Xiao J

References (57)

Title : A MOF nanozyme-mediated acetylcholinesterase-free colorimetric strategy for direct detection of organophosphorus pesticides - Xiao_2024_Chem.Commun.(Camb)__
Author(s) : Xiao J , Shi F , Zhang Y , Peng M , Xu J , Li J , Chen Z , Yang Z
Ref : Chem Commun (Camb) , : , 2024
Abstract : Although some simple and rapid colorimetric methods have been developed to detect organophosphorus pesticides (OPs), the difficult extraction and easy denaturation of acetylcholinesterase (AChE) are still drawbacks needing to be overcome. Here, we propose a MOF nanozyme-mediated AChE-free colorimetric strategy for the direct detection of OPs. In the presence of OPs (pirimiphos-methyl as a model), the intense blue of oxidized 3,3',5,5'-tetramethylbenzidine (TMB) becomes light due to the quenching effect of OPs towards hydroxyl radicals (OH) that are generated by the decomposition of H(2)O(2) catalyzed by the Cu(4)Co(6) ZIF nanozyme with excellent peroxidase (POD)-like activity. The developed colorimetric sensor exhibits assay performance and offers a universal and promising analysis strategy for detecting OPs in practical samples.
ESTHER : Xiao_2024_Chem.Commun.(Camb)__
PubMedSearch : Xiao_2024_Chem.Commun.(Camb)__
PubMedID: 38168820

Title : Simultaneous determination of HD56, a novel prodrug, and its active metabolite in cynomolgus monkey plasma using LC-MS\/MS for elucidating its pharmacokinetic profile - Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
Author(s) : Yao S , Zhang W , Xiao J , Zhang Z , Wang L , Ai H , Wu X , Chen A , Zhuang X
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1235 :124045 , 2024
Abstract : An LC-MS/MS method was developed and validated for the simultaneous determination of the carboxylic acid ester precursor HD56 and the active product HD561 in cynomolgus monkey plasma. Then, the pharmacokinetic characteristics of both compounds following single and multiple i.g. administrations in cynomolgus monkeys were elucidated. In the method, chromatographic separation was achieved with a C18 reversed-phase column and the target quantification was carried out by an electrospray ionization (ESI) source coupled with triple quadrupole mess detector in positive ionization mode with multiple reaction monitoring (MRM) approach. Using the quantification method, the in vitro stability of HD56 in plasma and HD56 pharmacokinetic behavior after i.g. administration in cynomolgus monkey were investigated. It was approved that HD56 did convert into HD561 post-administration. The overall systemic exposure of HD561 post-conversion from HD56 accounted for only about 17% of HD56. After repeated administration at the same dose, there was no significant difference in exposure levels of both HD56 and HD561. However, after multiple dosing, the exposure of HD56 tended to decrease while that of HD561 tended to increase, resulting in a 30% in the exposure ratio. Remarkably, with a carboxylesterase (CES) activity profile akin to humans, the observed in vivo pharmacokinetic profile in cynomolgus monkeys holds promise for predicting HD56/HD561 PK profiles in humans.
ESTHER : Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
PubMedSearch : Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
PubMedID: 38367406

Title : In Vitro and In Vivo Insights into a Broccoli Byproduct as a Healthy Ingredient for the Management of Alzheimer's Disease and Aging through Redox Biology - Navarro-Hortal_2024_J.Agric.Food.Chem_72_5197
Author(s) : Navarro-Hortal MD , Romero-Marquez JM , Lopez-Bascon MA , Sanchez-Gonzalez C , Xiao J , Sumalla-Cano S , Battino M , Forbes-Hernandez TY , Quiles JL
Ref : Journal of Agricultural and Food Chemistry , 72 :5197 , 2024
Abstract : Broccoli has gained popularity as a highly consumed vegetable due to its nutritional and health properties. This study aimed to evaluate the composition profile and the antioxidant capacity of a hydrophilic extract derived from broccoli byproducts, as well as its influence on redox biology, Alzheimer's disease markers, and aging in the Caenorhabditis elegans model. The presence of glucosinolate was observed and antioxidant capacity was demonstrated both in vitro and in vivo. The in vitro acetylcholinesterase inhibitory capacity was quantified, and the treatment ameliorated the amyloid-beta- and tau-induced proteotoxicity in transgenic strains via SOD-3 and SKN-1, respectively, and HSP-16.2 for both parameters. Furthermore, a preliminary study on aging indicated that the extract effectively reduced reactive oxygen species levels in aged worms and extended their lifespan. Utilizing broccoli byproducts for nutraceutical or functional foods could manage vegetable processing waste, enhancing productivity and sustainability while providing significant health benefits.
ESTHER : Navarro-Hortal_2024_J.Agric.Food.Chem_72_5197
PubMedSearch : Navarro-Hortal_2024_J.Agric.Food.Chem_72_5197
PubMedID: 38477041

Title : Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections - Xiao_2024_J.Control.Release_369_39
Author(s) : Xiao J , Yin M , Yang M , Ren J , Liu C , Lian J , Lu X , Jiang Y , Yao Y , Luo J
Ref : J Control Release , 369 :39 , 2024
Abstract : The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.
ESTHER : Xiao_2024_J.Control.Release_369_39
PubMedSearch : Xiao_2024_J.Control.Release_369_39
PubMedID: 38508523

Title : Rs15285, a functional polymorphism located in lipoprotein lipase, predicts the risk and prognosis of gastric cancer - Shen_2023_Appl.Microbiol.Biotechnol__
Author(s) : Shen K , Zhou X , Hu L , Xiao J , Cheng Q , Wang Y , Liu K , Fan H , Xu Z , Yang L
Ref : Applied Microbiology & Biotechnology , : , 2023
Abstract : Lipoprotein lipase (LPL), a crucial gene in lipid metabolism, has a significant role in the progression of malignant tumors. The purpose of this research was to investigate the impact of rs15285 found in the LPL gene's 3'UTR region on the risk, biological behavior, and gastric cancer (GC) prognosis as well as to examine its potential function. Genotyping of rs15285 in 888 GC cases and 874 controls was conducted by SNaPshot technology. We used bioinformatics analysis and in vitro experiments to study the role of rs15285. First, this study revealed for the first time that polymorphism rs15285 increases the risk of GC (OR = 1.48, 95%CI = 1.16-1.89, P = 0.002). Although no relationship was found between rs12585 and the pathological features of GC, the prognosis of individuals with the rs12585 TT genotype was poorer than that of patients with the CC or CC+CT genotype (HR = 2.39 for TT vs. CC, P = 0.025; HR = 2.38 for TT vs. CC+CT, P = 0.025). In addition, bioinformatics analysis showed rs12585 may affect the binding of miRNAs to LPL, resulting in an increase of LPL expression to promote cancer progression. Ultimately, in vitro tests revealed that the rs15285 T allele increased LPL expression on the mRNA as well as the protein levels, promoting GC cell proliferation, invasion, and metastasis. The LPL rs12528 TT genotype increased the risk of GC and predicted a poor prognosis. Mechanistically, the rs15285 T allele could improve the expression of LPL, and thus promotes the malignant phenotype of GC. Therefore, our study may provide new biological predictors and a theoretical basis for the prognosis and customized therapy of stomach cancer patients. KEY POINTS: Rs15285 polymorphism is a risk factor for GC. Rs12585 TT genotype predicts a bad outcome in GC individuals. Rs15285 T allele enhances GC cells malignant biological behavior.
ESTHER : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedSearch : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedID: 37036527
Gene_locus related to this paper: human-LPL

Title : Green-emitting carbon dots as a turn on fluorescence bio-probe for highly sensitive and selective detection of lipase in human serum - Al-Mashriqi_2023_Anal.Bioanal.Chem__
Author(s) : Al-Mashriqi HS , Sanga P , Chen J , Li X , Xiao J , Li Y , Qiu H
Ref : Anal Bioanal Chem , : , 2023
Abstract : Enzyme activity assays play a crucial role in numerous fields, including biotechnology, the food industry, and clinical diagnostics. Lipases are particularly important enzymes due to their widespread use in lipid metabolism and esterification reactions. Here, we present a pioneering method for the sensitive and selective determination of lipase activity using green carbon dots (G-CDs) for first time. G-CDs are a fascinating class of carbon nanomaterials with unique optical properties and biocompatibility, making them ideal candidates for enzyme activity assays. This approach eliminates the need for traditional fluorophores or chromogenic substrates, reducing costs, fast response time (1 min), and environmental impact with a quantum yield (QY) of 7.42%. As designed, the G-CDs fluorescent probe turn-on demonstrated a reliable linear detection range from 0 to 9 mg/mL under ideal conditions, with detection limit of 0.01 mg/mL and limit of quantification (LOQ) of 0.045 mg/mL, respectively. Furthermore, the G-CDs system was thoroughly evaluated in human serum samples, showing recoveries ranging from 100.0 to 105.0%. These findings highlight the promising applicability of the G-CDs probe for lipase detection, yielding highly favorable results.
ESTHER : Al-Mashriqi_2023_Anal.Bioanal.Chem__
PubMedSearch : Al-Mashriqi_2023_Anal.Bioanal.Chem__
PubMedID: 38082135

Title : Physiologically-based pharmacokinetic modeling to predict methylphenidate exposure affected by interplay among carboxylesterase 1 pharmacogenetics, drug-drug interactions, and sex - Xiao_2022_J.Pharm.Sci__
Author(s) : Xiao J , Shi J , Thompson BR , Smith DE , Zhang T , Zhu HJ
Ref : J Pharm Sci , : , 2022
Abstract : BACKGROUND AND OBJECTIVE: The pharmacokinetics (PK) of methylphenidate (MPH) differ significantly among individuals. Carboxylesterase 1 (CES1) is the primary enzyme metabolizing MPH, and its function is affected by genetic variants, drug-drug interaction (DDI), and sex. The object of this study is to evaluate CES1 pharmacogenetics as related to MPH metabolism using human liver samples and develop a physiologically-based pharmacokinetic (PBPK) modeling approach to investigate the influence of CES1 genotypes and other factors on MPH PK. METHODS: The effect of the CES1 variant G143E (rs71647871) on MPH metabolism was studied utilizing 102 individual human liver S9 (HLS9) fraction samples. PBPK models were developed using the population-based PBPK software PK-Sim(a) by incorporating the HLS9 incubation data. The established models were applied to simulate MPH PK profiles under various clinical scenarios, including different genotypes, drug-alcohol interactions, and the difference between males and females. RESULTSL: The HLS9 incubation study showed that subjects heterozygous for the CES1 variant G143E metabolized MPH at a rate of approximately 50% of that in non-carriers. The developed PBPK models successfully predicted the exposure alteration of MPH from the G143E genetic variant, ethanol-MPH DDI, and sex. Importantly, the study suggests that male G143E carriers who are alcohol consumers are at a higher risk of MPH overexposure. CONCLUSION: PBPK modeling provides a means for better understanding the mechanisms underlying interindividual variability in MPH PK and PD and could be utilized to develop a safer and more effective MPH pharmacotherapy regimen.
ESTHER : Xiao_2022_J.Pharm.Sci__
PubMedSearch : Xiao_2022_J.Pharm.Sci__
PubMedID: 35526575

Title : Advances in Fungal Phenaloenones-Natural Metabolites with Great Promise: Biosynthesis, Bioactivities, and an In Silico Evaluation of Their Potential as Human Glucose Transporter 1 Inhibitors - Ibrahim_2022_Molecules_27_
Author(s) : Ibrahim SRM , Omar AM , Muhammad YA , Alqarni AA , Alshehri AM , Mohamed SGA , Abdallah HM , Elfaky MA , Mohamed GA , Xiao J
Ref : Molecules , 27 : , 2022
Abstract : Phenaloenones are structurally unique aromatic polyketides that have been reported in both microbial and plant sources. They possess a hydroxy perinaphthenone three-fused-ring system and exhibit diverse bioactivities, such as cytotoxic, antimicrobial, antioxidant, and anti-HIV properties, and tyrosinase, alpha-glucosidase, lipase, AchE (acetylcholinesterase), indoleamine 2,3-dioxygenase 1, angiotensin-I-converting enzyme, and tyrosine phosphatase inhibition. Moreover, they have a rich nucleophilic nucleus that has inspired many chemists and biologists to synthesize more of these related derivatives. The current review provides an overview of the reported phenalenones with a fungal origin, including their structures, sources, biosynthesis, and bioactivities. Moreover, more than 135 metabolites have been listed, and 71 references have been cited. SuperPred, an artificial intelligence (AI) webserver, was used to predict the potential targets for selected phenalenones. Among these targets, we chose human glucose transporter 1 (hGLUT1) for an extensive in silico study, as it shows high probability and model accuracy. Among them, aspergillussanones C (60) and G (60) possessed the highest negative docking scores of -15.082 and -14.829 kcal/mol, respectively, compared to the native inhibitor of 5RE (score: -11.206 kcal/mol). The MD (molecular dynamics) simulation revealed their stability in complexes with GLUT1 at 100 ns. The virtual screening study results open up a new therapeutic approach by using some phenalenones as hGLUT1 inhibitors, which might be a potential target for cancer therapy.
ESTHER : Ibrahim_2022_Molecules_27_
PubMedSearch : Ibrahim_2022_Molecules_27_
PubMedID: 36296388

Title : Butenolides from the Coral-Derived Fungus Aspergillius terreus SCSIO41404 - Peng_2022_Mar.Drugs_20_
Author(s) : Peng Q , Chen W , Lin X , Xiao J , Liu Y , Zhou X
Ref : Mar Drugs , 20 : , 2022
Abstract : Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (-)-asperteretal G (1b), (+)-asperteretal H (2a), (-)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4-13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC(50) = 25 microg/mL) and Klebsiella pneumoniae (IC(50) = 50 microg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2-73.0% at a concentration of 50 microg/mL.
ESTHER : Peng_2022_Mar.Drugs_20_
PubMedSearch : Peng_2022_Mar.Drugs_20_
PubMedID: 35323511

Title : Evaluation of a Gene-Environment Interaction of PON1 and Low-Level Nerve Agent Exposure with Gulf War Illness: A Prevalence Case-Control Study Drawn from the U.S. Military Health Survey's National Population Sample - Haley_2022_Environ.Health.Perspect_130_57001
Author(s) : Haley RW , Kramer G , Xiao J , Dever JA , Teiber JF
Ref : Environmental Health Perspectives , 130 :57001 , 2022
Abstract : BACKGROUND: Consensus on the etiology of 1991 Gulf War illness (GWI) has been limited by lack of objective individual-level environmental exposure information and assumed recall bias. OBJECTIVES: We investigated a prestated hypothesis of the association of GWI with a gene-environment (GxE) interaction of the paraoxonase-1 (PON1) Q192R polymorphism and low-level nerve agent exposure. METHODS: A prevalence sample of 508 GWI cases and 508 nonpaired controls was drawn from the 8,020 participants in the U.S. Military Health Survey, a representative sample survey of military veterans who served during the Gulf War. The PON1 Q192R genotype was measured by real-time polymerase chain reaction (RT-PCR), and the serum Q and R isoenzyme activity levels were measured with PON1-specific substrates. Low-level nerve agent exposure was estimated by survey questions on having heard nerve agent alarms during deployment. RESULTS: The GxE interaction of the Q192R genotype and hearing alarms was strongly associated with GWI on both the multiplicative [prevalence odds ratio (POR) of the interaction = 3.41; 95% confidence interval (CI): 1.20, 9.72] and additive (synergy index = 4.71; 95% CI: 1.82, 12.19) scales, adjusted for measured confounders. The Q192R genotype and the alarms variable were independent (adjusted POR in the controls = 1.18; 95% CI: 0.81, 1.73; p = 0.35), and the associations of GWI with the number of R alleles and quartiles of Q isoenzyme were monotonic. The adjusted relative excess risk due to interaction (aRERI) was 7.69 (95% CI: 2.71, 19.13). Substituting Q isoenzyme activity for the genotype in the analyses corroborated the findings. Sensitivity analyses suggested that recall bias had forced the estimate of the GxE interaction toward the null and that unmeasured confounding is unlikely to account for the findings. We found a GxE interaction involving the Q-correlated PON1 diazoxonase activity and a weak possible GxE involving the Khamisiyah plume model, but none involving the PON1 R isoenzyme activity, arylesterase activity, paraoxonase activity, butyrylcholinesterase genotypes or enzyme activity, or pyridostigmine. DISCUSSION: Given gene-environment independence and monotonicity, the unconfounded aRERI > 0 supports a mechanistic interaction. Together with the direct evidence of exposure to fallout from bombing of chemical weapon storage facilities and the extensive toxicologic evidence of biochemical protection from organophosphates by the Q isoenzyme, the findings provide strong evidence for an etiologic role of low-level nerve agent in GWI. https://doi.org/10.1289/EHP9009.
ESTHER : Haley_2022_Environ.Health.Perspect_130_57001
PubMedSearch : Haley_2022_Environ.Health.Perspect_130_57001
PubMedID: 35543525

Title : Genome-Wide Identification and Analysis of Lipases in Fig Wasps (Chalcidoidea, Hymenoptera) - Wei_2022_Insects_13_
Author(s) : Wei X , Li J , Wang T , Xiao J , Huang D
Ref : Insects , 13 : , 2022
Abstract : Lipases are the main enzymes involved in lipid metabolism. However, the characteristics of lipases in insects were scarcely investigated. Here, we screened the recently sequenced genomes of 12 fig wasp species consisting of seven pollinator fig wasps (PFWs) and five non-pollinating fig wasps (NPFWs) for the six major lipase gene families. In total, 481 lipase genes were identified, and the two most numerous families were the neutral and acid lipases. Tandem duplication accounted for the expansion of the gene family. NPFWs had significantly more lipases than PFWs. A significant gene family contraction occurred in the clade of PFWs. The difference of lipases between NPFWs and PFWs might contribute to their distinction in life histories and feeding regimes. Phylogenetic analysis showed that the lipase genes of each fig wasp species was almost equally distributed in each clade, indicating that the lipase genes were conserved. The gene structures were similar within each clade, while they were different among clades. Most of the neutral and acid lipases were signal peptides and located extracellularly. The pathways of lipases involved were predicted. This genome-wide study provides a systematic analysis of lipase gene families in 12 hymenopteran insects and further insights towards understanding the potential functions of lipases.
ESTHER : Wei_2022_Insects_13_
PubMedSearch : Wei_2022_Insects_13_
PubMedID: 35621743

Title : Caulophyine A, a Rare Azapyrene Alkaloid from the Roots of Caulophyllum robustum - Wei_2022_Chem.Pharm.Bull.(Tokyo)_70_283
Author(s) : Wei W , Yuan YH , Jiao FR , Zhao X , Xiao L , Hu JY , Ji P , Xiao J , Wang XL
Ref : Chem Pharm Bull (Tokyo) , 70 :283 , 2022
Abstract : A novel alkaloid caulophyine A (1) was isolated from the roots of Caulophyllum robustum Maxim., along with six known alkaloids 2-7. The structure of 1 was elucidated by extensive NMR and high resolution-time-of-flight (HR-TOF)-MS analyses, it is a rare nitrogen containing polycyclic aromatic hydrocarbon. The in vitro bioassays revealed that 2 presented remarkable cytotoxicity against A549 with an IC(50) value of 3.83 microM in comparison with the positive control etoposide (IC(50) = 11.63 microM). Compounds 1 and 2 also displayed weak Acetylcholinesterase (AChE) inhibitory activity with IC(50) values of 123.03 and 80.74 microM respectively.
ESTHER : Wei_2022_Chem.Pharm.Bull.(Tokyo)_70_283
PubMedSearch : Wei_2022_Chem.Pharm.Bull.(Tokyo)_70_283
PubMedID: 35370205

Title : Carnosic acid ameliorated Abeta-mediated (amyloid-beta peptide) toxicity, cholinergic dysfunction and mitochondrial defect in Caenorhabditis elegans of Alzheimer's Model - Chen_2022_Food.Funct__
Author(s) : Chen Y , Wang Y , Qin Q , Zhang Y , Xie L , Xiao J , Cao Y , Su Z
Ref : Food Funct , : , 2022
Abstract : Amyloid-beta peptide (Abeta)-induced cholinergic system and mitochondrial dysfunction are major risk factors for Alzheimer's disease (AD). Our previous studies found that carnosic acid (CA), an important polyphenol antioxidant, could significantly delay Abeta(1-42)-mediated acute paralysis. However, many details and underlying mechanisms of CA's neuroprotection against Abeta-induced cholinergic system defects and mitochondrial dysfunction remain unclear. Herein, we deeply investigated the effects and the possible mechanisms of CA-mediated protection against Abeta toxicity in vivo through several AD Caenorhabditis elegans strains. The results showed CA delayed age-related paralysis and Abeta deposition, and significantly protected neurons from Abeta-induced toxicity. CA might downgrade the expression of ace-1 and ace-2 genes, and upregulate cha-1 and unc-17 genes to inhibit acetylcholinesterase activity and relieve Abeta-caused cholinergic system defects. Furthermore, CA might also ameliorate Abeta-induced mitochondrial imbalance and oxidative stress through up-regulating the expression of phb-1, phb-2, eat-3, and drp-1 genes. The enhancements of the cholinergic system and mitochondrial function might be the reasons for the amelioration of Abeta-mediated toxicity and Abeta aggregation mediated by CA. These findings have helped us to understand the CA anti-Abeta activity in C. elegans and the potential mechanism of action.
ESTHER : Chen_2022_Food.Funct__
PubMedSearch : Chen_2022_Food.Funct__
PubMedID: 35357374

Title : New Carboxamides and a New Polyketide from the Sponge-Derived Fungus Arthrinium sp. SCSIO 41421 - She_2022_Mar.Drugs_20_
Author(s) : She J , Chen Y , Ye Y , Lin X , Yang B , Xiao J , Liu Y , Zhou X
Ref : Mar Drugs , 20 : , 2022
Abstract : New carboxamides, (+/-)-vochysiamide C (1) and (+)-vochysiamide B (2), and a new polyketide, 4S,3aS,9aR-3a,9a-deoxy-3a hydroxy-1-dehydroxyarthrinone (3), were isolated and identified from the sponge-derived fungus Arthrinium sp. SCSIO 41421, together with other fifteen known natural products (4-18). Their structures including absolute configurations were determined by detailed NMR, MS spectroscopic analyses, calculated electronic circular dichroism (ECD), as well as quantum-chemical NMR calculations. Preliminary bioactivity screening and molecular docking analysis revealed that several natural products exhibited obvious enzyme inhibitory activities against acetylcholinesterase (AChE), such as 2,3,6,8-tetrahydroxy-1-methylxanthone (4) with an inhibitory rate 86% at 50 microg/mL.
ESTHER : She_2022_Mar.Drugs_20_
PubMedSearch : She_2022_Mar.Drugs_20_
PubMedID: 35892943

Title : Clinical and imaging analysis to evaluate the response of patients with anti-DPPX encephalitis to immunotherapy - Xiao_2022_BMC.Neurol_22_129
Author(s) : Xiao J , Fu PC , Li ZJ
Ref : BMC Neurol , 22 :129 , 2022
Abstract : BACKGROUND: To report the main spectrum and new clinical and imaging characteristics of dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, and to evaluate the effect of immunotherapy. METHODS: A retrospective analysis of nine patients with anti-DPPX encephalitis was performed, and all previously reported cases in the literature were reviewed. A cell-based indirect immunofluorescence assay using human embryonic kidney 293 cells transfected with DPPX was used. RESULTS: Nine patients were identified (median age, 51 years; range, 14-65 years) with prodromal fever, diarrhea, or weight loss, followed by rapid progressive encephalopathy characterized by cognitive disorder. One patient who received methylprednisolone therapy and a trial of tacrolimus showed substantial improvement and had no relapse by the 6-month follow-up. Our comprehensive literature review demonstrated that 53 cases were reported, of which more than half had prodromal weight loss (52.8%) and gastrointestinal disorders (58.5%). Cognitive disorders (74.6%) and brainstem/spinal cord disorders (75.5%) were the most common major symptoms. A greater proportion of Chinese patients than non-Chinese patients had abnormalities on brain magnetic resonance imaging specific for encephalitis (70.0% vs. 23.3%, P < 0.001). Our study is the first to report three patients with anti-DPPX encephalitis who had sleep disorders with rapid eye movement sleep behavior disorder, limb paralysis (two), severe pleocytosis, elevated protein levels (two) in the cerebrospinal fluid, and increased T2/FLAIR signal abnormalities in the bilateral hippocampus, temporal lobe, amygdala, basal ganglia, thalamus, centrum semiovale, and frontal and parietal lobes in seven patients (77.8%). CONCLUSION: Our study expands the clinical and imaging phenotypes of anti-DPPX encephalitis. Further studies elucidating the entire clinical spectrum of anti-DPPX encephalitis, its pathogenic mechanisms, and prognosis under long-term immunosuppressive therapy are warranted.
ESTHER : Xiao_2022_BMC.Neurol_22_129
PubMedSearch : Xiao_2022_BMC.Neurol_22_129
PubMedID: 35382765
Gene_locus related to this paper: human-DPP6

Title : Efficiency of donepezil in elderly patients undergoing orthopaedic surgery due to underlying post-operative cognitive dysfunction: study protocol for a multicentre randomised controlled trial - Zhu_2021_Trials_22_688
Author(s) : Zhu H , Cong L , Chen Y , Chen S , Chen L , Huang Z , Zhou J , Xiao J , Huang Y , Su D
Ref : Trials , 22 :688 , 2021
Abstract : BACKGROUND: Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer's disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery. METHODS: A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation. DISCUSSION: This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04423276 . Registered on 14 June 2020.
ESTHER : Zhu_2021_Trials_22_688
PubMedSearch : Zhu_2021_Trials_22_688
PubMedID: 34627332

Title : Plasma carboxylesterase 1 predicts methylphenidate exposure: a proof-of-concept study using plasma protein biomarker for hepatic drug metabolism - Shi_2021_Clin.Pharmacol.Ther__
Author(s) : Shi J , Xiao J , Wang X , Jung SM , Bleske BE , Markowitz JS , Patrick KS , Zhu HJ
Ref : Clinical Pharmacology & Therapeutics , : , 2021
Abstract : Hepatic drug-metabolizing enzymes (DMEs) play critical roles in determining the pharmacokinetics and pharmacodynamics of numerous therapeutic agents. As such, noninvasive biomarkers capable of predicting DME expression in the liver have the potential to be used to personalize pharmacotherapy and improve drug treatment outcomes. In the present study, we quantified carboxylesterase 1 (CES1) protein concentrations in plasma samples collected during a methylphenidate (MPH) PK study. CES1 is a prominent hepatic enzyme responsible for the metabolism of many medications containing small ester moieties, including MPH. The results revealed a significant inverse correlation between plasma CES1 protein concentrations and the area under the concentration-time curves (AUCs) of plasma d-MPH (p = 0.014, r = -0.617). In addition, when plasma CES1 protein levels were normalized to the plasma concentrations of 24 liver-enriched proteins to account for potential interindividual differences in hepatic protein release rate, the correlation was further improved (p = 0.003, r = -0.703), suggesting that plasma CES1 protein could explain approximately 50% of the variability in d-MPH AUCs in the study participants. A physiologically based pharmacokinetic (PBPK) modeling simulation revealed that the CES1-based individualized dosing strategy might significantly reduce d-MPH exposure variability in pediatric patients relative to conventional fixed dosing trial and error regimens. This proof-of-concept study indicates that the plasma protein of a hepatic DME may serve as a biomarker for predicting its metabolic function and the pharmacokinetics of its substrate drugs.
ESTHER : Shi_2021_Clin.Pharmacol.Ther__
PubMedSearch : Shi_2021_Clin.Pharmacol.Ther__
PubMedID: 34743324

Title : Impact of carboxylesterase 1 genetic polymorphism on trandolapril activation in human liver and the pharmacokinetics and pharmacodynamics in healthy volunteers - Wang_2021_Clin.Transl.Sci__
Author(s) : Wang X , Her L , Xiao J , Shi J , Wu AH , Bleske BE , Zhu HJ
Ref : Clin Transl Sci , : , 2021
Abstract : Trandolapril, an angiotensin-converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1-mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects. We performed an in vitro incubation study to assess trandolapril activation in human livers (5 G143E heterozygotes and 97 noncarriers) and conducted a single-dose (1 mg) PK and PD study of trandolapril in healthy volunteers (8 G143E heterozygotes and 11 noncarriers). The incubation study revealed that the mean trandolapril activation rate in G143E heterozygous livers was 42% of those not carrying the variant (p = 0.0015). The clinical study showed that, relative to noncarriers, G143E carriers exhibited 20% and 15% decreases, respectively, in the peak concentration (C(max) ) and area under the curve from 0 to 72 h (AUC(0-72 h) ) of the active metabolite trandolaprilat, although the differences were not statistically significant. Additionally, the average maximum reductions of systolic blood pressure and diastolic blood pressure in carriers were ~ 22% and 23% less than in noncarriers, respectively, but the differences did not reach a statistically significant level. In summary, the CES1 G143E variant markedly impaired trandolapril activation in the human liver under the in vitro incubation conditions; however, this variant had only a modest impact on the PK and PD of trandolapril in healthy human subjects.
ESTHER : Wang_2021_Clin.Transl.Sci__
PubMedSearch : Wang_2021_Clin.Transl.Sci__
PubMedID: 33660934

Title : Inhibiting Monoacylglycerol Lipase Suppresses RANKL-Induced Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss - Liu_2021_Front.Cell.Dev.Biol_9_640867
Author(s) : Liu H , Zhou C , Qi D , Gao Y , Zhu M , Tao T , Sun X , Xiao J
Ref : Front Cell Developmental Biology , 9 :640867 , 2021
Abstract : Osteoporosis is a common chronic metabolic bone disease characterized by reduced trabecular bone and increased bone fragility. Monoacylglycerol lipase (MAGL) is a lipolytic enzyme to catalyze the hydrolysis of monoglycerides and specifically degrades the 2-arachidonoyl glycerol (2-AG). Previous studies have identified that 2-AG is the mainly source for arachidonic acid and the most abundant endogenous agonist of cannabinoid receptors. Considering the close relationship between inflammatory mediators/cannabinoid receptors and bone metabolism, we speculated that MAGL may play a role in the osteoclast differentiation. In the present study, we found that MAGL protein expression increased during osteoclast differentiation. MAGL knockdown by adenovirus-mediated shRNA in bone marrow-derived macrophages demonstrated the suppressive effects of MAGL on osteoclast formation and bone resorption. In addition, pharmacological inhibition of MAGL by JZL184 suppressed osteoclast differentiation, bone resorption, and osteoclast-specific gene expression. Activation of the Mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) pathways was inhibited by JZL184 and deletion of MAGL. Our in vivo study indicated that JZL184 ameliorated bone loss in an ovariectomized mouse model. Furthermore, overexpressing H1 calponin partially alleviated the inhibition caused by JZL184 or MAGL deletion on osteoclastogenesis. Therefore, we conclude that targeting MAGL may be a novel therapeutic strategy for osteoporosis.
ESTHER : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedSearch : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedID: 33777947

Title : Genome-Wide Identification of GDSL-Type Esterase\/Lipase Gene Family in Dasypyrum villosum L. Reveals That DvGELP53 Is Related to BSMV Infection - Zhang_2021_Int.J.Mol.Sci_22_
Author(s) : Zhang H , Zhang X , Zhao J , Sun L , Wang H , Zhu Y , Xiao J , Wang X
Ref : Int J Mol Sci , 22 : , 2021
Abstract : GDSL-type esterase/lipase proteins (GELPs) characterized by a conserved GDSL motif at their N-terminus belong to the lipid hydrolysis enzyme superfamily. In plants, GELPs play an important role in plant growth, development and stress response. The studies of the identification and characterization of the GELP gene family in Triticeae have not been reported. In this study, 193 DvGELPs were identified in Dasypyrum villosum and classified into 11 groups (clade A-K) by means of phylogenetic analysis. Most DvGELPs contain only one GDSL domain, only four DvGELPs contain other domains besides the GDSL domain. Gene structure analysis indicated 35.2% DvGELP genes have four introns and five exons. In the promoter regions of the identified DvGELPs, we detected 4502 putative cis-elements, which were associated with plant hormones, plant growth, environmental stress and light responsiveness. Expression profiling revealed 36, 44 and 17 DvGELPs were highly expressed in the spike, the root and the grain, respectively. Further investigation of a root-specific expressing GELP, DvGELP53, indicated it was induced by a variety of biotic and abiotic stresses. The knockdown of DvGELP53 inhibited long-distance movement of BSMV in the tissue of D. villosum. This research provides a genome-wide glimpse of the D. villosum GELP genes and hints at the participation of DvGELP53 in the interaction between virus and plants.
ESTHER : Zhang_2021_Int.J.Mol.Sci_22_
PubMedSearch : Zhang_2021_Int.J.Mol.Sci_22_
PubMedID: 34830200

Title : Contributions of Cathepsin A and Carboxylesterase 1 to the hydrolysis of Tenofovir Alafenamide in the Human Liver, and the Effect of CES1 Genetic Variation on Tenofovir Alafenamide Hydrolysis - Li_2021_Drug.Metab.Dispos__
Author(s) : Li J , Shi J , Xiao J , Tran L , Wang X , Zhu HJ
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2021
Abstract : The prodrug tenofovir alafenamide (TAF) is a first-line antiviral agent for the treatment of chronic hepatitis B infection. TAF activation involves multiple steps, and the first step is an ester hydrolysis reaction catalyzed by hydrolases. This study was to determine the contributions of carboxylesterase 1 (CES1) and cathepsin A (CatA) to TAF hydrolysis in the human liver. Our in vitro incubation studies showed that both CatA and CES1 catalyzed TAF hydrolysis in a pH-dependent manner. At their physiological pH environment, the activity of CatA (pH 5.2) was approximately 1,000-fold higher than that of CES1 (pH 7.2). Given that the hepatic protein expression of CatA was approximately 200-fold lower than that of CES1, the contribution of CatA to TAF hydrolysis in the human liver was estimated to be much greater than that of CES1, which is contrary to the previous perception that CES1 is the primary hepatic enzyme hydrolyzing TAF. The findings were further supported by a TAF incubation study with the CatA inhibitor telaprevir and the CES1 inhibitor bis-(p-nitrophenyl) phosphate. Moreover, an in vitro study revealed that the CES1 variant G143E (rs71647871) is a loss-of-function variant for CES1-mediated TAF hydrolysis. In summary, our results suggest that CatA may play a more important role in the hepatic activation of TAF than CES1. Additionally, TAF activation in the liver could be affected by CES1 genetic variation, but the magnitude of impact appears to be limited due to the major contribution of CatA to hepatic TAF activation. Significance Statement Contrary to the general perception that carboxylesterase 1 (CES1) is the major enzyme responsible for tenofovir alafenamide (TAF) hydrolysis in the human liver, the present study demonstrated that cathepsin A (CatA) may play a more significant role in TAF hepatic hydrolysis. Furthermore, the CES1 variant G143E (rs71647871) was found to be a loss-of-function variant for CES1-mediated TAF hydrolysis.
ESTHER : Li_2021_Drug.Metab.Dispos__
PubMedSearch : Li_2021_Drug.Metab.Dispos__
PubMedID: 34933885
Gene_locus related to this paper: human-CES1 , human-CTSA

Title : A Lab-in-a-Syringe Device Integrated with a Smartphone Platform: Colorimetric and Fluorescent Dual-Mode Signals for On-Site Detection of Organophosphorus Pesticides - Wei_2021_ACS.Appl.Mater.Interfaces__
Author(s) : Wei D , Wang Y , Zhu N , Xiao J , Li X , Xu T , Hu X , Zhang Z , Yin D
Ref : ACS Appl Mater Interfaces , : , 2021
Abstract : Herein, a portable lab-in-a-syringe device integrated with a smartphone sensing platform was designed for rapid, visual quantitative determination of organophosphorus pesticides (OPs) via colorimetric and fluorescent signals. The device was chiefly made up of a conjugate pad labeled with cetyltrimethylammonium bromide-coated gold nanoparticles (CTAB-Au NPs) and a sensing pad modified by ratiometric probes (red-emission quantum dots@SiO(2) nanoparticles@green-emission quantum dots, rQDs@SiO(2)@gQDs probe), which was assembled through a disposable syringe and reusable plastic filter. In the detection system, thiocholine (Tch), the hydrolysis product of thioacetylcholine (ATch) by acetylcholinesterase (AchE), could trigger the aggregation of CTAB-Au NPs, resulting in a significant color change from red to purple. Then, CTAB-Au NPs flowed vertically upward and bound to the rQDs@SiO(2)@gQDs probe on the sensing pad, reducing the fluorescence resonance energy transfer effect between CTAB-Au NPs and gQDs. Meanwhile, rQDs embedded in SiO(2) NPs remained stable as internal reference fluorescence, achieving a color transition from red to green. Thus, based on the inhibition of AChE activity by OPs, a colorimetric and fluorescent dual-mode platform was constructed for on-site detection of OPs. Using glyphosate as a model, with the support of a color recognizer application (APP) on a smartphone, the ratio of red and green channel values could be utilized for accurate OP quantitative analysis ranging from 0 to 10 microM with a detection limit of 2.81 nM (recoveries, 90.8-122.4%; CV, 1.2-3.4%). Overall, the portable lab-in-a-syringe device based on a smartphone sensing platform integrated sample monitoring and result analysis in the field, implying great potential for on-site detection of OPs.
ESTHER : Wei_2021_ACS.Appl.Mater.Interfaces__
PubMedSearch : Wei_2021_ACS.Appl.Mater.Interfaces__
PubMedID: 34623807

Title : Effects of lincomycin hydrochloride on the neurotoxicity of zebrafish - Cheng_2020_Ecotoxicol.Environ.Saf_201_110725
Author(s) : Cheng B , Jiang F , Su M , Zhou L , Zhang H , Cao Z , Liao X , Xiong G , Xiao J , Liu F , Lu H
Ref : Ecotoxicology & Environmental Safety , 201 :110725 , 2020
Abstract : Lincomycin hydrochloride is one of the commonly used drugs in clinic. However, it has many side effects on patients, and its mechanism is still poorly understood. In this study, 6 h post-fertilization (6 hpf) zebrafish embryos were exposed to several concentrations of lincomycin hydrochloride (15, 30, 60 mug/mL) for up to 24 or 96 hpf to detect their developmental toxicity and neurotoxicity, and to 6 days post-fertilization (6 dpf) to detect their behavioral toxicity. Our results showed that lincomycin hydrochloride could lead to embryonic head deformities (unclear ventricles, smaller ventricles, fewer new neurons). The studies showed that the frequency of spontaneous tail flick of zebrafish embryo increased at 24 hpf, and the lincomycin hydrochloride exposed zebrafish embryos showed increased heart rate, shorter body length, and yolk sac edema with severe pericardial edema at 96 hpf. The studies also showed that lincomycin hydrochloride increased oxidative stress level, Acetylcholinesterase (AChE) activity, ATPase activity and apoptosis in zebrafish larvae. In addition, the swimming behavior of zebrafish larvae decreased with the increase of lincomycin hydrochloride concentration, but the angular velocity and meandering degree increased, which might be due to the decreased activity of AChE and ATPase, as well as the decreased expression of genes related to neurodevelopment and neurotransmitter system, leading to the change of their motor behaviors. In summary, we found that lincomycin hydrochloride induced developmental toxicity and neurotoxicity in zebrafish larvae, contributing to a more comprehensive evaluation of the safety of the drug.
ESTHER : Cheng_2020_Ecotoxicol.Environ.Saf_201_110725
PubMedSearch : Cheng_2020_Ecotoxicol.Environ.Saf_201_110725
PubMedID: 32474209

Title : FRACPRED-2D-PRM: A fraction prediction algorithm-assisted two-dimensional liquid chromatography-based parallel reaction monitoring-mass spectrometry approach for measuring low-abundance proteins in human plasma - Shi_2020_Proteomics__e2000175
Author(s) : Shi J , Xiao J , Li J , Wang X , Her L , Sorensen MJ , Zhu HJ
Ref : Proteomics , :e2000175 , 2020
Abstract : Multidimensional fractionation-based enrichment methods improve the sensitivity of proteomic analysis for low-abundance proteins. However, a major limitation of conventional multidimensional proteomics is the extensive labor and instrument time required for analyzing many fractions obtained from the first dimension separation. Here, we present a fraction prediction algorithm-assisted two-dimensional LC-based parallel reaction monitoring-mass spectrometry (FRACPRED-2D-PRM) approach for measuring low-abundance proteins in human plasma. Plasma digests were separated by the first dimension high-pH RP-LC with data-dependent acquisition (DDA). We then used the FRACPRED algorithm to predict the retention time of undetectable target peptides according to those of other abundant plasma peptides during the first dimension separation. Fractions predicted to contain target peptides were analyzed by the second dimension low-pH nano RP-LC PRM. We demonstrated the accuracy and robustness of fraction prediction with the FRACPRED algorithm by measuring two low-abundance proteins, aldolase B and carboxylesterase 1, in human plasma. The FRACPRED-2D-PRM proteomics approach demonstrated markedly improved efficiency and sensitivity over conventional 2D-LC proteomics assays. We expect that this approach will be widely used in the study of low-abundance proteins in plasma and other complex biological samples. This article is protected by copyright. All rights reserved.
ESTHER : Shi_2020_Proteomics__e2000175
PubMedSearch : Shi_2020_Proteomics__e2000175
PubMedID: 33085175

Title : Exposure to diclofop-methyl induces immunotoxicity and behavioral abnormalities in zebrafish embryos - Cao_2019_Aquat.Toxicol_214_105253
Author(s) : Cao Z , Zou L , Wang H , Zhang H , Liao X , Xiao J , Zhang S , Lu H
Ref : Aquat Toxicol , 214 :105253 , 2019
Abstract : Diclofop-methyl (DM) is widely used in agriculture and may lead to serious toxicity. However, a limited number of studies have been performed to evaluate the toxicity of DM in the immune and nervous systems of animals. Here, we utilized a good vertebrate model, zebrafish, to evaluate the toxicity of DM during the developmental process. Exposure of zebrafish embryos to 0.1, 0.3 and 0.5mg/l DM from 6h post fertilization (hpf) to 72 hpf induced developmental abnormalities, such as shorter body lengths and yolk sac edemas. The number of immune cells in zebrafish larvae was significantly reduced, but the inflammatory response was not influenced by DM treatment. The expression of immune-related genes were downregulated and the levels of oxidative stress were upregulated by DM exposure. Moreover, locomotor behaviors were inhibited by DM exposure. Therefore, our results suggest that DM has the potential to induce immunotoxicity and cause behavioral changes in zebrafish larvae. This study provides new evidence of the influence of DM exposure on aquatic ecosystems.
ESTHER : Cao_2019_Aquat.Toxicol_214_105253
PubMedSearch : Cao_2019_Aquat.Toxicol_214_105253
PubMedID: 31352076

Title : Laboratory and field evaluation of the aphidicidal activity of moso bamboo (Phyllostachys pubescens) leaf extract and identification of the active components - Gao_2019_Pest.Manag.Sci_75_3167
Author(s) : Gao Q , Shi Y , Liao M , Xiao J , Li X , Zhou L , Liu C , Liu P , Cao H
Ref : Pest Manag Sci , 75 :3167 , 2019
Abstract : BACKGROUND: Botanical pesticides increasingly play important roles in the control of agricultural pests. In this study, the aphidicidal effect of moso bamboo (Phyllostachys pubescens) extract against mustard aphid was confirmed, the main active compounds identified, and aphidicidal mechanism of the most active compound established. RESULTS: When the treatment concentration was 10.0 g L(-1) , the corrected mortality of bamboo leaf extract (BE) was 53.22 +/- 5.20% and the petroleum ether component of bamboo leaf extract (PE) reached 82.76 +/- 4.50%, which also showed a synergistic effect with imidacloprid. Four flavonoids were identified as the main active components in the BE via activity tracking and phytochemical method. Isoorientin had an LC50 of 313.22 mg L(-1) , and affected the activities of acetylcholinesterase and peroxidase significantly, revealing the possible aphidicidal mechanism. When the treatment of 11.1% PE.imidacloprid was 200 mL, the control effect was 99.07%, which was better than that observed with 10% of imidacloprid or 0.5% of matrine. CONCLUSIONS: These data provide a better understanding of the aphidicidal activity and aphidicidal mechanism of moso bamboo leaf extract and the most active compound, isoorientin. This will help in developing a more effective botanical aphicide. (c) 2019 Society of Chemical Industry.
ESTHER : Gao_2019_Pest.Manag.Sci_75_3167
PubMedSearch : Gao_2019_Pest.Manag.Sci_75_3167
PubMedID: 30941856

Title : Surrogating and redirection of pyrazolo[1,5-a]pyrimidin-7(4H)-one core, a novel class of potent and selective DPP-4 inhibitors - Deng_2018_Bioorg.Med.Chem_26_903
Author(s) : Deng X , Shen J , Zhu H , Xiao J , Sun R , Xie F , Lam C , Wang J , Qiao Y , Tavallaie MS , Hu Y , Du Y , Li J , Fu L , Jiang F
Ref : Bioorganic & Medicinal Chemistry , 26 :903 , 2018
Abstract : The initial focus on characterizing novel pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives as DPP-4 inhibitors, led to a potent and selective inhibitor compound b2. This ligand exhibits potent in vitro DPP-4 inhibitory activity (IC(50): 80 nM), while maintaining other key cellular parameters such as high selectivity, low cytotoxicity and good cell viability. Subsequent optimization of b2 based on docking analysis and structure-based drug design knowledge resulted in d1. Compound d1 has nearly 2-fold increase of inhibitory activity (IC(50): 49 nM) and over 1000-fold selectivity against DPP-8 and DPP-9. Further in vivo IPGTT assays showed that compound b2 effectively reduce glucose excursion by 34% at the dose of 10 mg/kg in diabetic mice. Herein we report the optimization and design of a potent and highly selective series of pyrazolo[1,5-a]pyrimidin-7(4H)-one DPP-4 inhibitors.
ESTHER : Deng_2018_Bioorg.Med.Chem_26_903
PubMedSearch : Deng_2018_Bioorg.Med.Chem_26_903
PubMedID: 29373269

Title : Polyphenols from wolfberry and their bioactivities - Zhou_2017_Food.Chem_214_644
Author(s) : Zhou ZQ , Xiao J , Fan HX , Yu Y , He RR , Feng XL , Kurihara H , So KF , Yao XS , Gao H
Ref : Food Chem , 214 :644 , 2017
Abstract : Nine new phenylpropanoids, one new coumarin, and 43 known polyphenols were isolated from wolfberry. Their structures were determined by spectroscopic analyses, chemical methods, and comparison of NMR data. Polyphenols, an important type of natural products, are notable constituents in wolfberry. 53 polyphenols, including 28 phenylpropanoids, four coumarins, eight lignans, five flavonoids, three isoflavonoids, two chlorogenic acid derivatives, and three other constituents, were identified from wolfberry. Lignans and isoflavonoids were firstly reported from wolfberry. 22 known polyphenols were the first isolates from the genus Lycium. This research presents a systematic study on wolfberry polyphenols, including their bioactivities. All these compounds exhibited oxygen radical absorbance capacity (ORAC), and some compounds displayed DPPH radical scavenging activity. One compound had acetylcholinesterase inhibitory activity. The discovery of new polyphenols and their bioactivities is beneficial for understanding the scientific basis of the effects of wolfberry.
ESTHER : Zhou_2017_Food.Chem_214_644
PubMedSearch : Zhou_2017_Food.Chem_214_644
PubMedID: 27507521

Title : Liver-Targeted Small-Molecule Inhibitors of Proprotein Convertase Subtilisin\/Kexin Type 9 Synthesis - McClure_2017_Angew.Chem.Int.Ed.Engl_56_16218
Author(s) : McClure KF , Piotrowski DW , Petersen D , Wei L , Xiao J , Londregan AT , Kamlet AS , Dechert-Schmitt AM , Raymer B , Ruggeri RB , Canterbury D , Limberakis C , Liras S , DaSilva-Jardine P , Dullea RG , Loria PM , Reidich B , Salatto CT , Eng H , Kimoto E , Atkinson K , King-Ahmad A , Scott D , Beaumont K , Chabot JR , Bolt MW , Maresca K , Dahl K , Arakawa R , Takano A , Halldin C
Ref : Angew Chem Int Ed Engl , 56 :16218 , 2017
Abstract : Targeting of the human ribosome is an unprecedented therapeutic modality with a genome-wide selectivity challenge. A liver-targeted drug candidate is described that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small molecules. Key to the concept was the identification of pharmacologically active zwitterions designed to be retained in the liver. Oral delivery of the poorly permeable zwitterions was achieved by prodrugs susceptible to cleavage by carboxylesterase 1. The synthesis of select tetrazole prodrugs was crucial. A cell-free in vitro translation assay containing human cell lysate and purified target mRNA fused to a reporter was used to identify active zwitterions. In vivo PCSK9 lowering by oral dosing of the candidate prodrug and quantification of the drug fraction delivered to the liver utilizing an oral positron emission tomography (18) F-isotopologue validated our liver-targeting approach.
ESTHER : McClure_2017_Angew.Chem.Int.Ed.Engl_56_16218
PubMedSearch : McClure_2017_Angew.Chem.Int.Ed.Engl_56_16218
PubMedID: 29073340

Title : Flavonoids, Antioxidant Potential, and Acetylcholinesterase Inhibition Activity of the Extracts from the Gametophyte and Archegoniophore of Marchantia polymorpha L - Wang_2016_Molecules_21_
Author(s) : Wang X , Cao J , Wu Y , Wang Q , Xiao J
Ref : Molecules , 21 : , 2016
Abstract : Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte of M. polymorpha L. have been reported. However, as the reproductive organ of M. polymorpha L., the bioactivity and flavonoids profile of the archegoniophore have not been reported, so in this work the flavonoid profiles, antioxidant and acetylcholinesterase inhibition activities of the extracts from the archegoniophore and gametophyte of M. polymorpha L. were compared by radical scavenging assay methods (DPPH, ABTS, O(2-)), reducing power assay, acetylcholinesterase inhibition assay and LC-MS analysis. The results showed that the total flavonoids content in the archegoniophore was about 10-time higher than that of the gametophyte. Differences between the archegoniophore and gametophyte of M. polymorpha L. were observed by LC-MS analysis. The archegoniophore extracts showed stronger bio-activities than those of the gametophyte. The archegoniophore extract showed a significant acetylcholinesterase inhibition, while the gametophyte extract hardly inhibited it.
ESTHER : Wang_2016_Molecules_21_
PubMedSearch : Wang_2016_Molecules_21_
PubMedID: 26999088

Title : Comparative Genomics Analysis of Streptomyces Species Reveals Their Adaptation to the Marine Environment and Their Diversity at the Genomic Level - Tian_2016_Front.Microbiol_7_998
Author(s) : Tian X , Zhang Z , Yang T , Chen M , Li J , Chen F , Yang J , Li W , Zhang B , Wu J , Zhang C , Long L , Xiao J
Ref : Front Microbiol , 7 :998 , 2016
Abstract : Over 200 genomes of streptomycete strains that were isolated from various environments are available from the NCBI. However, little is known about the characteristics that are linked to marine adaptation in marine-derived streptomycetes. The particularity and complexity of the marine environment suggest that marine streptomycetes are genetically diverse. Here, we sequenced nine strains from the Streptomyces genus that were isolated from different longitudes, latitudes, and depths of the South China Sea. Then we compared these strains to 22 NCBI downloaded streptomycete strains. Thirty-one streptomycete strains are clearly grouped into a marine-derived subgroup and multiple source subgroup-based phylogenetic tree. The phylogenetic analyses have revealed the dynamic process underlying streptomycete genome evolution, and lateral gene transfer is an important driving force during the process. Pan-genomics analyses have revealed that streptomycetes have an open pan-genome, which reflects the diversity of these streptomycetes and guarantees the species a quick and economical response to diverse environments. Functional and comparative genomics analyses indicate that the marine-derived streptomycetes subgroup possesses some common characteristics of marine adaptation. Our findings have expanded our knowledge of how ocean isolates of streptomycete strains adapt to marine environments. The availability of streptomycete genomes from the South China Sea will be beneficial for further analysis on marine streptomycetes and will enrich the South China Sea's genetic data sources.
ESTHER : Tian_2016_Front.Microbiol_7_998
PubMedSearch : Tian_2016_Front.Microbiol_7_998
PubMedID: 27446038
Gene_locus related to this paper: 9actn-a0a1e7k9d4 , 9actn-a0a1e7l883 , 9actn-a0a1e7kw84 , 9actn-a0a1e7kkk9 , 9actn-a0a1e7jip1 , 9actn-a0a1e7jjj1 , 9actn-a0a1e7k159 , 9actn-a0a1e7kfw2 , 9actn-a0a1e7l1n0 , 9actn-a0a1e7jf99

Title : Chemical composition and bioactivities of flavonoids-rich extract from Davallia cylindrica Ching - Cao_2014_Environ.Toxicol.Pharmacol_37_571
Author(s) : Cao J , Xia X , Dai X , Wang Q , Xiao J
Ref : Environ Toxicol Pharmacol , 37 :571 , 2014
Abstract : The flavonoids profiles and bioactivities of flavonoids-rich extract from Davallia cylindrica Ching were investigated. The total flavonoids content in D. cylindrica was determined as about 164.41mg/g. The main flavonoids in D. cylindrica were tentatively identified as quercetin-3-O-rutinoside, quercetin 7-O-glucoside, quercetin 7-O-glucoside, kaempferol 3-O-rutinoside, and quercitrin by UV and ESI-MS spectra. Flavonoids-rich extract (0.258mg/ml) from D. cylindrica showed similar or higher free radical (O2-, DPPH and ABTS) scavenging potential with that of rutin (0.25mg/ml). The reducing power of flavonoids-rich extract (0.258mg/ml) was slightly stronger than that of 0.25mg/ml rutin. The flavonoids extract from D. cylindrica exhibited cytotoxic effects on A549 cells. It exhibited a dose-dependent inhibition against acetylcholinesterase.
ESTHER : Cao_2014_Environ.Toxicol.Pharmacol_37_571
PubMedSearch : Cao_2014_Environ.Toxicol.Pharmacol_37_571
PubMedID: 24562055

Title : Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect - Xu_2014_BMC.Cancer_14_668
Author(s) : Xu H , Shen Z , Xiao J , Yang Y , Huang W , Zhou Z , Shen J , Zhu Y , Liu XY , Chu L
Ref : BMC Cancer , 14 :668 , 2014
Abstract : BACKGROUND: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy.
METHODS: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 x 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay.
RESULTS: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells. CONCLUSION: ZD55-AChE represented potential therapeutic effect for human gastric cancer.
ESTHER : Xu_2014_BMC.Cancer_14_668
PubMedSearch : Xu_2014_BMC.Cancer_14_668
PubMedID: 25220382

Title : New strategies in the management of Guillain-Barre syndrome - Xiao_2014_Clin.Rev.Allergy.Immunol_47_274
Author(s) : Xiao J , Simard AR , Shi FD , Hao J
Ref : Clin Rev Allergy Immunol , 47 :274 , 2014
Abstract : Guillain-Barre syndrome (GBS) is an acute and usually monophasic, neurological, demyelinating disease. Although most patients have good outcomes without sequelae after conventional plasma exchange and intravenous immunoglobulin therapy, 20% of patients continue to have severe disease and 5% die of their disease. Therefore, there is an obvious need for more acceptable and efficacious therapies. Experimental autoimmune neuritis (EAN) is the classical animal model for GBS. As there is no specific drug for GBS, several drugs targeting the humoral and cellular components of the immune response have been used to treat EAN in the endeavour to find new treatment alternatives for GBS. This review focused on some new strategies for GBS, which have been reported but have not yet been widely used, and on the main drugs which have been investigated in EAN.
ESTHER : Xiao_2014_Clin.Rev.Allergy.Immunol_47_274
PubMedSearch : Xiao_2014_Clin.Rev.Allergy.Immunol_47_274
PubMedID: 24057598

Title : Chrysin attenuates experimental autoimmune neuritis by suppressing immuno-inflammatory responses - Xiao_2014_Neurosci_262_156
Author(s) : Xiao J , Zhai H , Yao Y , Wang C , Jiang W , Zhang C , Simard AR , Zhang R , Hao J
Ref : Neuroscience , 262 :156 , 2014
Abstract : Guillain-Barre syndrome (GBS) is an acute, post-infectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. Experimental autoimmune neuritis (EAN) is an animal model of GBS. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. This study was designed to investigate the anti-inflammatory and neuroprotective properties of preventative and therapeutic chrysin treatment in EAN rats. For preventative treatment, chrysin was administered orally from day 1 to day 16 (50mg/kg once daily) while, for therapeutic treatment, rats received chrysin from day 7 to day 16 at the same dose once daily. Control animals received the same volume of the vehicle (phosphate-buffered saline/2% dimethylsulfoxide). Regardless of the treatment regimen, chrysin attenuated the severity and duration of the clinical course of EAN and reduced inflammatory cell infiltration and demyelination of sciatic nerves. In the sciatic nerves, the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor kappa B was reduced. Furthermore, chrysin inhibited the splenic mononuclear cell secretion of interleukin-1beta, interleukin-2, interleukin-6, inteleukin-12, interferon gamma and tumor necrosis factor alpha, and elevated the level of inteleukin-4. In summary, our data demonstrate that chrysin is a potentially useful agent for the treatment of EAN with its anti-inflammatory and neuroprotective effects.
ESTHER : Xiao_2014_Neurosci_262_156
PubMedSearch : Xiao_2014_Neurosci_262_156
PubMedID: 24412705

Title : Molecular traces of alternative social organization in a termite genome - Terrapon_2014_Nat.Commun_5_3636
Author(s) : Terrapon N , Li C , Robertson HM , Ji L , Meng X , Booth W , Chen Z , Childers CP , Glastad KM , Gokhale K , Gowin J , Gronenberg W , Hermansen RA , Hu H , Hunt BG , Huylmans AK , Khalil SM , Mitchell RD , Munoz-Torres MC , Mustard JA , Pan H , Reese JT , Scharf ME , Sun F , Vogel H , Xiao J , Yang W , Yang Z , Zhou J , Zhu J , Brent CS , Elsik CG , Goodisman MA , Liberles DA , Roe RM , Vargo EL , Vilcinskas A , Wang J , Bornberg-Bauer E , Korb J , Zhang G , Liebig J
Ref : Nat Commun , 5 :3636 , 2014
Abstract : Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation.
ESTHER : Terrapon_2014_Nat.Commun_5_3636
PubMedSearch : Terrapon_2014_Nat.Commun_5_3636
PubMedID: 24845553
Gene_locus related to this paper: zoone-a0a067r283 , zoone-a0a067qst6 , zoone-a0a067rbc7 , zoone-a0a067qz43 , zoone-a0a067qn94 , zoone-a0a067rbw9 , zoone-a0a067qx93 , zoone-a0a067rcf4 , zoone-a0a067r8q8 , zoone-a0a067rh81 , zoone-a0a067r506 , zoone-a0a067qxd4 , zoone-a0a067qy86 , zoone-a0a067qsw2 , zoone-a0a067qfp9 , zoone-a0a067ru91 , zoone-a0a067rwu7 , zoone-a0a067rmu8 , zoone-a0a067r773 , zoone-a0a067qlt8 , zoone-a0a067qhm6 , zoone-a0a067qjz2 , zoone-a0a067qs20 , zoone-a0a067rmu4 , zoone-a0a067qty7 , zoone-a0a067rk35 , zoone-a0a067rk64 , zoone-a0a067rj74 , zoone-a0a067rp97 , zoone-a0a067rjm1

Title : Lactobacillus casei-01 Facilitates the Ameliorative Effects of Proanthocyanidins Extracted from Lotus Seedpod on Learning and Memory Impairment in Scopolamine-Induced Amnesia Mice - Xiao_2014_PLoS.One_9_e112773
Author(s) : Xiao J , Li S , Sui Y , Wu Q , Li X , Xie B , Zhang M , Sun Z
Ref : PLoS ONE , 9 :e112773 , 2014
Abstract : Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (109 cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon, suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice.
ESTHER : Xiao_2014_PLoS.One_9_e112773
PubMedSearch : Xiao_2014_PLoS.One_9_e112773
PubMedID: 25396737

Title : Inhibition of flavonoids on acetylcholine esterase: binding and structure-activity relationship - Xie_2014_Food.Funct_5_2582
Author(s) : Xie Y , Yang W , Chen X , Xiao J
Ref : Food Funct , 5 :2582 , 2014
Abstract : The inhibitory effects of flavonoids on acetylcholinesterase (AChE) have attracted great interest among researchers. However, few reports have focused on the structure-activity relationship for AChE inhibition of flavonoids. This work mainly concerns the structural aspects of inhibitory activities and binding affinities of flavonoids as AChE inhibitors. The results show that hydroxyl groups in the A ring of flavonoids are favorable for inhibiting AChE, and the hydroxylation increases the affinities for AChE. However, methoxylation may decrease or increase the activities depending on the class of flavonoids. The glycosylation decreases the AChE inhibitory activities of flavonoids and lowers the affinities for AChE by 1 to 5 times depending on the conjunction site and the type of sugar moiety. The hydrogenation of the C2-C3 double bond of apigenin decreases both the affinity for AChE and AChE inhibition. The molecular property-affinity relationship reveals that the hydrogen bond force plays an important role in binding flavonoids to AChE. The AChE inhibitions generally increase with the increasing affinities of flavonoids within the class, especially for flavones and flavonols.
ESTHER : Xie_2014_Food.Funct_5_2582
PubMedSearch : Xie_2014_Food.Funct_5_2582
PubMedID: 25143139

Title : Transgenic CGI-58 expression in macrophages alleviates the atherosclerotic lesion development in ApoE knockout mice - Xie_2014_Biochim.Biophys.Acta_1841_1683
Author(s) : Xie P , Zeng X , Xiao J , Sun B , Yang D
Ref : Biochimica & Biophysica Acta , 1841 :1683 , 2014
Abstract : Comparative Gene Identification-58 (CGI-58), as an adipose triglyceride lipase (ATGL) activator, strongly increases ATGL-mediated triglyceride (TG) catabolism. Previous studies have shown that CGI-58 affects intestinal cholesterol homeostasis independently of ATGL activity. Therefore, we hypothesized that CGI-58 was involved in macrophage cholesterol metabolism and consequently atherosclerotic lesion formation. Here, we generated macrophage-specific CGI-58 transgenic mice (Mac-CGI-58 Tg) using an SRA promoter, which was further mated with ApoE-/- mice to create litters of CGI-58 Tg/ApoE-/- mice. These CGI-58 Tg/ApoE-/- mice exhibited an anti-atherosclerosis phenotype compared with wild type (WT) controls (CGI-58 WT/ApoE-/-), illustrated by less plaque area in aortic roots. Moreover, macrophage-specific CGI-58 overexpression in mice resulted in up-regulated levels of plasma total cholesterol and HDL-cholesterol. Consequently, higher expression levels of PPARa, PPARgamma, LXRalpha, ABCA1, and ABCG1 were detected in macrophages from CGI-58 Tg/ApoE-/- mice compared to CGI-58 WT/ApoE-/- counterparts, which were accompanied by elevated macrophage cholesterol efflux toward HDL and Apo A1. Nevertheless, serum levels of TNF-alpha and IL-6 were reduced by macrophage-specific CGI-58 overexpression. Finally, bone marrow (BM) transplantation experiments further revealed that ApoE-/- mice reconstituted with Mac-CGI-58 Tg BM cells (ApoE-/-/Tg-BM chimera) displayed a significant reduction of atherosclerosis lesions compared with control mice reconstituted with Mac-CGI-58 WT BM cells (ApoE-/-/WT-BM chimera). Collectively, these data strongly suggest that CGI-58 overexpression in macrophages may protect against atherosclerosis development in mice.
ESTHER : Xie_2014_Biochim.Biophys.Acta_1841_1683
PubMedSearch : Xie_2014_Biochim.Biophys.Acta_1841_1683
PubMedID: 25178844

Title : Rice OsPAD4 functions differently from Arabidopsis AtPAD4 in host-pathogen interactions - Ke_2014_Plant.J_78_619
Author(s) : Ke Y , Liu H , Li X , Xiao J , Wang S
Ref : Plant J , 78 :619 , 2014
Abstract : The extensively studied Arabidopsis phytoalexin deficient 4 (AtPAD4) gene plays an important role in Arabidopsis disease resistance; however, the function of its sequence ortholog in rice is unknown. Here, we show that rice OsPAD4 appears not to be the functional ortholog of AtPAD4 in host-pathogen interactions, and that the OsPAD4 encodes a plasma membrane protein but that AtPAD4 encodes a cytoplasmic and nuclear protein. Suppression of OsPAD4 by RNA interference (RNAi) increased rice susceptibility to the biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo), which causes bacteria blight disease in local tissue. OsPAD4-RNAi plants also show compromised wound-induced systemic resistance to Xoo. The increased susceptibility to Xoo was associated with reduced accumulation of jasmonic acid (JA) and phytoalexin momilactone A (MOA). Exogenous application of JA complemented the phenotype of OsPAD4-RNAi plants in response to Xoo. The following results suggest that OsPAD4 functions differently than AtPAD4 in response to pathogen infection. First, OsPAD4 plays an important role in wound-induced systemic resistance, whereas AtPAD4 mediates systemic acquired resistance. Second, OsPAD4-involved defense signaling against Xoo is JA-dependent, but AtPAD4-involved defense signaling against biotrophic pathogens is salicylic acid-dependent. Finally, OsPAD4 is required for the accumulation of terpenoid-type phytoalexin MOA in rice-bacterium interactions, but AtPAD4-mediated resistance is associated with the accumulation of indole-type phytoalexin camalexin.
ESTHER : Ke_2014_Plant.J_78_619
PubMedSearch : Ke_2014_Plant.J_78_619
PubMedID: 24617729
Gene_locus related to this paper: orysa-q53lh1

Title : Complete Genome Sequence of Acinetobacter baumannii ZW85-1 - Wang_2014_Genome.Announc_2_e01083
Author(s) : Wang X , Zhang Z , Hao Q , Wu J , Xiao J , Jing H
Ref : Genome Announc , 2 :e01083 , 2014
Abstract : Acinetobacter baumannii is an aerobic, nonmotile Gram-negative bacterium that causes nosocomial infections worldwide. Here, we report the complete genome sequence of Acinetobacter baumannii strain ZW85-1 and its two plasmids. One of the plasmids carries genes for NDM-1, which can hydrolyze a wide range of antibiotics.
ESTHER : Wang_2014_Genome.Announc_2_e01083
PubMedSearch : Wang_2014_Genome.Announc_2_e01083
PubMedID: 24459253
Gene_locus related to this paper: aciba-a0a009wzt4

Title : Comparative analysis of bat genomes provides insight into the evolution of flight and immunity - Zhang_2013_Science_339_456
Author(s) : Zhang G , Cowled C , Shi Z , Huang Z , Bishop-Lilly KA , Fang X , Wynne JW , Xiong Z , Baker ML , Zhao W , Tachedjian M , Zhu Y , Zhou P , Jiang X , Ng J , Yang L , Wu L , Xiao J , Feng Y , Chen Y , Sun X , Zhang Y , Marsh GA , Crameri G , Broder CC , Frey KG , Wang LF , Wang J
Ref : Science , 339 :456 , 2013
Abstract : Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor kappaB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.
ESTHER : Zhang_2013_Science_339_456
PubMedSearch : Zhang_2013_Science_339_456
PubMedID: 23258410
Gene_locus related to this paper: myods-l5mij9 , pteal-l5k8f5 , pteal-l5kjy3 , pteal-l5k6f0 , pteal-l5kxe2 , myods-l5m0a8 , myods-l5lvb4 , pteal-l5k7h7 , myods-l5lm42 , pteal-l5jz73 , pteal-l5kvh1.1 , pteal-l5kvh1.2 , pteal-l5kw21 , myods-l5lug5 , pteal-l5kv18 , myods-l5lbf8 , pteal-l5kwh0 , myods-l5lfh8 , myods-l5lfr7 , myods-l5lu20 , pteal-l5jzi4 , pteal-l5kib7 , pteal-l5kyq5 , myods-l5lf36 , myods-l5lnh7 , myods-l5lu25 , pteal-l5k0u1 , pteal-l5k2g6 , pteal-l5l3r3 , myods-l5mdx5 , pteal-l5k220 , myolu-g1pdp2 , pteal-l5l5n3 , pteal-l5k1s7 , myolu-g1nth4 , pteal-l5l7w7 , pteal-l5l537 , myods-l5lwe4 , pteal-l5klr9 , pteal-l5k670 , pteal-l5jr94 , pteal-l5kvb4 , myolu-g1q4e3 , pteal-l5jrl1

Title : Genome of the Chinese tree shrew - Fan_2013_Nat.Commun_4_1426
Author(s) : Fan Y , Huang ZY , Cao CC , Chen CS , Chen YX , Fan DD , He J , Hou HL , Hu L , Hu XT , Jiang XT , Lai R , Lang YS , Liang B , Liao SG , Mu D , Ma YY , Niu YY , Sun XQ , Xia JQ , Xiao J , Xiong ZQ , Xu L , Yang L , Zhang Y , Zhao W , Zhao XD , Zheng YT , Zhou JM , Zhu YB , Zhang GJ , Wang J , Yao YG
Ref : Nat Commun , 4 :1426 , 2013
Abstract : Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research.
ESTHER : Fan_2013_Nat.Commun_4_1426
PubMedSearch : Fan_2013_Nat.Commun_4_1426
PubMedID: 23385571
Gene_locus related to this paper: tupch-l9l8p0 , tupch-l9l7d8.1 , tupch-l9l7d8.2 , tupch-l9l7d8.3 , tupch-l8y4e3 , tupch-l9jqg5 , tupch-l9l3m0 , tupch-l9kxg8 , tupch-l9knn8 , tupch-l9kf47 , tupch-l9ja32 , tupch-l9l5b1 , tupch-l9khv5

Title : Flavonoids profiles, antioxidant, acetylcholinesterase inhibition activities of extract from Dryoathyrium boryanum (Willd.) Ching - Cao_2013_Food.Chem.Toxicol_55_121
Author(s) : Cao J , Xia X , Dai X , Xiao J , Wang Q , Andrae-Marobela K , Okatch H
Ref : Food & Chemical Toxicology , 55 :121 , 2013
Abstract : The profiles and bioactivities of flavonoids extracted from Dryoathyrium boryanum (Willd.) Ching were investigated. The total flavonoids content in extract from D. boryanum is about 145.8mg/g. By means of HPLC-DAD-ESI-MS, the main flavonoids in D. boryanum were tentatively identified as 3-hydroxyphloretin 6'-O-hexoside, quercetin-7-hexoside, apigenin7-O-glucoside, luteolin 7-O-glucoside, apigenin 7-O-galactoside, acacetin 7-O-(alpha-D-apio-furanosyl) (1-->6)-beta-d-glucoside, 3-hydroxy phloretin 6-O-hexoside, luteolin-6-C-glucoside. 0.21mg/ml flavonoids extract from D. boryanum showed very strong superoxide anion radical scavenging potential, which is higher than that of rutin (0.25mg/ml). The extract (0.21mg/ml of flavonoids) from D. boryanum exhibited similar DPPH scavenging potential with that of rutin (0.25mg/ml). However, rutin (0.25mg/ml) showed a significantly higher reducing power and ABTS scavenging potential than that of 0.21mg/ml flavonoids extract from D. boryanum. It had no effect on acetylcholinesterase. D. boryanum can be considered as a medicinal plant and the flavonoids from D. boryanum are excellent antioxidants.
ESTHER : Cao_2013_Food.Chem.Toxicol_55_121
PubMedSearch : Cao_2013_Food.Chem.Toxicol_55_121
PubMedID: 23313795

Title : Characterization of flavonoids from Dryopteris erythrosora and evaluation of their antioxidant, anticancer and acetylcholinesterase inhibition activities - Cao_2012_Food.Chem.Toxicol_51C_242
Author(s) : Cao J , Xia X , Chen X , Xiao J , Wang Q
Ref : Food & Chemical Toxicology , 51C :242 , 2012
Abstract : The profiles and bioactivities of flavonoids extracted from Dryopteris erythrosora were investigated. The total flavonoid content in full plant of D. Erythrosora is about 14.33%. The main flavonoids in D. Erythrosora were identified as gliricidin 7-O-hexoside, apigenin7-O-glucoside, quercetin 7-O-rutinoside, quercetin 7-O-galactoside, keampferol 7-O-gentiobioside, keampferol-3-O-rutinoside, myricetin 3-O-rhamnoside and quercitrin by means of HPLC-DAD-ESI-MS. Flavonoids (0.36mg/ml) extract from D. erythrosora showed similar 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH()), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS()), superoxide anion scavenging potential and ferric reducing antioxidant potential (FRAP) with that of rutin (0.80mg/ml). However, the antioxidant power by FRAP assay of 0.36mg/ml flavonoids extract from D. erythrosora was much weaker than that of 0.80mg/ml rutin. Moreover, the flavonoids extract from D. erythrosora showed obvious cytotoxic effects on A549 cells. The antioxidant activities of flavonoids extracts from 69 ferns showed a significant reciprocal proportion to the total flavonoids contents. The flavonoids extract from D. erythrosora exhibited a dose-dependent inhibition against acetylcholinesterase. Moreover, the anticancer activity slightly increased with improving antioxidant potential of fern flavonoids. Fern flavonoids are excellent function foods.
ESTHER : Cao_2012_Food.Chem.Toxicol_51C_242
PubMedSearch : Cao_2012_Food.Chem.Toxicol_51C_242
PubMedID: 23063594

Title : Edwardsiella comparative phylogenomics reveal the new intra\/inter-species taxonomic relationships, virulence evolution and niche adaptation mechanisms - Yang_2012_PLoS.One_7_e36987
Author(s) : Yang M , Lv Y , Xiao J , Wu H , Zheng H , Liu Q , Zhang Y , Wang Q
Ref : PLoS ONE , 7 :e36987 , 2012
Abstract : Edwardsiella bacteria are leading fish pathogens causing huge losses to aquaculture industries worldwide. E. tarda is a broad-host range pathogen that infects more than 20 species of fish and other animals including humans while E. ictaluri is host-adapted to channel catfish causing enteric septicemia of catfish (ESC). Thus, these two species consist of a useful comparative system for studying the intricacies of pathogen evolution. Here we present for the first time the phylogenomic comparisons of 8 genomes of E. tarda and E. ictaluri isolates. Genome-based phylogenetic analysis revealed that E. tarda could be separate into two kinds of genotypes (genotype I, EdwGI and genotype II, EdwGII) based on the sequence similarity. E. tarda strains of EdwGI were clustered together with the E. ictaluri lineage and showed low sequence conservation to E. tarda strains of EdwGII. Multilocus sequence analysis (MLSA) of 48 distinct Edwardsiella strains also supports the new taxonomic relationship of the lineages. We identified the type III and VI secretion systems (T3SS and T6SS) as well as iron scavenging related genes that fulfilled the criteria of a key evolutionary factor likely facilitating the virulence evolution and adaptation to a broad range of hosts in EdwGI E. tarda. The surface structure-related genes may underlie the adaptive evolution of E. ictaluri in the host specification processes. Virulence and competition assays of the null mutants of the representative genes experimentally confirmed their contributive roles in the evolution/niche adaptive processes. We also reconstructed the hypothetical evolutionary pathway to highlight the virulence evolution and niche adaptation mechanisms of Edwardsiella. This study may facilitate the development of diagnostics, vaccines, and therapeutics for this under-studied pathogen.
ESTHER : Yang_2012_PLoS.One_7_e36987
PubMedSearch : Yang_2012_PLoS.One_7_e36987
PubMedID: 22590641
Gene_locus related to this paper: 9gamm-a0a076lfv2

Title : Pan-genomic analysis provides insights into the genomic variation and evolution of Salmonella Paratyphi A - Liang_2012_PLoS.One_7_e45346
Author(s) : Liang W , Zhao Y , Chen C , Cui X , Yu J , Xiao J , Kan B
Ref : PLoS ONE , 7 :e45346 , 2012
Abstract : Salmonella Paratyphi A (S. Paratyphi A) is a highly adapted, human-specific pathogen that causes paratyphoid fever. Cases of paratyphoid fever have recently been increasing, and the disease is becoming a major public health concern, especially in Eastern and Southern Asia. To investigate the genomic variation and evolution of S. Paratyphi A, a pan-genomic analysis was performed on five newly sequenced S. Paratyphi A strains and two other reference strains. A whole genome comparison revealed that the seven genomes are collinear and that their organization is highly conserved. The high rate of substitutions in part of the core genome indicates that there are frequent homologous recombination events. Based on the changes in the pan-genome size and cluster number (both in the core functional genes and core pseudogenes), it can be inferred that the sharply increasing number of pseudogene clusters may have strong correlation with the inactivation of functional genes, and indicates that the S. Paratyphi A genome is being degraded.
ESTHER : Liang_2012_PLoS.One_7_e45346
PubMedSearch : Liang_2012_PLoS.One_7_e45346
PubMedID: 23028950

Title : Complete genome sequence of Streptococcus suis serotype 14 strain JS14 - Hu_2011_J.Bacteriol_193_2375
Author(s) : Hu P , Yang M , Zhang A , Wu J , Chen B , Hua Y , Yu J , Xiao J , Jin M
Ref : Journal of Bacteriology , 193 :2375 , 2011
Abstract : Streptococcus suis is an important zoonotic agent leading to a variety of diseases in swine and can be transmitted to human beings upon close contact. Here, we report the complete genome sequence of S. suis serotype 14 strain JS14 which was isolated from a diseased pig in Jiangsu Province, China.
ESTHER : Hu_2011_J.Bacteriol_193_2375
PubMedSearch : Hu_2011_J.Bacteriol_193_2375
PubMedID: 21398551
Gene_locus related to this paper: strej-e8uk64 , strsu-a4vws4 , strsu-q673u2 , strsy-a4vus4

Title : Natural variation in GS5 plays an important role in regulating grain size and yield in rice - Li_2011_Nat.Genet_43_1266
Author(s) : Li Y , Fan C , Xing Y , Jiang Y , Luo L , Sun L , Shao D , Xu C , Li X , Xiao J , He Y , Zhang Q
Ref : Nat Genet , 43 :1266 , 2011
Abstract : Increasing crop yield is one of the most important goals of plant science research. Grain size is a major determinant of grain yield in cereals and is a target trait for both domestication and artificial breeding(1). We showed that the quantitative trait locus (QTL) GS5 in rice controls grain size by regulating grain width, filling and weight. GS5 encodes a putative serine carboxypeptidase and functions as a positive regulator of grain size, such that higher expression of GS5 is correlated with larger grain size. Sequencing of the promoter region in 51 rice accessions from a wide geographic range identified three haplotypes that seem to be associated with grain width. The results suggest that natural variation in GS5 contributes to grain size diversity in rice and may be useful in improving yield in rice and, potentially, other crops(2).
ESTHER : Li_2011_Nat.Genet_43_1266
PubMedSearch : Li_2011_Nat.Genet_43_1266
PubMedID: 22019783
Gene_locus related to this paper: orysa-q5w727

Title : Complete genome sequence of Streptococcus suis serotype 3 strain ST3 - Hu_2011_J.Bacteriol_193_3428
Author(s) : Hu P , Yang M , Zhang A , Wu J , Chen B , Hua Y , Yu J , Chen H , Xiao J , Jin M
Ref : Journal of Bacteriology , 193 :3428 , 2011
Abstract : Streptococcus suis is a zoonotic pathogen causing economic loss in the swine industry and is also a threat to human health. To date, the mechanism of pathogenesis is not fully understood. Here, we report the complete genome sequence of S. suis strain ST3 of serotype 3, which provides opportunities to reveal genetic basis of infection of S. suis non-serotype 2 strains.
ESTHER : Hu_2011_J.Bacteriol_193_3428
PubMedSearch : Hu_2011_J.Bacteriol_193_3428
PubMedID: 21572001
Gene_locus related to this paper: strsu-b9wvz1

Title : Comparative genomic analysis of Streptococcus suis reveals significant genomic diversity among different serotypes - Zhang_2011_BMC.Genomics_12_523
Author(s) : Zhang A , Yang M , Hu P , Wu J , Chen B , Hua Y , Yu J , Chen H , Xiao J , Jin M
Ref : BMC Genomics , 12 :523 , 2011
Abstract : BACKGROUND: Streptococcus suis (S. suis) is a major swine pathogen and an emerging zoonotic agent. Serotypes 1, 2, 3, 7, 9, 14 and 1/2 are the most prevalent serotypes of this pathogen. However, almost all studies were carried out on serotype 2 strains. Therefore, characterization of genomic features of other serotypes will be required to better understand their virulence potential and phylogenetic relationships among different serotypes.
RESULTS: Four Chinese S. suis strains belonging to serotypes 1, 7, 9 and 1/2 were sequenced using a rapid, high-throughput approach. Based on the 13 corresponding serotype strains, including 9 previously completed genomes of this bacterium, a full comparative genomic analysis was performed. The results provide evidence that (i) the pan-genome of this species is open and the size increases with addition of new sequenced genomes, (ii) strains of serotypes 1, 3, 7 and 9 are phylogenetically distinct from serotype 2 strains, but all serotype 2 strains, plus the serotype 1/2 and 14 strains, are very closely related. (iii) all these strains, except for the serotype 1 strain, could harbor a recombinant site for a pathogenic island (89 K) mediated by conjugal transfer, and may have the ability to gain the 89 K sequence.
CONCLUSIONS: There is significant genomic diversity among different strains in S. suis, and the gain and loss of large amount of genes are involved in shaping their genomes. This is indicated by (i) pairwise gene content comparisons between every pair of these strains, (ii) the open pan-genome of this species, (iii) the observed indels, invertions and rearrangements in the collinearity analysis. Phylogenetic relationships may be associated with serotype, as serotype 2 strains are closely related and distinct from other serotypes like 1, 3, 7 and 9, but more strains need to be sequenced to confirm this.
ESTHER : Zhang_2011_BMC.Genomics_12_523
PubMedSearch : Zhang_2011_BMC.Genomics_12_523
PubMedID: 22026465
Gene_locus related to this paper: strsu-b9wvz1

Title : Paraoxonase 2 is down-regulated by the Pseudomonas aeruginosa quorumsensing signal N-(3-oxododecanoyl)-L-homoserine lactone and attenuates oxidative stress induced by pyocyanin - Horke_2010_Biochem.J_426_73
Author(s) : Horke S , Witte I , Altenhofer S , Wilgenbus P , Goldeck M , Forstermann U , Xiao J , Kramer GL , Haines DC , Chowdhary PK , Haley RW , Teiber JF
Ref : Biochemical Journal , 426 :73 , 2010
Abstract : Two virulence factors produced by Pseudomonas aeruginosa are pyocyanin and N-(3-oxododecanoyl)-L-homoserine lactone (3OC12). Pyocyanin damages host cells by generating ROS (reactive oxygen species). 3OC12 is a quorum-sensing signalling molecule which regulates bacterial gene expression and modulates host immune responses. PON2 (paraoxonase-2) is an esterase that inactivates 3OC12 and potentially attenuates Ps. aeruginosa virulence. Because increased intracellular Ca2+ initiates the degradation of PON2 mRNA and protein and 3OC12 causes increases in cytosolic Ca2+, we hypothesized that 3OC12 would also down-regulate PON2. 3OC12 and the Ca2+ ionophore A23187 caused a rapid cytosolic Ca2+ influx and down-regulated PON2 mRNA, protein and hydrolytic activity in A549 and EA.hy 926 cells. The decrease in PON2 hydrolytic activity was much more extensive and rapid than decreases in protein, suggesting a rapid post-translational mechanism which blocks PON2's hydrolytic activity. The Ca2+ chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] diminished the ability of 3OC12 to decrease PON2, demonstrating that the effects are mediated by Ca2+. PON2 also has antioxidative properties and we show that it protects cells from pyocyanin-induced oxidative stress. Knockdown of PON2 by transfecting cells with siRNA (small interfering RNA) rendered them more sensitive to, whereas overexpression of PON2 protected cells from, pyocyanin-induced ROS formation. Additionally, 3OC12 potentiated pyocyanin-induced ROS formation, presumably by inactivating PON2. These findings support a key role for PON2 in the defence against Ps. aeruginosa virulence, but also reveal a mechanism by which the bacterium may subvert the protection afforded by PON2.
ESTHER : Horke_2010_Biochem.J_426_73
PubMedSearch : Horke_2010_Biochem.J_426_73
PubMedID: 19925453

Title : Genome sequence of the versatile fish pathogen Edwardsiella tarda provides insights into its adaptation to broad host ranges and intracellular niches - Wang_2009_PLoS.One_4_e7646
Author(s) : Wang Q , Yang M , Xiao J , Wu H , Wang X , Lv Y , Xu L , Zheng H , Wang S , Zhao G , Liu Q , Zhang Y
Ref : PLoS ONE , 4 :e7646 , 2009
Abstract : BACKGROUND: Edwardsiella tarda is the etiologic agent of edwardsiellosis, a devastating fish disease prevailing in worldwide aquaculture industries. Here we describe the complete genome of E. tarda, EIB202, a highly virulent and multi-drug resistant isolate in China. METHODOLOGY/PRINCIPAL FINDINGS: E. tarda EIB202 possesses a single chromosome of 3,760,463 base pairs containing 3,486 predicted protein coding sequences, 8 ribosomal rRNA operons, and 95 tRNA genes, and a 43,703 bp conjugative plasmid harboring multi-drug resistant determinants and encoding type IV A secretion system components. We identified a full spectrum of genetic properties related to its genome plasticity such as repeated sequences, insertion sequences, phage-like proteins, integrases, recombinases and genomic islands. In addition, analysis also indicated that a substantial proportion of the E. tarda genome might be devoted to the growth and survival under diverse conditions including intracellular niches, with a large number of aerobic or anaerobic respiration-associated proteins, signal transduction proteins as well as proteins involved in various stress adaptations. A pool of genes for secretion systems, pili formation, nonfimbrial adhesions, invasions and hemagglutinins, chondroitinases, hemolysins, iron scavenging systems as well as the incomplete flagellar biogenesis might feature its surface structures and pathogenesis in a fish body. CONCLUSION/SIGNIFICANCE: Genomic analysis of the bacterium offered insights into the phylogeny, metabolism, drug-resistance, stress adaptation, and virulence characteristics of this versatile pathogen, which constitutes an important first step in understanding the pathogenesis of E. tarda to facilitate construction of a practical effective vaccine used for combating fish edwardsiellosis.
ESTHER : Wang_2009_PLoS.One_4_e7646
PubMedSearch : Wang_2009_PLoS.One_4_e7646
PubMedID: 19865481
Gene_locus related to this paper: edwte-d0zav8 , edwte-d0zg19 , edwtf-e0t1p5 , edwte-d0za01 , edwte-d0z9v1

Title : Dominant role of paraoxonases in inactivation of the Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl)-L-homoserine lactone - Teiber_2008_Infect.Immun_76_2512
Author(s) : Teiber JF , Horke S , Haines DC , Chowdhary PK , Xiao J , Kramer GL , Haley RW , Draganov DI
Ref : Infect Immun , 76 :2512 , 2008
Abstract : The pathogenic bacterium Pseudomonas aeruginosa causes serious infections in immunocompromised patients. N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL) is a key component of P. aeruginosa's quorum-sensing system and regulates the expression of many virulence factors. 3OC12-HSL was previously shown to be hydrolytically inactivated by the paraoxonase (PON) family of calcium-dependent esterases, consisting of PON1, PON2, and PON3. Here we determined the specific activities of purified human PONs for 3OC12-HSL hydrolysis, including the common PON1 polymorphic forms, and found they were in the following order: PON2 >> PON1(192R) > PON1(192Q) > PON3. PON2 exhibited a high specific activity of 7.6 +/- 0.4 micromols/min/mg at 10 microM 3OC12-HSL, making it the best PON2 substrate identified to date. By use of class-specific inhibitors, approximately 85 and 95% of the 3OC12-HSL lactonase activity were attributable to PON1 in mouse and human sera, respectively. In mouse liver homogenates, the activity was metal dependent, with magnesium- and manganese-dependent lactonase activities comprising 10 to 15% of the calcium-dependent activity. In mouse lung homogenates, all of the activity was calcium dependent. The calcium-dependent activities were irreversibly inhibited by extended EDTA treatment, implicating PONs as the major enzymes inactivating 3OC12-HSL. In human HepG2 and EA.hy 926 cell lysates, the 3OC12-HSL lactonase activity closely paralleled the PON2 protein levels after PON2 knockdown by small interfering RNA treatment of the cells. These findings suggest that PONs, particularly PON2, could be an important mechanism by which 3OC12-HSL is inactivated in mammals.
ESTHER : Teiber_2008_Infect.Immun_76_2512
PubMedSearch : Teiber_2008_Infect.Immun_76_2512
PubMedID: 18347034

Title : Investigation of the mechanism of enhanced effect of EGCG on huperzine A's inhibition of acetylcholinesterase activity in rats by a multispectroscopic method - Xiao_2008_J.Agric.Food.Chem_56_910
Author(s) : Xiao J , Chen X , Zhang L , Talbot SG , Li GC , Xu M
Ref : Journal of Agricultural and Food Chemistry , 56 :910 , 2008
Abstract : The mechanism of enhanced effect of (-)-epigallocatechin-3-gallate (EGCG) on huperzine A's (HUP) inhibition of acetylcholinesterase (AChE) activity in rats was investigated. The inhibitory effects of HUP at 10 and 5 microg/kg on AChE activity were quite weak in the whole phase. In contrast, upon addition of EGCG (100 mg/kg) to the HUP 10 and 5 microg/kg groups, remarkably enhanced inhibitory effects with maximum inhibitory percentages of 90.94 and 88.13% were observed under the same conditions. EGCG also can greatly prolong the inhibitory time. The mechanism of the enhanced effects of EGCG on HUP's inhibition of AChE activity was investigated by steady fluorescence spectroscopy, infrared spectroscopy, and ultraviolet spectroscopy. HUP hardly interacted with the main transport protein, whereas there was a very strong binding interaction between EGCG and bovine serum albumin. The enhanced transport of HUP is a possible cause of the enhanced effect of EGCG on HUP bioactivity.
ESTHER : Xiao_2008_J.Agric.Food.Chem_56_910
PubMedSearch : Xiao_2008_J.Agric.Food.Chem_56_910
PubMedID: 18193834

Title : [A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers] - Leng_2004_Zhonghua.Yu.Fang.Yi.Xue.Za.Zhi_38_94
Author(s) : Leng SG , Zheng YX , Pan ZF , Niu Y , Dai YF , Wang YW , Zhang WZ , Xiao J , Wang ZX , Li T , He FS
Ref : Zhonghua Yu Fang Yi Xue Za Zhi , 38 :94 , 2004
Abstract : OBJECTIVE: To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers.
METHODS: One hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction.
RESULTS: In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk. CONCLUSION: Significant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.
ESTHER : Leng_2004_Zhonghua.Yu.Fang.Yi.Xue.Za.Zhi_38_94
PubMedSearch : Leng_2004_Zhonghua.Yu.Fang.Yi.Xue.Za.Zhi_38_94
PubMedID: 15061915

Title : Histochemical and immunohistochemical studies of distribution of acetylcholinesterase-positive fibers and peptidergic terminals in the nasal mucosa of rats - Zhao_1998_Chin.Med.J.(Engl)_111_644
Author(s) : Zhao C , Tao Z , Xiao J , Zhao S , Qiao J
Ref : Chinese Medical Journal (Engl) , 111 :644 , 1998
Abstract : OBJECTIVE: To further investigate the mechanism of nasal secretion closely related to the innervation patterns in nasal mucosa with emphasis on the acetylcholinesterase (AChE)-positive fibers and peptidergic terminals in nasal mucosa as well as trigeminal ganglion (TG) cells.
METHODS: Histochemical demonstration of AChE-positive fibers, immunohistochemical study of the distribution patterns of multiple peptidergic terminals, double labelling of AChE and substance P (SP) and somatostatin (SOM) mRNA in situ hybridization were carried out in nasal mucosa and trigeminal ganglion (TG) in rats.
RESULTS: AChE-positive terminals were mainly distributed in the mid to posterior one third of septal nasal mucosa, with greater staining density on the walls of small vessels and glands. There were fewer such terminals in turbinate mucosa. Tachykinins-ergic terminals, including substance P (SP)-, neurokinin A (NKA)-, neurokinin B (NKB)- and calcitonin gene-related peptide (CGRP)-ergic terminals, had an extensive localizations in nasal mucosa, involving the following areas: between epithelial cells, submucosa, the walls of small vessels, glands and venous sinusoids in both septal and turbinate nasal mucosa. Septal mucosa had the greater density. There were overlaps in the distribution of these peptidergic terminals. There were also vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and galanin (GAL)-ergic terminals in nasal mucosa. But no neurotensin (NT)- and somatostatin (SOM)-ergic terminals were found. In situ hybridization revealed SOMmRNA expression in TG cells. AChE and nine neuropeptides existed in the cytoplasms of TG cells. Besides, AChE and SP could exist simultaneously in cytoplasms of TG cells.
CONCLUSIONS: AChE-positive (corresponding to parasympathetic nerves) and peptidergic terminals have different distribution patterns in the nasal mucosa of rats, although an overlap does exist, indicative of their different physiological effects on the regulation of nasal secretion and other functions; AChE and multiple neuropeptides in the cytoplasm of TG cells might play a role in modulating the nasal secretion in response to stimuli in the nasal mucosa.
ESTHER : Zhao_1998_Chin.Med.J.(Engl)_111_644
PubMedSearch : Zhao_1998_Chin.Med.J.(Engl)_111_644
PubMedID: 11245055