Yin H

References (22)

Title : Kinetic and thermodynamic-based studies on the interaction mechanism of novel R. roxburghii seed peptides against pancreatic lipase and cholesterol esterase - Yin_2024_Food.Chem_447_139006
Author(s) : Yin H , Zhu J , Zhong Y , Wang D , Deng Y
Ref : Food Chem , 447 :139006 , 2024
Abstract : Pancreatic lipase (PL) and cholesterol esterase (CE) are vital digestive enzymes that regulate lipid digestion. Three bioactive peptides (LFCMH, RIPAGSPF, YFRPR), possessing enzyme inhibitory activities, were identified in the seed proteins of R. roxburghii. It is hypothesized that these peptides could inhibit the activities of these enzymes by binding to their active sites or altering their conformation. The results showed that LFCMH exhibited superior inhibitory activity against these enzymes compared to the other peptides. The inhibition mechanisms of the three peptides were identified as either competitive or mixed, according to inhibition models. Further studies have shown that peptides could bind to the active sites of enzymes, thus affecting their spatial conformation and restricting substrate entry into the active site. Molecular simulation further proved that hydrogen bonds and hydrophobic interactions played a vital role in the binding of peptides to enzymes. This study enriches our understanding of interaction mechanisms of peptides on PL and CE.
ESTHER : Yin_2024_Food.Chem_447_139006
PubMedSearch : Yin_2024_Food.Chem_447_139006
PubMedID: 38492305

Title : A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease - Shan_2024_ACS.Nano__
Author(s) : Shan X , Lu Y , Luo Z , Zhao X , Pang M , Yin H , Guo X , Zhou H , Zhang J , Huang J , Shi Y , Lou J , Luo L , You J
Ref : ACS Nano , : , 2024
Abstract : Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Abeta accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.
ESTHER : Shan_2024_ACS.Nano__
PubMedSearch : Shan_2024_ACS.Nano__
PubMedID: 38517764

Title : Integrated transcriptomics and metabolomics analyses reveal the aerobic biodegradation and molecular mechanisms of 2,3',4,4',5-pentachlorodiphenyl (PCB 118) in Methylorubrum sp. ZY-1 - Wu_2024_Chemosphere__141921
Author(s) : Wu Y , Zhu M , Ouyang X , Qi X , Guo Z , Yuan Y , Dang Z , Yin H
Ref : Chemosphere , :141921 , 2024
Abstract : 2,3',4,4',5-pentachlorodiphenyl (PCB 118), a highly representative PCB congener, has been frequently detected in various environments, garnering much attention across the scientific community. The degradation of highly chlorinated PCBs by aerobic microorganisms is challenging due to their hydrophobicity and persistence. Herein, the biodegradation and adaptation mechanisms of Methylorubrum sp. ZY-1 to PCB 118 were comprehensively investigated using an integrative approach that combined degradation performance, product identification, metabolomic and transcriptomic analyses. The results indicated that the highest degradation efficiency of 0.5 mg L(-1) PCB 118 reached 75.66% after seven days of inoculation when the bacteria dosage was 1.0 g L(-1) at pH 7.0. A total of eleven products were identified during the degradation process, including low chlorinated PCBs, hydroxylated PCBs, and ring-opening products, suggesting that strain ZY-1 degraded PCB 118 through dechlorination, hydroxylation, and ring-opening pathways. Metabolomic analysis demonstrated that the energy supply and redox metabolism of strain ZY-1 was disturbed with exposure to PCB 118. To counteract this environmental stress, strain ZY-1 adjusted both the fatty acid synthesis and purine metabolism. The analysis of transcriptomics disclosed that multiple intracellular and extracellular oxidoreductases (e.g., monooxygenase, alpha/beta hydrolase and cytochrome P450) participated in the degradation of PCB 118. Besides, active efflux of PCB 118 and its degradation intermediates mediated by multiple transporters (e.g., MFS transporter and ABC transporter ATP-binding protein) might enhance bacterial resistance against these substances. These discoveries provided the inaugural insights into the biotransformation of strain ZY-1 to PCB 118 stress, illustrating its potential in the remediation of contaminated environments.
ESTHER : Wu_2024_Chemosphere__141921
PubMedSearch : Wu_2024_Chemosphere__141921
PubMedID: 38588902
Gene_locus related to this paper: meted-c7c8u4 , meted-c7cge7 , meted-c7ci36

Title : Dissecting the HGT network of carbon metabolic genes in soil-borne microbiota - Li_2023_Front.Microbiol_14_1173748
Author(s) : Li L , Liu Y , Xiao Q , Xiao Z , Meng D , Yang Z , Deng W , Yin H , Liu Z
Ref : Front Microbiol , 14 :1173748 , 2023
Abstract : The microbiota inhabiting soil plays a significant role in essential life-supporting element cycles. Here, we investigated the occurrence of horizontal gene transfer (HGT) and established the HGT network of carbon metabolic genes in 764 soil-borne microbiota genomes. Our study sheds light on the crucial role of HGT components in microbiological diversification that could have far-reaching implications in understanding how these microbial communities adapt to changing environments, ultimately impacting agricultural practices. In the overall HGT network of carbon metabolic genes in soil-borne microbiota, a total of 6,770 nodes and 3,812 edges are present. Among these nodes, phyla Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes are predominant. Regarding specific classes, Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Bacteroidia, Actinomycetia, Betaproteobacteria, and Clostridia are dominant. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional assignments of glycosyltransferase (18.5%), glycolysis/gluconeogenesis (8.8%), carbohydrate-related transporter (7.9%), fatty acid biosynthesis (6.5%), benzoate degradation (3.1%) and butanoate metabolism (3.0%) are primarily identified. Glycosyltransferase involved in cell wall biosynthesis, glycosylation, and primary/secondary metabolism (with 363 HGT entries), ranks first overwhelmingly in the list of most frequently identified carbon metabolic HGT enzymes, followed by pimeloyl-ACP methyl ester carboxylesterase, alcohol dehydrogenase, and 3-oxoacyl-ACP reductase. Such HGT events mainly occur in the peripheral functions of the carbon metabolic pathway instead of the core section. The inter-microbe HGT genetic traits in soil-borne microbiota genetic sequences that we recognized, as well as their involvement in the metabolism and regulation processes of carbon organic, suggest a pervasive and substantial effect of HGT on the evolution of microbes.
ESTHER : Li_2023_Front.Microbiol_14_1173748
PubMedSearch : Li_2023_Front.Microbiol_14_1173748
PubMedID: 37485539

Title : RNAi Mediated Gene Silencing of Detoxification Related Genes in the Ectropis oblique - Peng_2022_Genes.(Basel)_13_
Author(s) : Peng C , Yin H , Liu Y , Mao XF , Liu ZY
Ref : Genes (Basel) , 13 : , 2022
Abstract : Ectropis oblique is one of the main pests that feed on tea leaves. At present, the main control method is chemical control, but the long-term use of insecticides has been related to the development of insect resistance. One of the resistance mechanisms is the upregulation of relevant detoxification enzymes for defense. In this study, four genes with increased expression were screened from the gene sequences annotated from the transcriptome data of deltamethrin-treated larvae of E. oblique, which are acid phosphatase EoACP138, and cytochrome P450 EoCYP316, carboxylesterase EoCarE592 and acetylcholine esterase EoAchE989, respectively. The fourth instar larvae of E. oblique were stimulated by deltamethrin, chlorpyrifos and fenpropathrin respectively, and the expression levels of the genes were detected by qRT-PCR. The result showed that all four genes' expression had significantly increased under the stimulation of three insecticides. RNAi technology was used to silence the expression of genes of EoACP138, EoCYP316, EoCarE592 and EoAchE989 in the fourth instar larvae of E. oblique. The change in the expression levels of the above genes in the larvae treated with dsRNA and stimulated with pesticides was determined by qRT-PCR. The target genes have been effectively silenced after feeding on dsRNA and higher sensitivity with higher mortality to pesticides was observed in the larvae interfered with dsRNA. The above genes are related to the detoxification and metabolism of resistance of E. oblique, which lays a foundation for further study on the mechanism of insecticide resistance in E. oblique.
ESTHER : Peng_2022_Genes.(Basel)_13_
PubMedSearch : Peng_2022_Genes.(Basel)_13_
PubMedID: 35885924

Title : Modulation of oxidative stress and gut microbiota by selenium-containing peptides from Cardamine enshiensis and structural-based characterization - Zhang_2022_Food.Chem_395_133547
Author(s) : Zhang X , Jia L , He H , Yin H , Ming J , Hou T , Xiang J
Ref : Food Chem , 395 :133547 , 2022
Abstract : The antioxidant properties of Se-containing peptides from Cardamine enshiensis (SeCPPs) and their impact on gut microbiota were studied in d-galactose (d-gal)- injected mice and antibiotic-treated mice. The structures of SeCPPs were identified by UPLC-Q-Extractive Orbitrap MS. In d-gal ageing mice, SeCPPs were associated with significantly decreased acetyl cholinesterase (AchE) activity, malondialdehyde (MDA) content, increased glutathione peroxidase (GSH-Px) activity, downregulated tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) levels (p < 0.05), and improved memory. In antibiotic-treated mice, SeCPPs were associated with reduced Proteobacteria and evaluated Akkermansia abundances (p < 0.01). Eighty-five Se-containing peptides were identified in SeCPPs. Peptides such as RV-SeM-I, RA-SeM-T and R-SeC-K showed low binding energy with 1,1-diphenyl-2-picrylhydrazyl (DPPH), and their binding affinities were confirmed by molecular docking. Overall, compared with Na(2)SeO(3) and SeMet, SeCPPs showed superior antioxidant activity via their association with higher antioxidant enzyme activity, scavenging free radical properties and gut microbiome modulation.
ESTHER : Zhang_2022_Food.Chem_395_133547
PubMedSearch : Zhang_2022_Food.Chem_395_133547
PubMedID: 35780669

Title : Adipose triglyceride lipase promotes the proliferation of colorectal cancer cells via enhancing the lipolytic pathway - Yin_2021_J.Cell.Mol.Med__
Author(s) : Yin H , Li W , Mo L , Deng S , Lin W , Ma C , Luo Z , Luo C , Hong H
Ref : J Cell Mol Med , : , 2021
Abstract : Abnormal lipid metabolism is the sign of tumour cells. Previous researches have revealed that the lipolytic pathway may contribute to the progression of colorectal cancer (CRC). However, adipose triglyceride lipase (ATGL) role in CRC cells remains unclear. Here, we find that elevated ATGL positively correlates with CRC clinical stages and negatively associates with overall survival. Overexpression of ATGL significantly promotes CRC cell proliferation, while knockdown of ATGL inhibits the proliferation and promotes the apoptosis of CRC cells in vitro. Moreover, in vivo experiments, ATGL promotes the growth of CRC cells. Mechanistically, ATGL enhances the carcinogenic function of CRC cells via promoting sphingolipid metabolism and CoA biosynthesis pathway-related gene levels by degrading triglycerides, which provides adequate nutrition for the progression of CRC. Our researches clarify for the first time that ATGL is a novel oncogene in CRC and may provide an important prognostic factor and therapeutic target for CRC.
ESTHER : Yin_2021_J.Cell.Mol.Med__
PubMedSearch : Yin_2021_J.Cell.Mol.Med__
PubMedID: 33621408

Title : DNA damage, immunotoxicity, and neurotoxicity induced by deltamethrin on the freshwater crayfish, Procambarus clarkii - Hong_2020_Environ.Toxicol__
Author(s) : Hong Y , Huang Y , Yan G , Yin H , Huang Z
Ref : Environ Toxicol , : , 2020
Abstract : Pyrethroid pesticides are applied to both agricultural and aquacultural industries for pest control. However, information of their impact on the commercial important freshwater crayfish, Procambarus clarkii is scarce. Therefore, the present study aimed to characterize to effects of a commonly used pyrethroid pesticide, deltamethrin on DNA damage, immune response, and neurotoxicity in P. clarkii. Animals were exposed to 7, 14, and 28 ng/L of deltamethrin, which correspond to 1/8, 1/4, and 1/2 of the LC(50) (96 hours) of this pyrethroid to P. clarkii. Significant increase of olive tail moment (OTM) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was found after deltamethrin exposure in a dose-dependent way. Total hemocyte counts (THC) and activities of immune-related enzymes including acid phosphatase (ACP), lysozyme (LZM), and phenoloxidase (PO) were all decreased and significantly lower than control at concentration of 28 ng/L after 96 hours exposure. Acetylcholinesterase (AChE) activity, an indicator of neurotoxic effect was investigated and it was decreased significantly in muscles at 14 and 28 ng/L after 24 hours exposure. The level of intracellular reactive oxygen species (ROS) in hemocytes was also measured and the significant increase of ROS was found at 14 and 28 ng/L concentrations. The results revealed that deltamethrin induced DNA damage, immunotoxicity, and neurotoxicity in P. clarkii by excessive generation of ROS. Because of the dose-dependent responses of all parameters under exposure of deltamethrin at environmentally realistic concentrations, these parameters could be used as sensitive biomarkers for risk assessment of deltamethrin in aquaculture area.
ESTHER : Hong_2020_Environ.Toxicol__
PubMedSearch : Hong_2020_Environ.Toxicol__
PubMedID: 32757256

Title : Novel chromanone-dithiocarbamate hybrids as multifunctional AChE inhibitors with beta-amyloid anti-aggregation properties for the treatment of Alzheimer's disease - Jiang_2019_Bioorg.Chem_89_103027
Author(s) : Jiang N , Ding J , Liu J , Sun X , Zhang Z , Mo Z , Li X , Yin H , Tang W , Xie SS
Ref : Bioorg Chem , 89 :103027 , 2019
Abstract : By connecting chromanone with dithiocarbamate moieties through flexible linkers, a series of hybrids as novel multifunctional AChE inhibitors have been designed and synthesized. Most of these compounds displayed strong and excellently selective inhibition to eeAChE as well as potent inhibition to self- and AChE-induced Abeta aggregation. Among them, compound 6c showed the best activity to inhibit eeAChE (IC50=0.10muM) and AChE-induced Abeta aggregation (33.02% at 100muM), and could effectively inhibit self-induced Abeta aggregation (38.25% at 25muM). Kinetic analysis and docking study indicated that compound 6c could target both the CAS and PAS, suggesting that it was a dual binding site inhibitor for AChE. Besides, it exhibited good ability to penetrate the BBB and low neurotoxicity in SH-SY5Y cells. More importantly, compound 6c was well tolerated in mice (2500mg/kg, po) and could attenuate the memory impairment in a scopolamine-induced mouse model. Overall, these results highlight 6c as a promising multifunctional agent for treating AD and also demonstrate that the dithiocarbamate is a valid scaffold for design of multifunctional AChE inhibitors.
ESTHER : Jiang_2019_Bioorg.Chem_89_103027
PubMedSearch : Jiang_2019_Bioorg.Chem_89_103027
PubMedID: 31176237

Title : Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation - Yin_2018_Int.J.Mol.Med_41_649
Author(s) : Yin J , Liang Y , Wang D , Yan Z , Yin H , Wu D , Su Q
Ref : Int J Mol Med , 41 :649 , 2018
Abstract : Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.
ESTHER : Yin_2018_Int.J.Mol.Med_41_649
PubMedSearch : Yin_2018_Int.J.Mol.Med_41_649
PubMedID: 29207043

Title : Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester - Hui_2018_Drug.Deliv.Transl.Res_8_787
Author(s) : Hui A , Yin H , Zhang Z , Zhou A , Chen J , Yang L , Wu Z , Zhang W
Ref : Drug Deliv Transl Res , 8 :787 , 2018
Abstract : Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.
ESTHER : Hui_2018_Drug.Deliv.Transl.Res_8_787
PubMedSearch : Hui_2018_Drug.Deliv.Transl.Res_8_787
PubMedID: 29524164

Title : Assessment of the inhibitory effects of pyrethroids against human carboxylesterases - Lei_2017_Toxicol.Appl.Pharmacol_321_48
Author(s) : Lei W , Wang DD , Dou TY , Hou J , Feng L , Yin H , Luo Q , Sun J , Ge GB , Yang L
Ref : Toxicol Appl Pharmacol , 321 :48 , 2017
Abstract : Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibition towards CES1. The IC50 values of deltamethrin against CES1-mediated BMBT, DME, and DMCB hydrolysis were determined as 1.58muM, 2.39muM, and 3.3muM, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation. The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1.
ESTHER : Lei_2017_Toxicol.Appl.Pharmacol_321_48
PubMedSearch : Lei_2017_Toxicol.Appl.Pharmacol_321_48
PubMedID: 28242322

Title : Effects of caffeic acid on learning deficits in a model of Alzheimer's disease - Wang_2016_Int.J.Mol.Med_38_869
Author(s) : Wang Y , Li J , Hua L , Han B , Zhang Y , Yang X , Zeng Z , Bai H , Yin H , Lou J
Ref : Int J Mol Med , 38 :869 , 2016
Abstract : Caffeic acid is a type of phenolic acid and organic acid. It is found in food (such as tomatoes, carrots, strawberries, blueberries and wheat), beverages (such as wine, tea, coffee and apple juice) as well as Chinese herbal medicines. In the present study, we examined the effects of caffeic acid on learning deficits in a rat model of Alzheimer's disease (AD). The rats were randomly divided into three groups: i) control group, ii) AD model group and iii) caffeic acid group. Caffeic acid significantly rescued learning deficits and increased cognitive function in the rats with AD as demonstrated by the Morris water maze task. Furthermore, caffeic acid administration resulted in a significant decrease in acetylcholinesterase activity and nitrite generation in the rats with AD compared with the AD model group. Furthermore, caffeic acid suppressed oxidative stress, inflammation, nuclear factorkappaBp65 protein expression and caspase3 activity as well as regulating the protein expression of p53 and phosphorylated (p-)p38 MAPK expression in the rats with AD. These experimental results indicate that the beneficial effects of caffeic acid on learning deficits in a model of AD were due to the suppression of oxidative stress and inflammation through the p38 MAPK signaling pathway.
ESTHER : Wang_2016_Int.J.Mol.Med_38_869
PubMedSearch : Wang_2016_Int.J.Mol.Med_38_869
PubMedID: 27430591

Title : Poster: Development and validation of an alpha3beta4 nicotinic acetylcholine receptor (nAChR) high-throughput screening- (HTS-) ready assay -
Author(s) : Whiteaker P , Kassner M , Eaton JB , Petit J , Meurice N , Yin H
Ref : Biochemical Pharmacology , 97 :622 , 2015

Title : Association of and with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls - Ji_2015_Exp.Ther.Med_9_1831
Author(s) : Ji H , Dai D , Wang Y , Jiang D , Zhou X , Lin P , Ji X , Li J , Zhang Y , Yin H , Chen R , Zhang L , Xu M , Duan S , Wang Q
Ref : Exp Ther Med , 9 :1831 , 2015
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with beta-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date.
ESTHER : Ji_2015_Exp.Ther.Med_9_1831
PubMedSearch : Ji_2015_Exp.Ther.Med_9_1831
PubMedID: 26136901

Title : Rectal biopsy in children with Down syndrome and chronic constipation: Hirschsprung disease vs non-hirschsprung disease - Yin_2012_Pediatr.Dev.Pathol_15_87
Author(s) : Yin H , Boyd T , Pacheco MC , Schonfeld D , Bove KE
Ref : Pediatr Dev Pathol , 15 :87 , 2012
Abstract : Hirschsprung disease (HD) is reported in patients with Down syndrome with a frequency between 2% and 10%. The incidence of HD is 2% in our community-based registry that contains >700 patients with Down syndrome. We reviewed rectal biopsy findings in 32 of these patients who had suction rectal biopsy performed between 1980 and 2009 to investigate the cause of chronic constipation. We confirmed that 15 patients had diagnostic histologic and histochemical features of HD. More challenging were findings in 5 of 17 patients, in whom ganglia coexisted with equivocal acetylcholinesterase reaction patterns and/or hypertrophic submucosal nerves. In this retrospective study, we were able to resolve most of these discrepant findings by demonstrating normal calretinin-positive nerve twigs in the lamina propria and muscularis mucosae. The clinical significance of these unexpected findings in suction rectal biopsy specimens that did not satisfy strict criteria for a tissue diagnosis of HD is unknown. We speculate that a minority of these patients have transition zone morphology or an incomplete/atypical form of HD. Further investigations may help resolve discrepancies that arise when suction rectal biopsy is used to investigate chronic constipation in Down syndrome.
ESTHER : Yin_2012_Pediatr.Dev.Pathol_15_87
PubMedSearch : Yin_2012_Pediatr.Dev.Pathol_15_87
PubMedID: 21991983

Title : Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M(1) receptor function in the central nervous system - Lebois_2010_ACS.Chem.Neurosci_1_104
Author(s) : LeBois EP , Bridges TM , Lewis LM , Dawson ES , Kane AS , Xiang Z , Jadhav SB , Yin H , Kennedy JP , Meiler J , Niswender CM , Jones CK , Conn PJ , Weaver CD , Lindsley CW
Ref : ACS Chem Neurosci , 1 :104 , 2010
Abstract : Cholinergic transmission in the forebrain is mediated primarily by five subtypes of muscarinic acetylcholine receptors (mAChRs), termed M(1)-M(5). Of the mAChR subtypes, M(1) is among the most heavily expressed in regions that are critical for learning and memory, and has been viewed as the most critical mAChR subtype for memory and attention mechanisms. Unfortunately, it has been difficult to develop selective activators of M(1) and other individual mAChR subtypes, which has prevented detailed studies of the functional roles of selective activation of M(1). Using a functional HTS screen and subsequent diversity-oriented synthesis approach we have discovered a novel series of highly selective M(1) allosteric agonists. These compounds activate M(1) with EC(50) values in the 150 nM to 500 nM range and have unprecedented, clean ancillary pharmacology (no substantial activity at 10muM across a large panel of targets). Targeted mutagenesis revealed a potentially novel allosteric binding site in the third extracellular loop of the M(1) receptor for these allosteric agonists. Optimized compounds, such as VU0357017, provide excellent brain exposure after systemic dosing and have robust in vivo efficacy in reversing scopolamine-induced deficits in a rodent model of contextual fear conditioning. This series of selective M(1) allosteric agonists provides critical research tools to allow dissection of M(1)-mediated effects in the CNS and potential leads for novel treatments for Alzheimer's disease and schizophrenia.
ESTHER : Lebois_2010_ACS.Chem.Neurosci_1_104
PubMedSearch : Lebois_2010_ACS.Chem.Neurosci_1_104
PubMedID: 21961051

Title : Absorption, metabolism, and excretion of [14C]vildagliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans - He_2009_Drug.Metab.Dispos_37_536
Author(s) : He H , Tran P , Yin H , Smith H , Batard Y , Wang L , Einolf H , Gu H , Mangold JB , Fischer V , Howard D
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 37 :536 , 2009
Abstract : The absorption, metabolism, and excretion of (1-[[3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine (vildagliptin), an orally active and highly selective dipeptidyl peptidase 4 inhibitor developed for the treatment of type 2 diabetes, were evaluated in four healthy male subjects after a single p.o. 100-mg dose of [(14)C]vildagliptin. Serial blood and complete urine and feces were collected for 168 h postdose. Vildagliptin was rapidly absorbed, and peak plasma concentrations were attained at 1.1 h postdose. The fraction of drug absorbed was calculated to be at least 85.4%. Unchanged drug and a carboxylic acid metabolite (M20.7) were the major circulating components in plasma, accounting for 25.7% (vildagliptin) and 55% (M20.7) of total plasma radioactivity area under the curve. The terminal half-life of vildagliptin was 2.8 h. Complete recovery of the dose was achieved within 7 days, with 85.4% recovered in urine (22.6% unchanged drug) and the remainder in feces (4.54% unchanged drug). Vildagliptin was extensively metabolized via at least four pathways before excretion, with the major metabolite M20.7 resulting from cyano group hydrolysis, which is not mediated by cytochrome P450 (P450) enzymes. Minor metabolites resulted from amide bond hydrolysis (M15.3), glucuronidation (M20.2), or oxidation on the pyrrolidine moiety of vildagliptin (M20.9 and M21.6). The diverse metabolic pathways combined with a lack of significant P450 metabolism (1.6% of the dose) make vildagliptin less susceptible to potential pharmacokinetic interactions with comedications of P450 inhibitors/inducers. Furthermore, as vildagliptin is not a P450 inhibitor, it is unlikely that vildagliptin would affect the metabolic clearance of comedications metabolized by P450 enzymes.
ESTHER : He_2009_Drug.Metab.Dispos_37_536
PubMedSearch : He_2009_Drug.Metab.Dispos_37_536
PubMedID: 19074975

Title : Disposition of vildagliptin, a novel dipeptidyl peptidase 4 inhibitor, in rats and dogs - He_2009_Drug.Metab.Dispos_37_545
Author(s) : He H , Tran P , Yin H , Smith H , Flood D , Kramp R , Filipeck R , Fischer V , Howard D
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 37 :545 , 2009
Abstract : The pharmacokinetics, absorption, metabolism, and excretion of vildagliptin, a potent and orally active inhibitor of dipeptidyl peptidase 4, were evaluated in male rats and dogs. Vildagliptin was rapidly absorbed with peak plasma concentrations occurring between 0.5 and 1.5 h. Moderate to high bioavailability was observed in both species (45-100%). The distribution and elimination half-lives of vildagliptin were short: 0.57 h [82% of area under the plasma drug concentration-time curve (AUC)] and 8.8 h in the rat and 0.05 and 0.89 h (87% of AUC) in the dog, respectively. The volume of distribution was 1.6 and 8.6 l/kg in dogs and rats, respectively, indicating moderate to high tissue distribution. The plasma clearance of vildagliptin was relatively high for the rat (2.9 l/h/kg) and dog (1.3 l/h/kg) compared with their hepatic blood flow. The major circulating components in plasma after an intravenous or oral dose were the parent compound (rat and dog), a carboxylic acid metabolite from the hydrolysis of the amide bond M15.3 (dog), and a carboxylic acid metabolite from the hydrolysis of the cyano moiety M20.7 (rat and dog). After intravenous dosing, urinary excretion of radioactivity (47.6-72.4%) was the major route of elimination for rats and dogs as 18.9 to 21.3% of the dose was excreted into urine as unchanged parent drug. The recovery was good in both species (81-100% of the dose). Vildagliptin was mainly metabolized before excretion in both species. Similar to plasma, the most predominant metabolite in excreta was M20.7 in rats and dogs, and another major metabolite in dogs was M15.3.
ESTHER : He_2009_Drug.Metab.Dispos_37_545
PubMedSearch : He_2009_Drug.Metab.Dispos_37_545
PubMedID: 19074976

Title : Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats - Brady_2008_J.Pharmacol.Exp.Ther_327_941
Author(s) : Brady AE , Jones CK , Bridges TM , Kennedy JP , Thompson AD , Heiman JU , Breininger ML , Gentry PR , Yin H , Jadhav SB , Shirey JK , Conn PJ , Lindsley CW
Ref : Journal of Pharmacology & Experimental Therapeutics , 327 :941 , 2008
Abstract : Previous clinical and animal studies suggest that selective activators of M(1) and/or M(4) muscarinic acetylcholine receptors (mAChRs) have potential as novel therapeutic agents for treatment of schizophrenia and Alzheimer's disease. However, highly selective centrally penetrant activators of either M(1) or M(4) have not been available, making it impossible to determine the in vivo effects of selective activation of these receptors. We previously identified VU10010 [3-amino-N-(4-chlorobenzyl)-4, 6-dimethylthieno[2,3-b]pyridine-2-carboxamide] as a potent and selective allosteric potentiator of M(4) mAChRs. However, unfavorable physiochemical properties prevented use of this compound for in vivo studies. We now report that chemical optimization of VU10010 has afforded two centrally penetrant analogs, VU0152099 [3-amino-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4,6-dimethylthieno[2,3-b]pyridine carboxamide] and VU0152100 [3-amino-N-(4-methoxybenzyl)-4,6-dimethylthieno[2,3-b]pyridine carboxamide], that are potent and selective positive allosteric modulators of M(4). VU0152099 and VU0152100 had no agonist activity but potentiated responses of M(4) to acetylcholine. Both compounds were devoid of activity at other mAChR subtypes or at a panel of other GPCRs. The improved physiochemical properties of VU0152099 and VU0152100 allowed in vivo dosing and evaluation of behavioral effects in rats. Interestingly, these selective allosteric potentiators of M(4) reverse amphetamine-induced hyperlocomotion in rats, a model that is sensitive to known antipsychotic agents and to nonselective mAChR agonists. This is consistent with the hypothesis that M(4) plays an important role in regulating midbrain dopaminergic activity and raises the possibility that positive allosteric modulation of M(4) may mimic some of the antipsychotic-like effects of less selective mAChR agonists.
ESTHER : Brady_2008_J.Pharmacol.Exp.Ther_327_941
PubMedSearch : Brady_2008_J.Pharmacol.Exp.Ther_327_941
PubMedID: 18772318

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1

Title : Slow-binding inhibition of carboxylesterase and other serine hydrolases by chlorodifluoroacetaldehyde - Yin_1993_Chem.Res.Toxicol_6_630
Author(s) : Yin H , Jones JP , Anders MW
Ref : Chemical Research in Toxicology , 6 :630 , 1993
Abstract : The chlorofluorocarbon substitute 1,2-dichloro-1,1-difluoroethane (HCFC-132b) undergoes oxidative metabolism in rats to give a range of metabolites, including chlorodifluoroacetaldehyde [Harris and Anders (1991) Chem. Res. Toxicol. 4, 180]. The present experiments were undertaken after studies to characterize an unidentified metabolite of HCFC-132b revealed that chlorodifluoroacetaldehyde was toxic in vivo: rats given chlorodifluoroacetaldehyde died showing signs of cholinergic stimulation. Because some fluoroketones are known inhibitors of hydrolases, including acetylcholinesterase, the inhibitory effects of chlorodifluoroacetaldehyde on acetylcholinesterase (electric eel and human erythrocyte), on pseudocholinesterase (horse serum), on carboxylesterase (pig liver), and on alpha-chymotrypsin (bovine pancreas) were studied. In aqueous solution, the ratio chlorodifluoroacetaldehyde:chlorodifluroacetaldehyde hydrate, as determined by 1H nuclear magnetic resonance spectroscopy, was 1:157. Chlorodifluoroacetaldehyde was a slow-binding inhibitor of both acetylcholinesterases, of pseudocholinesterase, and of carboxylesterase; the Ki values, corrected for the aldehyde:hydrate ratio, were 150 nM, 1.7 nM, 3.7 nM, and 23 pM, respectively, as determined by final velocity of the progress curves; the kon values were 9.1 x 10(4), 1.1 x 10(5), 3.2 x 10(4), and 9.2 x 10(5) M-1 min-1, respectively. Chlorodifluoroacetaldehyde did not inhibit alpha-chymotrypsin. Acetaldehyde and trichloroacetaldehyde were classical competitive inhibitors of acetylcholinesterase. These results show that hydrochlorofluorocarbon metabolites may exert significant biological effects.
ESTHER : Yin_1993_Chem.Res.Toxicol_6_630
PubMedSearch : Yin_1993_Chem.Res.Toxicol_6_630
PubMedID: 8292740