He Q

References (22)

Title : Sequence-based design and construction of synthetic nanobody library - Liu_2024_Biotechnol.Bioeng__
Author(s) : Liu C , Li Y , He Q , Fu J , Wei Q , Lin H , Luo Y , Tu Z
Ref : Biotechnol Bioeng , : , 2024
Abstract : Nanobody (Nb), the smallest antibody fragments known to bind antigens, is now widely applied to various studies, including protein structure analysis, bioassay, diagnosis, and biomedicine. The traditional approach to generating specific nanobodies involves animal immunization which is time-consuming and expensive. As the understanding of the antibody repertoire accumulation, the synthetic library, which is devoid of animals, has attracted attention widely in recent years. Here, we describe a synthetic phage display library (S-Library), designed based on the systematic analysis of the next-generation sequencing (NGS) of nanobody repertoire. The library consists of a single highly conserved scaffold (IGHV3S65*01-IGHJ4*01) and complementary determining regions of constrained diversity. The S-Library containing 2.19 x 10(8) independent clones was constructed by the one-step assembly and rapid electro-transformation. The S-Library was screened against various targets (Nb G8, fusion protein of Nb G8 and green fluorescent protein, bovine serum albumin, ovalbumin, and acetylcholinesterase). In comparison, a naive library (N-Library) from the source of 13 healthy animals was constructed and screened against the same targets as the S-Library. Binders were isolated from both S-Library and N-Library. The dynamic affinity was evaluated by the biolayer interferometry. The data confirms that the feature of the Nb repertoire is conducive to reducing the complexity of library design, thus allowing the S-Library to be built on conventional reagents and primers.
ESTHER : Liu_2024_Biotechnol.Bioeng__
PubMedSearch : Liu_2024_Biotechnol.Bioeng__
PubMedID: 38548653

Title : Mix-and-Read Nanobody-Based Sandwich Homogeneous Split-Luciferase Assay for the Rapid Detection of Human Soluble Epoxide Hydrolase - He_2023_Anal.Chem__
Author(s) : He Q , McCoy MR , Yang H , Lin M , Cui X , Zhao S , Morisseau C , Li D , Hammock BD
Ref : Analytical Chemistry , : , 2023
Abstract : The soluble epoxide hydrolase (sEH) is possibly both a marker for and target of numerous diseases. Herein, we describe a homogeneous mix-and-read assay for the detection of human sEH based on using split-luciferase detection coupled with anti-sEH nanobodies. Selective anti-sEH nanobodies were individually fused with NanoLuc Binary Technology (NanoBiT), which consists of a large and small portion of NanoLuc (LgBiT and SmBiT, respectively). Different orientations of the LgBiT and SmBiT-nanobody fusions were expressed and investigated for their ability to reform the active NanoLuc in the presence of the sEH. After optimization, the linear range of the assay could reach 3 orders of magnitude with a limit of detection (LOD) of 1.4 ng/mL. The assay has a high sensitivity to human sEH and reached a similar detection limit to our previously reported conventional nanobody-based ELISA. The procedure of the assay was faster (30 min total) and easy to operate, providing a more flexible and simple way to monitor human sEH levels in biological samples. In general, the immunoassay proposed here offers a more efficient detection and quantification approach that can be easily adapted to numerous macromolecules.
ESTHER : He_2023_Anal.Chem__
PubMedSearch : He_2023_Anal.Chem__
PubMedID: 36972550

Title : The Generation of a Nanobody-Based ELISA for Human Microsomal Epoxide Hydrolase - He_2023_Int.J.Mol.Sci_24_
Author(s) : He Q , McCoy MR , Qi M , Morisseau C , Yang H , Xu C , Shey R , Goodman MC , Zhao S , Hammock BD
Ref : Int J Mol Sci , 24 : , 2023
Abstract : A microsomal epoxide hydrolase (mEH) metabolizes in vivo in both xenobiotic and endogenous epoxides associated with signaling function. Findings in patients suggest that mEH might be a biomarker for several diseases, including metastatic cancer and viral hepatitis. To easily quantify mEH, nanobodies specific to the human mEH were isolated from a phage library of llama VHHs. Four unique clones were obtained and used for developing ELISAs. Three formats of double antibody sandwich assays were investigated using different detection strategies. Using PolyHRP, the signal was strongly amplified, yielding a 22-fold lower LOD (12 pg mL(-1)) than the 'conventional'. To further validate the performance of the immunoassays, human tissue samples were analyzed by nanobody-based ELISAs and compared to the enzyme activities (R(2) > 0.95). The results demonstrate that these nanobodies are powerful tools for the quantification of human mEH and could eventually result in a bedside assay.
ESTHER : He_2023_Int.J.Mol.Sci_24_
PubMedSearch : He_2023_Int.J.Mol.Sci_24_
PubMedID: 37834144

Title : Soluble Epoxide Hydrolase Contributes to Cell Senescence and ER Stress in Aging Mice Colon - Wang_2023_Int.J.Mol.Sci_24_4570
Author(s) : Wang W , Wagner KM , Wang Y , Singh N , Yang J , He Q , Morisseau C , Hammock BD
Ref : Int J Mol Sci , 24 :4570 , 2023
Abstract : Aging, which is characterized by enhanced cell senescence and functional decline of tissues, is a major risk factor for many chronic diseases. Accumulating evidence shows that age-related dysfunction in the colon leads to disorders in multiple organs and systemic inflammation. However, the detailed pathological mechanisms and endogenous regulators underlying colon aging are still largely unknown. Here, we report that the expression and activity of the soluble epoxide hydrolase (sEH) enzyme are increased in the colon of aged mice. Importantly, genetic knockout of sEH attenuated the age-related upregulation of senescent markers p21, p16, Tp53, and beta-galactosidase in the colon. Moreover, sEH deficiency alleviated aging-associated endoplasmic reticulum (ER) stress in the colon by reducing both the upstream regulators Perk and Ire1 as well as the downstream pro-apoptotic effectors Chop and Gadd34. Furthermore, treatment with sEH-derived linoleic acid metabolites, dihydroxy-octadecenoic acids (DiHOMEs), decreased cell viability and increased ER stress in human colon CCD-18Co cells in vitro. Together, these results support that the sEH is a key regulator of the aging colon, which highlights its potential application as a therapeutic target for reducing or treating age-related diseases in the colon.
ESTHER : Wang_2023_Int.J.Mol.Sci_24_4570
PubMedSearch : Wang_2023_Int.J.Mol.Sci_24_4570
PubMedID: 36901999

Title : Quantification of soluble epoxide hydrolase inhibitors in experimental and clinical samples using the nanobody-based ELISA - Yang_2023_J.Pharm.Anal_13_1013
Author(s) : Yang H , Qi M , He Q , Hwang SH , Yang J , McCoy M , Morisseau C , Zhao S , Hammock BD
Ref : J Pharm Anal , 13 :1013 , 2023
Abstract : To ensure proper dosage of a drug, analytical quantification of it in biofluid is necessary. Liquid chromatography mass spectrometry (LC-MS) is the conventional method of choice as it permits accurate identification and quantification. However, it requires expensive instrumentation and is not appropriate for bedside use. Using soluble epoxide hydrolase (sEH) inhibitors (EC5026 and TPPU) as examples, we report development of a nanobody-based enzyme-linked immunosorbent assay (ELISA) for such small molecules and its use to accurately quantify the drug chemicals in human samples. Under optimized conditions, two nanobody-based ELISAs were successfully established for EC5026 and TPPU with low limits of detection of 0.085 ng/mL and 0.31 ng/mL, respectively, and two order of magnitude linear ranges with high precision and accuracy. The assay was designed to detect parent and two biologically active metabolites in the investigation of a new drug candidate EC5026. In addition, the ELISAs displayed excellent correlation with LC-MS analysis and evaluation of inhibitory potency. The results indicate that nanobody-based ELISA methods can efficiently analyze drug like compounds. These methods could be easily implemented by the bedside, in the field in remote areas or in veterinary practice. This work illustrates that nanobody based assays offer alternative and supplementary analytical tools to mass spectrometry for monitoring small molecule medicines during clinical development and therapy. Attributes of nanobody based pharmaceutical assays are discussed.
ESTHER : Yang_2023_J.Pharm.Anal_13_1013
PubMedSearch : Yang_2023_J.Pharm.Anal_13_1013
PubMedID: 37842656

Title : The FoxO1-ATGL axis alters milk lipolysis homeostasis through PI3K\/AKT signaling pathway in dairy goat mammary epithelial cells - He_2023_J.Anim.Sci__
Author(s) : He Q , GaoLiang J , Zhang F , Yao W , Wu J , Song N , Luo J , Zhang Y
Ref : J Anim Sci , : , 2023
Abstract : Goat milk is enriched in fatty acids which beneficial to human health. Previous research has revealed that 98% of milk fat is composed of triglycerides. However, the mechanisms regulating of milk fat composition remain unclear. Forkhead box protein O1 (FoxO1) is a crucial regulatory factor involved in lipid metabolism across various cell types. Chromatin immunoprecipitation sequencing (ChIP)--seq data) and RNA sequencing (RNA-seq) data revealed thathave indicated a close association between FoxO1 was closed related toand lipid metabolism during lactation in dairy goats. The objective of this study was to investigate the mechanisms by which FoxO1 regulates lipid metabolism in goat mammary epithelial cells (GMECs). FoxO1 knockdown significantly downregulated the expression of adipose triglyceride lipase (ATGL) and suppressed the activity of the ATGL promoter. Consistently, the number of lipid droplets decreased significantly in FoxO1-overexpressing cells, and increased in ATGL-knockdown cells. To further verify the effect of FoxO1 on ATGL promoter activity, cells were transfected with four promoter fragments of different lengths. We found that the core region of the ATGL promoter was located between -882 bp and -524 bp, encompassing two FoxO1 binding sites (FKH1 and FKH2). Mutations in the FoxO1 binding sites significantly downregulated ATGL promoter activity in GMECs. Luciferase reporter assays demonstrated that FoxO1 overexpression markedly enhanced ATGL promoter activity. Furthermore, site-directed mutation confirmed that FKH1 and FKH2 sites were simultaneously mutated significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activities simultaneous mutation of FKH1 and FKH2 sites significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activity. ChIP assays showed that FoxO1 directly binds to the FKH2 element located in the ATGL promoter in vivo. Finally, immunofluorescence staining revealed that insulin promotes the translocation of FoxO1 from the nucleus to the cytoplasm, thereby attenuating the FoxO1-induced activation of the ATGL promoter. Collectively, these findings uncover a novel pathway where by FoxO1 may regulate lipid metabolism in GMECs specifically by modulating the transcriptional activity of ATGL.
ESTHER : He_2023_J.Anim.Sci__
PubMedSearch : He_2023_J.Anim.Sci__
PubMedID: 37638641

Title : Determinants of Meal-Induced Changes in Circulating FFA Epoxides, Diols, and Diol-to-Epoxide Ratios as Indices of Soluble Epoxide Hydrolase Activity - Oh_2023_Int.J.Mol.Sci_24_
Author(s) : Oh YT , Yang J , Morisseau C , He Q , Hammock B , Youn JH , Stefanovski D
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Soluble epoxide hydrolase (sEH) is an important enzyme for metabolic and cardiovascular health. sEH converts FFA epoxides (EpFAs), many of which are regulators of various cellular processes, to biologically less active diols. In human studies, diol (sEH product) to EpFA (sEH substrate) ratios in plasma or serum have been used as indices of sEH activity. We previously showed these ratios profoundly decreased in rats during acute feeding, possibly reflecting decreases in tissue sEH activities. The present study was designed to test which tissue(s) these measurements in the blood represent and if factors other than sEH activity, such as renal excretion or dietary intake of EpFAs and diols, significantly alter plasma EpFAs, diols, and/or their ratios. The results show that postprandial changes in EpFAs and diols and their ratios in plasma were very similar to those observed in the liver but not in other tissues, suggesting that the liver is largely responsible for these changes in plasma levels. EpFAs and diols were excreted into the urine, but their levels were not significantly altered by feeding, suggesting that renal excretion of EpFAs and diols may not play a major role in postprandial changes in circulating EpFAs, diols, or their ratios. Diet intake had significant impacts on circulating EpFA and diol levels but not on diol-to-EpFA (D-to-E) ratios, suggesting that these ratios, reflecting sEH activities, may not be significantly affected by the availability of sEH substrates (i.e., EpFAs). In conclusion, changes in FFA D-to-E ratios in plasma may reflect those in the liver, which may in turn represent sEH activities in the liver, and they may not be significantly affected by renal excretion or the dietary intake of EpFAs and diols.
ESTHER : Oh_2023_Int.J.Mol.Sci_24_
PubMedSearch : Oh_2023_Int.J.Mol.Sci_24_
PubMedID: 37445935 || 38139180

Title : Aaptamine - a dual acetyl - and butyrylcholinesterase inhibitor as potential anti-Alzheimer's disease agent - Miao_2022_Pharm.Biol_60_1502
Author(s) : Miao S , He Q , Li C , Wu Y , Liu M , Chen Y , Qi S , Gong K
Ref : Pharm Biol , 60 :1502 , 2022
Abstract : CONTEXT: Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are promising therapeutic targets for AD. OBJECTIVE: To evaluate the inhibitory effects of aaptamine on two cholinesterases and investigate the in vivo therapeutic effect on AD in a zebrafish model. MATERIALS AND METHODS: Aaptamine was isolated from the sponge Aaptos suberitoides Brondsted (Suberitidae). Enzyme inhibition, kinetic analysis, surface plasmon resonance (SPR) and molecular docking assays were used to determine its inhibitory effect on AChE and BuChE in vitro. Zebrafish were divided into six groups: control, model, 8 microM donepezil, 5 , 10 and 20 microM aaptamine. After three days of drug treatment, the behaviour assay was performed. RESULTS: The IC(50) values of aaptamine towards AChE and BuChE were 16.0 and 4.6 microM. And aaptamine directly inhibited the two cholinesterases in the mixed inhibition type, with K(i) values of 6.96 +/- 0.04 and 6.35 +/- 0.02 microM, with K(d) values of 87.6 and 10.7 microM. Besides, aaptamine interacts with the crucial anionic sites of AChE and BuChE. In vivo studies indicated that the dyskinesia recovery rates of 5 , 10 and 20 microM aaptamine group were 34.8, 58.8 and 60.0%, respectively, and that of donepezil was 63.7%. DISCUSSION AND CONCLUSIONS: Aaptamine showed great potential to exert its anti-AD effects by directly inhibiting the activities of AChE and BuChE. Therefore, this study identified a novel medicinal application of aaptamine and provided a new structural scaffold for the development of anti-AD drugs.
ESTHER : Miao_2022_Pharm.Biol_60_1502
PubMedSearch : Miao_2022_Pharm.Biol_60_1502
PubMedID: 35968601

Title : miRNA-Mediated Low Expression of EPHX3 Is Associated with Poor Prognosis and Tumor Immune Infiltration in Head and Neck Squamous Cell Carcinomas - Ding_2022_J.Oncol_2022_7633720
Author(s) : Ding S , Hong Q , Duan T , Xu Z , He Q , Qiu D , Li L , Yan J , Zhang Q , Mu Z
Ref : J Oncol , 2022 :7633720 , 2022
Abstract : The aim of this study was to explore the regulatory role of epoxide hydrolase 3 (EPHX3) in head and neck squamous cell carcinoma (HNSCC) and to analyze its bioinformatic function, as well as, to screen and predict the miRNAs that can regulate EPHX3 expression in HNSCC. We examined the expression profile and prognostic potential of EPHX3 in TCGA and GTEX databases and performed functional enrichment analysis of EPHX3 using string database. Subsequently, we analyzed the regulatory role of miRNAs on EPHX3, including expression analysis, correlation analysis, and survival analysis. In addition, we also used TIMER to investigate the relationship among EPHX3 expression level, immune checkpoints, and immune infiltration in HNSCC. The results of data analysis after TGCA showed that EPHX3 is a key regulator of tumorigenesis in 13 cancers and can be used as a marker of poor prognosis in HNSCC patients. Bioinformatics analysis revealed that miR-4713-3p is a key miRNA of EPHX3 in HNSCC. Together, our findings indicate that EPHX3 exerts its anticancer effects by suppressing tumor immune checkpoint expression and immune cell infiltration. Overall, our data uncovered miRNA-mediated EPHX3 downregulation as a contributor to poor HNSCC prognosis and reduced tumor immune infiltration.
ESTHER : Ding_2022_J.Oncol_2022_7633720
PubMedSearch : Ding_2022_J.Oncol_2022_7633720
PubMedID: 35401746

Title : Dual-Modal Nanoscavenger for Detoxification of Organophosphorus Compounds - Zou_2022_ACS.Appl.Mater.Interfaces__
Author(s) : Zou S , Wang B , Wang Q , Liu G , Song J , Zhang F , Li J , Wang F , He Q , Zhu Y , Zhang L
Ref : ACS Appl Mater Interfaces , : , 2022
Abstract : Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte-liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers in vitro. Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood-brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. In vitro, the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. In vivo, apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, in vitro and in vivo studies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning.
ESTHER : Zou_2022_ACS.Appl.Mater.Interfaces__
PubMedSearch : Zou_2022_ACS.Appl.Mater.Interfaces__
PubMedID: 36089739

Title : One-step orientated immobilization of nanobodies and its application for immunoglobulin purification - Fu_2019_J.Chromatogr.A_1603_15
Author(s) : Fu J , Li J , Wang W , Wu H , Zhou P , Li Y , He Q , Tu Z
Ref : Journal of Chromatography A , 1603 :15 , 2019
Abstract : Affinity chromatography technologies play an important role in the purification of antibodies. To prepare affinity materials, prior isolation and purification of affinity ligands are required before coupling onto solid supports, which is quite expensive and laborious in large-scale applications. In this study, a one-step approach which circumvents the ligand purification procedures was developed to fabricate affinity gel for purifying immunoglobulin G (IgG). A self-labeling tag, haloalkane dehalogenase, was fused to the C-terminal of an anti-Fc variable domain of the heavy chain of the heavy-chain antibody (AFV) which was isolated in previous work. The AFV binds to various sources of IgG and is highly thermal stable. The fusion protein, namely HAFV, was expressed in Escherichia coli as a soluble protein. The binding affinity of HAFV to the Fc region of IgG was characterized and compared with the untagged anti-Fc nanobody. Next, the HAFV was immobilized directly from the crude cell lysate of isopropylthio-beta-D-galactoside (IPTG) induced E. coli. The effects of NaCl concentrations and pH on the capacity of the HAFV resin were investigated. In addition, the one-step coupled HAFV resin was compared with the AFV resin and commercial resins (Protein A and Protein G) by evaluating the static capacity and stability. Though the Protein A (8.34+/-0.37mg/ml) and Protein G (9.19+/-0.28mg/ml) showed higher static capacity, the static capacity of HAFV resin (8.21+/-0.30mg/ml) was better than that of the untagged AFV gel (6.48+/-0.56mg/ml). The recovery results calculated for the reusability and stability show that there is no significant difference between the results obtained for the HAFV gel with those of the untagged AFV gel and commercial Protein A and G. After stored at 37 for 7 days and recycled 10 times, the static capacity of HAFV gel remains above 78%. Our strategy is site-specific, cost-effective, reproducible, and has the potential to dramatically cut down the costs of affinity materials for IgG purification.
ESTHER : Fu_2019_J.Chromatogr.A_1603_15
PubMedSearch : Fu_2019_J.Chromatogr.A_1603_15
PubMedID: 31213362
Gene_locus related to this paper: xanau-halo1

Title : Efficient resolution of (R,S)-1-(1-naphthyl)ethylamine by Candida antarctica lipase B in ionic liquids - Wang_2018_Mol.Catal_448_116
Author(s) : Wang B , Zhang C , He Q , Qin H , Liang G , Liu W
Ref : Molecular Catalysis , 448 :116 , 2018
Abstract : The resolution of (R,S)-1-(1-naphthyl)ethylamine ((R,S)-NEA) by Candida antarctica lipase B (CALB) in ionic liquids (ILs) containing 1-alkyl-3-methylimidazolium cations ([Cnmim]+) and [Tf2N]-, [BF4]-, and [PF6]- anions was investigated. When the alkyl chain on the cation contained less than six carbons, the lipase activity corresponded with the hydrophobicity of the ILs, but further increase in the chain length suppressed the enzyme activity. The enzyme activity decreased depending on the anion, where [Tf2N]- > [PF6]- > [BF4]-. The effects of acyl donors, pH, temperature, water activity, and substrate concentration on the resolution were determined. Under the optimal conditions, the conversion of (R,S)-NEA and enantiomer excess of (R)-n-octyl acyl-NEA was 49.3% and 99.2%, respectively. The resolution kinetics of (R,S)-NEA by CALB in [C6mim][Tf2N] were studied and a ping-pong mechanism with a two substrate inhibition model was selected. The kinetic parameters of the fitting results were as follows: Michaelis constant of (R,S)-NEA Kma, 461.8 mmol/L; Michaelis constant of vinyl n-octanoateKmb, 262.1 mmol/L; inhibition constant of (R,S)-NEA Kia, 8737.2 mmol/L; inhibition constant of vinyl n-octanoateKib, 62336.8 mmol/L; maximum reaction rate rmax, 0.352 mmol/(mg min). Moreover, circular dichroism revealed that incubation of CALB in [C6mim][Tf2N] resulted in increased beta-sheet content; its secondary structure was stable.
ESTHER : Wang_2018_Mol.Catal_448_116
PubMedSearch : Wang_2018_Mol.Catal_448_116
PubMedID:

Title : Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation - He_2018_Bioorg.Chem_81_512
Author(s) : He Q , Liu J , Lan JS , Ding J , Sun Y , Fang Y , Jiang N , Yang Z , Sun L , Jin Y , Xie SS
Ref : Bioorg Chem , 81 :512 , 2018
Abstract : A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068muM and 0.0089muM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114microM for hAChE; 0.101microM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
ESTHER : He_2018_Bioorg.Chem_81_512
PubMedSearch : He_2018_Bioorg.Chem_81_512
PubMedID: 30245233

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 : Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer - Sun_2013_Oncogene_32_234
Author(s) : Sun H , Jiang L , Luo X , Jin W , He Q , An J , Lui K , Shi J , Rong R , Su W , Lucchesi C , Liu Y , Sheikh MS , Huang Y
Ref : Oncogene , 32 :234 , 2013
Abstract : Human monoglyceride lipase (MGL) is a recently identified lipase and very little is known about its regulation and function in cellular regulatory processes, particularly in context to human malignancy. In this study, we investigated the regulation and function of MGL in human cancer(s) and report that MGL expression was either absent or reduced in the majority of primary colorectal cancers. Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells. MGL was found to reside in the core surface of a cellular organelle named 'lipid body'. Furthermore, it was found to interact selectively with a number of phospholipids, including phosphatidic acid and phosphoinositol(3,4,5)P3, phosphoinositol(3,5)P2, phosphoinositol(3,4)P2 and several other phosphoinositides, and among all phosphoinositides analyzed, its interaction with PI(3,4,5)P3 was found to be the strongest. In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation. Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth.
ESTHER : Sun_2013_Oncogene_32_234
PubMedSearch : Sun_2013_Oncogene_32_234
PubMedID: 22349814

Title : Draft genome sequence of Streptomyces globisporus C-1027, which produces an antitumor antibiotic consisting of a nine-membered enediyne with a chromoprotein - Wang_2012_J.Bacteriol_194_4144
Author(s) : Wang L , Wang S , He Q , Yu T , Li Q , Hong B
Ref : Journal of Bacteriology , 194 :4144 , 2012
Abstract : Streptomyces globisporus C-1027 is the producer of antitumor antibiotic C-1027, a nine-membered enediyne-containing compound. Here we present a draft genome sequence of S. globisporus C-1027 containing the intact biosynthetic gene cluster for this antibiotic. The genome also carries numerous sets of genes for the biosynthesis of diverse secondary metabolites.
ESTHER : Wang_2012_J.Bacteriol_194_4144
PubMedSearch : Wang_2012_J.Bacteriol_194_4144
PubMedID: 22815456
Gene_locus related to this paper: strgl-a0a0u3kbg5

Title : BZYX, a novel acetylcholinesterase inhibitor, significantly improved chemicals-induced learning and memory impairments on rodents and protected PC12 cells from apoptosis induced by hydrogen peroxide - Zhang_2009_Eur.J.Pharmacol_613_1
Author(s) : Zhang J , Zhu D , Sheng R , Wu H , Hu Y , Wang F , Cai T , Yang B , He Q
Ref : European Journal of Pharmacology , 613 :1 , 2009
Abstract : BZYX was designed as a dual-binding-site acetylcholinesterase (AChE) inhibitor and selected from series of indanone derivatives. The present study was designed to examine the cognition-enhanced, anti-cholinesterase, and neuroprotective effects of BZYX. In the passive avoidance performance and radial arm maze, BZYX showed a comparable effect to donepezil and rivastigmine on memory deficits in different stages induced by scopolamine, NaNO(2) and ethanol, respectively. Ellman's assay indicated BZYX exhibited high inhibition on AChE activity. IC(50) values for BZYX: 0.058+/-0.022 microM; donepezil: 0.019+/-0.004 microM; rivastigmine: 3.81+/-2.81 microM; glantamine: 3.01+/-1.85 microM and huperzine A: 0.053+/-0.016 microM. BZYX also presented great neuroprotecive function from apoptosis induced by hydrogen peroxide(H(2)O(2)) in PC12 cells. MTT assay and Annexin V-FITC Apoptosis Detection showed the viability of PC12 cells remarkably decreased with 400 microM H(2)O(2), while it significantly increased when the cells were pretreated with 0.1-1.0 microM BZYX. BZYX pretreatment remarkably reversed the loss of mitochondria membrane potential (DeltaPsim), scavenged reactive oxygen species formation induced by H(2)O(2) and resulted in up-regulation of procaspase3 and xIAP protein level and down-regulation of phosphorylated JNK protein, p53 protein level and cleavage of caspase 3. It is speculated that the mitochondrial pathway, mediated by Bcl-2 family and Mitogen-Activated Protein Kinases (MAPKs), might involved in the neuroprotection of BZYX. These results first demonstrated that BZYX had neuroprotective effects as well as cognition enhancement and acetylcholinesterase inhibition. It is hopeful that BZYX becomes a potential candidate for use in the intervention for neurodegenerative diseases.
ESTHER : Zhang_2009_Eur.J.Pharmacol_613_1
PubMedSearch : Zhang_2009_Eur.J.Pharmacol_613_1
PubMedID: 19345205

Title : Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors - Jia_2009_Eur.J.Med.Chem_44_772
Author(s) : Jia P , Sheng R , Zhang J , Fang L , He Q , Yang B , Hu Y
Ref : Eur Journal of Medicinal Chemistry , 44 :772 , 2009
Abstract : A new series of galanthamine derivatives have been designed, synthesized and evaluated as acetylcholinesterase inhibitors. All of the new compounds prepared showed high AChE inhibitory activities, with compound 3e that has an N-hexyl-benzyl piperidine substituent on the nitrogen atom reaching the best inhibitory activity for AChE (IC(50)=5.62 nM). The docking study performed with AutoDock demonstrated that 3e was nicely accommodated by AChE.
ESTHER : Jia_2009_Eur.J.Med.Chem_44_772
PubMedSearch : Jia_2009_Eur.J.Med.Chem_44_772
PubMedID: 18550228

Title : Synthesis and biological evaluation of novel flavonoid derivatives as dual binding acetylcholinesterase inhibitors - Shen_2009_J.Enzyme.Inhib.Med.Chem_24_372
Author(s) : Shen Y , Zhang J , Sheng R , Dong X , He Q , Yang B , Hu Y
Ref : J Enzyme Inhib Med Chem , 24 :372 , 2009
Abstract : A new series of flavonoid derivatives have been designed, synthesised and evaluated as acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme. Among them, fifteen derivatives were found to inhibit the enzyme in the micromolar range and isoflavone derivatives possessed more potent inhibitory activity than other flavonoid derivatives. The best compound 9a had its inhibitory activity (IC(50) = 0.093 microM) in the same range as the reference compound, donepezil (IC(50) = 0.025 microM). Preliminary structure-activity relationships and a molecular modeling study for 9a have revealed that the isoflavone moiety plays a key role in the interaction of this series of derivatives with AChE by acting as an anchor in its peripheral anionic site.
ESTHER : Shen_2009_J.Enzyme.Inhib.Med.Chem_24_372
PubMedSearch : Shen_2009_J.Enzyme.Inhib.Med.Chem_24_372
PubMedID: 18830885

Title : 2-Phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors: a study on the importance of modifications at the side chain on the activity - Shen_2008_Bioorg.Med.Chem_16_7646
Author(s) : Shen Y , Sheng R , Zhang J , He Q , Yang B , Hu Y
Ref : Bioorganic & Medicinal Chemistry , 16 :7646 , 2008
Abstract : As a part of our project aimed at developing new agents of potential application in AD, a new series of 2-phenoxy-indan-1-one derivatives which possess alkylamine side chain were designed, synthesized, and evaluated for their inhibitory activity against AChE and BuChE. Most of the compounds were found to inhibit AChE in the nanomolar range. The optimum inhibitor 3g exhibited 34-fold increase in AChE inhibition than donepezil and displayed neuroprotective effect against H(2)O(2)-induced cell death.
ESTHER : Shen_2008_Bioorg.Med.Chem_16_7646
PubMedSearch : Shen_2008_Bioorg.Med.Chem_16_7646
PubMedID: 18662884

Title : Molecular dynamics of detoxification and toxin-tolerance genes in brown planthopper (Nilaparvata lugens Stal., Homoptera: Delphacidae) feeding on resistant rice plants - Yang_2005_Arch.Insect.Biochem.Physiol_59_59
Author(s) : Yang Z , Zhang F , He Q , He G
Ref : Archives of Insect Biochemistry & Physiology , 59 :59 , 2005
Abstract : To investigate the molecular response of brown planthopper, Nilaparvata lugens (BPH) to BPH-resistant rice plants, we isolated cDNA fragments of the genes encoding for carboxylesterase (CAR), trypsin (TRY), cytochrome P450 monooxygenase (P450), NADH-quinone oxidoreductase (NQO), acetylcholinesterase (ACE), and Glutathione S-transferase (GST). Expression profiles of the genes were monitored on fourth instar nymphs feeding on rice varieties with different resistance levels. Northern blot hybridization showed that, compared with BPH reared on susceptible rice TN1, expression of the genes for P450 and CAR was apparently up-regulated and TRY mRNA decreased in BPH feeding on a highly resistant rice line B5 and a moderately resistant rice variety MH63, respectively. Two transcripts of GST increased in BPH feeding on B5; but in BPH feeding on MH63, this gene was inducible and its expression reached a maximum level at 24 h, and then decreased slightly. The expression of NQO gene was enhanced in BPH on B5 plants but showed a constant expression in BPH on MH63 plants. No difference in ACE gene expression among BPH on different rice plants was detected by the RT-PCR method. The results suggest these genes may play important roles in the defense response of BPH to resistant rice.
ESTHER : Yang_2005_Arch.Insect.Biochem.Physiol_59_59
PubMedSearch : Yang_2005_Arch.Insect.Biochem.Physiol_59_59
PubMedID: 15898115

Title : [Microsomal epoxide hydrolase gene polymorphism and susceptibility to chronic obstructive pulmonary disease in Han nationality of North China] - Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_11
Author(s) : Zhang R , Zhang A , He Q , Lu B
Ref : Zhonghua Nei Ke Za Zhi , 41 :11 , 2002
Abstract : OBJECTIVE We investigated whether polymorphism in gene for microsomal epoxide hydrolase (mEH) has any bearing on individual susceptibility to the development of chronic obstructive pulmonary disease. METHOD: The genotypes of 55 patients with COPD and 52 healthy smoking control subjects were tested with polymerase chain reaction followed by restriction fragment length polymorphism for mEH gene. RESULT: The frequency of polymorphic genotypes of mEH showed no difference between the COPD group and the control group. In COPD group mEH exon 3 homozygous wild-type, heterozygote and homozygous mutant was 27.3%, 27.3% and 45.5% respectively and exon 4 homozygous wild-type, heterozygote and homozygous mutant was 72.7%, 18.2% and 9.1% respectively. CONCLUSION: Genetic polymorphism in mEH is not associated with development of COPD in Han nationality of North China.
ESTHER : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_11
PubMedSearch : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_11
PubMedID: 11940289