcriptome sequencing (RNA-seq) analysis of the venom glands collected from the spiders after long-term Cd exposure. RNA-seq yielded a total of 2826 differentially expressed genes (DEGs), and most of the DEGs were annotated into the process of protein synthesis, processing and degradation. Furthermore, a mass of genes involved in protein recognition and endoplasmic reticulum (ER) -associated protein degradation were down-regulated. The reduction of protease activities supports the view that protein synthesis and degradation in organelles and cytoplasm were dramatically inhibited. Collectively, our outcomes illustrate that Cd poses adverse effects on the expression of protective enzymes and protein, which potentially down-regulates the immune function in the venom glands of the spiders via the alteration of protein processing and degradation in the ER.
ESTHER : Lv_2020_Environ.Pollut_268_115847
PubMedSearch : Lv_2020_Environ.Pollut_268_115847
PubMedID: 33130443

Title : Donepezil down-regulates propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation in the brain of bilateral common carotid artery occlusion-induced vascular dementia rats - Wang_2020_Clin.Exp.Pharmacol.Physiol__
Author(s) : Wang H , Lu J , Gao WC , Ma X , Li N , Ding Z , Wu C , Zhu M , Qiao G , Xiao C , Zhang C , Chen C , Weng Z , Yang W , Zheng CB
Ref : Clinical & Experimental Pharmacology & Physiology , : , 2020
Abstract : Vascular dementia (VaD), caused by stroke or small vessel disease, is the second-most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris Water Maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Abeta1-42 in BCCAO rats by enzyme-linked immunosorbent assay. Posttranslational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlightes the importance of PTMs in neurodegenerative diseases. In this study, we used Western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl-PTMs.
ESTHER : Wang_2020_Clin.Exp.Pharmacol.Physiol__
PubMedSearch : Wang_2020_Clin.Exp.Pharmacol.Physiol__
PubMedID: 32424975

Title : Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways - Ji_2020_Environ.Pollut_264_114747
Author(s) : Ji X , Li N , Ma M , Rao K , Yang R , Wang Z
Ref : Environ Pollut , 264 :114747 , 2020
Abstract : Tricresyl phosphates (TCPs), as representative aromatic organophosphate flame retardants (OPFRs), have received much attention due to their potential neurotoxicity and endocrine-disrupting effects. However, the role of estrogen receptor alpha (ERalpha) and G protein-coupled estrogen receptor (GPER) in their estrogen disrupting effects remains poorly understood. Therefore, in this study, three TCP isomers, tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) and tri-p-cresyl phosphate (TpCP), were examined for their activities on ERalpha by using two-hybrid yeast assay, and action on GPER by using Boyden chamber assay, cAMP production assay, calcium mobilization assay and molecular docking analysis. The results showed that three TCP isomers were found to act as ERalpha antagonists. Conversely, they had agonistic activity on GPER to promote GPER-mediated cell migration of MCF7 cells and SKBR3 cells. Both ToCP and TpCP activated GPER-mediated cAMP production and calcium mobilization, whereas TmCP had different mode of action, it only triggered GPER-mediated calcium mobilization, as evidenced by using the specific GPER inhibitor (G15) and GPER overexpressing experiments. Molecular docking further revealed that the way of interaction of TmCP and TpCP with GPER was different from that of ToCP with GPER, and higher activity of ToCP in activating GPER-mediated pathways might be associated with the alkyl substitution at the ortho position of the aromatic ring. Our results, for the first time, found a new target, GPER, for TCPs exerting their estrogen-disrupting effects, and demonstrated complex estrogen-disrupting effects of three TCP isomers involved their opposite activities toward ERalpha and GPER.
ESTHER : Ji_2020_Environ.Pollut_264_114747
PubMedSearch : Ji_2020_Environ.Pollut_264_114747
PubMedID: 32559878

Title : Donepezil promotes neurogenesis via Src signaling pathway in a rat model of chronic cerebral hypoperfusion - Man_2020_Brain.Res_1736_146782
Author(s) : Man J , Cui K , Fu X , Zhang D , Lu Z , Gao Y , Yu L , Li N , Wang J
Ref : Brain Research , 1736 :146782 , 2020
Abstract : Donepezil, a selective acetylcholinesterase (AchE) inhibitor, enhances stroke-induced neurogenesis within subventricular zone (SVZ). Src/Pyk-2 is one of the downstream pathways of acetylcholine receptors (AchRs), and has been shown to participate in the activation of fibroblast growth factor receptor (FGFR)/epidermal growth factor receptor (EGFR) signaling in cancer cells. In this study, we investigated whether donepezil could promote SVZ neurogenesis in chronic cerebral hypoperfusion (CCH) injury via Src signaling pathway. In the bilateral carotid artery occlusion (2VO) rat model, we observed more nestin/5-bromo-2'-deoxyuridine (BrdU)-positive cells and doublecortin (DCX)/BrdU-positive cells in the SVZ than that in the sham group. Further, donepezil obviously improved neurologic function after 2VO, induced the greater number of SVZ proliferative NSCs and neuroblasts, and elevated levels of Src, p-FGFR1, p-EGFR, p-Akt and p-Raf in ipsilateral SVZ. Lastly, Src inhibitor KX-01 abolished the beneficial effects of donepezil in 2VO rats. These results suggest that donepezil could upregulate Src signaling pathway to enhance CCH-induced SVZ neurogenesis.
ESTHER : Man_2020_Brain.Res_1736_146782
PubMedSearch : Man_2020_Brain.Res_1736_146782
PubMedID: 32184165

Title : Suppression of inflammation and fibrosis using soluble epoxide hydrolase inhibitors enhances cardiac stem cell-based therapy - Sirish_2020_Stem.Cells.Transl.Med_9_1570
Author(s) : Sirish P , Thai PN , Lee JH , Yang J , Zhang XD , Ren L , Li N , Timofeyev V , Lee KSS , Nader CE , Rowland DJ , Yechikov S , Ganaga S , Young N , Lieu DK , Yamoah EN , Hammock BD , Chiamvimonvat N
Ref : Stem Cells Transl Med , 9 :1570 , 2020
Abstract : Stem cell replacement offers a great potential for cardiac regenerative therapy. However, one of the critical barriers to stem cell therapy is a significant loss of transplanted stem cells from ischemia and inflammation in the host environment. Here, we tested the hypothesis that inhibition of the soluble epoxide hydrolase (sEH) enzyme using sEH inhibitors (sEHIs) to decrease inflammation and fibrosis in the host myocardium may increase the survival of the transplanted human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in a murine postmyocardial infarction model. A specific sEHI (1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea [TPPU]) and CRISPR/Cas9 gene editing were used to test the hypothesis. TPPU results in a significant increase in the retention of transplanted cells compared with cell treatment alone. The increase in the retention of hiPSC-CMs translates into an improvement in the fractional shortening and a decrease in adverse remodeling. Mechanistically, we demonstrate a significant decrease in oxidative stress and apoptosis not only in transplanted hiPSC-CMs but also in the host environment. CRISPR/Cas9-mediated gene silencing of the sEH enzyme reduces cleaved caspase-3 in hiPSC-CMs challenged with angiotensin II, suggesting that knockdown of the sEH enzyme protects the hiPSC-CMs from undergoing apoptosis. Our findings demonstrate that suppression of inflammation and fibrosis using an sEHI represents a promising adjuvant to cardiac stem cell-based therapy. Very little is known regarding the role of this class of compounds in stem cell-based therapy. There is consequently an enormous opportunity to uncover a potentially powerful class of compounds, which may be used effectively in the clinical setting.
ESTHER : Sirish_2020_Stem.Cells.Transl.Med_9_1570
PubMedSearch : Sirish_2020_Stem.Cells.Transl.Med_9_1570
PubMedID: 32790136

Title : Rhodopseudomonas palustris wastewater treatment: Cyhalofop-butyl removal, biochemicals production and mathematical model establishment - Wu_2019_Bioresour.Technol_282_390
Author(s) : Wu P , Chen Z , Zhang Y , Wang Y , Zhu F , Cao B , Wu Y , Li N
Ref : Bioresour Technol , 282 :390 , 2019
Abstract : Simultaneous (SPW and cyhalofop-butyl) wastewater treatment and the production of biochemicals by Rhodopseudomonas palustris (R. palustris) was investigated with supplementation of soybean processing wastewater (SPW). Compared to control group, cyhalofop-butyl was removed and single cell protein, carotenoid, bacteriochlorophyll productions were enhanced with the supplementation of SPW. Cyhalofop-butyl removal reached 100% after 5days under 4000mg/L COD group. Cyhalofop-butyl induced chbH gene expression to synthesize cyhalofop-butyl-hydrolyzing carboxylesterase through activating MAPKKKs, MAPKKs, MAPKs genes in MAPK signal transduction pathway. The induction process took one day for R. palustris. However, lack of organics in original wastewater did not maintain R. palustris growth for over one day. The supplementation of SPW provided sufficient carbon source. This new method resulted in the mixed wastewater treatment and improvement of biochemicals simultaneously, as well as the realization of reutilization of R. palustris. High-order non-linear mathematical model of the relationship between Rchb, Xc, and Xt was established.
ESTHER : Wu_2019_Bioresour.Technol_282_390
PubMedSearch : Wu_2019_Bioresour.Technol_282_390
PubMedID: 30884459

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 : Screening and determination for potential acetylcholinesterase inhibitory constituents from ginseng stem-leaf saponins using ultrafiltration (UF)-LC-ESI-MS(2) - Yang_2019_Phytochem.Anal_30_26
Author(s) : Yang Y , Liang X , Jin P , Li N , Zhang Q , Yan W , Zhang H , Sun J
Ref : Phytochem Anal , 30 :26 , 2019
Abstract : INTRODUCTION: Previous studies have demonstrated that several ginsenosides have remarkable inhibitory effect on acetylcholinesterase (AChE). In the present study, ginseng stem-leaf saponins (GSLS) can improve learning and memory of Alzheimer's disease patients. However, much comprehensive information regarding AChE inhibition of GSLS and its metabolites is yet unknown. OBJECTIVE: The present study aims to screen and determine the potential of AChE inhibitors (AChEIs) from GSLS. METHODOLOGY: The active fraction of the GSLS detected in vitro AChE inhibition assays was selected as a starting material for the screening of the potential of AChEIs using ultrafiltration liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (UF-LC-ESI-MS(2) ). RESULTS: The results showed that 31 ginsenosides were identified with analysis using rapid resolution liquid chromatography with a diode array detector combined with electrospray ionisation tandem mass spectrometry (RRLC-DAD-ESI-MS(2) ) from the active fraction, and there are 27 compounds with AChE binding activity. Among them, 11 ginsenosides were evaluated and confirmed using in vitro enzymatic assay, and ginsenosides F1 , Rd, Rk3 , 20(S)-Rg3 , F2 and Rb2 were found to possess strong AChE inhibitory activities. CONCLUSION: The proposed UF-LC-ESI-MS(2) method was a powerful tool for the discovery of AChEIs from traditional Chinese medicine (TCM).
ESTHER : Yang_2019_Phytochem.Anal_30_26
PubMedSearch : Yang_2019_Phytochem.Anal_30_26
PubMedID: 30159954

Title : The effect on congenital heart diseases of maternal EPHX1 polymorphisms modified by polycyclic aromatic hydrocarbons exposure - Tao_2019_Medicine.(Baltimore)_98_e16556
Author(s) : Tao J , Li N , Liu Z , Deng Y , Li X , Chen M , Yu J , Zhu J , Yu P , Wang Y
Ref : Medicine (Baltimore) , 98 :e16556 , 2019
Abstract : Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure.
ESTHER : Tao_2019_Medicine.(Baltimore)_98_e16556
PubMedSearch : Tao_2019_Medicine.(Baltimore)_98_e16556
PubMedID: 31348278

Title : Phytochemical constituents from Uncaria rhynchophylla in human carboxylesterase 2 inhibition: Kinetics and interaction mechanism merged with docking simulations - Wang_2018_Phytomedicine_51_120
Author(s) : Wang YL , Dong PP , Liang JH , Li N , Sun CP , Tian XG , Huo XK , Zhang BJ , Ma XC , Lv CZ
Ref : Phytomedicine , 51 :120 , 2018
Abstract : BACKGROUND: Carboxylesterases (CEs) belong to the serine hydrolase family, and are in charge of hydrolyzing chemicals with carboxylic acid ester and amide functional groups via Ser-His-Glu. Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a famous traditional Chinese medicine used in managing hyperpyrexia, epilepsy, preeclampsia, and hypertension in China. HYPOTHESIS/PURPOSE: To discover the potential natural human carboxylesterase 2 (hCE 2) inhibitors from U. rhynchophylla. METHODS: Compounds were obtained from the hooks of U. rhynchophylla by silica gel and preparative HPLC. Their structures were elucidated by using HRESIMS, 1D and 2D NMR spectra. Their inhibitory activeties and inhibition kinetics against hCE 2 were assayed by the fluorescent probe, and potential mechanisms were also investigated by molecular docking. RESULTS: Twenty-three compounds, including a new phenolic acid uncariarhyine A (1), eight known triterpenoids (2-9), and ten known aromatic derivatives (10, 13-16, and 19-23), were isolated from U. rhynchophylla. Compounds 1-5, 7, 9, and 15 showed significant inhibitory activities against hCE 2 with IC50 values from 4.01 +/-0.61 microM to 18.60+/-0.21 microM, and their inhibition kinetic analysis results revealed that compounds 1, 5, 9, and 15 were non-competitive; compounds 3 and 4 were mixed-type, and compounds 2 and 7 were uncompetitive. Molecular docking studies indicated inhibition mechanisms of compounds 1-5, 7, 9, and 15 against hCE 2. CONCLUSION: Our present findings highlight potential natural hCE 2 inhibitors from U. rhynchophylla.
ESTHER : Wang_2018_Phytomedicine_51_120
PubMedSearch : Wang_2018_Phytomedicine_51_120
PubMedID: 30466609

Title : Recent progress of the development of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus - Li_2018_Eur.J.Med.Chem_151_145
Author(s) : Li N , Wang LJ , Jiang B , Li XQ , Guo CL , Guo SJ , Shi DY
Ref : Eur Journal of Medicinal Chemistry , 151 :145 , 2018
Abstract : Diabetes is a fast growing chronic metabolic disorder around the world. Dipeptidyl peptidase-4 (DPP-4) is a new promising target during type 2 diabetes glycemic control. Thus, a number of potent DPP-4 inhibitors were developed and play a rapidly evolving role in the management of type 2 diabetes in recent years. This article reviews the development of synthetic and natural DPP-4 inhibitors from 2012 to 2017 and provides their physico-chemical properties, biological activities against DPP-4 and selectivity over dipeptidyl peptidase-8/9. Moreover, the glucose-lowering mechanisms and the active site of DPP-4 are also discussed. We also discuss strategies and structure-activity relationships for identifying potent DPP-4 inhibitors, which will provide useful information for developing potent DPP-4 drugs as type 2 diabtes treatments.
ESTHER : Li_2018_Eur.J.Med.Chem_151_145
PubMedSearch : Li_2018_Eur.J.Med.Chem_151_145
PubMedID: 29609120

Title : Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors - Li_2018_Bioorg.Med.Chem.Lett_28_2131
Author(s) : Li N , Wang LJ , Jiang B , Guo SJ , Li XQ , Chen XC , Luo J , Li C , Wang Y , Shi DY
Ref : Bioorganic & Medicinal Chemistry Lett , 28 :2131 , 2018
Abstract : A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC50 values of 64.47nM, 188.7nM and 65.36nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure-activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes.
ESTHER : Li_2018_Bioorg.Med.Chem.Lett_28_2131
PubMedSearch : Li_2018_Bioorg.Med.Chem.Lett_28_2131
PubMedID: 29773502

Title : A bioactive new protostane-type triterpenoid from Alisma plantago-aquatica subsp. orientale (Sam.) Sam - Wang_2017_Nat.Prod.Res__1
Author(s) : Wang YL , Zhao JC , Liang JH , Tian XG , Huo XK , Feng L , Ning J , Wang C , Zhang BJ , Chen G , Li N , Sun CP
Ref : Nat Prod Res , :1 , 2017
Abstract : A new protostane-type triterpenoid, 5beta,29-dihydroxy alisol A (1) was isolated from Alisma plantago-aquatica subsp. orientale (Sam.) Sam. as well as 12-deoxyphorbol-13alpha-pentadecanoate (2). We first report the presence of compound 2 in the genus Alisma. Their structures were established on the basis of 1D and 2D NMR, and HRESIMS spectroscopic analyses. All the isolated compounds were assayed for their inhibitory effects against human carboxylesterase 2 (HCE-2). Compounds 1 and 2 displayed inhibitory activities against HCE-2 with IC50 values of 29.2 and 4.6 muM, respectively. The interaction mechanisms of HCE-2 with compounds 1 and 2 were investigated by molecular docking, respectively.
ESTHER : Wang_2017_Nat.Prod.Res__1
PubMedSearch : Wang_2017_Nat.Prod.Res__1
PubMedID: 29183156

Title : Effect of elevated CO2 concentration and temperature on antioxidant capabilities of multiple generations of Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae) - Li_2017_J.Insect.Physiol_103_91
Author(s) : Li N , Li Y , Zhang S , Fan Y , Liu T
Ref : J Insect Physiol , 103 :91 , 2017
Abstract : A rise in atmospheric carbon dioxide concentration ([CO2]) and a warming climate are two of the most conspicuous characteristics of global climate change in this century. However, studies addressing the combined impact of rising [CO2] and temperature on herbivore insect physiology are still limited. In this study we investigated the combined effects of elevated [CO2] and temperature on major antioxidative enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidases (POD) and detoxification enzymes of glutathione-S-transferases (GST) and acetylcholinesterase (AChE) in three consecutive generations of Bemisia tabaci Middle East-Asia Minor 1 (MEAM1, commonly known as B biotype) adults. The results indicated that the antioxidant capabilities of B. tabaci differed significantly during different treatments across different generations. Elevated [CO2] markedly increased POD, GST and AChE activities in the first generation, and SOD, CAT and GST activities in the second generation, but reduced POD activity in the third generation at ambient temperature. Under elevated temperature, elevated [CO2] significantly increased GST and AChE activities in the first generation and CAT activity in the third generation, reduced SOD activity in the third generation and reduced AChE activity in the second generation. [CO2], temperature and insect generation interacted to affect the antioxidant capabilities of B. tabaci. These results suggest both that changes in antioxidant capabilities vary in response to either [CO2] or temperature, or a combination of both, leading to oxidative stress and also that antioxidant enzymes play important roles in reducing oxidative damage in B. tabaci. Changes in the exposure of antioxidant compounds over the course of three generations suggest that acclimation and/or adaptation to elevated [CO2] and temperature may have occurred. This study represents the first comprehensive report on the antioxidant defense mechanism in successive multiple generations of an insect species under combined elevated [CO2] and temperature levels. These results offer further insights into the effects of elevated [CO2] and temperature on different generations of insect herbivores and provide more detailed information for population predictions.
ESTHER : Li_2017_J.Insect.Physiol_103_91
PubMedSearch : Li_2017_J.Insect.Physiol_103_91
PubMedID: 29056516

Title : ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice - Wang_2017_Behav.Brain.Res_316_145
Author(s) : Wang J , Fu X , Zhang D , Yu L , Li N , Lu Z , Gao Y , Wang M , Liu X , Zhou C , Han W , Yan B
Ref : Behavioural Brain Research , 316 :145 , 2017
Abstract : The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as well as neurotransmitters, have been shown to play important roles in SVZ neurogenesis. Recently, a previously unknown population of choline acetyltransferase (ChAT)+ neurons residing in rodent SVZ were identified to have direct control over neural stem cell proliferation by indirectly activating fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal control over SVZ neurogenesis. In this study, we assessed whether these ChAT+ neurons also participate in stroke-induced neurogenesis. We used a permanent middle cerebral artery occlusion (MCAO) model produced by transcranial electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR] antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the role of ChAT+ neurons in stroke-induced neurogenesis. We found that mAchRs, phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were upregulated in mice on day 7 after MCAO. MCAO also significantly increased the number of BrdU/doublecortin-positive cells and protein levels of phosphorylated-neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was activated in the SVZ, and doublecortin-positive cells increased in the peri-infarction region. These post-stroke neurogenic effects were enhanced by donepezil and partially decreased by atropine. Neither atropine nor donepezil affected peri-infarct microglial activation or serum concentrations of TNF-alpha, IFN-gamma, or TGF-beta on day 7 after MCAO. We conclude that ChAT+ neurons in the SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism for neurogenesis after stroke.
ESTHER : Wang_2017_Behav.Brain.Res_316_145
PubMedSearch : Wang_2017_Behav.Brain.Res_316_145
PubMedID: 27609645

Title : Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice - Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
Author(s) : Li N , Liu C , Jing S , Wang M , Wang H , Sun J , Wang C , Chen J , Li H
Ref : Evid Based Complement Alternat Med , 2017 :8632016 , 2017
Abstract : Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement.
ESTHER : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedSearch : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedID: 28814961

Title : Developmental neurotoxicity of polybrominated diphenyl ethers mixture de71 in Sprague-Dawley rats - Gill_2016_J.Toxicol.Environ.Health.A_79_482
Author(s) : Gill S , Hou Y , Li N , Pulido O , Bowers W
Ref : J Toxicol Environ Health A , 79 :482 , 2016
Abstract : Polybrominated diphenyl ethers (PBDE) are a class of brominated flame retardants that are recognized as global environmental contaminants and a potential adverse health risk. The objective of this study was to evaluate the developmental impacts on rat Sprague-Dawley (SD) pups at postnatal day (PND) 11, 21, 50, 105, and 250 after perinatal exposure to a DE71 mixture. These PNDs corresponded to juveniles, young, and mature adults, respectively. The analysis included histopathological, transcriptional evaluation, and Western blots in both hippocampus and midbrain. There were no marked histopathological changes, but significant transcriptional alterations were observed at PND 21 and 250 in midbrain. These changes occurred in a number of the markers of the cholinergic system, including acetylcholinesterase, muscarinic and nicotinic receptors, and structural gene,s including those of neurofilaments, cell adhesion molecules including N-cadherin and CAMKII, and cytokines. The markers were upregulated at least twofold or greater at PND 21. These biomarkers were predominantly altered in males at low dose (0.3 mg/kg), whereas females were affected only at high concentration (30 mg/kg). At PND 250 both males and females showed downregulation of markers in both intermediate- and high-dose groups. Our results support the findings that in utero and lactational exposure to DE71 mixture leads to transcriptional alterations in midbrain of adult SD rats.
ESTHER : Gill_2016_J.Toxicol.Environ.Health.A_79_482
PubMedSearch : Gill_2016_J.Toxicol.Environ.Health.A_79_482
PubMedID: 27294297

Title : Complete Genome Sequence of Fish Pathogen Aeromonas hydrophila JBN2301 - Yang_2016_Genome.Announc_4_
Author(s) : Yang W , Li N , Li M , Zhang D , An G
Ref : Genome Announc , 4 : , 2016
Abstract : Aeromonas hydrophila is one of the most important fish pathogens in China. Here, we report complete genome sequence of a virulent strain, A. hydrophila JBN2301, which was isolated from diseased crucian carp.
ESTHER : Yang_2016_Genome.Announc_4_
PubMedSearch : Yang_2016_Genome.Announc_4_
PubMedID: 26823580
Gene_locus related to this paper: aerhy-a0a0s3bhm4

Title : Constitutively active PKA regulates neuronal acetylcholine release and contractility of guinea pig urinary bladder smooth muscle - Xin_2016_Am.J.Physiol.Renal.Physiol__ajprenal 00026 2016
Author(s) : Xin W , Li N , Fernandes VS , Petkov GV
Ref : American Journal of Physiology Renal Physiol , :ajprenal 00026 2016 , 2016
Abstract : Autonomic and somatic motor neurons that innervate the urinary bladder and urethra control the highly coordinated functions of the lower urinary tract, the storage and emptying of urine. Acetylcholine (ACh) is the primary excitatory neurotransmitter in the bladder. Here, we aimed to determine whether protein kinase A (PKA) regulates neuronal ACh release and related nerve-evoked detrusor smooth muscle (DSM) contractions in the guinea pig urinary bladder. Isometric DSM tension recordings were used to measure spontaneous phasic, electrical field stimulation (EFS)- and carbachol-induced DSM contractions with a combination of pharmacological tools. The colorimetric method was used to measure ACh released by the parasympathetic nerves in DSM isolated strips. The pharmacological inhibition of PKA with H-89 (10 microM) increased the spontaneous phasic contractions, while it attenuated the EFS-induced DSM contractions. Intriguingly, H-89 (10 microM) attenuated the (primary) cholinergic component while it simultaneously increased the (secondary) purinergic component of the nerve-evoked contractions in DSM isolated strips. The acetylcholinesterase inhibitor, eserine (10 microM), increased EFS-induced DSM contractions and the subsequent addition of H-89 attenuated the contractions. H-89 (10 microM) significantly increased DSM phasic contractions induced by the cholinergic agonist carbachol. The inhibition of PKA decreased the neuronal release of ACh in DSM tissues. This study revealed that PKA-mediated signaling pathways differentially regulate nerve-evoked and spontaneous phasic contractions of guinea pig DSM. Constitutively active PKA in the bladder nerves controls synaptic ACh release, thus regulating the nerve-evoked DSM contractions, whereas PKA in DSM cells controls the spontaneous phasic contractility.
ESTHER : Xin_2016_Am.J.Physiol.Renal.Physiol__ajprenal 00026 2016
PubMedSearch : Xin_2016_Am.J.Physiol.Renal.Physiol__ajprenal 00026 2016
PubMedID: 27029424

Title : Species Comparison of Pre-systemic Bioactivation of Vicagrel, a New Acetate Derivative of Clopidogrel - Qiu_2016_Front.Pharmacol_7_366
Author(s) : Qiu ZX , Gao WC , Dai Y , Zhou SF , Zhao J , Lu Y , Chen XJ , Li N
Ref : Front Pharmacol , 7 :366 , 2016
Abstract : Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inactive carboxylic acid metabolite (CAM). This study demonstrated the interspecies differences of the vicagrel bioactivation by comparing the critical vicagrel metabolites formation in rats, dogs and human. The pharmacokinetic studies with rats and dogs were conducted after intragastric administration of vicagrel, followed by in vitro metabolism investigation in venous system, intestinal/hepatic microsomes from rats, dogs and human. An obvious disparity was observed in system exposure to AM (99.0 vs. 635.1 microg h/L, p < 0.05) and CAM (10119 vs. 2634 microg h/L, p < 0.05) in rats and dogs. It was shown that the cleavage of vicagrel was almost completed in intestine with great different clearance (53.28 vs. 3.643 L h(-1) kg(-1), p < 0.05) in rats and dogs. With no further hydrolysis to CAM, the greatest clearance of AM (3.26 mL h(-1) kg(-1)) was found in dog intestine. In rat plasma, 2-oxo-clopidogrel was much more extensively hydrolyzed to CAM than in dog and human. Albeit similar hydrolysis clearance and AM production was observed among hepatic microsomes of the three species, the production velocity of CAM ranked highest in dogs (7.55 pmol/min/mg protein). Therefore, the unconformity of AM and CAM exposure cross species mainly came from the metabolism of 2-oxo-clopidogrel associated largely with tissue specificity and interspecies differences of esterases. In human, the pharmacokinetics of vicagrel might be more optimistic due to less inactivation hydrolysis before reaching liver.
ESTHER : Qiu_2016_Front.Pharmacol_7_366
PubMedSearch : Qiu_2016_Front.Pharmacol_7_366
PubMedID: 27774067

Title : Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation - Song_2016_J.Mol.Neurosci_60_115
Author(s) : Song J , Li N , Xia Y , Gao Z , Zou SF , Yan YH , Li SH , Wang Y , Meng YK , Yang JX , Kang TG
Ref : Journal of Molecular Neuroscience , 60 :115 , 2016
Abstract : Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-kappaB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-alpha and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKalpha and IKKbeta) expression and inhibit NF-kappaB signaling pathway activity; moreover, the increased miRNA-199a suppresses cholinesterases to increase cholinergic signaling, resulting in decreased expression of proinflammatory cytokines. ARC treatment confers protection for SH-SY5Y cells through positive regulation of miRNA expression, thereby reducing the inflammatory response. In turn, these effects accelerate injury repair in the scratch-induced injury model. These results might provide insights into the pharmacological role of ARC in anti-inflammation and neuroprotection in neural cells.
ESTHER : Song_2016_J.Mol.Neurosci_60_115
PubMedSearch : Song_2016_J.Mol.Neurosci_60_115
PubMedID: 27389368

Title : MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis - Jin_2015_Sci.Rep_5_15026
Author(s) : Jin BX , Zhang YH , Jin WJ , Sun XY , Qiao GF , Wei YY , Sun LB , Zhang WH , Li N
Ref : Sci Rep , 5 :15026 , 2015
Abstract : An important unresolved clinical issue is to distinguish hepatitis B virus (HBV) infection caused chronic hepatitis and their corresponding liver cirrhosis (LC). Recent research suggests that circulating microRNAs are useful biomarkers for a wide array of diseases. We analyzed microRNA profiles in the plasmas of a total of 495 chronic hepatitis B (CHB) patients, LC patients and healthy donors and identified 10 miRNAs that were differentially expressed between CHB and LC patients. Our logistic models show that three panels of miRNAs have promising diagnostic performances in discriminating CHB from LC. Blinded tests were subsequently conducted to evaluate the diagnostic performances in clinical practice and a sensitivity of 85% and specificity of 70% have been achieved in separating CHB from LC pateints. The expression levels of some circulating miRNAs were significantly correlated with HBV DNA load and liver function, such as prothrombin activity (PTA) and levels of alanin aminotransferase (ALT), albumin (ALB) and cholinesterase (CHE). Our results provide important information for developing novel diagnostic tools for distinguishing chronic HBV hepatitis and their corresponding cirrhosis.
ESTHER : Jin_2015_Sci.Rep_5_15026
PubMedSearch : Jin_2015_Sci.Rep_5_15026
PubMedID: 26456479

Title : Colorimetric and Phosphorimetric Dual-Signaling Strategy Mediated by Inner Filter Effect for Highly Sensitive Assay of Organophosphorus Pesticides - Zhang_2015_J.Agric.Food.Chem_63_8947
Author(s) : Zhang R , Li N , Sun J , Gao F
Ref : Journal of Agricultural and Food Chemistry , 63 :8947 , 2015
Abstract : We describe here a colorimetric and phosphorimetric dual-signaling strategy for sensitive assay of organophosphorus pesticides (OPPs). The principle for assay depends on the phenomenon that the phosphorescence of Mn-ZnS quantum dots (QDs) can be dramatically quenched by Au nanoparticles (AuNPs) through the inner filter effect (IFE) and the activity of acetylcholinesterase (AChE), an enzyme that catalytically hydrolyzes acetylthiocholine to thiocholine that can be inhibited by OPPs. By virtue of the variations of absorbance and phosphorescence of the analytical system, a dual-readout assay for OPPs has been proposed. The limits of detection for different OPPs including paraoxon, parathion, omethoate, and dimethyl dichlorovinyl phosphate (DDVP) are found to be 0.29, 0.59, 0.67, and 0.44 ng/L, respectively. The proposed assay was allowed to detect pesticides in real spiked samples and authentic contaminated apples with satisfactory results, suggesting its potential applications to detect pesticides in complicated samples.
ESTHER : Zhang_2015_J.Agric.Food.Chem_63_8947
PubMedSearch : Zhang_2015_J.Agric.Food.Chem_63_8947
PubMedID: 26411607

Title : Highly sensitive and selective detection of human carboxylesterase 1 activity by liquid chromatography with fluorescence detection - Wang_2015_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1008_212
Author(s) : Wang DD , Jin Q , Hou J , Feng L , Li N , Li SY , Zhou Q , Zou LW , Ge GB , Wang JG , Yang L
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1008 :212 , 2015
Abstract : Human carboxylesterases 1 (hCE1), one of the most important human drug metabolizing enzymes, catalyzes the hydrolysis of a large number of structurally diverse of endogenous and exogenous substrates. However, a practical, reliable and sensitive method for the precise measurement of hCE1 activities in complex biological samples has been rarely reported. In this study, a liquid chromatography-fluorescence detection (LC-FD) based method was developed for highly selective and sensitive measurement of hCE1 activities in human tissue and cell preparations. This method was based on the fluorimetric detection of HMBT, the hydrolyzed product of BMBT which was a newly developed specific probe substrate for hCE1. The developed LC-FD method was fully validated in terms of specificity, sensitivity, linearity, precision, recovery and stability. With the help of LC separation, most polar endogenous compounds in biological samples could be eluted in the column dead time, which is very beneficial for accurate determination of hCE1 activities in complex biological samples. The lower limit of quantification for HMBT (product of hCE1) of this LC-FD based method was as low as 20nM, which was quite lower than other reported methods. The method also exhibited good precision, both intra- and inter- assay variances were both lower than 2.5%. Furthermore, the newly developed method was successfully applied to measure hCE1 activity in human liver preparations from individual donors (n=12), as well as in homogenates from eleven different human cell lines. All these findings combined with this practical method are very helpful for the deep understanding of the expression and function of hCE1 in human biological samples.
ESTHER : Wang_2015_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1008_212
PubMedSearch : Wang_2015_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1008_212
PubMedID: 26673230

Title : Identification and Characterization of Lipase Activity and Immunogenicity of LipL from Mycobacterium tuberculosis - Cao_2015_PLoS.One_10_e0138151
Author(s) : Cao J , Dang G , Li H , Li T , Yue Z , Li N , Liu Y , Liu S , Chen L
Ref : PLoS ONE , 10 :e0138151 , 2015
Abstract : Lipids and lipid-metabolizing esterases/lipases are highly important for the mycobacterial life cycle and, possibly, for mycobacterial virulence. In this study, we expressed 10 members of the Lip family of Mycobacterium tuberculosis. Among the 10 proteins, LipL displayed a significantly high enzymatic activity for the hydrolysis of long-chain lipids. The optimal temperature for the lipase activity of LipL was demonstrated to be 37 degrees C, and the optimal pH was 8.0. The lipase active center was not the conserved motif G-x-S-x-G, but rather the S-x-x-K and GGG motifs, and the key catalytic amino acid residues were identified as G50, S88, and K91, as demonstrated through site-directed mutagenesis experiments. A three-dimensional modeling structure of LipL was constructed, which showed that the GGG motif was located in the surface of a pocket structure. Furthermore, the subcellular localization of LipL was demonstrated to be on the mycobacterial surface by Western blot analysis. Our results revealed that the LipL protein could induce a strong humoral immune response in humans and activate a CD8+ T cell-mediated response in mice. Overall, our study identified and characterized a novel lipase denoted LipL from M. tuberculosis, and demonstrated that LipL functions as an immunogen that activates both humoral and cell-mediated responses.
ESTHER : Cao_2015_PLoS.One_10_e0138151
PubMedSearch : Cao_2015_PLoS.One_10_e0138151
PubMedID: 26398213
Gene_locus related to this paper: myctu-Rv1076 , myctu-Rv2485c , myctu-Rv3097c

Title : Transgenic mouse milk expressing human bile salt-stimulated lipase improves the survival and growth status of premature mice - Wang_2015_Mol.Biotechnol_57_287
Author(s) : Wang Y , Sheng Z , Li Q , Gao Y , Dai Y , Liu G , Zhao Y , Li N
Ref : Mol Biotechnol , 57 :287 , 2015
Abstract : The lactating human mammary gland and the pancreas both produce bile salt-stimulated lipase (BSSL), a lipolytic enzyme acting on a wide range of substrates, including triglyceride, cholesterol esters, and fat-soluble vitamins esters. Breast milk BSSL has a particularly important role in the digestion of milk fat by newborn infants. We report the generation of transgenic mice that harbored a human BSSL gene controlled by a mammary gland-specific promoter. BSSL levels in transgenic mouse milk were raised to 376.8 mug/ml, corresponding to an activity of 9.15 U/ml. Premature wild-type neonates nursed by transgenic dams exhibited significantly higher survival rate than did the control neonates nursed by wild dams (95 vs. 83.3 % and, P < 0.05). They also showed 43.8 % greater body weight gain and 33.3 % lesser fecal crude fat levels than did the controls. This study provides significant evidence that increased levels of BSSL in milk may reduce mortality and improve the growth and fat absorption in premature mice during neonatal development.
ESTHER : Wang_2015_Mol.Biotechnol_57_287
PubMedSearch : Wang_2015_Mol.Biotechnol_57_287
PubMedID: 25385005

Title : Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis - Li_2014_PLoS.One_9_e94092
Author(s) : Li L , Li N , Pang W , Zhang X , Hammock BD , Ai D , Zhu Y
Ref : PLoS ONE , 9 :e94092 , 2014
Abstract : Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; manipulation of their levels is a potentially useful pharmacological strategy. EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to form the corresponding diols, thus altering and reducing the activity of these oxylipins. To better understand the phenotypic impact of sEH disruption, we compared the effect of EPHX2 gene knockout (EPHX2-/-) and sEH inhibition in mouse models. Measurement of plasma oxylipin profiles confirmed that the ratio of EETs/DHETs was increased in EPHX2-/- and sEH-inhibited mice. However, plasma concentrations of 9, 11, 15, 19-HETE were elevated in EPHX2-/- but not sEH-inhibited mice. Next, we investigated the role of this difference in cardiac dysfunction induced by Angiotensin II (AngII). Both EPHX2 gene deletion and inhibition protected against AngII-induced cardiac hypertrophy. Interestingly, cardiac dysfunction was attenuated by sEH inhibition rather than gene deletion. Histochemical staining revealed that compared with pharmacological inhibition, EPHX2 deletion aggravated AngII-induced myocardial fibrosis; the mRNA levels of fibrotic-related genes were increased. Furthermore, cardiac inflammatory response was greater in EPHX2-/- than sEH-inhibited mice with AngII treatment, as evidenced by increased macrophage infiltration and expression of MCP-1 and IL-6. In vitro, AngII-upregulated MCP-1 and IL-6 expression was significantly attenuated by sEH inhibition but promoted by EPHX2 deletion in cardiofibroblasts. Thus, compared with pharmacological inhibition of sEH, EPHX2 deletion caused the shift in arachidonic acid metabolism, which may led to pathological cardiac remodeling, especially cardiac fibrosis.
ESTHER : Li_2014_PLoS.One_9_e94092
PubMedSearch : Li_2014_PLoS.One_9_e94092
PubMedID: 24718617

Title : Molecular mechanism of inflammatory response in mouse liver caused by exposure to CeCl3 - Li_2013_Environ.Toxicol_28_349
Author(s) : Li N , Cheng J , Cheng Z , Hu R , Cai J , Gao G , Cui Y , Wang L , Hong F
Ref : Environ Toxicol , 28 :349 , 2013
Abstract : To investigate the molecular mechanism of inflammatory response in the mouse liver caused by exposure to CeCl3 , we measured the liver indices, and cerium content, evaluated the liver histopathological section, detected serum biochemical parameters of liver function, and the immunoglobulin M (IgM) content, analyzed the liver mRNA and protein expression levels of Toll-like receptor 2, 4 (TLR2, TLR4), and inflammatory cytokines in liver using real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that exposure to CeCl3 decreased body weight and caused cerium accumulation in the mouse liver and histopathological changes of liver (such as inflammatory cell infiltration). Furthermore, biochemical assays suggested that CeCl3 could promote the activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, pseudocholinesterase, and leucine aminopeptidase, decrease serum IgM, upregulate the levels of TLR2, TLR4, nuclear factor-kappaB (NF-kappaB), NF-kappaBp52, NF-kappaBp65, NF-kappaB-inducing kinase (NIK), IkappaB kinase alpha (IKK-alpha), IkappaB kinase beta (IKK-beta), and tumor necrosis factor-alpha (TNF-alpha) expression, and suppress NF-kappaB-inhibiting factor (IkappaB) and interleukin-2 (IL-2) expression in liver. Taken together, the inflammation of mice liver caused by exposure to CeCl3 might be closely associated with the alteration of inflammatory cytokine expressions in the mouse liver, the signal-transducing events happening in CeCl3 -induced macrophages of liver sequentially might occur via activation of TLRs-->TNF-alpha-->NIK-->IkappaB kinase (including IKK1, IKK2)-->NF-kappaB (including NF-kappaBP52, NF-kappaBP65)--> inflammation. (c) 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.
ESTHER : Li_2013_Environ.Toxicol_28_349
PubMedSearch : Li_2013_Environ.Toxicol_28_349
PubMedID: 21656643

Title : A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARgamma to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction - Xu_2013_Int.J.Cardiol_167_1298
Author(s) : Xu DY , Davis BB , Wang ZH , Zhao SP , Wasti B , Liu ZL , Li N , Morisseau C , Chiamvimonvat N , Hammock BD
Ref : Int J Cardiol , 167 :1298 , 2013
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). METHODS AND
RESULTS: EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24h with or without peroxisome proliferator activated receptor gamma (PPARgamma) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1alpha (HIF-1alpha) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-alpha. Lastly, we provide evidence that these effects were PPARgamma dependent. CONCLUSION: The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARgamma pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.
ESTHER : Xu_2013_Int.J.Cardiol_167_1298
PubMedSearch : Xu_2013_Int.J.Cardiol_167_1298
PubMedID: 22525341

Title : The duck genome and transcriptome provide insight into an avian influenza virus reservoir species - Huang_2013_Nat.Genet_45_776
Author(s) : Huang Y , Li Y , Burt DW , Chen H , Zhang Y , Qian W , Kim H , Gan S , Zhao Y , Li J , Yi K , Feng H , Zhu P , Li B , Liu Q , Fairley S , Magor KE , Du Z , Hu X , Goodman L , Tafer H , Vignal A , Lee T , Kim KW , Sheng Z , An Y , Searle S , Herrero J , Groenen MA , Crooijmans RP , Faraut T , Cai Q , Webster RG , Aldridge JR , Warren WC , Bartschat S , Kehr S , Marz M , Stadler PF , Smith J , Kraus RH , Ren L , Fei J , Morisson M , Kaiser P , Griffin DK , Rao M , Pitel F , Wang J , Li N
Ref : Nat Genet , 45 :776 , 2013
Abstract : The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its beta-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.
ESTHER : Huang_2013_Nat.Genet_45_776
PubMedSearch : Huang_2013_Nat.Genet_45_776
PubMedID: 23749191
Gene_locus related to this paper: anapl-BCHE , anapl-r0lw36 , anapl-r0m5n4 , anapl-thioe , anapl-u3iqr9 , anapl-r0l4n7 , anapl-u3j4v8 , anapl-u3icy5 , anapl-u3ivv9 , anapl-u3j4g1 , anapl-u3j4i2 , anapl-u3j4v5 , anapl-r0kv25 , anapl-u3ild2 , anapl-u3imh5 , anapl-b6dzk9 , anapl-u3imp7 , anapl-u3i5h5 , anapl-u3id17 , anapl-r0m1y3 , anapl-r0lhc4 , anapl-r0ktn0 , anapl-r0l8l1 , anapl-r0lin6 , anapl-r0jhf3

Title : Genome sequence of benzo(a)pyrene-degrading bacterium Novosphingobium pentaromativorans US6-1 - Luo_2012_J.Bacteriol_194_907
Author(s) : Luo YR , Kang SG , Kim SJ , Kim MR , Li N , Lee JH , Kwon KK
Ref : Journal of Bacteriology , 194 :907 , 2012
Abstract : Novosphingobium pentaromativorans US6-1 showed a good ability to degrade high-molecular-weight polycyclic aromatic hydrocarbons. We report the draft genome sequence of strain US6-1, which contains a main chromosome (5,096,413 bp, G+C content of 63.1%) and two plasmids (188,476 and 60,085 bp). The majority of the aromatic-hydrocarbon-degrading genes are encoded in the larger plasmid.
ESTHER : Luo_2012_J.Bacteriol_194_907
PubMedSearch : Luo_2012_J.Bacteriol_194_907
PubMedID: 22275104
Gene_locus related to this paper: 9sphn-g6e733 , 9sphn-g6efp8 , 9sphn-g6eg77 , 9sphn-g6e775 , 9sphn-g6ecp9

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : Resolution of 2-nitroalcohols by Burkholderia cepacia lipase-catalyzed enantioselective acylation - Li_2012_Biotechnol.Lett_34_153
Author(s) : Li N , Hu SB , Feng GY
Ref : Biotechnol Lett , 34 :153 , 2012
Abstract : Racemic 2-nitro-1-phenylethanol was resolved by via enantioselective transesterification catalyzed by Burkholderia cepacia lipase. The reaction afforded excellent E values (E > 200) and enantioselectivity (up to >99% enantiomeric excesses [ee]) of both remaining substrates and acetylated product. Moreover, the lipase displayed high enantioselectivity in the resolution of additional 2-nitroalcohols (E up to >200). This method provides an efficient alternative for obtaining enantiopure 2-nitroalcohols.
ESTHER : Li_2012_Biotechnol.Lett_34_153
PubMedSearch : Li_2012_Biotechnol.Lett_34_153
PubMedID: 21972142

Title : Over-expression of human lipoprotein lipase in mouse mammary glands leads to reduction of milk triglyceride and delayed growth of suckling pups - Wang_2011_PLoS.One_6_e20895
Author(s) : Wang Y , Tong J , Li S , Zhang R , Chen L , Zheng M , Wang M , Liu G , Dai Y , Zhao Y , Li N
Ref : PLoS ONE , 6 :e20895 , 2011
Abstract : BACKGROUND: The mammary gland is a conserved site of lipoprotein lipase expression across species and lipoprotein lipase attachment to the luminal surface of mammary gland vascular endothelial cells has been implicated in the direction of circulating triglycerides into milk synthesis during lactation. PRINCIPAL FINDINGS: Here we report generation of transgenic mice harboring a human lipoprotein lipase gene driven by a mammary gland-specific promoter. Lipoprotein lipase levels in transgenic milk was raised to 0.16 mg/ml, corresponding to an activity of 8772.95 mU/ml. High lipoprotein lipase activity led to a significant reduction of triglyceride concentration in milk, but other components were largely unchanged. Normal pups fed with transgenic milk showed inferior growth performances compared to those fed with normal milk. CONCLUSION: Our study suggests a possibility to reduce the triglyceride content of cow milk using transgenic technology.
ESTHER : Wang_2011_PLoS.One_6_e20895
PubMedSearch : Wang_2011_PLoS.One_6_e20895
PubMedID: 21698114

Title : Highly regioselective synthesis of undecylenic acid esters of purine nucleosides catalyzed by Candida antarctica lipase B - Gao_2011_Biotechnol.Lett_33_2233
Author(s) : Gao WL , Li N , Zong MH
Ref : Biotechnol Lett , 33 :2233 , 2011
Abstract : Regioselective undecylenoylation of purine nucleosides as potential dual prodrugs was achieved by Candida antarctica lipase B using adenosine as a model reactant. The optimum organic solvent, molar ratio of vinyl ester to nucleoside, enzyme dosage, reaction temperature and molecular sieve amount were anhydrous THF, 5:1, 20 U/ml, 45 degrees C and 75 mg/ml, respectively. Under the optimum conditions, the initial reaction rate, yield and 5'-regioselectivity were 1.1 mM/h, 90% and >99%, respectively. The enzymatic acylation of various nucleosides furnished the desired 5'-ester derivatives with the yields of 60-95% and 5'-regioselectivities of >99%. In addition, the lipase displayed excellent operational stability in THF, and retained 96% of its initial activity after reused for five batches.
ESTHER : Gao_2011_Biotechnol.Lett_33_2233
PubMedSearch : Gao_2011_Biotechnol.Lett_33_2233
PubMedID: 21744146

Title : A functional EDS1 ortholog is differentially regulated in powdery mildew resistant and susceptible grapevines and complements an Arabidopsis eds1 mutant - Gao_2010_Planta_231_1037
Author(s) : Gao F , Shu X , Ali MB , Howard S , Li N , Winterhagen P , Qiu W , Gassmann W
Ref : Planta , 231 :1037 , 2010
Abstract : Vitis vinifera (grapevine) is the most economically important deciduous fruit crop, but cultivated grapevine varieties lack adequate innate immunity to a range of devastating diseases. To identify genetic resources for grapevine innate immunity and understand pathogen defense pathways in a woody perennial plant, we focus in this study on orthologs of the central Arabidopsis thaliana defense regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). The family of EDS1-like genes is expanded in grapevine, and members of this family were previously found to be constitutively upregulated in the resistant variety 'Norton' of the North American grapevine species Vitis aestivalis, while they were induced by Erysiphe necator, the causal agent of grapevine powdery mildew (PM), in the susceptible V. vinifera variety 'Cabernet Sauvignon'. Here, we determine the responsiveness of individual EDS1-like genes in grapevine to PM and salicylic acid, and find that EDS1-like paralogs are differentially regulated in 'Cabernet Sauvignon', while two are constitutively upregulated in 'Norton'. Sequencing of VvEDS1 and VaEDS1 cDNA and genomic clones revealed high conservation in the protein-encoding sequence and some divergence of the promoter sequence in the two grapevine varieties. Complementation of the Arabidopsis eds1-1 mutant showed that the EDS1-like gene with highest predicted amino acid sequence similarity to AtEDS1 from either grapevine varieties is a functional ortholog of AtEDS1. Together, our analyses show that differential susceptibility to PM is correlated with differences in EDS1 expression, not differences in EDS1 function, between resistant 'Norton' and susceptible 'Cabernet Sauvignon'.
ESTHER : Gao_2010_Planta_231_1037
PubMedSearch : Gao_2010_Planta_231_1037
PubMedID: 20145949
Gene_locus related to this paper: arath-eds1

Title : Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice - Duan_2010_Biomaterials_31_894
Author(s) : Duan Y , Liu J , Ma L , Li N , Liu H , Wang J , Zheng L , Liu C , Wang X , Zhao X , Yan J , Wang S , Wang H , Zhang X , Hong F
Ref : Biomaterials , 31 :894 , 2010
Abstract : In an effort to examine liver injury, immune response, and other physiological effects in mice caused by intragastric administration of nanoparticulate anatase titanium dioxide (5nm), we assessed T lymphocytes, B lymphocyte and NK lymphocyte counts, hematological indices, biochemical parameters of liver functions, and histopathological changes in nanoparticulate titanium dioxide -treated mice. Indeed, mice treated with higher dose nanoparticulate titanium dioxide displayed a reduction in body weight, an increase in coefficients of the liver and histopathological changes in the liver. Specifically, in these nanoparticulate titanium dioxide -treated mice, interleukin-2 activity, white blood cells, red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, thrombocytes, reticulocytes, T lymphocytes (CD3(+), CD4(+), CD8(+)), NK lymphocytes, B lymphocytes, and the ratio of CD4 to CD8 of mice were decreased, whereas NO level, mean corpuscular volume, mean corpuscular haemoglobin, red (cell) distribution width, platelets, hematocrit, mean platelet volume of mice were increased. Furthermore, liver functions were also disrupted, as evidenced by the enhanced activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and cholinesterase, an increase of the total protein, and the reduction of ratio of albumin to globulin, the total bilirubin, triglycerides, and the total cholesterol levels. These results suggested that the liver function damage observed in mice treated with higher dose nanoparticulate titanium dioxide is likely associated with the damage of haemostasis blood system and immune response. However, low dose nanoparticulate anatase TiO(2) has little influences on haemostasis blood system and immune response in mice.
ESTHER : Duan_2010_Biomaterials_31_894
PubMedSearch : Duan_2010_Biomaterials_31_894
PubMedID: 19857890

Title : A highly regioselective route to arbutin esters by immobilized lipase from Penicillium expansum - Yang_2010_Bioresour.Technol_101_1
Author(s) : Yang RL , Li N , Li RF , Smith TJ , Zong MH
Ref : Bioresour Technol , 101 :1 , 2010
Abstract : Immobilized lipase from Penicillium expansum, a novel and inexpensive enzyme preparation that we immobilized in our laboratory, was an excellent catalyst for highly regioselective acylation of arbutin with fatty acid vinyl esters. For the enzymatic butanoylation of arbutin, under the optimal conditions, initial reaction rate was 75.1 mM/h, and substrate conversion and regioselectivity were greater than 99%. In addition, a variety of 6'-esters of arbutin were prepared with high conversion (>99%) and excellent regioselectivity (>99%). It was found that the enzymatic reaction rate varied widely with different acyl donors, presumably owing to their different interactions with the active site of the lipase. The immobilized lipase from P. expansum displayed highest catalytic activity with medium-length straight-chain acyl donors. Acyl donors bearing a substituent or a conjugate double bond gave reduced reaction rates.
ESTHER : Yang_2010_Bioresour.Technol_101_1
PubMedSearch : Yang_2010_Bioresour.Technol_101_1
PubMedID: 19695875

Title : Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity - Ma_2010_Biomaterials_31_99
Author(s) : Ma L , Liu J , Li N , Wang J , Duan Y , Yan J , Liu H , Wang H , Hong F
Ref : Biomaterials , 31 :99 , 2010
Abstract : In order to study the mechanisms underlying the effects of TiO(2) nanoparticles on the brain, ICR mice were injected with nanoparticulate anatase TiO(2) (5 nm) of various doses into the abdominal cavity daily for 14 days. We then examined the coefficient of the brain, the brain pathological changes and oxidative stress-mediated responses, and the accumulation of nanoparticulate anatase TiO(2) and levels of neurochemicals in the brain. The results showed that high-dose nanoparticulate anatase TiO(2) could induce some neurons to turn into filamentous shapes and others into inflammatory cells. The concentration of nanoparticulate anatase TiO(2) in the brain was increased as increases in nanoparticulate anatase TiO(2) dosages used. The oxidative stress and injury of the brain occurred as nanoparticulate anatase TiO(2) appeared to trigger a cascade of reactions such as lipid peroxidation, the decreases of the total anti-oxidation capacity and activities of antioxidative enzymes, the excessive release of nitric oxide, the reduction of glutamic acid, and the downregulated level of acetylcholinesterase activities. We concluded that TiO(2) nanoparticles injected at the abdominal cavity could be translocated into the brain and in turn caused the brain injury.
ESTHER : Ma_2010_Biomaterials_31_99
PubMedSearch : Ma_2010_Biomaterials_31_99
PubMedID: 19783296

Title : Characterization of a unique proline iminopeptidase from white-rot basidiomycetes Phanerochaete chrysosporium - Li_2010_Biochimie_92_779
Author(s) : Li N , Wu JM , Zhang LF , Zhang YZ , Feng H
Ref : Biochimie , 92 :779 , 2010
Abstract : A putative gene encoding proline iminopeptidase (PchPiPA) was cloned from Phanerochaete chrysosporium BKM-F-1767 by RT-PCR and expressed successfully in Escherichia coli. The cDNA is 942 bp in length and encodes 313 amino acids. The recombinant enzyme was only able to hydrolyze Pro-pNA among the tested synthetic substrates. There is no activity detected toward Leu-pNA, Phe-pNA and Tyr-pNA, as well as GGG-pNA, SGR-pNA, AAV-pNA, AAPL-pNA, AAVA-pNA. And the recombinant enzyme could cleave the peptides derived from enzyme-hydrolytic natural proteins to release free lysine, which was confirmed using synthetic oligopeptides with lysine at N termini as substrate. The optimal pH and temperature for this enzyme were 8.0 and 45 degrees C, respectively. The catalytic activity was inhibited slightly by Mg(2+), Al(3+), Ca(2+), Fe(3+), Fe(2+) and Ba(2+); strongly by Ni(2+), Mn(2+) and Co(2+), and almost inactivated by Zn(2+), Cu(2+) and Hg(2+). In addition, the enzyme was not sensitive to EDTA-Na(2), as well as redoxes of DTT, beta-ME and H(2)O(2). The protease inhibitors of benzamidine hydrochloride and phenylmethyl sulfonyfluoride caused a moderate inhibition. The V(max), K(m) and k(cat) toward Pro-pNA were 347.86 mumol min(-1) mg(-1), 2.15 mM and 218.10 S(-1), respectively. The deduced catalytic triad of Ser(107), Asp(264) and His(292) was confirmed by site-directed mutagenesis because the individual replacement of Ser(107) to Asp, Asp(264) to Ala or His(292) to Leu led complete inactivation. Transcriptional analysis by RT-PCR showed that PchPiPA could be expressed under ligninolytic and non-ligninolytic conditions. Conclusively, it was suggested that the proline iminopeptidase may be a member of the proteolytic system in this fungus. The availability of recombinant protein may be potentially used in certain proteolytic processing.
ESTHER : Li_2010_Biochimie_92_779
PubMedSearch : Li_2010_Biochimie_92_779
PubMedID: 20188787
Gene_locus related to this paper: phach-c6ki04

Title : Efficient regioselective synthesis of 3'-O-crotonylfloxuridine catalysed by Pseudomonas cepacia lipase - Zhao_2009_Biotechnol.Appl.Biochem_52_45
Author(s) : Zhao Z , Zong M , Li N
Ref : Biotechnol Appl Biochem , 52 :45 , 2009
Abstract : Pseudomonas cepacia lipase-catalysed preferential acylation of the secondary hydroxy group of FUdR (floxuridine) with vinyl crotonate was carried out in spite of the presence of the primary hydroxy group, and 3'-O-crotonylfloxuridine was prepared successfully for the first time. The isomerization of the double bond of crotonate, which occurs in conventional organic synthesis, could be effectively avoided during the enzymatic acylation. The effects of some key factors such as reaction medium, initial a(w) (water activity), molar ratio of vinyl crotonate to FUdR, FUdR concentration and reaction temperature on the reaction were examined. Under the optimized reaction conditions, the initial reaction rate, substrate conversion and 3'-regioselectivity of the reaction were as high as 24 mM/h, 98% and 85% respectively.
ESTHER : Zhao_2009_Biotechnol.Appl.Biochem_52_45
PubMedSearch : Zhao_2009_Biotechnol.Appl.Biochem_52_45
PubMedID: 18373494

Title : Thermomyces lanuginosus lipase-catalyzed regioselective acylation of nucleosides: Enzyme substrate recognition - Li_2009_J.Biotechnol_140_250
Author(s) : Li N , Zong MH , Ma D
Ref : J Biotechnol , 140 :250 , 2009
Abstract : Substrate recognition of Thermomyces lanuginosus lipase in the acylation of nucleosides was revealed through rational substrate engineering for the first time. T. lanuginosus lipase displayed higher catalytic activities and excellent 5'-regioselectivities (94->99%) in the acylation of ribonucleosides 1f-1j as compared to those in the acylation of 2'-deoxynucleosides 1a-1e. The higher reaction rates and excellent 5'-regioselectivities might derive from a favorable hydrogen bonding between the 2'-hydroxyl group of 1f-1j and phenolic hydroxyl group of Tyr21 present in the hydrophilic region of the lipase.
ESTHER : Li_2009_J.Biotechnol_140_250
PubMedSearch : Li_2009_J.Biotechnol_140_250
PubMedID: 19428721
Gene_locus related to this paper: humla-1lipa

Title : Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches - Li_2009_J.Mol.Cell.Cardiol_47_835
Author(s) : Li N , Liu JY , Timofeyev V , Qiu H , Hwang SH , Tuteja D , Lu L , Yang J , Mochida H , Low R , Hammock BD , Chiamvimonvat N
Ref : Journal of Molecular & Cellular Cardiology , 47 :835 , 2009
Abstract : Myocardial infarction (MI) leading to myocardial cell loss represents one of the common causes leading to cardiac failure. We have previously demonstrated the beneficial effects of several potent soluble epoxide hydrolase (sEH) inhibitors in cardiac hypertrophy. sEH catalizes the conversion of epoxyeicosatrienoic acids (EETs) to form the corresponding dihydroxyeicosatrienoic acids (DHETs). EETs are products of cytochrome P450 epoxygenases that have vasodilatory properties. Additionally, EETs inhibit the activation of nuclear factor (NF)-kappaB-mediated gene transcription. Motivated by the potential to uncover a new class of therapeutic agents for cardiovascular diseases which can be effectively used in clinical setting, we directly tested the biological effects of sEH inhibitors (sEHIs) on the progression of cardiac remodeling using a clinically relevant murine model of MI. We demonstrated that sEHIs were highly effective in the prevention of progressive cardiac remodeling post MI. Using metabolomic profiling of the inflammatory lipid mediators, we documented a significant decrease in EETs/DHETs ratio in MI model predicting a heightened inflammatory state. Treatment with sEHIs resulted in a change in the pattern of lipid mediators from one of inflammation towards resolution. Moreover, the oxylipin profiling showed a striking parallel to the changes in inflammatory cytokines in this model. Our study provides evidence for a possible new therapeutic strategy to improve cardiac function post MI.
ESTHER : Li_2009_J.Mol.Cell.Cardiol_47_835
PubMedSearch : Li_2009_J.Mol.Cell.Cardiol_47_835
PubMedID: 19716829

Title : Biochemical characterization and transcriptional analysis of the epoxide hydrolase from white-rot fungus Phanerochaete chrysosporium - Li_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_638
Author(s) : Li N , Zhang Y , Feng H
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :638 , 2009
Abstract : The white-rot basidiomycetes Phanerochaete chrysosporium is a model fungus used to investigate the secondary metabolism and lignin degradation. Genomic sequencing reveals the presence of at least 18 genes encoding putative epoxide hydrolases (EHs). One cDNA encoding EH (designated as PchEHA) was cloned and expressed in Escherichia coli. Transcriptional analysis demonstrated that the transcripts of PchEHA could be detected under the ligninolytic and nonligninolytic conditions as well as amended with anthracene. The recombinant enzyme exhibits broad hydrolytic activity toward several racemic epoxides including styrene oxide, epichlorohydrin, and 1,2-epoxybutane, but with different specificity. Using racemic styrene oxide as the substrate, the optimal pH and temperature are pH 9.0 and 40 degrees C, respectively. The enzyme is not sensitive to EDTA, and is inhibited by H2O2, and several metal ions including Zn(2+), Cd(2+), and Hg(2+) at various extents. Several organic cosolvents including acetone, dimethylsulfoxide, formamide, glycerol and ethanol at 10% (v/v) cause slight or no inhibition of the hydrolytic reaction. More importantly, the recombinant enzyme displays distinct enantioselective preference to several chiral epoxides. The enzyme showed good enantioselectivity toward chiral styrene oxide with preferential hydrolysis of (R)-enantiomer. PchEHA is likely a novel soluble EH based on the sequence analysis and catalytic properties, and is a great potential biocatalyst for the preparation of enantiopure styrene oxide in racemic kinetic resolution.
ESTHER : Li_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_638
PubMedSearch : Li_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_638
PubMedID: 19657565
Gene_locus related to this paper: phach-b0fsq0

Title : Unexpected reversal of the regioselectivity in Thermomyces lanuginosus lipase-catalyzed acylation of floxuridine - Li_2009_Biotechnol.Lett_31_1241
Author(s) : Li N , Zong MH , Ma D
Ref : Biotechnol Lett , 31 :1241 , 2009
Abstract : Unexpected inversion of the 3':5'-regioselectivity was observed in the enzymatic methacryloylation, crotonylation and cinnamoylation of floxuridine (1.5:1, 2.3:1 and 4.4:1, respectively), where Thermomyces lanuginosus lipase preferentially catalyzed the acylation of 3'-hydroxyl rather than that of 5'-hydroxyl group. The possible reason might be the presence of a remote interaction between the unsaturated bond in the acyl group and the aromatic ring of amino acid residue Trp89 in the lid of the lipase.
ESTHER : Li_2009_Biotechnol.Lett_31_1241
PubMedSearch : Li_2009_Biotechnol.Lett_31_1241
PubMedID: 19360390

Title : The genome of a lepidopteran model insect, the silkworm Bombyx mori - Xia_2008_Insect.Biochem.Mol.Biol_38_1036
Author(s) : Xia Q , Wang J , Zhou Z , Li R , Fan W , Cheng D , Cheng T , Qin J , Duana J , Xu H , Li Q , Li N , Wang M , Dai F , Liu C , Lin Y , Zhao P , Zhang H , Liu S , Zha X , Li C , Zhao A , Pan M , Pan G , Shen Y , Gao Z , Wang Z , Wang G , Wu Z , Hou Y , Chai C , Yu Q , He N , Zhang Z , Li S , Yang H , Lu C , Xiang Z , Mita K , Kasahara M , Nakatani Y , Yamamoto K , Abe H , Ahsan B , Daimoni T , Doi K , Fujii T , Fujiwara H , Fujiyama A , Futahashi R , Hashimotol S , Ishibashi J , Iwami M , Kadono-Okuda K , Kanamori H , Kataoka H , Katsuma S , Kawaoka S , Kawasaki H , Kohara Y , Kozaki T , Kuroshu RM , Kuwazaki S , Matsushima K , Minami H , Nagayasu Y , Nakagawa T , Narukawa J , Nohata J , Ohishi K , Ono Y , Osanai-Futahashi M , Ozaki K , Qu W , Roller L , Sasaki S , Sasaki T , Seino A , Shimomura M , Shin-I T , Shinoda T , Shiotsuki T , Suetsugu Y , Sugano S , Suwa M , Suzuki Y , Takiya S , Tamura T , Tanaka H , Tanaka Y , Touhara K , Yamada T , Yamakawa M , Yamanaka N , Yoshikawa H , Zhong YS , Shimada T , Morishita S
Ref : Insect Biochemistry & Molecular Biology , 38 :1036 , 2008
Abstract : Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes.
ESTHER : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedSearch : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedID: 19121390
Gene_locus related to this paper: bommo-a0mnw6 , bommo-a1yw85 , bommo-a9ls22 , bommo-ACHE1 , bommo-ACHE2 , bommo-b0fgv8 , bommo-b1q137 , bommo-b1q139 , bommo-b1q140 , bommo-b1q141 , bommo-b2zdz0 , bommo-b3gef6 , bommo-b3gef7 , bommo-b3gs55 , bommo-b3gs56 , bommo-d2ktu3 , bommo-d2ktu5 , bommo-d9ile0 , bommo-e1cga5 , bommo-e1cga6 , bommo-g8fpz6 , bommo-h9iu43 , bommo-h9iu46 , bommo-h9iu47.1 , bommo-h9iu47.2 , bommo-h9iue5 , bommo-h9ivg2 , bommo-h9iwj7 , bommo-h9iwj8 , bommo-h9ix58 , bommo-h9ixi1.1 , bommo-h9ixi1.2 , bommo-h9iy47 , bommo-h9izw1 , bommo-h9j0s4 , bommo-h9j1y0 , bommo-h9j3r0 , bommo-h9j3w6 , bommo-h9j3w7 , bommo-h9j5t0 , bommo-h9j8g3 , bommo-h9j9k9 , bommo-h9j066 , bommo-h9j067 , bommo-h9j593 , bommo-h9j594 , bommo-h9j990 , bommo-h9jde8 , bommo-h9jde9 , bommo-h9jdf0 , bommo-h9jds4 , bommo-h9jle7 , bommo-h9jn83 , bommo-h9jn85 , bommo-h9jrg2 , bommo-h9jyh9 , bommo-JHE , bommo-m1rmh6 , bommo-q1hq05 , bommo-q4tte1 , bommo-h9j592 , bommo-h9j604 , bommo-h9jpm8 , bommo-h9iss4 , bommo-h9j2c7

Title : Functional variants of the lipoprotein lipase gene and the risk of preeclampsia among non-Hispanic Caucasian women - Zhang_2006_Clin.Genet_69_33
Author(s) : Zhang C , Austin MA , Edwards KL , Farin FM , Li N , Hsu L , Srinouanprachanh SL , Williams MA
Ref : Clin Genet , 69 :33 , 2006
Abstract : Hypertriglyceridemia is an important pathophysiologic feature of preeclampsia, a common vascular disorder of pregnancy. Three well-documented functional variants (N291S, S447X, and D9N) of the lipoprotein lipase gene were related to hypertriglyceridemia. Results from the only two studies concerning the relationship between these variants and preeclampsia risk have been inconsistent. We investigated this relationship in a case-control study including 144 preeclamptic and 290 normotensive pregnant women (all non-Hispanic Caucasians). We estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for maternal age, pre-pregnancy body mass index, and parity. After adjusting for covariates, women with the 291 N/S or S/S genotype had significantly increased risk of preeclampsia (OR 6.9, 95% CI 1.9-25.4) compared with women with the common 291N/N genotype. The 447 S/X or X/X genotype was not significantly associated with preeclampsia risk. The frequency of the 9N variant allele was 1.8% in controls, while this allele was not observed among cases. Haplotype 9D/291S/447S was strongly associated with higher risk of preeclampsia as compared with the most common haplotype 9D/291N/447S (adjusted OR 6.6, 95% CI 1.7-25.0). Results from our study support the thesis that abnormal lipid metabolism is important in the pathogenesis of preeclampsia.
ESTHER : Zhang_2006_Clin.Genet_69_33
PubMedSearch : Zhang_2006_Clin.Genet_69_33
PubMedID: 16451134

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Leukotriene A4 hydrolase in rat and human esophageal adenocarcinomas and inhibitory effects of bestatin - Chen_2003_J.Natl.Cancer.Inst_95_1053
Author(s) : Chen X , Li N , Wang S , Wu N , Hong J , Jiao X , Krasna MJ , Beer DG , Yang CS
Ref : J Natl Cancer Inst , 95 :1053 , 2003
Abstract : BACKGROUND: Esophageal adenocarcinoma (EAC) is increasing at the most rapid rate of any cancer in the United States. An esophagogastroduodenal anastomosis (EGDA) surgical model in rats mimics human gastroesophageal reflux and results in EAC. Leukotriene A4 hydrolase (LTA4H), a protein overexpressed in EAC in this model, is a rate-limiting enzyme in the biosynthesis of leukotriene B4 (LTB4), a potent inflammatory mediator. We used this model and human EAC and non-tumor tissues to elucidate the expression pattern of LTA4H and to evaluate it as a target for chemoprevention.
METHODS: LTA4H expression was examined by western blotting and immunohistochemistry. The functional role of LTA4H in carcinogenesis was investigated by use of an LTA4H inhibitor, bestatin, in the rat EGDA model. All statistical tests were two-sided.
RESULTS: LTA4H was overexpressed in all 10 rat EACs examined, compared with its level in normal rat tissue; it was also overexpressed in four of six human EAC tumor samples, compared with its level in adjacent non-tumor tissue. In tissue sections from 20 EGDA rats and 92 patients (86 with EAC, one with dysplasia, and five with columnar-lined esophagus), LTA4H was expressed in infiltrating inflammatory cells and overexpressed in the columnar cells of preinvasive lesions and cancers, especially in well-differentiated EACs, as compared with the basal cells of the normal esophageal squamous epithelium. Bestatin statistically significantly inhibited LTB4 biosynthesis in the esophageal tissues of EGDA rats (without bestatin = 8.28 ng/mg of protein; with bestatin = 4.68 ng/mg of protein; difference = 3.60, 95% CI = 1.59 to 5.61; P = .002) and reduced the incidence of EAC in the EGDA rats from 57.7% (15 of 26 rats) to 26.1% (6 of 23 rats) (difference = 31.6%, 95% CI = 0.3% to 56.2%; P = .042). CONCLUSION: LTA4H overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of EAC.
ESTHER : Chen_2003_J.Natl.Cancer.Inst_95_1053
PubMedSearch : Chen_2003_J.Natl.Cancer.Inst_95_1053
PubMedID: 12865451

Title : Inverse acyl phosph(on)ates: substrates or inhibitors of beta-lactam-recognizing enzymes? - Morrison_2001_Bioorg.Chem_29_271
Author(s) : Morrison MJ , Li N , Pratt RF
Ref : Bioorg Chem , 29 :271 , 2001
Abstract : Acyl phosph(on)ates represent a new class of inhibitors of beta-lactam-recognizing enzymes. Previously described members of this class were aroyl phosph(on)ates. These compounds have been shown to acylate and/or phosphylate the active site serine residue, leading to either transient or essentially irreversible inhibition [Li, N., and Pratt, R. F. (1998) J. Am. Chem. Soc.120, 4264-4268]. The present paper describes the synthesis and evaluation as inhibitors of an inverse pair of acyl phosph(on)ates that incorporate the amido side chain that represents a major substrate specificity determinant of these enzymes. Thus, N-(phenylacetyl)glycyl phenyl phosphate and benzoyl N-(benzyloxycarbonyl)aminomethyl phosphonate were prepared. The former of these compounds was found to be a substrate of typical class A and C beta-lactamases and of the DD-peptidase of Streptomyces R61; it thus acylates the active site serine. In contrast, the latter compound was an irreversible inhibitor of the above enzymes, probably by phosphonylation of the active site serine. With each of these enzymes therefore, the amido side chain rather than the acyl group dictates the orientation of the bound phosph(on)ate and thus the mode of reaction.
ESTHER : Morrison_2001_Bioorg.Chem_29_271
PubMedSearch : Morrison_2001_Bioorg.Chem_29_271
PubMedID: 16256697

Title : Determination of a protein structure by iodination: the structure of iodinated acetylxylan esterase - Ghosh_1999_Acta.Crystallogr.D.Biol.Crystallogr_55_779
Author(s) : Ghosh D , Erman M , Sawicki M , Lala P , Weeks DR , Li N , Pangborn W , Thiel DJ , Jornvall H , Gutierrez R , Eyzaguirre J
Ref : Acta Crystallographica D Biol Crystallogr , 55 :779 , 1999
Abstract : Enzymatic and non-enzymatic iodination of the amino acid tyrosine is a well known phenomenon. The iodination technique has been widely used for labeling proteins. Using high-resolution X-ray crystallographic techniques, the chemical and three-dimensional structures of iodotyrosines formed by non-enzymatic incorporation of I atoms into tyrosine residues of a crystalline protein are described. Acetylxylan esterase (AXE II; 207 amino-acid residues) from Penicillium purpurogenum has substrate specificities towards acetate esters of D-xylopyranose residues in xylan and belongs to a new class of alpha/beta hydrolases. The crystals of the enzyme are highly ordered, tightly packed and diffract to better than sub-angstrom resolution at 85 K. The iodination technique has been utilized to prepare an isomorphous derivative of the AXE II crystal. The structure of the enzyme determined at 1.10 A resolution exclusively by normal and anomalous scattering from I atoms, along with the structure of the iodinated complex at 1.80 A resolution, demonstrate the formation of covalent bonds between I atoms and C atoms at ortho positions to the hydroxyl groups of two tyrosyl moieties, yielding iodotyrosines.
ESTHER : Ghosh_1999_Acta.Crystallogr.D.Biol.Crystallogr_55_779
PubMedSearch : Ghosh_1999_Acta.Crystallogr.D.Biol.Crystallogr_55_779
PubMedID: 10089308
Gene_locus related to this paper: penpu-axylest

Title : Characterization of crystals of Penicillium purpurogenum acetyl xylan esterase from high-resolution x-ray diffraction - Pangborn_1996_Proteins_24_523
Author(s) : Pangborn W , Erman M , Li N , Burkhart BM , Pletnev VZ , Duax WL , Gutierrez R , Peirano A , Eyzaguirre J , Thiel DJ , Ghosh D
Ref : Proteins , 24 :523 , 1996
Abstract : Acetyl xylan esterase from Penicillium purpurogenum, a single-chain 23 kDa member of a newly characterized family of esterases that cleaves side chain ester linkages in xylan, has been crystallized. The crystals diffract to better than 1 A resolution at the Cornell High Energy Synchrotron Source (CHESS) and are highly stable in the synchrotron radiation. The space group is P2(1)2(1)2(1) and cell dimensions are a = 34.9 A, b = 61.0 A, C = 72.5 A.
ESTHER : Pangborn_1996_Proteins_24_523
PubMedSearch : Pangborn_1996_Proteins_24_523
PubMedID: 8860002

Title : Structure of uncomplexed and linoleate-bound Candida cylindracea cholesterol esterase - Ghosh_1995_Structure_3_279
Author(s) : Ghosh D , Wawrzak Z , Pletnev VZ , Li N , Kaiser R , Pangborn W , Jornvall H , Erman M , Duax WL
Ref : Structure , 3 :279 , 1995
Abstract : BACKGROUND Candida cylindracea cholesterol esterase (CE) reversibly hydrolyzes cholesteryl linoleate and oleate. CE belongs to the same alpha/beta hydrolase superfamily as triacylglycerol acyl hydrolases and cholinesterases. Other members of the family that have been studied by X-ray crystallography include Torpedo californica acetylcholinesterase, Geotrichum candidum lipase and Candida rugosa lipase. CE is homologous to C. rugosa lipase 1, a triacylglycerol acyl hydrolase, with which it shares 89% sequence identity. The present study explores the details of dimer formation of CE and the basis for its substrate specificity. RESULTS: The structures of uncomplexed and linoleate-bound CE determined at 1.9 A and 2.0 A resolution, respectively, reveal a dimeric association of monomers in which two active-site gorges face each other, shielding hydrophobic surfaces from the aqueous environment. The fatty-acid chain is buried in a deep hydrophobic pocket near the active site. The positioning of the cholesteryl moiety of the substrate is equivocal, but could be modeled in the hydrophobic core of the dimer interface.
CONCLUSIONS: The monomer structure is the same in both the complexed and uncomplexed crystal forms. The dimers differ in the relative positions of the two monomers at the dimer interface. Of the 55 residues that are different in CE from those in C. rugosa lipase 1, 23 are located in the active site and at the dimer interface. The altered substrate specificity is a direct consequence of these substitutions.
ESTHER : Ghosh_1995_Structure_3_279
PubMedSearch : Ghosh_1995_Structure_3_279
PubMedID: 7788294
Gene_locus related to this paper: canru-3lipa