Huang M

References (34)

Title : Construction of Virtual Compound Library and Screening of Acetylcholinesterase Inhibitor for the Medicinal Chemistry Laboratory - Yang_2024_J.Chem.Educ_101_1673
Author(s) : Yang J , Yuan Y , Wang N , Liu X , Gu J , Zeng R , Huang M , Zheng P , Wang Y , Huang C , Ouyang Q
Ref : Journal of Chemical Education , 101 :1673 , 2024
Abstract : The utilization of virtual compound libraries and virtual screening has become a routine method in drug discovery and has accelerated the research of pharmacy and translational medicine. With the development of computer-aided drug design (CADD), it is essential to incorporate virtual experiments into the education of medicinal chemistry. Herein, we describe a series of virtual experiments conducted by undergraduate students, including the construction of a virtual compound library, molecular docking, and the virtual screening of acetylcholinesterase inhibitors. Student feedback indicates that the virtual experiments are popular with students and effectively promote their interest in the drug discovery process.
ESTHER : Yang_2024_J.Chem.Educ_101_1673
PubMedSearch : Yang_2024_J.Chem.Educ_101_1673

Title : Collagen derived Gly-Pro-type DPP-IV inhibitory peptides: Structure-activity relationship, inhibition kinetics and inhibition mechanism - Xu_2024_Food.Chem_441_138370
Author(s) : Xu Q , Zheng L , Huang M , Zhao M
Ref : Food Chem , 441 :138370 , 2024
Abstract : Our previous study has demonstrated that both the amino acid at N3 position and peptide length affected the DPP-IV inhibitory activity of Gly-Pro-type peptides. To further elucidate their molecular mechanism, a combined approach of QSAR modeling, enzymatic kinetics and molecular docking was used. Results showed that the QSAR models of Gly-Pro-type tripeptides and Gly-Pro-type peptides containing 3-12 residues were successfully constructed by 5z-scale descriptor with R(2) of 0.830 and 0.797, respectively. The lower values of electrophilicity, polarity, and side-chain bulk of amino acid at N3 position caused higher DPP-IV inhibitory activity of Gly-Pro-type peptides. Moreover, an appropriate increase in the length of Gly-Pro-type peptides did not change their competitive inhibition mode, but decreased their inhibition constants (K(i) values) and increased interactions with DPP-IV. More importantly, the interactions between the residues at C-terminal of Gly-Pro-type peptides containing 5 - 6 residues with S2 extensive subsites (Ser209, Phe357, Arg358) of DPP-IV increased the interactions of Gly residue at N1 position with the S2 subsites (Glu205, Glu206, Asn710, Arg125, Tyr662) and decreased the acylation level of DPP-IV-peptide complex, and thereby increasing peptides' DPP-IV inhibitory activity.
ESTHER : Xu_2024_Food.Chem_441_138370
PubMedSearch : Xu_2024_Food.Chem_441_138370
PubMedID: 38199113

Title : ACE2-using merbecoviruses: Further evidence of convergent evolution of ACE2 recognition by NeoCoV and other MERS-CoV related viruses - Xiong_2024_Cell.Insight_3_100145
Author(s) : Xiong Q , Ma C , Liu C , Tong F , Huang M , Yan H
Ref : Cell Insight , 3 :100145 , 2024
Abstract : Angiotensin-converting enzyme 2 (ACE2) was recognized as an entry receptor shared by coronaviruses from Sarbecovirus and Setracovirus subgenera, including three human coronaviruses: SARS-CoV, SARS-CoV-2, and NL63. We recently disclosed that NeoCoV and three other merbecoviruses (PDF-2180, MOW15-22, PnNL 2018B), which are MERS-CoV relatives found in African and European bats, also utilize ACE2 as their functional receptors through unique receptor binding mechanisms. This unexpected receptor usage assumes significance, particularly in light of the prior recognition of Dipeptidyl peptidase-4 (DPP4) as the only known protein receptor for merbecoviruses. In contrast to other ACE2-using coronaviruses, NeoCoV and PDF-2180 engage a distinct and relatively compact binding surface on ACE2, facilitated by protein-glycan interactions, which is demonstrated by the Cryo-EM structures of the receptor binding domains (RBDs) of these viruses in complex with a bat ACE2 orthologue. These findings further support the hypothesis that phylogenetically distant coronaviruses, characterized by distinct RBD structures, can independently evolve to acquire ACE2 affinity during inter-species transmission and adaptive evolution. To date, these viruses have exhibited limited efficiency in entering human cells, although single mutations like T510F in NeoCoV can overcome the incompatibility with human ACE2. In this review, we present a comprehensive overview of ACE2-using merbecoviruses, summarize our current knowledge regarding receptor usage and host tropism determination, and deliberate on potential strategies for prevention and intervention, with the goal of mitigating potential future outbreaks caused by spillover of these viruses.
ESTHER : Xiong_2024_Cell.Insight_3_100145
PubMedSearch : Xiong_2024_Cell.Insight_3_100145
PubMedID: 38476250

Title : Myclobutanil induces neurotoxicity by activating autophagy and apoptosis in zebrafish larvae (Danio rerio) - Zhu_2024_Chemosphere__142027
Author(s) : Zhu J , Huang M , Jiang P , Wang J , Zhu R , Liu C
Ref : Chemosphere , :142027 , 2024
Abstract : Myclobutanil (MYC), a typical broad-spectrum triazole fungicide, is often detected in surface water. This study aimed to explore the neurotoxicity of MYC and the underlying mechanisms in zebrafish and in PC12 cells. In this study, zebrafish embryos were exposed to 0, 0.5 and 1 mg/L of MYC from 4 to 96 hours post fertilization (hpf) and neurobehavior was evaluated. Our data showed that MYC decreased the survival rate, hatching rate and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal neurobehaviors characterized by decreased swimming distance and movement time. MYC impaired cerebral histopathological morphology and inhibited neurogenesis in HuC:egfp transgenic zebrafish. MYC also reduced the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and downregulated neurodevelopment related genes (gfap, syn2a, gap43 and mbp) in zebrafish and PC12 cells. Besides, MYC activated autophagy through enhanced expression of the LC3-II protein and suppressed expression of the p62 protein and autophagosome formation, subsequently triggering apoptosis by upregulating apoptotic genes (p53, bax, bcl-2 and caspase 3) and the cleaved caspase-3 protein in zebrafish and PC12 cells. These processes were restored by the autophagy inhibitor 3-methyladenine (3-MA) both in vivo and in vitro, indicating that MYC induces neurotoxicity by activating autophagy and apoptosis. Overall, this study revealed the potential autophagy and apoptosis mechanisms of MYC-induced neurotoxicity and provided novel strategies to counteract its toxicity.
ESTHER : Zhu_2024_Chemosphere__142027
PubMedSearch : Zhu_2024_Chemosphere__142027
PubMedID: 38621487

Title : Neuroprotection of macamide in a mouse model of Alzheimer's disease involves Nrf2 signaling pathway and gut microbiota - Xia_2024_Eur.J.Pharmacol_975_176638
Author(s) : Xia N , Xu L , Huang M , Xu D , Li Y , Wu H , Mei Z , Yu Z
Ref : European Journal of Pharmacology , 975 :176638 , 2024
Abstract : The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique ingredients in maca. Improvement effects and mechanisms of macamide on cognitive impairment have not been revealed. In this study, Vina 1.1.2 was used for docking to evaluate the binding abilities of 12 main macamides to acetylcholinesterase (AChE). N-benzyl-(9Z,12Z)-octadecadienamide (M 18:2) was selected to study the following experiments because it can stably bind to AChE with a strong binding energy. The animal experiments showed that M 18:2 prevented the scopolamine (SCP)-induced cognitive impairment and neurotransmitter disorders, increased the positive rates of Nrf2 and HO-1 in hippocampal CA1, improved the synaptic plasticity by maintaining synaptic morphology and increasing the synapse density. Moreover, the contents of IL-1beta, IL-6, and TNF-alpha in the hippocampus, serum, and colon were reduced by M 18:2. Furthermore, M 18:2 promoted colonic epithelial integrity and partially restored the composition of the gut microbiota to normal, including decreased genera Clostridiales_unclassified and Lachnospiraceae_unclassified, as well as increased genera Muribaculaceae_unclassified, Muribaculum, Alistipes, and Bacteroides, which may be the possible biomarkers of cognitive aging. In summary, M 18:2 exerted neuroprotective effects on SCP-induced AD mice possibly via activating the Nrf2/HO-1 signaling pathway and modulating the gut microbiota.
ESTHER : Xia_2024_Eur.J.Pharmacol_975_176638
PubMedSearch : Xia_2024_Eur.J.Pharmacol_975_176638
PubMedID: 38734297

Title : How Closely Does Induced Agarwood's Biological Activity Resemble That of Wild Agarwood? - Ma_2023_Molecules_28_
Author(s) : Ma S , Huang M , Fu Y , Qiao M , Li Y
Ref : Molecules , 28 : , 2023
Abstract : Continuous innovation in artificially-induced agarwood technology is increasing the amount of agarwood and substantially alleviating shortages. Agarwood is widely utilized in perfumes and fragrances; however, it is unclear whether the overall pharmacological activity of induced agarwood can replace wild agarwood for medicinal use. In this study, the volatile components, total chromone content, and the differences in the overall activities of wild agarwood and induced agarwood, including the antioxidant, anti-acetylcholinesterase, and anti-glucosidase activity were all determined. The results indicated that both induced and wild agarwood's chemical makeup contains sesquiterpenes and 2-(2-phenylethyl)chromones. The total chromone content in generated agarwood can reach 82.96% of that in wild agarwood. Induced agarwood scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+)) radicals and inhibited acetylcholinesterase activity and alpha-glucosidase activity with IC(50) values of 0.1873 mg/mL, 0.0602 mg/mL, 0.0493 mg/mL, and 0.2119 mg/mL, respectively, reaching 80.89%, 93.52%, 93.52%, and 69.47% of that of wild agarwood, respectively. Accordingly, the results distinguished that induced agarwood has the potential to replace wild agarwood in future for use in medicine because it has a similar chemical makeup to wild agarwood and has comparable antioxidant, anti-acetylcholinesterase, and anti-glucosidase capabilities.
ESTHER : Ma_2023_Molecules_28_
PubMedSearch : Ma_2023_Molecules_28_
PubMedID: 37049682

Title : Curcumin protects against fenvalerate-induced neurotoxicity in zebrafish (Danio rerio) larvae through inhibition of oxidative stress - Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
Author(s) : Zhu J , Huang M , Liu C , Wang J , Zou L , Yang F , Zhu R
Ref : Ecotoxicology & Environmental Safety , 264 :115484 , 2023
Abstract : Fenvalerate (FEN), a typical type II pyrethroid pesticide, is widely used in agriculture. FEN has been detected in the environment and human body. However, the neurotoxicity of FEN has not been well elucidated. This study aimed to explore the mechanisms underlying FEN-induced neurotoxicity using the zebrafish (Danio rerio) model. We also investigated whether curcumin (CUR), a polyphenol antioxidant that exhibits neuroprotective properties, can prevent FEN-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 3.5, 7 and 14 microg/L of FEN from 4 to 96 h post fertilization (hpf) and neurotoxicity was assessed. Our results showed that FEN decreased the survival rate, heart rate, body length and spontaneous movement, and increased malformation rate. FEN caused neurobehavioral alterations, including decreased swimming distance and velocity, movement time and clockwise rotation times. FEN also suppressed neurogenesis in transgenic HuC:egfp zebrafish, reduced cholinesterase activity and downregulated the expression of neurodevelopment related genes (elavl3, gfap, gap43 and mbp). In addition, FEN enhanced oxidative stress via excessive reactive oxygen species and antioxidant enzyme inhibition, then triggered apoptosis by upregulation of apoptotic genes (p53, bcl-2, bax and caspase 3). These adverse outcomes were alleviated by CUR, indicating that CUR mitigated FEN-induced neurotoxicity by inhibiting oxidative stress. Overall, this study revealed that CUR ameliorated FEN-induced neurotoxicity via its antioxidant, indicating a promising protection of CUR against environmental pollutant-induced developmental anomalies.
ESTHER : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedSearch : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedID: 37716069

Title : ATG14 plays a critical role in hepatic lipid droplet homeostasis - Huang_2023_Metabolism_148_155693
Author(s) : Huang M , Zhang Y , Park J , Chowdhury K , Xu J , Lu A , Wang L , Zhang W , Ekser B , Yu L , Dong XC
Ref : Metabolism , 148 :155693 , 2023
Abstract : BACKGROUND & AIMS: Autophagy-related 14 (ATG14) is a key regulator of autophagy. ATG14 is also localized to lipid droplet; however, the function of ATG14 on lipid droplet remains unclear. In this study, we aimed to elucidate the role of ATG14 in lipid droplet homeostasis. METHODS: ATG14 loss-of-function and gain-of-function in lipid droplet metabolism were analyzed by fluorescence imaging in ATG14 knockdown or overexpression hepatocytes. Specific domains involved in the ATG14 targeting to lipid droplets were analyzed by deletion or site-specific mutagenesis. ATG14-interacting proteins were analyzed by co-immunoprecipitation. The effect of ATG14 on lipolysis was analyzed in human hepatocytes and mouse livers that were deficient in ATG14, comparative gene identification-58 (CGI-58), or both. RESULTS: Our data show that ATG14 is enriched on lipid droplets in hepatocytes. Mutagenesis analysis reveals that the Barkor/ATG14 autophagosome targeting sequence (BATS) domain of ATG14 is responsible for the ATG14 localization to lipid droplets. Co-immunoprecipitation analysis illustrates that ATG14 interacts with adipose triglyceride lipase (ATGL) and CGI-58. Moreover, ATG14 also enhances the interaction between ATGL and CGI-58. In vitro lipolysis analysis demonstrates that ATG14 deficiency remarkably decreases triglyceride hydrolysis. CONCLUSIONS: Our data suggest that ATG14 can directly enhance lipid droplet breakdown through interactions with ATGL and CGI-58.
ESTHER : Huang_2023_Metabolism_148_155693
PubMedSearch : Huang_2023_Metabolism_148_155693
PubMedID: 37741434
Gene_locus related to this paper: human-ABHD5

Title : Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target - Xu_2022_PLoS.Pathog_18_e1010615
Author(s) : Xu Y , Yang J , Li W , Song S , Shi Y , Wu L , Sun J , Hou M , Wang J , Jia X , Zhang H , Huang M , Lu T , Gan J , Feng Y
Ref : PLoS Pathog , 18 :e1010615 , 2022
Abstract : Tuberculosis (TB) is one of the leading infectious diseases of global concern, and one quarter of the world's population are TB carriers. Biotin metabolism appears to be an attractive anti-TB drug target. However, the first-stage of mycobacterial biotin synthesis is fragmentarily understood. Here we report that three evolutionarily-distinct BioH isoenzymes (BioH1 to BioH3) are programmed in biotin synthesis of Mycobacterium smegmatis. Expression of an individual bioH isoform is sufficient to allow the growth of an Escherichia coli deltabioH mutant on the non-permissive condition lacking biotin. The enzymatic activity in vitro combined with biotin bioassay in vivo reveals that BioH2 and BioH3 are capable of removing methyl moiety from pimeloyl-ACP methyl ester to give pimeloyl-ACP, a cognate precursor for biotin synthesis. In particular, we determine the crystal structure of dimeric BioH3 at 2.27A, featuring a unique lid domain. Apart from its catalytic triad, we also dissect the substrate recognition of BioH3 by pimeloyl-ACP methyl ester. The removal of triple bioH isoforms (deltabioH1/2/3) renders M. smegmatis biotin auxotrophic. Along with the newly-identified Tam/BioC, the discovery of three unusual BioH isoforms defines an atypical 'BioC-BioH(3)' paradigm for the first-stage of mycobacterial biotin synthesis. This study solves a long-standing puzzle in mycobacterial nutritional immunity, providing an alternative anti-TB drug target.
ESTHER : Xu_2022_PLoS.Pathog_18_e1010615
PubMedSearch : Xu_2022_PLoS.Pathog_18_e1010615
PubMedID: 35816546
Gene_locus related to this paper: mycs2-a0r6y0

Title : Chain-locked precursor ion scanning based HPLC-MS\/MS for in-depth molecular analysis of lipase-catalyzed transesterification of structured phospholipids containing w-3 fatty acyl chains - Zhang_2022_Food.Chem_399_133982
Author(s) : Zhang M , Wang P , Jin D , Jian S , Wu J , Huang M , Xie H , Zhao Q , Yang H , Luo P , Yuan H , Xue J , Shen Q
Ref : Food Chem , 399 :133982 , 2022
Abstract : Lipase-catalyzed transesterification of structured phospholipids (sPLs) is a hot topic, but the structural variation of the fatty acyl chains in intact phospholipids at the molecular level remains unclear to date. The present study explored the detailed characteristics of synthesized phospholipids through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in precursor ion scan mode. The optimal conditions were in-depth inspected and determined for the reaction system, including phospholipase A1 as catalyst, 15% lipase loading, and 1% water content. The sPLs enriched with EPA/DHA were structurally and quantitatively characterized by focusing on the fragments of m/z 301.6 (eicosapentaenoic acid, EPA) and m/z 327.6 (docosahexaenoic acid, DHA), and the results were statistically analyzed using partial least squares discriminant analysis and clustered heatmap hierarchical clustering analysis. PC 38:6 (18:1/20:5), PC 38:7 (18:2/20:5), PC o-40:6 (o-18:0/22:6), and PE 40:8 (18:2/22:6) etc. were revealed as the main variables that were active in the reaction.
ESTHER : Zhang_2022_Food.Chem_399_133982
PubMedSearch : Zhang_2022_Food.Chem_399_133982
PubMedID: 36027811

Title : Serum levels of IL-12, IL-18, and IL-21 are indicators of viral load in patients chronically infected with HBV - Zhou_2022_Braz.J.Med.Biol.Res_55_e12320
Author(s) : Zhou F , Xiong H , Zhen S , Chen A , Huang M , Luo Y
Ref : Brazilian Journal of Medical & Biological Research , 55 :e12320 , 2022
Abstract : This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.
ESTHER : Zhou_2022_Braz.J.Med.Biol.Res_55_e12320
PubMedSearch : Zhou_2022_Braz.J.Med.Biol.Res_55_e12320
PubMedID: 36383803

Title : Identification, characterization and mRNA transcript abundance profiles of the carboxylesterase (CXE5) gene in Eriocheir sinensis suggest that it may play a role in methyl farnesoate degradation - Li_2021_Comp.Biochem.Physiol.B.Biochem.Mol.Biol__110630
Author(s) : Li X , Chen T , Xu R , Huang M , Huang J , Xie Q , Liu F , Su S , Ma K
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , :110630 , 2021
Abstract : The sesquiterpenoid methyl farnesoate (MF) is a de-epoxidized form of insect juvenile hormone (JH) III in crustaceans, and its precise titer plays important roles in regulating many critical physiological processes, including reproduction and ovarian maturation. Understanding the synthetic and degradation pathways of MF is equally important for determining how to maintain MF titers at appropriate levels and thus for potential applications in crab aquaculture. Although the synthetic pathway of MF has been well established, little is known about MF degradation. Previous research proposed that specific carboxylesterases (CXEs) that degrade MF in crustaceans are conserved from those of JH III. In this study, we identified a novel Es-CXE5 gene from Eriocheir sinensis. The Es-CXE5 protein contains some conserved motifs, including catalytic triad and oxyanion hole, which are characteristics of the biologically active CXE family. The phylogenetic analysis showed that Es-CXE5 belongs to the hormone/semiochemical processing group of the CXE family. Moreover, Tissue and stage-specific expression results suggested that Es-CXE5 expression in hepatopancreas was highest and associated with the hemolymph MF titer. Furthermore, Es-CXE5 mRNA transcripts were detected in both in vitro and in vivo experiments and ESA experiment in the hepatopancreas and ovary. The results of this study showed that Es-CXE5 mRNA abundance in the hepatopancreas was notably induced by MF addition but had no effect on the ovary. Taken together, our results suggest that Es-CXE5 may degrade MF in the hepatopancreas and may thus be involved in ovarian development in E. sinensis.
ESTHER : Li_2021_Comp.Biochem.Physiol.B.Biochem.Mol.Biol__110630
PubMedSearch : Li_2021_Comp.Biochem.Physiol.B.Biochem.Mol.Biol__110630
PubMedID: 34062270
Gene_locus related to this paper: erisi-a0a7d5ly28

Title : Structural and biochemical mechanisms of NLRP1 inhibition by DPP9 - Huang_2021_Nature__
Author(s) : Huang M , Zhang X , Toh GA , Gong Q , Wang J , Han Z , Wu B , Zhong F , Chai J
Ref : Nature , : , 2021
Abstract : Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find domain (FIIND)(1-7). In resting cells, the dipeptidyl peptidases DPP8 and DPP9 interact with the FIIND of NLRP1 and suppress spontaneous NLRP1 activation(8,9); however, the mechanisms through which this occurs remain unknown. Here we present structural and biochemical evidence that full-length rat NLRP1 (rNLRP1) and rat DPP9 (rDPP9) form a 2:1 complex that contains an autoinhibited rNLRP1 molecule and an active UPA-CARD fragment of rNLRP1. The ZU5 domain is required not only for autoinhibition of rNLRP1 but also for assembly of the 2:1 complex. Formation of the complex prevents UPA-mediated higher-order oligomerization of UPA-CARD fragments and strengthens ZU5-mediated NLRP1 autoinhibition. Structure-guided biochemical and functional assays show that both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on the activation of the NLRP1 inflammasome.
ESTHER : Huang_2021_Nature__
PubMedSearch : Huang_2021_Nature__
PubMedID: 33731929
Gene_locus related to this paper: rat-dpp9

Title : Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease - Wang_2020_RSC.Med.Chem_11_225
Author(s) : Wang XB , Yin FC , Huang M , Jiang N , Lan JS , Kong LY
Ref : RSC Med Chem , 11 :225 , 2020
Abstract : A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). In vitro studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for hMAO-B. In particular, compound 5c presented the most balanced potential for ChE inhibition (BuChE: IC(50) = 5.24 microM; AChE: IC(50) = 0.37 microM) and hMAO-B selectivity (IC(50) = 0.272 microM, SI = 247). Molecular modeling and kinetic studies suggested that 5c was a mixed-type inhibitor, binding simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood-brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's disease therapy.
ESTHER : Wang_2020_RSC.Med.Chem_11_225
PubMedSearch : Wang_2020_RSC.Med.Chem_11_225
PubMedID: 33479629

Title : Stereodivergent Protein Engineering of a Lipase To Access All Possible Stereoisomers of Chiral Esters with Two Stereocenters - Xu_2019_J.Am.Chem.Soc_141_7934
Author(s) : Xu J , Cen Y , Singh W , Fan J , Wu L , Lin X , Zhou J , Huang M , Reetz MT , Wu Q
Ref : Journal of the American Chemical Society , 141 :7934 , 2019
Abstract : Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two stereocenters and thus four stereoisomeric products are involved, obtaining stereodivergent enzyme mutants for individually accessing all four stereoisomers would be ideal. Although significant success has been achieved in directed evolution of enzymes in general, stereodivergent engineering of one enzyme into four highly stereocomplementary variants for obtaining the full complement of stereoisomers bearing multiple stereocenters remains a challenge. Using Candida antarctica lipase B (CALB) as a model, we report the protein engineering of this enzyme into four highly stereocomplementary variants needed for obtaining all four stereoisomers in transesterification reactions between racemic acids and racemic alcohols in organic solvents. By generating and screening less than 25 variants of each isomer, we achieved >90% selectivity for all of the four possible stereoisomers in the model reaction. This difficult feat was accomplished by developing a strategy dubbed "focused rational iterative site-specific mutagenesis" (FRISM) at sites lining the enzyme's binding pocket. The accumulation of single mutations by iterative site-specific mutagenesis using a restricted set of rationally chosen amino acids allows the formation of ultrasmall mutant libraries requiring minimal screening for stereoselectivity. The crystal structure of all stereodivergent CALB variants, flanked by MD simulations, uncovered the source of selectivity.
ESTHER : Xu_2019_J.Am.Chem.Soc_141_7934
PubMedSearch : Xu_2019_J.Am.Chem.Soc_141_7934
PubMedID: 31023008
Gene_locus related to this paper: canar-LipB

Title : Artificial cysteine-lipases with high activity and altered catalytic mechanism created by laboratory evolution - Cen_2019_Nat.Commun_10_3198
Author(s) : Cen Y , Singh W , Arkin M , Moody TS , Huang M , Zhou J , Wu Q , Reetz MT
Ref : Nat Commun , 10 :3198 , 2019
Abstract : Engineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring enzymes is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing a Ser --> Cys exchange at the respective catalytic triads, but this generally induced a breakdown of activity. We now report that this long-standing dogma no longer pertains, provided additional mutations are introduced by directed evolution. By employing Candida antarctica lipase B (CALB) as the model enzyme with the Ser-His-Asp catalytic triad, a highly active cysteine-lipase having a Cys-His-Asp catalytic triad and additional mutations W104V/A281Y/A282Y/V149G can be evolved, showing a 40-fold higher catalytic efficiency than wild-type CALB in the hydrolysis of 4-nitrophenyl benzoate, and tolerating bulky substrates. Crystal structures, kinetics, MD simulations and QM/MM calculations reveal dynamic features and explain all results, including the preference of a two-step mechanism involving the zwitterionic pair Cys105(-)/His224(+) rather than a concerted process.
ESTHER : Cen_2019_Nat.Commun_10_3198
PubMedSearch : Cen_2019_Nat.Commun_10_3198
PubMedID: 31324776
Gene_locus related to this paper: canar-LipB

Title : The allosteric dopamine D1 receptor potentiator, DETQ, ameliorates subchronic phencyclidine-induced object recognition memory deficits and enhances cortical acetylcholine efflux in male humanized D1 receptor knock-in mice - Meltzer_2019_Behav.Brain.Res_361_139
Author(s) : Meltzer HY , Rajagopal L , Matrisciano F , Hao J , Svensson KA , Huang M
Ref : Behavioural Brain Research , 361 :139 , 2019
Abstract : Diminished dopamine D1 stimulation may contribute to cognitive impairment in Alzheimer's and Parkinson's diseases, schizophrenia, and other neuropsychiatric disorders. However, orthosteric D1 receptor (D1R) agonists produce receptor desensitization and an inverted U-shaped dose-response curve, but positive allosteric modulators (PAMs) do not. We examined the cognitive effects of DETQ, a D1R PAM, in mice genetically modified to express the human D1 receptor ("hD1 mice"). Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor antagonist, dosed seven days (subchronic), followed by withdrawal, produced a prolonged deficit in novel object recognition (NOR) memory, which was reversed by acute treatment with DETQ, with no evidence for an inverted U-shaped response. This was blocked by the D1R antagonist, SCH391660. Single doses of D1R agonists, SKF38393 and SKF82958, and the acetylcholinesterase inhibitor, rivastigmine, alone and the combination of subeffective doses of both DETQ and rivastigmine, also restored NOR in both subchronic PCP-treated in hD1 mice. DETQ increased cortical and hippocampal acetylcholine efflux after both acute and subchronic dosing in hD1 mice. Subchronic but not acute DETQ, inhibited glutamate and GABA efflux. DETQ-induced acetylcholine efflux was absent in subchronic PCP-treated mice, indicating that restoration of NOR in subchronic PCP-treated mice does not require cortical acetylcholine efflux. This is additional evidence that DETQ stimulates D1R without producing an inverted-U-shaped response curve and increases neurotransmitter release in the mPFC and HIP without causing tolerance. The ability of D1 PAMs to improve cognition in humans with neuropsychiatric disorders without evidence of tolerance or an inverted-U-shaped response curve needs to be established clinically.
ESTHER : Meltzer_2019_Behav.Brain.Res_361_139
PubMedSearch : Meltzer_2019_Behav.Brain.Res_361_139
PubMedID: 30521930

Title : Assessment of phthalate ester residues and distribution patterns in Baijiu raw materials and Baijiu - Dong_2019_Food.Chem_283_508
Author(s) : Dong W , Guo R , Sun X , Li H , Zhao M , Zheng F , Sun J , Huang M , Wu J
Ref : Food Chem , 283 :508 , 2019
Abstract : Phthalate esters (PAEs) are harmful to human health and have been repeatedly identified in Baijiu samples. In our study, the distribution and degradation characteristics of 14 PAEs in Baijiu raw materials (BRMs) and Baijiu during distillation were detected using QuEChERS or vortex-assisted surfactant-enhanced-emulsification liquid-liquid micro-extraction (VSLLME) methods coupled with gas chromatography-mass spectrometry. The same five PAEs were detected in all tested samples, values ranged from 0.003 to 0.292 mg/kg; however, higher concentrations existed in BRMs compared to Baijiu samples. Using multivariate statistical analysis, detailed distinctions between different varieties of Baijiu and BRMs and separation-related PAE markers were revealed. PAEs concentration during Baijiu distillation showed a decreasing trend. The highest concentrations detected in distillate heads, were 1.6-, 2.3-, and 8.1-fold higher than those in heart1, heart2, and tail distillates, respectively. These findings revealed that PAEs may migrate from BRMs; moreover, that PAEs content can be regulated by distillation.
ESTHER : Dong_2019_Food.Chem_283_508
PubMedSearch : Dong_2019_Food.Chem_283_508
PubMedID: 30722905

Title : Phomopsichin A-D\; Four New Chromone Derivatives from Mangrove Endophytic Fungus Phomopsis sp. 33 - Huang_2016_Mar.Drugs_14_
Author(s) : Huang M , Li J , Liu L , Yin S , Wang J , Lin Y
Ref : Mar Drugs , 14 : , 2016
Abstract : Four new chromone derivatives, phomopsichins A-D (1-4), along with a known compound, phomoxanthone A (5), were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated based on comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction or theoretical calculations of electronic circular dichroism (ECD). They feature a tricyclic framework, in which a dihydropyran ring is fused with the chromone ring. Compounds 1-5 showed weak inhibitory activities on acetylcholinesterase as well as alpha-glucosidase, weak radical scavenging effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as OH, and weak antimicrobial activities. Compounds 1-4 showed no cytotoxic activity against MDA-MB-435 breast cancer cells. Their other bioactivities are worthy of further study, considering their unique molecular structures.
ESTHER : Huang_2016_Mar.Drugs_14_
PubMedSearch : Huang_2016_Mar.Drugs_14_
PubMedID: 27879655

Title : Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy - Peng_2016_Acta.Pharmacol.Sin_37_1442
Author(s) : Peng LL , Zhao YQ , Zhou ZY , Jin J , Zhao M , Chen XM , Chen LY , Cai YF , Li JL , Huang M
Ref : Acta Pharmacol Sin , 37 :1442 , 2016
Abstract : AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy.
METHODS: A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit.
RESULTS: Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). CONCLUSION: A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.
ESTHER : Peng_2016_Acta.Pharmacol.Sin_37_1442
PubMedSearch : Peng_2016_Acta.Pharmacol.Sin_37_1442
PubMedID: 27641736

Title : In vivo knockdown of basal forebrain p75 neurotrophin receptor stimulates choline acetyltransferase activity in the mature hippocampus - Barrett_2016_J.Neurosci.Res_94_389
Author(s) : Barrett GL , Naim T , Trieu J , Huang M
Ref : Journal of Neuroscience Research , 94 :389 , 2016
Abstract : This study seeks to determine whether knockdown of basal forebrain p75 neurotrophin receptor (p75(NTR) ) expression elicits increased hippocampal choline acetyltransferase (ChAT) activity in mature animals. Antisense (AS) oligonucleotides (oligos) targeting p75(NTR) were infused into the medial septal area of mature rats continuously for 4 weeks. In all rats, the cannula outlet was placed equidistant between the left and the right sides of the vertical diagonal band of Broca. We tested phosphorothioate (PS), morpholino (Mo), and gapmer (mixed PS/RNA) oligos. Gapmer AS infusions of 7.5 and 22 mug/day decreased septal p75(NTR) mRNA by 34% and 48%, respectively. The same infusions increased hippocampal ChAT activity by 41% and 55%. Increased hippocampal ChAT activity correlated strongly with septal p75(NTR) downregulation in individual rats. Infusions of PS and Mo AS oligos did not downregulate p75(NTR) mRNA or stimulate ChAT activity. These results demonstrate that p75(NTR) can dynamically regulate hippocampal ChAT activity in the mature CNS. They also reveal the different efficacies of three diverse AS oligo chemistries when infused intracerebrally. Among the three types, gapmer oligos worked best. (c) 2016 Wiley Periodicals, Inc.
ESTHER : Barrett_2016_J.Neurosci.Res_94_389
PubMedSearch : Barrett_2016_J.Neurosci.Res_94_389
PubMedID: 26864466

Title : The proto-oncogene c-Src and its downstream signaling pathways are inhibited by the metastasis suppressor, NDRG1 - Liu_2015_Oncotarget_6_8851
Author(s) : Liu W , Yue F , Zheng M , Merlot A , Bae DH , Huang M , Lane D , Jansson P , Lui GY , Richardson V , Sahni S , Kalinowski D , Kovacevic Z , Richardson DR
Ref : Oncotarget , 6 :8851 , 2015
Abstract : N-myc downstream regulated gene-1 (NDRG1) is a potent metastasis suppressor that plays a key role in regulating signaling pathways involved in mediating cancer cell invasion and migration, including those derived from prostate, colon, etc. However, the mechanisms and molecular targets through which NDRG1 reduces cancer cell invasion and migration, leading to inhibition of cancer metastasis, are not fully elucidated. In this investigation, using NDRG1 over-expression models in three tumor cell-types (namely, DU145, PC3MM and HT29) and also NDRG1 silencing in DU145 and HT29 cells, we reveal that NDRG1 decreases phosphorylation of a key proto-oncogene, cellular Src (c-Src), at a well-characterized activating site (Tyr416). NDRG1-mediated down-regulation of EGFR expression and activation were responsible for the decreased phosphorylation of c-Src (Tyr416). Indeed, NDRG1 prevented recruitment of c-Src to EGFR and c-Src activation. Moreover, NDRG1 suppressed Rac1 activity by modulating phosphorylation of a c-Src downstream effector, p130Cas, and its association with CrkII, which acts as a "molecular switch" to activate Rac1. NDRG1 also affected another signaling molecule involved in modulating Rac1 signaling, c-Abl, which then inhibited CrkII phosphorylation. Silencing NDRG1 increased cell migration relative to the control and inhibition of c-Src signaling using siRNA, or a pharmacological inhibitor (SU6656), prevented this increase. Hence, the role of NDRG1 in decreasing cell migration is, in part, due to its inhibition of c-Src activation. In addition, novel pharmacological agents, which induce NDRG1 expression and are currently under development as anti-metastatic agents, markedly increase NDRG1 and decrease c-Src activation. This study leads to important insights into the mechanism involved in inhibiting metastasis by NDRG1 and how to target these pathways with novel therapeutics.
ESTHER : Liu_2015_Oncotarget_6_8851
PubMedSearch : Liu_2015_Oncotarget_6_8851
PubMedID: 25860930

Title : Simultaneous production of fatty acid methyl esters and diglycerides by four recombinant Candida rugosa lipase's isozymes - Chang_2014_Food.Chem_155_140
Author(s) : Chang SW , Huang M , Hsieh YH , Luo YT , Wu TT , Tsai CW , Chen CS , Shaw JF
Ref : Food Chem , 155 :140 , 2014
Abstract : In this study, the catalytic efficiency of four recombinant CRL (Candida rugosa lipase) isozymes (LIP1-LIP4) towards the production of fatty acid methyl ester (FAME) was compared and evaluated as an alternative green method for industrial applications. The results indicated that the recombinant C. rugosa LIP1 enzyme exhibited the highest catalytic efficiency for FAME production compared to the recombinant C. rugosa LIP2-LIP4 enzymes. The optimal conditions were as follows: pH 7.0, methanol/soybean oil molar ratio: 3/1, enzyme amount: 2U (1.6muL), reaction temperature: 20 degrees C, 22h of reaction time, and 3 times of methanol addition (1mol/6h), and resulted in 61.5+/-1.5wt.% of FAME conversion. The reaction product contained also 10wt.% of DAG with a ratio of 1,3-DAG to 1,2-DAG of approximately 4:6, and can be potentially used in industrial applications as a food emulsifier.
ESTHER : Chang_2014_Food.Chem_155_140
PubMedSearch : Chang_2014_Food.Chem_155_140
PubMedID: 24594166

Title : The novel alpha7 nicotinic acetylcholine receptor agonist EVP-6124 enhances dopamine, acetylcholine, and glutamate efflux in rat cortex and nucleus accumbens - Huang_2014_Psychopharmacology.(Berl)_231_4541
Author(s) : Huang M , Felix AR , Flood DG , Bhuvaneswaran C , Hilt D , Koenig G , Meltzer HY
Ref : Psychopharmacology (Berl) , 231 :4541 , 2014
Abstract : BACKGROUND: Alpha7 and alpha4beta2 nicotinic acetylcholine receptor (nAChR) agonists have been shown to improve cognition in various animal models of cognitive impairment and are of interest as treatments for schizophrenia, Alzheimer's disease, and other cognitive disorders. Increased release of dopamine (DA), acetylcholine (ACh), glutamate (Glu), and gamma-aminobutyric acid (GABA) in cerebral cortex, hippocampus, and nucleus accumbens (NAC) has been suggested to contribute to their beneficial effects on cognition.
RESULTS: Using in vivo microdialysis, we found that EVP-6124 [(R)-7-chloro-N-quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide], a high-affinity alpha7 nAChR partial agonist, at 0.1 mg/kg, s.c., increased DA efflux in the medial prefrontal cortex (mPFC) and NAC. EVP-6124, 0.1 and 0.3 mg/kg, also increased efflux of ACh in the mPFC but not in the NAC. Similarly, EVP-6124, 0.1 mg/kg, but not 0.03 and 0.3 mg/kg, significantly increased mPFC Glu efflux. Thus, EVP-6124 produced an inverted U-shaped curve for DA and Glu release, as previously reported for other alpha7 nAChR agonists. The three doses of EVP-6124 did not produce a significant effect on GABA efflux in either region. Pretreatment with the selective alpha7 nAChR antagonist, methyllycaconitine (MLA, 1.0 mg/kg), significantly blocked cortical DA and Glu efflux induced by EVP-6124 (0.1 mg/kg), suggesting that the effects of EVP-6124 on these neurotransmitters were due to alpha7 nAChR agonism. MLA only partially blocked the effects of EVP-6124 on ACh efflux in the mPFC. CONCLUSION: These results suggest increased cortical DA, ACh, and Glu release, which may contribute to the ability of the alpha7 nAChR agonist, EVP-6124, to treat cognitive impairment and possibly other dimensions of psychopathology.
ESTHER : Huang_2014_Psychopharmacology.(Berl)_231_4541
PubMedSearch : Huang_2014_Psychopharmacology.(Berl)_231_4541
PubMedID: 24810107

Title : The alpha-7 nicotinic receptor partial agonist\/5-HT3 antagonist RG3487 enhances cortical and hippocampal dopamine and acetylcholine release - Huang_2014_Psychopharmacology.(Berl)_231_2199
Author(s) : Huang M , Felix AR , Kwon S , Lowe D , Wallace T , Santarelli L , Meltzer HY
Ref : Psychopharmacology (Berl) , 231 :2199 , 2014
Abstract : RATIONALE: Alpha-7 nicotinic acetylcholine receptor (nAChR) agonists may ameliorate cognitive deficits in schizophrenia, in part, because of their ability to enhance dopaminergic and cholinergic neurotransmission. OBJECTIVES: In the current study, the effects of partial nAChR agonist and 5-HT3 receptor antagonist RG3487 (previously R3487/MEM3454) on dopamine (DA) and acetylcholine (ACh) effluxes in rat prefrontal cortex (mPFC) and hippocampus (HIP) were investigated in awake, freely moving rats.
RESULTS: R3487/MEM3454, at doses of 0.1-10 mg/kg, s.c., enhanced DA and ACh effluxes in rat mPFC and (HIP), with a peak effect at 0.3- to 0.6-mg/kg doses, producing a bell-shaped dose-response curve. Pretreatment with the selective nAChR antagonist, methyllycaconitine (1.0 mg/kg), completely blocked RG3487-induced (0.45 mg/kg) DA but not ACh efflux, while the selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (1.0 mg/kg) partially inhibited cortical ACh but not DA efflux. RG3487 (0.45 mg/kg) combined with atypical antipsychotic drug (APD) risperidone (0.1 mg/kg), but not typical APD haloperidol (0.1 mg/kg), induced a significantly greater increase in HIP ACh efflux. Their combined effect on DA efflux was additive. RG3487, combined with other atypical APDs, namely aripiprazole (0.3 mg/kg), olanzapine (1.0 mg/kg), and quetiapine (30 mg/kg), also produced additive effects on DA efflux.
CONCLUSIONS: These results suggest that RG3487 enhances DA efflux by nAChR stimulation, whereas ACh efflux is primarily mediated via 5-HT3 receptor antagonism, and that RG3487 alone or as augmentation may improve cognitive impairment in schizophrenia.
ESTHER : Huang_2014_Psychopharmacology.(Berl)_231_2199
PubMedSearch : Huang_2014_Psychopharmacology.(Berl)_231_2199
PubMedID: 24317442

Title : Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization - Xie_2012_Eur.J.Med.Chem_52_205
Author(s) : Xie H , Zeng L , Zeng S , Lu X , Zhang G , Zhao X , Cheng N , Tu Z , Li Z , Xu H , Yang L , Zhang X , Huang M , Zhao J , Hu W
Ref : Eur Journal of Medicinal Chemistry , 52 :205 , 2012
Abstract : We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.
ESTHER : Xie_2012_Eur.J.Med.Chem_52_205
PubMedSearch : Xie_2012_Eur.J.Med.Chem_52_205
PubMedID: 22475866

Title : Chrysin attenuates allergic airway inflammation by modulating the transcription factors T-bet and GATA-3 in mice - Du_2012_Mol.Med.Rep_6_100
Author(s) : Du Q , Gu X , Cai J , Huang M , Su M
Ref : Mol Med Rep , 6 :100 , 2012
Abstract : Chrysin, a flavonoid obtained from various natural sources, has been reported to possess anti-inflammatory, antitumor, antioxidant and anti-allergic activities. However, its anti-inflammatory and immunoregulatory activities in asthma animal models are poorly understood. In the present study, we examined the effects of chrysin on airway inflammation and the possible mechanisms through which it acts in a murine model of allergic asthma. BALB/c mice sensitized and challenged to ovalbumin (OVA) were administered intragastrically with chrysin at a dose of 50 mg/kg daily. Chrysin significantly suppressed OVA-induced airway hyperresponsiveness (AHR) to acetylcholine chloride (Ach). Chrysin administration significantly inhibited the total inflammatory cell and eosinophil counts in bronchoalveolar lavage fluid (BALF) and total immunoglobulin E (IgE) levels in serum. Histological examination of lung tissue demonstrated that chrysin significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. In addition, chrysin triggered a switch of the immune response to allergens towards a T-helper type 1 (Th1) profile by modulating the transcription factors T-bet and GATA-3 in allergic mice. These data suggest that chrysin exhibits anti-inflammatory and immunoregulatory properties and provides new insights into the immunopharmacological role of chrysin in terms of its effects in a murine model of asthma.
ESTHER : Du_2012_Mol.Med.Rep_6_100
PubMedSearch : Du_2012_Mol.Med.Rep_6_100
PubMedID: 22552848

Title : Complete genome sequences of Mycobacterium tuberculosis strains CCDC5079 and CCDC5080, which belong to the Beijing family - Zhang_2011_J.Bacteriol_193_5591
Author(s) : Zhang Y , Chen C , Liu J , Deng H , Pan A , Zhang L , Zhao X , Huang M , Lu B , Dong H , Du P , Chen W , Wan K
Ref : Journal of Bacteriology , 193 :5591 , 2011
Abstract : Mycobacterium tuberculosis is one of most prevalent pathogens in the world. Drug-resistant strains of this pathogen caused by the excessive use of antibiotics have long posed serious threats to public health worldwide. A broader picture of drug resistance mechanisms at the genomic level can be obtained only with large-scale comparative genomic methodology. Two closely related Beijing family isolates, one resistant to four first-line drugs (CCDC5180) and one sensitive to them (CCDC5079), were completely sequenced. These sequences will serve as valuable references for further drug resistance site identification studies and could be of great importance for developing drugs targeting these sites.
ESTHER : Zhang_2011_J.Bacteriol_193_5591
PubMedSearch : Zhang_2011_J.Bacteriol_193_5591
PubMedID: 21914894
Gene_locus related to this paper: myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-Rv0160c , myctu-Rv1069c , myctu-RV1215C , myctu-Rv2045c , myctu-RV3452 , myctu-RV3724 , myctu-Rv3802c , myctu-y0571

Title : Poster: The alpha-7 receptor agonist EVP-6124 increases dopamine and glutamate efflux in rat medial prefrontal cortex and nucleus accumbens -
Author(s) : Huang M , Felix AR , Bhuvaneswaran C , Hilt D , Konig G , Meltzer HY
Ref : Biochemical Pharmacology , 82 :1040 , 2011

Title : Crystal structure of a triacylglycerol lipase from Penicillium expansum at 1.3 A determined by sulfur SAD -
Author(s) : Bian C , Yuan C , Chen L , Meehan EJ , Jiang L , Huang Z , Lin L , Huang M
Ref : Proteins , 78 :1601 , 2010
PubMedID: 20146362
Gene_locus related to this paper: penex-Q9HFW6

Title : The neurotensin analog NT69L enhances medial prefrontal cortical dopamine and acetylcholine efflux: potentiation of risperidone-, but not haloperidol-, induced dopamine efflux - Prus_2007_Brain.Res_1184_354
Author(s) : Prus AJ , Huang M , Li Z , Dai J , Meltzer HY
Ref : Brain Research , 1184 :354 , 2007
Abstract : NT69L is a novel neurotensin (8-13) analog that produces atypical antipsychotic-like effects in animal models. Because atypical antipsychotic drugs increase dopamine (DA) and acetylcholine (ACh) efflux in the medial prefrontal cortex and DA efflux in the nucleus accumbens, the present study sought to further evaluate the putative antipsychotic-like effects of NT69L by assessing DA and ACh efflux in these regions. Dual probe microdialysis was conducted in awake freely moving male rats, without using an acetylcholinesterase inhibitor in the perfusion medium. NT69L (1.0 and 3.0 mg/kg) produced significant increases in extracellular DA and ACh efflux in the medial prefrontal cortex. NT69L (1.0 mg/kg, but not 3.0 mg/kg) produced a significant increase of DA, but not ACh, efflux in the nucleus accumbens. Pretreatment with the serotonin (5-HT)(1A) receptor antagonist WAY100635 (0.2 mg/kg) significantly attenuated the 3.0 mg/kg NT69L-induced increase in medial prefrontal cortical DA efflux. Pretreatment with NT69L (1.0 mg/kg) significantly potentiated the effects of the atypical antipsychotic drug risperidone (0.1 mg/kg) on DA, but not ACh, efflux in the medial prefrontal cortex, while pretreatment with NT69L 1.0 mg/kg failed to alter the effects of haloperidol (0.1 mg/kg) on DA or ACh efflux in either region. These findings further suggest that NT analogs may be useful alone or adjunctively for the treatment of schizophrenia.
ESTHER : Prus_2007_Brain.Res_1184_354
PubMedSearch : Prus_2007_Brain.Res_1184_354
PubMedID: 17988654

Title : The alpha1 subunit of nicotinic acetylcholine receptors in the inner ear: transcriptional regulation by ATOH1 and co-expression with the gamma subunit in hair cells - Scheffer_2007_J.Neurochem_103_2651
Author(s) : Scheffer D , Sage C , Plazas PV , Huang M , Wedemeyer C , Zhang DS , Chen ZY , Elgoyhen AB , Corey DP , Pingault V
Ref : Journal of Neurochemistry , 103 :2651 , 2007
Abstract : Acetylcholine is a key neurotransmitter of the inner ear efferent system. In this study, we identify two novel nAChR subunits in the inner ear: alpha1 and gamma, encoded by Chrna1 and Chrng, respectively. In situ hybridization shows that the messages of these two subunits are present in vestibular and cochlear hair cells during early development. Chrna1 and Chrng expression begin at embryonic stage E13.5 in the vestibular system and E17.5 in the organ of Corti. Chrna1 message continues through P7, whereas Chrng is undetectable at post-natal stage P6. The alpha1 and gamma subunits are known as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus oocytes of the alpha1 subunit does not change the electrophysiological properties of the alpha9alpha10 receptor. We suggest that hair cells transiently express alpha1gamma-containing nAChRs in addition to alpha9alpha10, and that these may have a role during development of the inner ear innervation.
ESTHER : Scheffer_2007_J.Neurochem_103_2651
PubMedSearch : Scheffer_2007_J.Neurochem_103_2651
PubMedID: 17961150

Title : Purification and preliminary crystallographic analysis of a Penicillium expansum lipase - Bian_2005_Biochim.Biophys.Acta_1752_99
Author(s) : Bian C , Yuan C , Lin L , Lin J , Shi X , Ye X , Huang Z , Huang M
Ref : Biochimica & Biophysica Acta , 1752 :99 , 2005
Abstract : PF898 is a strain of Penicillium expansum optimized for the high level production of Penicillium expansum lipase (PEL). This PEL is unique compared with other lipases in several aspects, For example, the PEL shows low sequence identities (<30%) to all other known lipases, and high percentage of hydrophobic residues in the N-terminal region. The PEL was purified to homogeneity and shown to be 28 kDa by SDS-PAGE. Crystals suitable for X-ray diffraction analysis were obtained by the sitting-drop method of vapor diffusion with ammonia sulfate as the precipitating agent at 298 K. The crystals have tetragonal lattice and unit-cell parameters of a=b=88.09 A, c=126.54 A. Diffraction data were collected to a resolution of 2.08 A on an in-house rotating-anode generator.
ESTHER : Bian_2005_Biochim.Biophys.Acta_1752_99
PubMedSearch : Bian_2005_Biochim.Biophys.Acta_1752_99
PubMedID: 16112629

Title : Molecular characterization of the Pseudomonas putida 2,3-butanediol catabolic pathway. - Huang_1994_FEMS.Microbiol.Lett_124_141
Author(s) : Huang M , Oppermann FB , Steinbuchel A
Ref : FEMS Microbiology Letters , 124 :141 , 1994
Abstract : The 2,3-butanediol dehydrogenase and the acetoin-cleaving system were simultaneously induced in Pseudomonas putida PpG2 during growth on 2,3-butanediol and on acetoin. Hybridization with a DNA probe covering the genes for the E1 subunits of the Alcaligenes eutrophus acetoin cleaving system and nucleotide sequence analysis identified acoA (975 bp), acoB (1020 bp), apoC (1110 bp), acoX (1053 bp) and adh (1086 bp) in a 6.3-kb genomic region. The amino acid sequences deduced from acoA, acoB, and acoC for E1 alpha (M(r) 34639), E1 beta (M(r) 37268), and E2 (M(r) 39613) of the P. putida acetoin cleaving system exhibited striking similarities to those of the corresponding components of the A. eutrophus acetoin cleaving system and of the acetoin dehydrogenase enzyme system of Pelobacter carbinolicus and other bacteria. Strong sequence similarities of the adh translational product (2,3-butanediol dehydrogenase, M(r) 38361) were obtained to various alcohol dehydrogenases belonging to the zinc- and NAD(P)-dependent long-chain (group I) alcohol dehydrogenases. Expression of the P. putida ADH in Escherichia coli was demonstrated. The aco genes and adh constitute presumably one single operon which encodes all enzymes required for the conversion of 2,3-butanediol to central metabolites.
ESTHER : Huang_1994_FEMS.Microbiol.Lett_124_141
PubMedSearch : Huang_1994_FEMS.Microbiol.Lett_124_141
PubMedID: 7813883
Gene_locus related to this paper: psepu-acoc