Huang G

References (14)

Title : ABHD15 promotes cell viability, glycolysis, and inhibits apoptosis in cardiomyocytes under hypoxia - Huang_2021_Nutr.Metab.Cardiovasc.Dis_31_681
Author(s) : Huang G , Guo X , Guo J , Zhang P , Liang W , Bai C , Zhang Y
Ref : Nutr Metab Cardiovasc Dis , 31 :681 , 2021
Abstract : BACKGROUND AND AIMS: Myocardial infarction (MI) has been an important heart disease affecting human health. The aim of this study was to investigate the regulatory effect of abhydrolase domain containing 15 (ABHD15) on hypoxic cardiomyocytes. METHODS AND RESULTS: Hypoxic cardiomyocytes are commonly used as an vitro model for the study of MI. We found that cardiomyocyte viability was decreased under hypoxia, but cell glucose uptake, insulin receptor phosphorylation level and apoptosis were increased. Interestingly, ABHD15 expression was up-regulated in hypoxia-induced cardiomyocytes. Then, we identified the function of ABHD15 in hypoxic cardiomyocytes by using ABHD15 overexpression vector or short interfering RNA (siRNA) against ABHD15. The results showed that overexpression of ABHD15 promoted hypoxic cardiomyocyte viability, glucose uptake and IR phosphorylation (p-IR), and inhibited cell apoptosis. However, knockdown of ABHD15 attenuated hypoxic cardiomyocyte viability, glucose uptake and IR phosphorylation, and promoted apoptosis. Moreover, we found that ABHD15 promoted glucose transporter 4 (GLUT4) expression, translocation and enhance rate-limiting enzyme activation of glycolysis, thereby affecting glucose uptake. Furthermore, our study suggested that ABHD15 may affect the viability and apoptosis of hypoxic cardiomyocytes through IR/Ras/Raf/ERK/MEK and IR/PI3K/AKT/Bcl2/Bad/caspase9 signaling pathways, respectively. When the phosphorylation of IR, Raf or ERK was blocked by inhibitors, the protective effect of overexpressing ABHD15 on the viability of hypoxic cardiomyocytes was eliminated. Furthermore, inhibiting the phosphorylation of IR, AKT or Bcl2 abolished the inhibitory effect of overexpressing ABHD15 on hypoxic cardiomyocyte apoptosis. CONCLUSION: ABHD15 regulated myocardial cell viability, glycolysis, and apoptosis under hypoxia, providing a novel potential therapeutic strategy for MI.
ESTHER : Huang_2021_Nutr.Metab.Cardiovasc.Dis_31_681
PubMedSearch : Huang_2021_Nutr.Metab.Cardiovasc.Dis_31_681
PubMedID: 33257193

Title : The biological activities of butyrylcholinesterase inhibitors - Zhou_2021_Biomed.Pharmacother_146_112556
Author(s) : Zhou S , Huang G
Ref : Biomed Pharmacother , 146 :112556 , 2021
Abstract : Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
ESTHER : Zhou_2021_Biomed.Pharmacother_146_112556
PubMedSearch : Zhou_2021_Biomed.Pharmacother_146_112556
PubMedID: 34953393

Title : Synthesis and biological activities of butyrylcholinesterase inhibitors - Zhou_2021_Chem.Biol.Drug.Des__
Author(s) : Zhou S , Huang G
Ref : Chemical Biology Drug Des , : , 2021
Abstract : Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
ESTHER : Zhou_2021_Chem.Biol.Drug.Des__
PubMedSearch : Zhou_2021_Chem.Biol.Drug.Des__
PubMedID: 34942058

Title : Synthesis and activities of acetylcholinesterase inhibitors - Zhou_2021_Chem.Biol.Drug.Des_98_997
Author(s) : Zhou S , Huang G
Ref : Chemical Biology Drug Des , 98 :997 , 2021
Abstract : Cholinesterase (ChE) inhibitors can be divided into two categories: acetylcholinesterase (AChE) inhibitors and butylcholinesterase (BuChE) inhibitors. Therefore, the development of selective inhibition of AChE and BuChE activities is the central content of ChE pharmacochemistry research. In order to clarify the progress of AChE inhibitor-based design, synthesis, and activity studies, we reviewed the pharmacochemical and pharmacological properties of selective AChE inhibitors over the past decade. We hope that this review will make it easier for readers to understand the development of new drug chemistry methods for AChE inhibitors in order to develop more effective and selective AChE inhibitors.
ESTHER : Zhou_2021_Chem.Biol.Drug.Des_98_997
PubMedSearch : Zhou_2021_Chem.Biol.Drug.Des_98_997
PubMedID: 34570966

Title : Nose-to-brain delivery of drug nanocrystals by using Ca(2+) responsive deacetylated gellan gum based in situ-nanogel - Huang_2020_Int.J.Pharm__120182
Author(s) : Huang G , Xie J , Shuai S , Wei S , Chen Y , Guan Z , Zheng Q , Yue P , Wang C
Ref : Int J Pharm , :120182 , 2020
Abstract : The objective of this study is to use a carbohydrate polymer deacetylated gellan gum (DGG) as matrix to design nanocrystals based intranasal in situ gel (IG) for nose-to -brain delivery of drug. The harmine nanocrystals (HAR-NC) as model drug were prepared by coupling homogenization and spray-drying technology. The HAR-NC was redispersed in the(DGG)solutions and formed the ionic-triggered harmine nanocrystals based in situ gel(HAR-NC-IG). The crystal state of HAR remained unchanged during the homogenization and spray-drying. And the HAR-NC-IG with 0.5% DGG exhibited excellent in situ-gelation ability, water retention property and in vitro release behavior. The bioavailability in brain of intranasal HAR-NC-IG were 25-fold higher than that of oral HAR-NC, which could be attributed to nanosizing effect of HAR-NC and bioadhesive property of DGG triggered by nasal fluid. And the HAR-NC-IG could significantly inhibit the expression of acetylcholinesterase (AchE) and increase the content of acetylcholin (ACh) in brain compared with those of reference formulations (p <0.01). The DGG based nanocrystals-in situ gel was a promising carrier for nose-to-brain delivery of poorly soluble drug, which could prolong the residence time and improve the bioavailability of poorly soluble drugs in brain.
ESTHER : Huang_2020_Int.J.Pharm__120182
PubMedSearch : Huang_2020_Int.J.Pharm__120182
PubMedID: 33346126

Title : Autotransporter domain-dependent enzymatic analysis of a novel extremely thermostable carboxylesterase with high biodegradability towards pyrethroid pesticides - Cai_2017_Sci.Rep_7_3461
Author(s) : Cai X , Wang W , Lin L , He D , Huang G , Shen Y , Wei W , Wei D
Ref : Sci Rep , 7 :3461 , 2017
Abstract : The EstPS1 gene, which encodes a novel carboxylesterase of Pseudomonas synxantha PS1 isolated from oil well-produced water, was cloned and sequenced. EstPS1 has an open reading frame of 1923 bp and encodes the 640-amino acid carboxylesterase (EstPS1), which contains an autotransporter (AT) domain (357-640 amino acids). Homology analysis revealed that EstPS1 shared the highest identity (88%) with EstA from Pseudomonas fluorescens A506 (NCBI database) and belonged to the carboxylesterase family (EC 3.1.1.1). The optimum pH and temperature of recombinant EstPS1 were found to be 8.0 and 60 degrees C, respectively. EstPS1 showed high thermostability, and the half-lives (T1/2 thermal inactivation) at 60, 70, 80, 90, and 100 degrees C were 14 h, 2 h, 31 min, 10 min, and 1 min, respectively. To understand the role of the AT domain in carboxylesterase, AT domain-truncated carboxylesterase (EstPS1DeltaAT) was generated. EstPS1DeltaAT showed a clearly decreased secretion rate, owing to the AT domain strongly improved secretory expression in the heterogeneous system. EstPS1 degraded various pyrethroid pesticides, and hydrolysis efficiencies were dependent on the pyrethroid molecular structure. EstPS1 degraded all the tested pyrethroid pesticides and hydrolysed the p-nitrophenyl esters of medium-short-chain fatty acids, indicating that EstPS1 is an esterase with broad specificity.
ESTHER : Cai_2017_Sci.Rep_7_3461
PubMedSearch : Cai_2017_Sci.Rep_7_3461
PubMedID: 28615636

Title : The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut - Bertioli_2016_Nat.Genet_48_438
Author(s) : Bertioli DJ , Cannon SB , Froenicke L , Huang G , Farmer AD , Cannon EK , Liu X , Gao D , Clevenger J , Dash S , Ren L , Moretzsohn MC , Shirasawa K , Huang W , Vidigal B , Abernathy B , Chu Y , Niederhuth CE , Umale P , Araujo AC , Kozik A , Kim KD , Burow MD , Varshney RK , Wang X , Zhang X , Barkley N , Guimaraes PM , Isobe S , Guo B , Liao B , Stalker HT , Schmitz RJ , Scheffler BE , Leal-Bertioli SC , Xun X , Jackson SA , Michelmore R , Ozias-Akins P
Ref : Nat Genet , 48 :438 , 2016
Abstract : Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of -2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut.
ESTHER : Bertioli_2016_Nat.Genet_48_438
PubMedSearch : Bertioli_2016_Nat.Genet_48_438
PubMedID: 26901068
Gene_locus related to this paper: aradu-a0a6p4dix2 , aradu-a0a6p4dpj0 , aradu-a0a6p4dix7

Title : Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution - Li_2015_Nat.Biotechnol_33_524
Author(s) : Li F , Fan G , Lu C , Xiao G , Zou C , Kohel RJ , Ma Z , Shang H , Ma X , Wu J , Liang X , Huang G , Percy RG , Liu K , Yang W , Chen W , Du X , Shi C , Yuan Y , Ye W , Liu X , Zhang X , Liu W , Wei H , Wei S , Zhu S , Zhang H , Sun F , Wang X , Liang J , Wang J , He Q , Huang L , Cui J , Song G , Wang K , Xu X , Yu JZ , Zhu Y , Yu S
Ref : Nat Biotechnol , 33 :524 , 2015
Abstract : Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum.
ESTHER : Li_2015_Nat.Biotechnol_33_524
PubMedSearch : Li_2015_Nat.Biotechnol_33_524
PubMedID: 25893780
Gene_locus related to this paper: gosra-a0a0d2rxs2 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , goshi-a0a1u8hr03 , gosra-a0a0d2vdc5 , goshi-a0a1u8ljh5 , gosra-a0a0d2vj24 , goshi-a0a1u8pxd3 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8mt09 , goshi-a0a1u8kis4 , goshi-a0a1u8ibk3 , goshi-a0a1u8ieg2 , goshi-a0a1u8iki6 , goshi-a0a1u8jvp4 , goshi-a0a1u8jw35 , gosra-a0a0d2pzd7 , goshi-a0a1u8ied7

Title : Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with 'inverted' binding mode - Darras_2014_Bioorg.Med.Chem_22_4867
Author(s) : Darras FH , Wehle S , Huang G , Sotriffer CA , Decker M
Ref : Bioorganic & Medicinal Chemistry , 22 :4867 , 2014
Abstract : Selective and nanomolar acetylcholinesterase inhibitors were obtained by connecting tri- and tetracyclic quinazolinones-previously described as moderately active and unselective cholinesterase (ChE) inhibitors-via a hydroxyl group in para position to an anilinic nitrogen with different amines linked via a three carbon atom spacer. These tri- and tetracyclic quinazolinones containing different alicyclic ring sizes and connected to tertiary amines were docked to a high-resolution hAChE crystal structure to investigate the preferred binding mode in relation to results obtained by experimental structure-activity relationships. While the 'classical orientation' locating the heterocycle in the active site was rarely found, an alternative binding mode with the basic aliphatic amine in the active center ('inverted' orientation) was obtained for most compounds. Analyses of extended SARs based on this inverted binding mode are able to explain the compounds' binding affinities at AChE.
ESTHER : Darras_2014_Bioorg.Med.Chem_22_4867
PubMedSearch : Darras_2014_Bioorg.Med.Chem_22_4867
PubMedID: 25047936

Title : Identification of a neuroprotective and selective butyrylcholinesterase inhibitor derived from the natural alkaloid evodiamine - Huang_2014_Eur.J.Med.Chem_81C_15
Author(s) : Huang G , Kling B , Darras FH , Heilmann J , Decker M
Ref : Eur Journal of Medicinal Chemistry , 81C :15 , 2014
Abstract : Two sets of carbamates based on the natural alkaloid evodiamine were designed, synthesized and evaluated as potential butyrylcholinesterase inhibitors. Although a set of carbamates of 3-hydroxyevodiamine (10a-f) is inactive both at AChE and BChE, carbamates of 5-deoxo-3-hydroxyevodiamine (11a-f) exhibit much better potency with selectivity toward BChE. The heptyl carbamate of 5-deoxo-3-hydroxyevodiamine (11c) shows the best potency with an IC50 value of 77 nM and very good selectivity over AChE. ORAC and cell-based assays indicate 11c owns pronounced antioxidant properties with 1.75 Trolox equivalents and strong neuroprotection even from 1 muM onwards. These combined activities might enable compound 11c to be a potential candidate for treatment of Alzheimer's disease.
ESTHER : Huang_2014_Eur.J.Med.Chem_81C_15
PubMedSearch : Huang_2014_Eur.J.Med.Chem_81C_15
PubMedID: 24819955

Title : Synthesis, Biological Evaluation, and Computational Studies of Tri- and Tetracyclic Nitrogen-Bridgehead Compounds as Potent Dual-Acting AChE Inhibitors and hH3 Receptor Antagonists - Darras_2014_ACS.Chem.Neurosci_5_225
Author(s) : Darras FH , Pockes S , Huang G , Wehle S , Strasser A , Wittmann HJ , Nimczick M , Sotriffer CA , Decker M
Ref : ACS Chem Neurosci , 5 :225 , 2014
Abstract : Combination of AChE inhibiting and histamine H3 receptor antagonizing properties in a single molecule might show synergistic effects to improve cognitive deficits in Alzheimer's disease, since both pharmacological actions are able to enhance cholinergic neurotransmission in the cortex. However, whereas AChE inhibitors prevent hydrolysis of acetylcholine also peripherally, histamine H3 antagonists will raise acetylcholine levels mostly in the brain due to predominant occurrence of the receptor in the central nervous system. In this work, we designed and synthesized two novel classes of tri- and tetracyclic nitrogen-bridgehead compounds acting as dual AChE inhibitors and histamine H3 antagonists by combining the nitrogen-bridgehead moiety of novel AChE inhibitors with a second N-basic fragment based on the piperidinylpropoxy pharmacophore with different spacer lengths. Intensive structure-activity relationships (SARs) with regard to both biological targets led to compound 41 which showed balanced affinities as hAChE inhibitor with IC50 = 33.9 nM, and hH3R antagonism with Ki = 76.2 nM with greater than 200-fold selectivity over the other histamine receptor subtypes. Molecular docking studies were performed to explain the potent AChE inhibition of the target compounds and molecular dynamics studies to explain high affinity at the hH3R.
ESTHER : Darras_2014_ACS.Chem.Neurosci_5_225
PubMedSearch : Darras_2014_ACS.Chem.Neurosci_5_225
PubMedID: 24422467

Title : Hepatic lipolysis in broiler chickens with different fat deposition during embryonic development - Zhao_2010_Res.Vet.Sci_88_321
Author(s) : Zhao S , Ma H , Huang G , Zou S
Ref : Res Vet Sci , 88 :321 , 2010
Abstract : The aim of this study was to explore the hepatic lipolysis in broiler chickens with different fat deposition during embryonic development. The mRNA expression of CPT-1 (carmitine palmtoyltransferase-1), PPARalpha (peroxisome proliferator-activated receptor alpha) and LPL (lipoprotein lipase) genes were determined using Real time RT-PCR. The start of incubation was called day 1 (E1) and after hatching called day 1 (H1). On incubation days 9 (E9), 14 (E14) and 19 (E19) as well as at hatching (H1), samples of liver were collected. Blood samples were obtained during days 14 (E14) and 19 (E19) of embryonic development and at hatching. This study showed that serum TG (triglycerol) decreased and TC (total cholesterol) and NEFA (non-estered fatty acid) increased during embryonic development. The expression of CPT-1, PPARalpha and LPL genes exhibited different developmental changes. For example, little LPL gene was expressed at hatching and PPARalpha gene expression peaked before hatching. However, CPT-1 gene exhibited no significance during the embryonic development. Our results showed that expression of these genes in Arbor Acres (AA) broilers was significantly higher than that in San Huang (SH) broilers. Therefore, this study suggested that hepatic lipolysis in broiler chickens exhibited developmental changes during embryogenesis and breed difference which may be one of the factors in the fat deposition difference between fat line and lean line broilers during embryonic development.
ESTHER : Zhao_2010_Res.Vet.Sci_88_321
PubMedSearch : Zhao_2010_Res.Vet.Sci_88_321
PubMedID: 19709700

Title : A DHA14 drug efflux gene from Xanthomonas albilineans confers high-level albicidin antibiotic resistance in Escherichia coli - Bostock_2006_J.Appl.Microbiol_101_151
Author(s) : Bostock JM , Huang G , Hashimi SM , Zhang L , Birch RG
Ref : J Appl Microbiol , 101 :151 , 2006
Abstract : AIMS: Identification of a gene for self-protection from the antibiotic-producing plant pathogen Xanthomonas albilineans, and functional testing by heterologous expression. METHODS AND RESULTS: Albicidin antibiotics and phytotoxins are potent inhibitors of prokaryote DNA replication. A resistance gene (albF) isolated by shotgun cloning from the X. albilineans albicidin-biosynthesis region encodes a protein with typical features of DHA14 drug efflux pumps. Low-level expression of albF in Escherichia coli increased the MIC of albicidin 3000-fold, without affecting tsx-mediated albicidin uptake into the periplasm or resistance to other tested antibiotics. Bioinformatic analysis indicates more similarity to proteins involved in self-protection in polyketide-antibiotic-producing actinomycetes than to multi-drug resistance pumps in other gram-negative bacteria. A complex promoter region may co-regulate albF with genes for hydrolases likely to be involved in albicidin activation or self-protection. CONCLUSIONS: AlbF is the first apparent single-component antibiotic-specific efflux pump from a gram-negative antibiotic producer. It shows extraordinary efficiency as measured by resistance level conferred upon heterologous expression. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of the clinical potential of albicidins as potent bactericidial antibiotics against diverse bacteria has been limited because of low yields in culture. Expression of albF with recently described albicidin-biosynthesis genes may enable large-scale production. Because albicidins are X. albilineans pathogenicity factors, interference with AlbF function is also an opportunity for control of the associated plant disease.
ESTHER : Bostock_2006_J.Appl.Microbiol_101_151
PubMedSearch : Bostock_2006_J.Appl.Microbiol_101_151
PubMedID: 16834602
Gene_locus related to this paper: xanal-q53b17

Title : Abnormal distribution of acetylcholinesterase activity in the hippocampal formation of the dreher mutant mouse - Sekiguchi_1993_Brain.Res_622_203
Author(s) : Sekiguchi M , Nowakowski RS , Shimai K , Huang G , Inoue T , Abe H
Ref : Brain Research , 622 :203 , 1993
Abstract : The distribution of acetylcholinesterase(AChE) in the hippocampal formation of the dreher mutant mouse was studied by comparing homozygous mutant (drsst-J/drsst-J) with littermate control (+/? or +/+). In the control mice, AChE activity was most intense in the inner one-third of the stratum oriens and lacnosum of the hippocampus, and in the inner one-fifth of the molecular layer of the dentate gyrus. In contrast, in homozygous dreher mice, AChE activity in area CA3c of the hippocampus was not restricted to the stratum oriens, and extended upward into the infrapyramidal and suprapyramidal mossy fiber layers, the lower part of the stratum radiatum, the pyramidal cell layer, and downward toward the alveus. In addition, the distribution of AChE activity was modified by accompanying with ectopic pyramidal cells or with disruption of the pyramidal cell layer. AChE activity in the dentate gyrus of the dreher mouse was not confined to the inner one-fifth of the molecular layer. These findings indicated that the cholinergic input to the hippocampal formation is not normal in the dreher mutant mouse. Since the areas of AChE activity correspond to the presence of ectopic pyramidal cells in the dreher mouse, incoming cholinergic fibers may form synapses with these ectopic cells and with the dendrites of normal pyramidal cells that extend into the expanded area of AChE activity.
ESTHER : Sekiguchi_1993_Brain.Res_622_203
PubMedSearch : Sekiguchi_1993_Brain.Res_622_203
PubMedID: 8242357