Yan L

References (18)

Title : Exposure to synthesized tribromobisphenol A and critical effects: Metabolic pathways, disease signature, and benchmark dose derivation - Kuang_2024_Sci.Total.Environ_932_173117
Author(s) : Kuang HX , Dong CY , Yan L , Zhou Y , Xiang MD , Yu YJ
Ref : Sci Total Environ , 932 :173117 , 2024
Abstract : 2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, gamma-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 microg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.
ESTHER : Kuang_2024_Sci.Total.Environ_932_173117
PubMedSearch : Kuang_2024_Sci.Total.Environ_932_173117
PubMedID: 38734097

Title : Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation - Zhou_2024_J.Mol.Model_30_68
Author(s) : Zhou C , Yan L , Xu J , Hamezah HS , Wang T , Du F , Tong X , Han R
Ref : J Mol Model , 30 :68 , 2024
Abstract : CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity. METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrodinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.
ESTHER : Zhou_2024_J.Mol.Model_30_68
PubMedSearch : Zhou_2024_J.Mol.Model_30_68
PubMedID: 38347278

Title : Generic detection of organophosphorus nerve agent adducts to butyrylcholinesterase in plasma using liquid chromatography-tandem mass spectrometry combined with an improved procainamide-gel separation and pepsin digestion method - Liu_2023_J.Chromatogr.A_1697_463990
Author(s) : Liu CC , Liang LH , Yan L , Chen B , Liu XJ , Yang Y , Liu SL , Xi HL
Ref : Journal of Chromatography A , 1697 :463990 , 2023
Abstract : Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be applied to confirm exposure in humans. A sensitive method for generic detection of G- and V-series OPNA adducts to BChE in plasma was developed by combining an improved procainamide-gel separation (PGS) and pepsin digestion protocol with ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Residual matrix interferences from prior PGS purification of OPNA-BChE adducts from plasma were found to be a critical cause of significantly reduced UHPLC-MS/MS detection sensitivity. In our developed on-column PGS approach, the matrix interference was successfully removed by adding an appropriate concentration of NaCl to the washing buffer, and it could capture <=92.5% of the BChE in plasma. The lower pH value and the longer digestion time in all previous pepsin digestion methods were found to be a key accelerated aging factor of several adducts such as tabun (GA)-, cyclohexylsarin (GF)-, and soman (GD)-BChE nonapeptide adducts, making them difficult to detect. The aging event of several OPNA-BChE nonapeptide adducts was so successfully addressed that the formic acid level in enzymatic buffer and digestion time were lowered to 0.05% (pH 2.67) and 0.5 h, respectively, and the post-digestion reaction was immediately terminated. The improved condition parameters were optimal for pepsin digestion of all types of OPNA-BChE adducts into their individual unaged nonapeptide adducts with the highest yields, expanding the applicability of the method. The method had a nearly one-fold decrease in sample preparation time through the reduction of digestion time and removal of ultrafiltration procedure after digestion. The limit of identification (LOI) were determined respectively as 0.13 ng mL(-1), 0.28 ng mL(-1), 0.50 ng mL(-1), 0.41 ng mL(-1) and 0.91 ng mL(-1) for VX-, sarin (GB)-, GA-, GF-, and GD-exposed human plasma, being low exposure value compared to previously documented approaches. The approach was utilized to fully characterize the adducted (aged and unaged) BChE levels of five OPNAs in a series of their individual exposed concentration (1.00-400 nM) of plasma sample, and successfully detect OPNA exposure from all unknown plasma samples from OPCW's second and third biomedical proficiency tests. The OPNA-BChE adducts, their aged adducts, and unadducted BChE from OPNA-exposed plasma can simultaneously be measured using the method. The study provides a recommended diagnostic tool for generic verification of any OPNA exposure with high confidence by detecting its corresponding BChE adduct.
ESTHER : Liu_2023_J.Chromatogr.A_1697_463990
PubMedSearch : Liu_2023_J.Chromatogr.A_1697_463990
PubMedID: 37075496

Title : Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial - Xu_2023_BMC.Med_21_388
Author(s) : Xu M , Sun K , Xu W , Wang C , Yan D , Li S , Cong L , Pi Y , Song W , Sun Q , Xiao R , Peng W , Wang J , Peng H , Zhang Y , Duan P , Zhang M , Liu J , Huang Q , Li X , Bao Y , Zeng T , Wang K , Qin L , Wu C , Deng C , Huang C , Yan S , Zhang W , Li M , Sun L , Wang Y , Li H , Wang G , Pang S , Zheng X , Wang H , Wang F , Su X , Ma Y , Li Z , Xie Z , Xu N , Ni L , Zhang L , Deng X , Pan T , Dong Q , Wu X , Shen X , Zhang X , Zou Q , Jiang C , Xi J , Ma J , Sun J , Yan L
Ref : BMC Med , 21 :388 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.
ESTHER : Xu_2023_BMC.Med_21_388
PubMedSearch : Xu_2023_BMC.Med_21_388
PubMedID: 37814306

Title : Endophytic Fungal Community of Huperzia serrata: Diversity and Relevance to the Production of Huperzine A by the Plant Host - Cui_2021_Molecules_26_
Author(s) : Cui L , Noushahi HA , Zhang Y , Liu J , Cosoveanu A , Liu Y , Yan L , Zhang J , Shu S
Ref : Molecules , 26 : , 2021
Abstract : As the population ages globally, there seem to be more people with Alzheimer's disease. Unfortunately, there is currently no specific treatment for the disease. At present, Huperzine A (HupA) is one of the best drugs used for the treatment of Alzheimer's disease and has been used in clinical trials for several years in China. HupA was first separated from Huperzia serrata, a traditional medicinal herb that is used to cure fever, contusions, strains, hematuria, schizophrenia, and snakebite for several hundreds of years in China, and has been confirmed to have acetylcholinesterase inhibitory activity. With the very slow growth of H. serrata, resources are becoming too scarce to meet the need for clinical treatment. Some endophytic fungal strains that produce HupA were isolated from H. serrate in previous studies. In this article, the diversity of the endophytic fungal community within H. serrata was observed and the relevance to the production of HupA by the host plant was further analyzed. A total of 1167 strains were obtained from the leaves of H. serrata followed by the stems (1045) and roots (824). The richness as well as diversity of endophytic fungi within the leaf and stem were higher than in the root. The endophytic fungal community was similar within stems as well as in leaves at all taxonomic levels. The 11 genera (Derxomyces, Lophiostoma, Cyphellophora, Devriesia, Serendipita, Kurtzmanomyces, Mycosphaerella, Conoideocrella, Brevicellicium, Piskurozyma, and Trichomerium) were positively correlated with HupA content. The correlation index of Derxomyces with HupA contents displayed the highest value (CI = 0.92), whereas Trichomerium showed the lowest value (CI = 0.02). Through electrospray ionization mass spectrometry (ESI-MS), it was confirmed that the HS7-1 strain could produce HupA and the total alkaloid concentration was 3.7 ug/g. This study will enable us to screen and isolate the strain that can produce HupA and to figure out the correlation between endophytic fungal diversity with HupA content in different plant organs. This can provide new insights into the screening of strains that can produce HupA more effectively.
ESTHER : Cui_2021_Molecules_26_
PubMedSearch : Cui_2021_Molecules_26_
PubMedID: 33567664

Title : Genome-wide analysis of the serine carboxypeptidase-like protein family in Triticum aestivum reveals TaSCPL184-6D is involved in abiotic stress response - Xu_2021_BMC.Genomics_22_350
Author(s) : Xu X , Zhang L , Zhao W , Fu L , Han Y , Wang K , Yan L , Li Y , Zhang XH , Min DH
Ref : BMC Genomics , 22 :350 , 2021
Abstract : BACKGROUND: The serine carboxypeptidase-like protein (SCPL) family plays a vital role in stress response, growth, development and pathogen defense. However, the identification and functional analysis of SCPL gene family members have not yet been performed in wheat. RESULTS: In this study, we identified a total of 210 candidate genes encoding SCPL proteins in wheat. According to their structural characteristics, it is possible to divide these members into three subfamilies: CPI, CPII and CPIII. We uncovered a total of 209 TaSCPL genes unevenly distributed across 21 wheat chromosomes, of which 65.7% are present in triads. Gene duplication analysis showed that ~ 10.5% and ~ 64.8% of the TaSCPL genes are derived from tandem and segmental duplication events, respectively. Moreover, the Ka/Ks ratios between duplicated TaSCPL gene pairs were lower than 0.6, which suggests the action of strong purifying selection. Gene structure analysis showed that most of the TaSCPL genes contain multiple introns and that the motifs present in each subfamily are relatively conserved. Our analysis on cis-acting elements showed that the promoter sequences of TaSCPL genes are enriched in drought-, ABA- and MeJA-responsive elements. In addition, we studied the expression profiles of TaSCPL genes in different tissues at different developmental stages. We then evaluated the expression levels of four TaSCPL genes by qRT-PCR, and selected TaSCPL184-6D for further downstream analysis. The results showed an enhanced drought and salt tolerance among TaSCPL184-6D transgenic Arabidopsis plants, and that the overexpression of the gene increased proline and decreased malondialdehyde levels, which might help plants adapting to adverse environments. Our results provide comprehensive analyses of wheat SCPL genes that might work as a reference for future studies aimed at improving drought and salt tolerance in wheat. CONCLUSIONS: We conducte a comprehensive bioinformatic analysis of the TaSCPL gene family in wheat, which revealing the potential roles of TaSCPL genes in abiotic stress. Our analysis also provides useful resources for improving the resistance of wheat.
ESTHER : Xu_2021_BMC.Genomics_22_350
PubMedSearch : Xu_2021_BMC.Genomics_22_350
PubMedID: 33992092

Title : Subchronic effects of dietary selenium yeast and selenite on growth performance and the immune and antioxidant systems in Nile tilapia Oreochromis niloticus - Chen_2019_Fish.Shellfish.Immunol_97_283
Author(s) : Chen H , Li J , Yan L , Cao J , Li D , Huang GY , Shi WJ , Dong W , Zha J , Ying GG , Zhong H , Wang Z , Huang Y , Luo Y , Xie L
Ref : Fish Shellfish Immunol , 97 :283 , 2019
Abstract : Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 mug/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 mug/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1beta, IFN-gamma and TNF-alpha) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 mug/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme alpha-glucosidase (alpha-Glu) in the intestine at 12 mug/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus.
ESTHER : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedSearch : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedID: 31863904

Title : Fluoride reactivation-enabled sensitive quantification of tabun adducts on human serum albumin by GC-MS\/MS via isotope dilution - Li_2019_Bioanalysis_11_2145
Author(s) : Li XS , Wu JN , Yan L , Xing ZF , Liu CC , Chen B , Yuan L , Yang Y
Ref : Bioanalysis , 11 :2145 , 2019
Abstract : Organophosphorus nerve agents inhibit the cholinesterase activity by phosphylation of the active site serine. The resulting phosphylated cholinesterase and adducts on human serum albumin (HSA) are appropriate biomarkers for nerve agents exposure. Several methods have been developed for the detection of nerve agents, including fluoride reactivation or alkaline cleavage. It was previously thought that some nerve agents adducts to HSA could not be detected via fluoride regeneration. In our study, the results showed that tabun (GA) adducts of HSA could be detected by fluoride regeneration. The sample preparation included acetone precipitation, washing and SPE. Deuterated tabun (d5-GA) was applied as the internal standard. The product of regenerated fluorotabun is detected with a good linearity (R(2) > 0.997) in the concentration range from 0.02 to 100.0 ng/ml, small relative standard deviation (
ESTHER : Li_2019_Bioanalysis_11_2145
PubMedSearch : Li_2019_Bioanalysis_11_2145
PubMedID: 31729243

Title : Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk - Yang_2019_Cancer.Res_79_505
Author(s) : Yang Y , Wu L , Shu X , Lu Y , Shu XO , Cai Q , Beeghly-Fadiel A , Li B , Ye F , Berchuck A , Anton-Culver H , Banerjee S , Benitez J , Bjorge L , Brenton JD , Butzow R , Campbell IG , Chang-Claude J , Chen K , Cook LS , Cramer DW , deFazio A , Dennis J , Doherty JA , Dork T , Eccles DM , Edwards DV , Fasching PA , Fortner RT , Gayther SA , Giles GG , Glasspool RM , Goode EL , Goodman MT , Gronwald J , Harris HR , Heitz F , Hildebrandt MA , Hogdall E , Hogdall CK , Huntsman DG , Kar SP , Karlan BY , Kelemen LE , Kiemeney LA , Kjaer SK , Koushik A , Lambrechts D , Le ND , Levine DA , Massuger LF , Matsuo K , May T , McNeish IA , Menon U , Modugno F , Monteiro AN , Moorman PG , Moysich KB , Ness RB , Nevanlinna H , Olsson H , Onland-Moret NC , Park SK , Paul J , Pearce CL , Pejovic T , Phelan CM , Pike MC , Ramus SJ , Riboli E , Rodriguez-Antona C , Romieu I , Sandler DP , Schildkraut JM , Setiawan VW , Shan K , Siddiqui N , Sieh W , Stampfer MJ , Sutphen R , Swerdlow AJ , Szafron LM , Teo SH , Tworoger SS , Tyrer JP , Webb PM , Wentzensen N , White E , Willett WC , Wolk A , Woo YL , Wu AH , Yan L , Yannoukakos D , Chenevix-Trench G , Sellers TA , Pharoah PDP , Zheng W , Long J
Ref : Cancer Research , 79 :505 , 2019
Abstract : DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
ESTHER : Yang_2019_Cancer.Res_79_505
PubMedSearch : Yang_2019_Cancer.Res_79_505
PubMedID: 30559148

Title : A liquid chromatography tandem mass spectrometric method on in vitro nerve agents poisoning characterization and reactivator efficacy evaluation by determination of specific peptide adducts in acetylcholinesterase - Yan_2016_J.Chromatogr.A_1450_86
Author(s) : Yan L , Chen J , Xu B , Guo L , Xie Y , Tang J , Xie J
Ref : Journal of Chromatography A , 1450 :86 , 2016
Abstract : The terroristic availability of highly toxic nerve agents (NAs) highlights the necessity for a deep understanding of their toxicities and effective medical treatments. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a characterization of the NAs poisoning and an evaluation on the efficacy of reactivators in in vitro was developed for the first time. After exposure to sarin or VX and pepsin digestion, the specific peptides of acetylcholinesterase (AChE) in a purified status, i.e. undecapeptide "GESAGAASVGM" in free, unaged, or aged status was identified and quantified. A key termination procedure is focused to make the reaction system "frozen" and precisely "capture" the poisoning, aging and spontaneous reactivation status of AChE, and the abundance of such specific peptides can thus be simultaneously measured. In our established method, as low as 0.72% and 0.84% inhibition level of AChE induced by 0.5nM sarin and VX can be detected from the measurement of peptide adducts, which benefits a confirmation of NAs exposure, especially at extremely low levels. Comparing with conventional colorimetric Ellman assays, our method provides not only enzyme activity and inhibition rate, but also the precise poisoning status of NAs exposed AChE. Based on the full information provided by this method, the efficacy of reactivators, such as HI-6, obidoxime and pralidoxime, in the typical treatment of NAs poisoned AChE in in vitro was further evaluated. Our results showed that this method is a promising tool for the characterization of NAs poisoning and the evaluation of reactivator efficacy.
ESTHER : Yan_2016_J.Chromatogr.A_1450_86
PubMedSearch : Yan_2016_J.Chromatogr.A_1450_86
PubMedID: 27179675

Title : Yu Ping Feng San reverses cisplatin-induced multi-drug resistance in lung cancer cells via regulating drug transporters and p62\/TRAF6 signalling - Lou_2016_Sci.Rep_6_31926
Author(s) : Lou JS , Yan L , Bi CWC , Chan GK , Wu KQY , Liu EYL , Huang Y , Yao P , Du CY , Dong TTX , Tsim KWK
Ref : Sci Rep , 6 :31926 , 2016
Abstract : Yu Ping Feng San (YPFS), an ancient Chinese herbal decoction composed of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, has been used in the clinic for treating immune deficiency. In cancer therapy, YPFS is being combined with chemotherapy drugs to achieve improved efficacy; however, scientific evidence to illustrate this combination effect is lacking. The present study aims to demonstrate the anti-drug resistance of YPFS in cisplatin (DDP)-resistant non-small cell lung cancer cells (A549/DDP). The application of YPFS exhibited a synergistic enhancement of DDP-induced cytotoxicity as well as of the apoptotic signalling molecules. DDP-induced expression of the multi-drug-resistance efflux transporters was markedly reduced in the presence of YPFS, resulting in a higher intracellular concentration of DDP. In addition, the application of YPFS increased DDP-induced ROS accumulation and MMP depletion, decreased p62/TRAF6 signalling in DDP-treated A549/DDP cells. The co-treatment of DDP and YPFS in tumour-bearing mice reduced the tumour size robustly (by more than 80%), which was much better than the effect of DDP alone. These results indicate that YPFS can notably improve the DDP-suppressed cancer effect, which may be a consequence of the elevation of intracellular DDP via the drug transporters as well as the down regulation of p62/TRAF6 signalling.
ESTHER : Lou_2016_Sci.Rep_6_31926
PubMedSearch : Lou_2016_Sci.Rep_6_31926
PubMedID: 27558312

Title : DWARF14 is a non-canonical hormone receptor for strigolactone - Yao_2016_Nature_536_469
Author(s) : Yao R , Ming Z , Yan L , Li S , Wang F , Ma S , Yu C , Yang M , Chen L , Li Y , Yan C , Miao D , Sun Z , Yan J , Sun Y , Wang L , Chu J , Fan S , He W , Deng H , Nan F , Li J , Rao Z , Lou Z , Xie D
Ref : Nature , 536 :469 , 2016
Abstract : Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The alpha/beta hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.
ESTHER : Yao_2016_Nature_536_469
PubMedSearch : Yao_2016_Nature_536_469
PubMedID: 27479325
Gene_locus related to this paper: arath-AtD14

Title : Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization - Lin_2014_Anal.Bioanal.Chem_406_5213
Author(s) : Lin Y , Chen J , Yan L , Guo L , Wu B , Li C , Feng J , Liu Q , Xie J
Ref : Anal Bioanal Chem , 406 :5213 , 2014
Abstract : A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.
ESTHER : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedSearch : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedID: 24633564

Title : Flavonoids, derived from traditional Chinese medicines, show roles in the differentiation of neurons: possible targets in developing health food products - Xu_2013_Birth.Defects.Res.C.Embryo.Today_99_292
Author(s) : Xu SL , Zhu KY , Bi CWC , Yan L , Men SW , Dong TTX , Tsim KWK
Ref : Birth Defects Res C Embryo Today , 99 :292 , 2013
Abstract : Flavonoids, a family of phenolic compounds, are distributed in a variety of fruits, vegetables, tea, and wine. More importantly, many flavonoids are served as the active ingredients in traditional Chinese herbal medicines, which in general do not have side effects. Several lines of evidence support that flavonoids have impacts on many aspects of human health, including anti-tumor, anti-oxidation, and anti-inflammation. Recently, there is significant attention focused on the neuronal beneficial effects of flavonoids, including the promotion of nervous system development, neuroprotection against neurotoxin stress, as well as the promotion of memory, learning, and cognitive functions. Here, the activities of flavonoids on the development of nervous system are being summarized and discussed. The flavonoids from diverse herbal medicines have significant effects in different developmental stages of nervous systems, including neuronal stem cell differentiation, neurite outgrowth, and neuronal plasticity. These findings imply that flavonoids are potential candidates for the development of health supplements in preventing birth defects and neuronal diseases.
ESTHER : Xu_2013_Birth.Defects.Res.C.Embryo.Today_99_292
PubMedSearch : Xu_2013_Birth.Defects.Res.C.Embryo.Today_99_292
PubMedID: 24339039

Title : Systematic review and meta-analysis of the relationship between EPHX1 polymorphisms and colorectal cancer risk - Liu_2012_PLoS.One_7_e43821
Author(s) : Liu F , Yuan D , Wei Y , Wang W , Yan L , Wen T , Xu M , Yang J , Li B
Ref : PLoS ONE , 7 :e43821 , 2012
Abstract : BACKGROUND: Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.
METHODS: Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.
RESULTS: This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83-0.98; dominant model, OR = 0.92, 95%CI = 0.85-0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies' publication time, the results were persistent and robust. CONCLUSION: This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.
ESTHER : Liu_2012_PLoS.One_7_e43821
PubMedSearch : Liu_2012_PLoS.One_7_e43821
PubMedID: 22928041

Title : Transcriptomic and phylogenetic analysis of Culex pipiens quinquefasciatus for three detoxification gene families - Yan_2012_BMC.Genomics_13_609
Author(s) : Yan L , Yang P , Jiang F , Cui N , Ma E , Qiao C , Cui F
Ref : BMC Genomics , 13 :609 , 2012
Abstract : ABSTRACT BACKGROUND The genomes of three major mosquito vectors of human diseases Anopheles gambiae Aedes aegypti and Culex pipiens quinquefasciatus have been previously sequenced C p quinquefasciatus has the largest number of predicted protein-coding genes which partially results from the expansion of three detoxification gene families cytochrome P450 monooxygenases P450 glutathione S-transferases GST and carboxyl/cholinesterases CCE However unlike An gambiae and Ae aegypti which have large amounts of gene expression data C p quinquefasciatus has limited transcriptomic resources Knowledge of complete gene expression information is very important for the exploration of the functions of genes involved in specific biological processes In the present study the three detoxification gene families of C p quinquefasciatus were analyzed for phylogenetic classification and compared with those of three other dipteran insects Gene expression during various developmental stages and the differential expression responsible for parathion resistance were profiled using the digital gene expression DGE technique RESULTS A total of 302 detoxification genes were found in C p quinquefasciatus including 71 CCE 196 P450 and 35 cytosolic GST genes Compared with three other dipteran species gene expansion in Culex mainly occurred in the CCE and P450 families where the genes of alpha-esterases juvenile hormone esterases and CYP325 of the CYP4 subfamily showed the most pronounced expansion on the genome For the five DGE libraries 3.5-3.8 million raw tags were generated and mapped to 13314 reference genes Among 302 detoxification genes 225 75 were detected for expression in at least one DGE library One fourth of the CCE and P450 genes were detected uniquely in one stage indicating potential developmentally regulated expression A total of 1511 genes showed different expression levels between a parathion-resistant and a susceptible strain Fifteen detoxification genes including 2 CCEs 6 GSTs and 7 P450s were expressed at higher levels in the resistant strain CONCLUSIONS The results of the present study provide new insights into the functions and evolution of three detoxification gene families in mosquitoes and comprehensive transcriptomic resources for C p quinquefasciatus which will facilitate the elucidation of molecular mechanisms underlying the different biological characteristics of the three major mosquito vectors.
ESTHER : Yan_2012_BMC.Genomics_13_609
PubMedSearch : Yan_2012_BMC.Genomics_13_609
PubMedID: 23140097

Title : The B73 maize genome: complexity, diversity, and dynamics - Schnable_2009_Science_326_1112
Author(s) : Schnable PS , Ware D , Fulton RS , Stein JC , Wei F , Pasternak S , Liang C , Zhang J , Fulton L , Graves TA , Minx P , Reily AD , Courtney L , Kruchowski SS , Tomlinson C , Strong C , Delehaunty K , Fronick C , Courtney B , Rock SM , Belter E , Du F , Kim K , Abbott RM , Cotton M , Levy A , Marchetto P , Ochoa K , Jackson SM , Gillam B , Chen W , Yan L , Higginbotham J , Cardenas M , Waligorski J , Applebaum E , Phelps L , Falcone J , Kanchi K , Thane T , Scimone A , Thane N , Henke J , Wang T , Ruppert J , Shah N , Rotter K , Hodges J , Ingenthron E , Cordes M , Kohlberg S , Sgro J , Delgado B , Mead K , Chinwalla A , Leonard S , Crouse K , Collura K , Kudrna D , Currie J , He R , Angelova A , Rajasekar S , Mueller T , Lomeli R , Scara G , Ko A , Delaney K , Wissotski M , Lopez G , Campos D , Braidotti M , Ashley E , Golser W , Kim H , Lee S , Lin J , Dujmic Z , Kim W , Talag J , Zuccolo A , Fan C , Sebastian A , Kramer M , Spiegel L , Nascimento L , Zutavern T , Miller B , Ambroise C , Muller S , Spooner W , Narechania A , Ren L , Wei S , Kumari S , Faga B , Levy MJ , McMahan L , Van Buren P , Vaughn MW , Ying K , Yeh CT , Emrich SJ , Jia Y , Kalyanaraman A , Hsia AP , Barbazuk WB , Baucom RS , Brutnell TP , Carpita NC , Chaparro C , Chia JM , Deragon JM , Estill JC , Fu Y , Jeddeloh JA , Han Y , Lee H , Li P , Lisch DR , Liu S , Liu Z , Nagel DH , McCann MC , SanMiguel P , Myers AM , Nettleton D , Nguyen J , Penning BW , Ponnala L , Schneider KL , Schwartz DC , Sharma A , Soderlund C , Springer NM , Sun Q , Wang H , Waterman M , Westerman R , Wolfgruber TK , Yang L , Yu Y , Zhang L , Zhou S , Zhu Q , Bennetzen JL , Dawe RK , Jiang J , Jiang N , Presting GG , Wessler SR , Aluru S , Martienssen RA , Clifton SW , McCombie WR , Wing RA , Wilson RK
Ref : Science , 326 :1112 , 2009
Abstract : We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.
ESTHER : Schnable_2009_Science_326_1112
PubMedSearch : Schnable_2009_Science_326_1112
PubMedID: 19965430
Gene_locus related to this paper: maize-b4ffc7 , maize-b6u7e1 , maize-c0pcy5 , maize-c0pgf7 , maize-c0pgw1 , maize-c0pfl3 , maize-b4fpr7 , maize-k7vy73 , maize-a0a096swr3 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a1d6nse2 , maize-c4j9a1 , maize-k7uba1

Title : Characterization of the human CUTA isoform2 present in the stably transfected HeLa cells - Yang_2009_Mol.Biol.Rep_36_63
Author(s) : Yang J , Yang H , Yan L , Yang L , Yu L
Ref : Mol Biol Rep , 36 :63 , 2009
Abstract : CUTA, Homo sapiens divalent cation tolerance homolog, has been implicated in anchoring of acetylcholinesterase in neuronal cell membranes. However, a protein highly homologous to CUTA in Rattus norvegicus is structurally similar to the signal transduction protein PII, and this similarity suggests an intriguing role of CUTA in signal transduction. Recent researches indicated that CUTA was one of the 35 key genes responsible for lactation in mammary gland development. However, the physiological role of CUTA is still unclear, so more information of this gene is needed. In this study, the expression profile of CUTA gene in human tissues was examined, and our research revealed that CUTA gene was constitutively expressed in all of the 18 tissues tested. As reported, CUTA gene has five variant transcripts encoding three isoforms with different N terminals. CUTA isoform2 is encoded by three of the five variant transcripts as the common part of the three isoforms. So CUTA isoform2 was chose as representative to characterize the CUTA protein. We constructed a HeLa cell line stably transfected with the encoding sequence of CUTA isoform2 for further study. The subcellular location and oligomeric structure of the CUTA isoform2 was analyzed in the stable cell lines. It was found that the CUTA isoform2 was mainly located in mitochondria as a new potential mitochondrial protein. Furthermore, CUTA isoform2 formed trimers in cell lysate with the possible occurrence of heteropolymers. These findings would be helpful to the further study on the specific function of CUTA protein.
ESTHER : Yang_2009_Mol.Biol.Rep_36_63
PubMedSearch : Yang_2009_Mol.Biol.Rep_36_63
PubMedID: 17924204