Zhou H

References (89)

Title : Quantitative proteomic analysis reveals the mechanism and key esterase of beta-cypermethrin degradation in a bacterial strain from fermented food - Peng_2024_Pestic.Biochem.Physiol_201_105858
Author(s) : Peng C , Tang J , Zhou X , Zhou H , Zhang Y , Wang S , Wang W , Xiang W , Zhang Q , Yu X , Cai T
Ref : Pestic Biochem Physiol , 201 :105858 , 2024
Abstract : Beta-cypermethrin (beta-CY) residues in food are an important threat to human health. Microorganisms can degrade beta-CY residues during fermentation of fruits and vegetables, while the mechanism is not clear. In this study, a comprehensively investigate of the degradation mechanism of beta-CY in a food microorganism was conducted based on proteomics analysis. The beta-CY degradation bacteria Gordonia alkanivorans GH-1 was derived from fermented Pixian Doubanjiang. Its crude enzyme extract could degrade 77.11% of beta-CY at a concentration of 45 mg/L within 24 h. Proteomics analysis revealed that the ester bond of beta-CY is broken under the action of esterase to produce 3-phenoxy benzoic acid, which was further degraded by oxidoreductase and aromatic degrading enzyme. The up-regulation expression of oxidoreductase and esterase was confirmed by transcriptome and quantitative reverse transcription PCR. Meanwhile, the expression of esterase Est280 in Escherichia coli BL21 (DE3) resulted in a 48.43% enhancement in the degradation efficiency of beta-CY, which confirmed that this enzyme was the key enzyme in the process of beta-CY degradation. This study reveals the degradation mechanism of beta-CY by microorganisms during food fermentation, providing a theoretical basis for the application of food microorganisms in beta-CY residues.
ESTHER : Peng_2024_Pestic.Biochem.Physiol_201_105858
PubMedSearch : Peng_2024_Pestic.Biochem.Physiol_201_105858
PubMedID: 38685237

Title : Biodegradation of phthalic acid esters (PAEs) by Janthinobacterium sp. strain E1 under stress conditions - Zhang_2024_J.Gen.Appl.Microbiol__
Author(s) : Zhang K , Zhou H , Ke J , Feng H , Lu C , Chen S , Liu A
Ref : J Gen Appl Microbiol , : , 2024
Abstract : Phthalates esters (PAEs) are a kind of polymeric material additives widely been added into plastics to improve products' flexibility. It can easily cause environmental pollution which are hazards to public health. In this study, we isolated an efficient PAEs degrading strain, Janthinobacterium sp. E1, and determined its degradation effect of di-2-ethylhexyl phthalate (DEHP) under stress conditions. Strain E1 showed an obvious advantage in pollutants degradation under various environmental stress conditions. Degradation halo clearly occurred around the colony of strain E1 on agar plate supplemented with triglyceride. Strain E1's esterase is a constitutively expressed intracellular enzyme. The esterase purified from strain E1 showed a higher catalytic effect on short-chain PAEs than long-chain PAEs. The input of DEHP, DBP (dibutyl phthalate) and DMP (dimethyl phthalate) into the tested soil did not change the species composition of soil prokaryotic community, but altered the dominant species in specific environmental conditions. And the community diversity and richness decreased to a certain extent. However, the diversity and richness of the microbial community were improved after the contaminated soil was treated with the strain E1. Our results also suggested that strain E1 exhibited a tremendous potential in environmental bioremediation in the real environment, which provides a new insight into the elimination of the pollutants contamination in the urban environment.
ESTHER : Zhang_2024_J.Gen.Appl.Microbiol__
PubMedSearch : Zhang_2024_J.Gen.Appl.Microbiol__
PubMedID: 38220211

Title : Isolation, characteristics, and poly(butylene adipate-co-terephthalate) (PBAT) degradation mechanism of a marine bacteria Roseibium aggregatum ZY-1 - Pan_2024_Mar.Pollut.Bull_201_116261
Author(s) : Pan H , Yu T , Zheng Y , Ma H , Shan J , Yi X , Liu Y , Zhan J , Wang W , Zhou H
Ref : Mar Pollut Bull , 201 :116261 , 2024
Abstract : Marine microorganisms have been reported to degrade microplastics. However, the degradation mechanisms are still poorly understood. In this study, a bacterium Roseibium aggregatum ZY-1 was isolated from seawater, which can degrade poly(butylene adipate-co-terephthalate) (PBAT). The PBAT-PLA(polylactic acid, PLA) films, before and after degradation, were characterized by scanning electron microscope (SEM) and Fourier transform infrared spectrometer (FTIR), the weight loss rate and water contact angle were measured. The results indicate that ZY-1 colonized on PBAT-PLA film, changed the functional groups and decreased water contact angle of PBAT-PLA film. Moreover, liquid chromatography mass spectrometry (LC-MS) analysis reveales that PBAT was degraded into its oligomers (TB, BTB) and monomers (T, A) during 10 days, and adipic acid (A) could be used as a sole carbon source. The whole genome sequencing analyses illustrate the mechanisms and enzymes such as PETase, carboxylesterases, arylesterase (PpEst) and genes like pobA, pcaBCDFGHIJKT, dcaAEIJK, paaGHJ involved in PBAT degradation. Therefore, the R. aggregatum ZY-1 will be a promising candidate of PBAT degradation.
ESTHER : Pan_2024_Mar.Pollut.Bull_201_116261
PubMedSearch : Pan_2024_Mar.Pollut.Bull_201_116261
PubMedID: 38537567

Title : Polyethylene Terephthalate Hydrolases in Human Gut Microbiota and Their Implications for Human Health - Zhou_2024_Microorganisms_12_138
Author(s) : Zhou H , Shi S , You Q , Zhang K , Chen Y , Zheng D , Sun J
Ref : Microorganisms , 12 :138 , 2024
Abstract : Polyethylene terephthalate (PET), primarily utilized for food and beverage packaging, consistently finds its way into the human gut, thereby exerting adverse effects on human health. PET hydrolases, critical for the degradation of PET, have been predominantly sourced from environmental microbial communities. Given the fact that the human gut harbors a vast and intricate consortium of microorganisms, inquiry into the presence of potential PET hydrolases within the human gut microbiota becomes imperative. In this investigation, we meticulously screened 22,156 homologous sequences that could potentially encode PET hydrolases using the hidden Markov model (HMM) paradigm, drawing from 4984 cultivated genomes of healthy human gut bacteria. Subsequently, we methodically validated the hydrolytic efficacy of five selected candidate PET hydrolases on both PET films and powders composed of micro-plastics (MPs). Notably, our study also unveiled the influence of both diverse PET MP powders and their resultant hydrolysates on the modulation of cytokine expression in macrophages. In summary, our research underscores the ubiquitous prevalence and considerable potential of the human gut microbiota in PET hydrolysis. Furthermore, our study significantly contributes to the holistic evaluation of the potential health hazards posed by PET MPs to human well-being.
ESTHER : Zhou_2024_Microorganisms_12_138
PubMedSearch : Zhou_2024_Microorganisms_12_138
PubMedID: 38257965
Gene_locus related to this paper: 9firm-a0a4r3svb5 , heyc2-f7z2k4 , 9clot-a0a3r6ruf5 , 9firm-a0a413uca3 , entcl-j7gkj7

Title : Metformin inhibits OCTN1- and OCTN2-mediated hepatic accumulation of doxorubicin and alleviates its hepatotoxicity in mice - Chen_2024_Toxicology__153757
Author(s) : Chen M , Yi Y , Chen B , Zhang H , Dong M , Yuan L , Zhou H , Jiang H , Ma Z
Ref : Toxicology , :153757 , 2024
Abstract : Doxorubicin (DOX) is a widely used antitumor agent; however, its clinical application is limited by dose-related organ damage. Because organic cation/carnitine transporters (OCTN1 and OCTN2), which are critical for DOX uptake, are highly expressed in hepatocytes, we aimed to elucidate the role of these transporters in hepatic DOX uptake. The results indicated that inhibitors and RNA interference both significantly reduced DOX accumulation in HepG2 and HepaRG cells, suggesting that OCTN1/2 contribute substantially to DOX uptake by hepatocytes. To determine whether metformin (MET, an inhibitor of OCTN1 and OCTN2) ameliorates DOX-induced hepatotoxicity, we conducted in vitro and in vivo studies. MET (1-100microM) inhibited DOX (500nM) accumulation and cytotoxicity in vitro in a concentration-dependent manner. Furthermore, intravenous MET administration at 250 or 500mg/kg or by gavage at 50, 100, or 200mg/kg reduced DOX (8mg/kg) accumulation in a dose-dependent manner in the mouse liver and attenuated the release of alanine aminotransferase, aspartate aminotransferase, and carboxylesterase 1. Additionally, MET reduced the distribution of DOX in the heart, liver, and kidney and enhanced the urinary elimination of DOX; however, it did not increase the nephric toxicity of DOX. In conclusion, our study demonstrated that MET alleviates DOX hepatotoxicity by inhibiting OCTN1- and OCTN2-mediated DOX uptake in vitro (mouse hepatocytes and HepaRG or HepG2 cells) and in mice.
ESTHER : Chen_2024_Toxicology__153757
PubMedSearch : Chen_2024_Toxicology__153757
PubMedID: 38364893

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

Title : Development of Sustainable Insecticide Candidates for Protecting Pollinators: Insight into the Bioactivities, Selective Mechanism of Action and QSAR of Natural Coumarin Derivatives against Aphids - Zhou_2023_J.Agric.Food.Chem_71_18359
Author(s) : Zhou H , Jian Y , Shao Q , Guo F , Zhang M , Wan F , Yang L , Liu Y , Li Y , Yang P , Li Z , Li S , Ding W
Ref : Journal of Agricultural and Food Chemistry , 71 :18359 , 2023
Abstract : Plants employ abundant toxic secondary metabolites to withstand insect attack, while pollinators can tolerate some natural defensive compounds. Coumarins, as promising green alternatives to chemical insecticides, possess wide application prospects in the crop protection field. Herein, the bioactivities of 30 natural coumarin derivatives against Aphis gossypii were assessed and revealed that 6-methylcoumarin exhibited potent aphicidal activity against aphids but displayed no toxicity to honeybees. Additionally, using biochemical, bioinformatic, and molecular assays, we confirmed that the action mode of 6-methylcoumarin against aphids was by inhibiting acetylcholinesterase (AChE). Meanwhile, functional assays revealed that the difference in action site, which located in Lys585 in aphid AChE (equivalent to Val548 in honeybee AChE), was the principal reason for 6-methylcoumarin being toxic to aphids but safe to pollinators. This action site was further validated by mutagenesis data, which uncovered how 6-methylcoumarin was unique selective to the aphid over honeybee or mammalian AChE. Furthermore, a 2D-QSAR model was established, revealing that the central structural feature was H3m, which offers guidance for the future design of more potent coumarin compounds. This work provides a sustainable strategy to take advantage of coumarin analogues for pest management while protecting nontarget pollinators.
ESTHER : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedSearch : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedID: 37965968

Title : Discovery of pyranonaphthoquinones and an eighteen-membered ring macrolide from the rhizospheric soil-derived fungus Phialocephala sp. YUD18001 by OSMAC strategy - Xie_2023_Fitoterapia__105690
Author(s) : Xie F , Sun Y , Zi ZF , Wang WJ , Wan DY , Zhou H , Ding ZT
Ref : Fitoterapia , :105690 , 2023
Abstract : Two new pyranonaphthoquinones, phialoyxinones A (1) and B (2), a new eighteen-membered ring lactone, phialoyxtone (3), and five known pyranonaphthoquinone derivatives were identified from the fungus Phialocephala sp. YUD18001, which was isolated from the rhizospheric soil associated with Gastrodia elata. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1-3 was defined by a combination of TDDFT calculations, and the DP4+ probability analysis based on NMR chemical shift calculations. All of the new compounds 1-3 were evaluated for cytotoxicity and acetylcholinesterase inhibitory, compound 2 exhibited in vitro cytotoxic activities against five human cancer cell lines (HL-60, SMMC-7721, A549, MCF-7 and SW480) with IC(50) values ranging from 11.80 to 19.32 microM. Compounds 2 and 3 exhibited moderate AChE inhibitory activities. A putative biosynthetic pathway for the pyranonaphthoquinones was proposed.
ESTHER : Xie_2023_Fitoterapia__105690
PubMedSearch : Xie_2023_Fitoterapia__105690
PubMedID: 37757923

Title : Biosynthesis of diisooctyl 2,5-furandicarboxylate by Candida antarctica lipase B (CALB) immobilized on a macroporous epoxy resin - Mang_2023_Biotechnol.Appl.Biochem__
Author(s) : Mang R , Zhou Y , Du X , Zhou H , Zhu M
Ref : Biotechnol Appl Biochem , : , 2023
Abstract : Diisooctyl 2,5-furandicarboxylate (DEF), an ester derivative of 2,5-furandicarboxylic acid (FDCA, a bio-based platform chemical), resembles the physical and chemical properties of phthalates. Due to its excellent biodegradability, DEF is considered a safer alternative to the hazardous phthalate plasticizers. Although FDCA esters are currently mainly produced by chemical synthesis, the enzymatic synthesis of DEF is a green, promising alternative. The current study investigated the biosynthesis of DEF by Candida antarctica lipase B (CALB) immobilized on macroporous resins. Out of five macroporous resins (NKA-9, LX-1000EP, LX-1000HA, XAD-7HP, and XAD-8) evaluated, the LX-1000EP epoxy resin was identified as the best carrier for CALB, and the XAD-7HP weakly polar resin was identified as the second best. The optimal immobilization conditions were as follows: CALB (500 microL) and LX-1000EP (0.1 g) were incubated in phosphate butter (20 mM, pH 6.0) for 10 h at 35 degreesC. The resulting immobilized CALB (EP-CALB) showed an activity of 639 U/g in the hydrolysis of p-nitrophenyl acetate, with an immobilization efficiency of 87.8% and an activity recovery rate of 56.4%. Using 0.02 g EP-CALB as the catalyst in 10 mL toluene, and the molar ratio of 2,5-dimethyl furanediformate (1 mmol/mL) and isooctyl alcohol (4 mmol/mL) that was 1:4, a DEF conversion rate of 91.3% was achieved after a 24-h incubation at 50 degreesC. EP-CALB had similar thermal stability and organic solvent tolerance compared to Novozym 435, and both were superior to CALB immobilized on the XAD-7HP resin. EP-CALB also exhibited excellent operational stability, with a conversion rate of 52.6% after 10 repeated uses. EP-CALB could be a promising alternative to Novozym 435 in the biomanufacturing of green and safe plasticizers such as DEF.
ESTHER : Mang_2023_Biotechnol.Appl.Biochem__
PubMedSearch : Mang_2023_Biotechnol.Appl.Biochem__
PubMedID: 37264706

Title : Structural insights into the oligomeric effects on catalytic activity of a decameric feruloyl esterase and its application in ferulic acid production - Du_2023_Int.J.Biol.Macromol__126540
Author(s) : Du G , Wang Y , Zhang Y , Yu H , Liu S , Ma X , Cao H , Wei X , Wen B , Li Z , Fan S , Zhou H , Xin F
Ref : Int J Biol Macromol , :126540 , 2023
Abstract : Oligomeric feruloyl esterase (FAE) has great application prospect in industry due to its potentially high stability and fine-tuned activity. However, the relationship between catalytic capability and oligomeric structure remains undetermined. Here we identified and characterized a novel, cold-adapted FAE (BtFae) derived from Bacteroides thetaiotaomicron. Structural studies unraveled that BtFae adopts a barrel-like decameric architecture unique in esterase families. By disrupting the interface, the monomeric variant exhibited significantly reduced catalytic activity and stability toward methyl ferulate, potentially due to its impact on the flexibility of the catalytic triad. Additionally, our results also showed that the monomerization of BtFae severely decreased the ferulic acid release from de-starched wheat bran and insoluble wheat arabinoxylan by 75 % and 80 %, respectively. Collectively, this study revealed novel connections between oligomerization and FAE catalytic function, which will benefit for further protein engineering of FAEs at the quaternary structure level for improved industrial applications.
ESTHER : Du_2023_Int.J.Biol.Macromol__126540
PubMedSearch : Du_2023_Int.J.Biol.Macromol__126540
PubMedID: 37634773
Gene_locus related to this paper: bactn-BT4077

Title : Pharmacological effect and mechanism of orlistat in anti-tumor therapy: A review - Hao_2023_Medicine.(Baltimore)_102_e34671
Author(s) : Hao X , Zhu X , Tian H , Lai G , Zhang W , Zhou H , Liu S
Ref : Medicine (Baltimore) , 102 :e34671 , 2023
Abstract : Research has demonstrated that obesity is an important risk factor for cancer progression. Orlistat is a lipase inhibitor with promising therapeutic effects on obesity. In addition to being regarded as a slimming drug, a growing number of studies in recent years have suggested that orlistat has anti-tumor activities, while the underlying mechanism is still not well elucidated. This paper reviewed recent pharmacological effects and mechanisms of orlistat against tumors and found that orlistat can target cancer cells through activation or suppression of multiple signaling pathways. It can induce tumor cells apoptosis or death, interfere with tumor cells' cycles controlling, suppress fatty acid synthase activity, increase ferroptosis, inhibit tumor angiogenesis, and improve tumor cells glycolytic. Thus, this review may shed new light on anti-tumor mechanism and drug repurposing of orlistat, and anti-tumor drug development.
ESTHER : Hao_2023_Medicine.(Baltimore)_102_e34671
PubMedSearch : Hao_2023_Medicine.(Baltimore)_102_e34671
PubMedID: 37682175

Title : Correlation between smoking and serum lipoprotein-associated phospholipase A2 level in overweight and obese men - Zhou_2023_Zhong.Nan.Da.Xue.Xue.Bao.Yi.Xue.Ban_48_191
Author(s) : Zhou H , Zhao L
Ref : Zhong Nan Da Xue Xue Bao Yi Xue Ban , 48 :191 , 2023
Abstract : OBJECTIVES: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vaso-specific inflammatory marker that exacerbates atherosclerotic through inflammatory responses. It can be used to predict the occurrence of adverse cardiovascular events and to assess the residual risk of cardiovascular diseases. This study aims to investigate the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men, and to provide evidence for preventing the cardiovascular diseases. METHODS: Male subjects, who participated in health examination at the Health Management Center, Third Xiangya Hospital, Central South University from May 1, 2020 to April 30, 2021, were selected. The smoking status and other information were collected by the Self-test Scale of Physical Examination. According to the smoking status, they were divided into a never-smoking group, a current smoking group, a quit smoking group and a passive smoking group. According to the daily smoking amount, the current smoking subjects were divided into a <10 cigarettes group, a 10 to 20 cigarettes group, a 21 to 30 cigarettes group, and a >30 cigarettes group. According to the smoking years, the current smoking subjects were divided into a <5 years group, a 5 to 10 years group, a 11 to 20 years group, and a >20 years group.Serum Lp-PLA2 levels and other clinical indexes in different smoking groups were measured and compared, the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men was analyzed by logistic regression analysis. RESULTS: Serum Lp-PLA2 levels were significantly different between the never-smoking group and the current smoking group (P<0.05). Logistic regression analysis showed that, before adjusting other influencing factors and in terms of smoking status, the current smoking group (OR=1.81, 95% CI 1.27 to 2.58, P<0.01) and the quit smoking group (OR=2.09, 95% CI 1.12 to 3.90, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the passive smoking group had no correlation with serum Lp-PLA2 levels (OR=1.27, 95% CI 0.59 to 2.73, P>0.05). In terms of daily smoking amount, the 10 to 20 cigarettes group (OR=2.09, 95% CI 1.40 to 3.12, P<0.001) and the 21 to 30 cigarettes group (OR=1.98, 95% CI 1.22 to 3.20, P<0.01) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <10 cigarettes group (OR=1.45, 95% CI 0.81 to 2.60, P>0.05) and the >30 cigarettes group (OR=1.17, 95% CI 0.60 to 2.28, P>0.05) had no correlation with serum Lp-PLA2 levels. In terms of smoking years, the 5 to 10 years group (OR=1.94, 95% CI 1.07 to 3.53, P<0.05), the 11 to 20 years group (OR=2.06, 95% CI 1.33 to 3.18, P<0.01), and the >20 years group (OR=1.66, 95% CI 1.11 to 2.47, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <5 years group had no correlation with serum Lp-PLA2 levels (OR=1.12, 95% CI 0.38 to 3.33, P>0.05). After adjusting for age and other indicators, the correlation between smoking years and serum Lp-PLA2 levels was the same as before adjustment among the above smoking groups, except that the correlation between the smoking 5 to 10 years group and serum Lp-PLA2 levels was not significant (OR=1.77, 95% CI 0.95 to 3.29, P>0.05). CONCLUSIONS: Smoking is correlated with serum Lp-PLA2 levels in overweight and obese men.
ESTHER : Zhou_2023_Zhong.Nan.Da.Xue.Xue.Bao.Yi.Xue.Ban_48_191
PubMedSearch : Zhou_2023_Zhong.Nan.Da.Xue.Xue.Bao.Yi.Xue.Ban_48_191
PubMedID: 36999465

Title : Biosynthesis of trans-AT PKS-Derived Shuangdaolides Featuring a trans-acting Enzyme for Online Epoxidation - Liu_2023_ACS.Chem.Biol__
Author(s) : Liu Y , Zhou H , Zhao S , Hao X , Dai G , Zhong L , Ren X , Sui H , Zhang Y , Yan F , Bian X
Ref : ACS Chemical Biology , : , 2023
Abstract : Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) synthesize natural products with intricate structures and potent biological activities. They generally contain various unusual modules or trans-acting enzymes. Herein, we report the trans-AT PKS-derived biosynthetic pathway of the shuangdaolide with a rare internal 2-hydroxycyclopentenone moiety. The multidomain protein SdlR catalyzes the synthesis of 16,17-epoxide during polyketide chain elongation. The SdlR contains a ketoreductase, an acyl carrier protein, a flavoprotein monooxygenase, and a serine hydrolase domain. This online epoxidation occurs at unusual positions away from the thioester. Then, two tailoring enzymes, SdlB and SdlQ, convert a methylene to a carbonyl group and oxidize a hydroxyl group to a carbonyl group, respectively. The following spontaneous opening of 16,17-epoxide induces the formation of a new C-C bond to generate the 2-hydroxycyclopentenone moiety. The characterization of the shuangdaolide pathway extends the understanding of the trans-AT PKSs, facilitating the mining and identification of this class of natural products.
ESTHER : Liu_2023_ACS.Chem.Biol__
PubMedSearch : Liu_2023_ACS.Chem.Biol__
PubMedID: 37992317

Title : Smartphone-based colorimetric sensor array using gold nanoparticles for rapid distinguishment of multiple pesticides in real samples - Zhao_2023_Food.Chem_404_134768
Author(s) : Zhao T , Liang X , Guo X , Yang X , Guo J , Zhou X , Huang X , Zhang W , Wang Y , Liu Z , Jiang Z , Zhou H
Ref : Food Chem , 404 :134768 , 2023
Abstract : A simple, sensitive method for pesticide distinguishment based on a colorimetric sensor array using diverse gold nanoparticles (AuNPs) at room temperature is presented in this study. Acetylcholinesterase (AChE) hydrolysis ability was influenced by different pesticides and produced different concentrations of thiocholine by hydrolyzing acetylthiocholine iodide (ATCh). Thiocholine could be easily linked to the AuNPs through an Aus-sS covalent bond, and AuNPs underwent aggregation, resulting in a visible color change due to alteration of surface plasmon resonance properties. Based on these results, we successfully distinguished eight pesticides (glyphosate, thiram, imidacloprid, tribenuron methyl, nicosulfuron, thifensulfuron methyl, dichlorprop, and fenoprop) utilizing five different AuNPs by colorimetric assay. The limit of detection (LOD) of this visual method for all pesticides was less than 1.5x 10(-7) M, which was more sensitive than the U.S. Environmental Protection Agency regulations specify (1.18s-s3.91x10(-6) M). This method was further improved by combining a portable smartphone device with a color picking application using (color name AR) and RGB (red, green, blue) values. The method was successfully applied to pesticide residue distinguishment in real samples by linear discriminant analysis (LDA).
ESTHER : Zhao_2023_Food.Chem_404_134768
PubMedSearch : Zhao_2023_Food.Chem_404_134768
PubMedID: 36444090

Title : Identification and analysis of the secretome of plant pathogenic fungi reveals lifestyle adaptation - Jia_2023_Front.Microbiol_14_1171618
Author(s) : Jia M , Gong X , Fan M , Liu H , Zhou H , Gu S , Liu Y , Dong J
Ref : Front Microbiol , 14 :1171618 , 2023
Abstract : The secretory proteome plays an important role in the pathogenesis of phytopathogenic fungi. However, the relationship between the large-scale secretome of phytopathogenic fungi and their lifestyle is not fully understood. In the present study, the secretomes of 150 plant pathogenic fungi were predicted and the characteristics associated with different lifestyles were investigated. In total, 94,974 secreted proteins (SPs) were predicted from these fungi. The number of the SPs ranged from 64 to 1,662. Among these fungi, hemibiotrophic fungi had the highest number (average of 970) and proportion (7.1%) of SPs. Functional annotation showed that hemibiotrophic and necrotroph fungi, differ from biotrophic and symbiotic fungi, contained much more carbohydrate enzymes, especially polysaccharide lyases and carbohydrate esterases. Furthermore, the core and lifestyle-specific SPs orthogroups were identified. Twenty-seven core orthogroups contained 16% of the total SPs and their motif function annotation was represented by serine carboxypeptidase, carboxylesterase and asparaginase. In contrast, 97 lifestyle-specific orthogroups contained only 1% of the total SPs, with diverse functions such as PAN_AP in hemibiotroph-specific and flavin monooxygenases in necrotroph-specific. Moreover, obligate biotrophic fungi had the largest number of effectors (average of 150), followed by hemibiotrophic fungi (average of 120). Among these effectors, 4,155 had known functional annotation and pectin lyase had the highest proportion in the functionally annotated effectors. In addition, 32 sets of RNA-Seq data on pathogen-host interactions were collected and the expression levels of SPs were higher than that of non-SPs, and the expression level of effector genes was higher in biotrophic and hemibiotrophic fungi than in necrotrophic fungi, while secretase genes were highly expressed in necrotrophic fungi. Finally, the secretory activity of five predicted SPs from Setosphearia turcica was experimentally verified. In conclusion, our results provide a foundation for the study of pathogen-host interaction and help us to understand the fungal lifestyle adaptation.
ESTHER : Jia_2023_Front.Microbiol_14_1171618
PubMedSearch : Jia_2023_Front.Microbiol_14_1171618
PubMedID: 37152749

Title : Serum cholinesterase may independently predict prognosis in non-small-cell lung cancer - Ran_2022_BMC.Cancer_22_93
Author(s) : Ran H , Ma J , Cai L , Zhou H , Yuan Z , Chen Y , Chang W , Huang Y , Xiao Y
Ref : BMC Cancer , 22 :93 , 2022
Abstract : BACKGROUND: Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients. METHODS: A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients. RESULTS: The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67-0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR < 2.95, HR: 0.71, 95% CI: 0.56-0.89, p = 0.003), of adenocarcinoma (HR: 0.66, 95% CI: 0.54-0.80, p < 0.001), in advanced stage (HR: 0.77, 95% CI: 0.66-0.92, p < 0.01), and received chemotherapy (HR: 0.75, 95% CI: 0.59-0.96, p < 0.02). CONCLUSION: Baseline ChE may have independent prognostic value for NSCLC patients. Longitudinal studies should be performed to corroborate this finding.
ESTHER : Ran_2022_BMC.Cancer_22_93
PubMedSearch : Ran_2022_BMC.Cancer_22_93
PubMedID: 35062903

Title : Improved Aitongxiao prescription (I-ATXP) induces apoptosis, cell cycle arrest and blocks exosomes release in hepatocellular carcinoma (HCC) cells - Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
Author(s) : Huang MB , Gao Z , Xia M , Zhao X , Fan X , Lin S , Zhang L , Huang L , Wei A , Zhou H , Wu JY , Roth WW , Bond VC , Leng J
Ref : Int Journal de Physiologie Pathophysiol Pharmacol , 14 :90 , 2022
Abstract : BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy globally, after lung cancer, accounting for 85-90% of primary liver cancer. Hepatitis B virus (HBV) infection is considered the leading risk factor for HCC development in China. HCC is a highly malignant cancer whose metastasis is primarily influenced by the tumor microenvironment. The role of exosomes in cancer development has become the focus of much research due to the many newly described contents of exosomes, which may contribute to tumorigenesis. However, the possible role exosomes play in the interactions between HCC cells and their surrounding hepatic milieu is mainly unknown. We discovered an Improved Aitongxiao Prescription (I-ATXP): an 80% alcohol extract from a mix of 15 specific plant and animal compounds, which had been shown to have an anticancer effect through inducing apoptosis and cell cycle arrest and blocking exosomes release in HCC cells. However, the anticancer mechanism of I-ATXP on human liver carcinoma is still unclear. OBJECTIVE: Due to its inhibitory effects on chemical carcinogenesis and inflammation, I-ATXP has been proposed as an effective agent for preventing or treating human liver carcinoma. In this study, we aimed to explore the effect of I-ATXP on proliferation, apoptosis, and cell cycles of different HCC cell lines. We investigated the impact of I-ATXP on exosomes' secretion derived from these HCC cells. METHODS: The inhibitory effect of I-ATXP on proliferation and cytotoxicity of HepG2, SMMC7721, HKCL-C3 HCC cell lines, and MIHA immortalized hepatocyte cell line was assessed by CCK-8 assay. The cell cycle distribution and cell apoptosis were determined by flow cytometry using Annexin V-FITC/PI staining. The expression of Alix and CD63 of exosome marker proteins was detected by western blotting. The exosome protein concentration was measured by a fluorescent plate reader. The exosome-specific enzyme activity was measured by acetylcholinesterase (AchE) assay, and exosome morphological characteristics were identified by transmission electron microscopy (TEM). RESULTS: I-ATXP inhibited the growth of HCC cells in a dose and time-dependent manner. Flow cytometry analysis showed that I-ATXP induced G0/G1 phase arrest and cell apoptosis. The I-ATX reduced HepG2, SMMC7721, and HKCI-C HCC cell lines exosomes release and low-dose I-ATXP significantly enhanced the growth inhibition induced by 5-Fu. Western blot analysis shows that after HCC cell lines were treated with various concentrations of I-ATXP (0.125-1 mg/ml) for 24 h, exosomes derived from three different HCC cells expressed exosome-specific proteins Alix and CD63. Compared with the untreated group, with the increment of the concentration of I-ATXP, the expression of exosome-specific proteins Alix and CD63 were reduced. These results suggest that I-ATXP can inhibit the release of exosomes with Alix and CD63 protein from HCC cells. CONCLUSIONS: I-ATXP is a traditional Chinese medicine that acts as an effective agent for preventing or treating human liver carcinoma. (i) I-ATXP can effectively inhibit cell proliferation of different HCC cells in a time and dose-dependent manner. Compared with 5-Fu, I-ATXP exhibited more selective proliferation inhibition in HCC cells, displaying traditional Chinese medicine advantages on tumor therapy and providing the experimental basis for I-ATXP clinical application. (ii) I-ATXP can induce apoptosis and cell cycle arrest in HCC cells. The CCK-8 assay results indicated that I-ATXP could inhibit HCC cell proliferation mediated by apoptosis and cell cycle arrest. (iii) I-ATXP can inhibit both the exosome releases and expression of CD63, and Alix derived from HCC cells, but the exosomes derived from liver cancer cells affect liver cancer cells' biological properties such as proliferation, invasion, and migration. These suggest that I-ATXP may affect HCC cells via regulation of exosomes of HCC cells, further indicating the potential clinical values of I-ATXP for the prevention or treatment of human liver carcinoma.
ESTHER : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedSearch : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedID: 35619665

Title : Altereporenes A-E, five epoxy octa-hydronaphthalene polyketides produced by an endophytic fungus Alternaria sp. YUD20002 - Xia_2022_RSC.Adv_12_22295
Author(s) : Xia DD , Duan HJ , Xie F , Xie TP , Zhang Y , Sun Y , Lu JM , Gao YH , Zhou H , Ding ZT
Ref : RSC Adv , 12 :22295 , 2022
Abstract : Five previously undescribed epoxy octa-hydronaphthalene polyketides, altereporenes A-E (1-5) were isolated from rice culture of the endophytic fungus Alternaria sp. YUD20002 derived from the tubers of Solanum tuberosum. Their structures were determined on the basis of comprehensive spectroscopic analyses, while the absolute configurations were elucidated by the comparison of experimental and calculated specific rotations. Meanwhile, the antimicrobial, cytotoxic, anti-inflammatory and acetylcholinesterase inhibitory activities of compounds 1-5 were also investigated.
ESTHER : Xia_2022_RSC.Adv_12_22295
PubMedSearch : Xia_2022_RSC.Adv_12_22295
PubMedID: 36043060

Title : A reverse catalytic triad Asp containing loop shaping a wide substrate binding pocket of a feruloyl esterase from Lactobacillus plantarum - Zhang_2021_Int.J.Biol.Macromol_184_92
Author(s) : Zhang H , Wen B , Liu Y , Du G , Wei X , Khandaker S , Zhou H , Fan S , Wang F , Wang Y , Xin F
Ref : Int J Biol Macromol , 184 :92 , 2021
Abstract : Feruloyl esterase is an indispensable biocatalyst in food processing, pesticide and pharmaceutical industries, catalyzing the cleavage of the ester bond cross-linked between the polysaccharide side chain of hemicellulose and ferulic acid in plant cell walls. LP_0796 from Lactobacillus plantarum was identified as a feruloyl esterase that may have potential applications in the food industry, but the lack of the substrate recognition and catalytic mechanisms limits its application. Here, LP_0796 showed the highest activity towards methyl caffeate at pH 6.6 and 40 degreesC. The crystal structure of LP_0796 was determined at 2.5 A resolution and featured a catalytic triad Asp195-containing loop facing the opposite direction, thus forming a wider substrate binding pocket. Molecular docking simulation and site-directed mutagenesis studies further demonstrated that in addition to the catalytic triad (Ser94, Asp195, His225), Arg125 and Val128 played essential roles in the function of the active site. Our data also showed that Asp mutation of Ala23 and Ile198 increased the catalytic efficiency to 4- and 5-fold, respectively. Collectively, this work provided a better understanding of the substrate recognition and catalytic mechanisms of LP_0796 and may facilitate the future protein design of this important feruloyl esterase.
ESTHER : Zhang_2021_Int.J.Biol.Macromol_184_92
PubMedSearch : Zhang_2021_Int.J.Biol.Macromol_184_92
PubMedID: 34116094
Gene_locus related to this paper: lacpl-LP.0796

Title : The alpha-Helical Cap Domain of a Novel Esterase from Gut Alistipes shahii Shaping the Substrate-Binding Pocket - Wei_2021_J.Agric.Food.Chem__
Author(s) : Wei X , Wang YL , Wen BT , Liu SJ , Wang L , Sun L , Gu TY , Li Z , Bao Y , Fan SL , Zhou H , Wang F , Xin F
Ref : Journal of Agricultural and Food Chemistry , : , 2021
Abstract : The human gut microbiota regulates nutritional metabolism, especially by encoding specific ferulic acid esterases (FAEs) to release functional ferulic acid (FA) from dietary fiber. In our previous study, we observed seven upregulated FAE genes during in vitro fecal slurry fermentation using wheat bran. Here, a 29 kDa FAE (AsFAE) from Alistipes shahii of Bacteroides was characterized and identified as the type-A FAE. The X-ray structure of AsFAE has been determined, revealing a unique alpha-helical domain comprising five alpha-helices, which was first characterized in FAEs from the gut microbiota. Further molecular docking analysis and biochemical studies revealed that Tyr100, Thr122, Tyr219, and Ile220 are essential for substrate binding and catalytic efficiency. Additionally, Glu129 and Lys130 in the cap domain shaped the substrate-binding pocket and affected the substrate preference. This is the first report on A. shahii FAE, providing a theoretical basis for the dietary metabolism in the human gut.
ESTHER : Wei_2021_J.Agric.Food.Chem__
PubMedSearch : Wei_2021_J.Agric.Food.Chem__
PubMedID: 33979121
Gene_locus related to this paper: 9bact-d4inh0

Title : AlphaFold 2: Why It Works and Its Implications for Understanding the Relationships of Protein Sequence, Structure, and Function - Skolnick_2021_J.Chem.Inf.Model__
Author(s) : Skolnick J , Gao M , Zhou H , Singh S
Ref : J Chem Inf Model , : , 2021
Abstract : AlphaFold 2 (AF2) was the star of CASP14, the last biannual structure prediction experiment. Using novel deep learning, AF2 predicted the structures of many difficult protein targets at or near experimental resolution. Here, we present our perspective of why AF2 works and show that it is a very sophisticated fold recognition algorithm that exploits the completeness of the library of single domain PDB structures. It has also learned local side chain packing rearrangements that enable it to refine proteins to high resolution. The benefits and limitations of its ability to predict the structures of many more proteins at or close to atomic detail are discussed.
ESTHER : Skolnick_2021_J.Chem.Inf.Model__
PubMedSearch : Skolnick_2021_J.Chem.Inf.Model__
PubMedID: 34586808

Title : Kuwanon G protects HT22 cells from advanced glycation end product-induced damage - Gan_2021_Exp.Ther.Med_21_425
Author(s) : Gan WJ , Gao CL , Zhang WQ , Gu JL , Zhao TT , Guo HL , Zhou H , Xu Y , Yu LL , Li LF , Gui DK , Xu YH
Ref : Exp Ther Med , 21 :425 , 2021
Abstract : The incidence of diabetic encephalopathy is increasing as the population ages. Evidence suggests that formation and accumulation of advanced glycation end products (AGEs) plays a pivotal role in disease progression, but limited research has been carried out in this area. A previous study demonstrated that Kuwanon G (KWG) had significant anti-oxidative stress and anti-inflammatory properties. As AGEs are oxidative products and inflammation is involved in their generation it is hypothesized that KWG may have effects against AGE-induced neuronal damage. In the present study, mouse hippocampal neuronal cell line HT22 was used. KWG was shown to significantly inhibit AGE-induced cell apoptosis in comparison with a control treatment, as determined by both MTT and flow cytometry. Compared with the AGEs group, expression of pro-apoptotic protein Bax was reduced and expression of anti-apoptotic protein Bcl-2 was increased in the AGEs + KWG group. Both intracellular and extracellular levels of acetylcholine and choline acetyltransferase were significantly elevated after KWG administration in comparison with controls whilethe level of acetylcholinesterase decreased. These changes in protein expression were accompanied by increased levels of superoxide dismutase and glutathione peroxidase synthesis and reduced production of malondialdehyde and reactive oxygen species. Intracellular signaling pathway protein levels were determined by western blot and immunocytochemistry. KWG administration was found to prevent AGE-induced changes to the phosphorylation levels of Akt, IkappaB-alpha, glycogen synthase kinase 3 (GSK3)-alpha and beta, p38 MAPK and NF-kappaB p65 suggesting a potential neuroprotective effect of KWG against AGE-induced damage was via the PI3K/Akt/GSK3alphabeta signaling pathway. The findings of the present study suggest that KWG may be a potential treatment for diabetic encephalopathy.
ESTHER : Gan_2021_Exp.Ther.Med_21_425
PubMedSearch : Gan_2021_Exp.Ther.Med_21_425
PubMedID: 33747164

Title : Enzymatic acylation of rutin with benzoic acid ester and lipophilic, antiradical, and antiproliferative properties of the acylated derivatives - Li_2021_J.Food.Sci__
Author(s) : Li HM , Xu TT , Peng QX , Chen YS , Zhou H , Lu YY , Yan RA
Ref : J Food Sci , : , 2021
Abstract : Rutin (3',4',5,7-tetrahydroxy-flavone-3-rutinoside) was enzymatically acylated with benzoic acid and its esters (methyl benzoate and vinyl benzoate) using Thermomyces lanuginosus lipase (Lipozyme TLIM). The acylation reaction was optimized by varying the reaction medium, reaction temperature, acyl donor, substrate molar ratio, and reaction time. The highest conversion yield (76%) was obtained in tert-amyl alcohol (60 degreesC, 72 hr) using vinyl benzoate (molar ratio of 1:10) as acyl donor. The acylation occurred at the 2'''-OH and 4'''-OH of the rhamnose unit and the 2''-OH position of the glucose moieties. Three novel rutin acylated derivatives (compounds 1-3) were purified and characterized by HR-MS and 1D and 2D NMR spectroscopy. We found that acylation significantly improved lipophilicity, capacity to inhibit lipid peroxidation, anticancer capacity and substantially maintained the antioxidant activity of rutin. This research provides important insights in the acylation of flavonoids with different glycosyl moieties. PRACTICAL APPLICATION: In this study, three novel rutin derivatives were successfully synthesized and the highest conversion yield (76%) was obtained by reacting the rutin and vinyl benzoate at molar ratio of 1:10 in tert-amyl alcohol for 72 hr at 60 degreesC. Introducing a benzoic acid substituent into rutin molecule significantly improved their lipophilicity and inhibition of lipid peroxidation in lipophilic system. Furthermore, this study demonstrated that acylation significantly improved anticancer capacity and substantially maintained the antioxidant activity.
ESTHER : Li_2021_J.Food.Sci__
PubMedSearch : Li_2021_J.Food.Sci__
PubMedID: 33844282

Title : DECR1 directly activates HSL to promote lipolysis in cervical cancer cells - Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
Author(s) : Zhou H , Zhang J , Yan Z , Qu M , Zhang G , Han J , Wang F , Sun K , Wang L , Yang X
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159090 , 2021
Abstract : Fatty acids have a high turnover rate in cancer cells to supply energy for tumor growth and proliferation. Lipolysis is particularly important for the regulation of fatty acid homeostasis and in the maintenance of cancer cells. In the current study, we explored how 2,4-Dienoyl-CoA reductase (DECR1), a short-chain dehydrogenase/reductase associated with mitochondrial and cytoplasmic compartments, promotes cancer cell growth. We report that DECR1 overexpression significantly reduced the triglyceride (TAG) content in HeLa cells; conversely, DECR1 silencing increased intracellular TAG content. Subsequently, our experiments demonstrate that DECR1 promotes lipolysis via effects on hormone sensitive lipase (HSL). The direct interaction of DECR1 with HSL increases HSL phosphorylation and activity, facilitating the translocation of HSL to lipid droplets. The ensuing enhancement of lipolysis thus increases the release of free fatty acids. Downstream effects include the promotion of cervical cancer cell migration and growth, associated with the enhanced levels of p62 protein. In summary, high levels of DECR1 serves to enhance lipolysis and the release of fatty acid energy stores to support cervical cancer cell growth.
ESTHER : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedSearch : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedID: 34896618

Title : Discovery, biological evaluation and molecular dynamic simulations of butyrylcholinesterase inhibitors through structure-based pharmacophore virtual screening - Lu_2021_Future.Med.Chem_13_769
Author(s) : Lu T , Liu Y , Chen H , Han C , Feng X , Zhou H , Li Y
Ref : Future Med Chem , 13 :769 , 2021
Abstract : Aim: Butyrylcholinesterase (BChE) is a crucial therapeutic target because it is associated with multiple pathological elements of Alzheimer's disease (AD). An integrated computational strategy was employed to exploit effective BChE inhibitors. Methods & results: Ten compounds derived from the Enamine database by structure-based pharmacophore virtual screening were further evaluated for biological activity; out of the ten, only five had an IC(50) of less than 100 microM. Among these five compounds, a new molecule, 970180, presented the most potency against BChE, with an IC(50) of 4.24 +/- 0.16 microM, and acted as a mixed-type inhibitor. Molecular dynamic simulations and absorption, distribution, metabolism and excretion prediction further confirmed its high potential as a good candidate of BChE inhibitor. Furthermore, cytotoxicity of molecule 970180 was not observed at concentrations up to 50 microM, and the molecule also showed a prominent neuroprotective effect compared with tacrine at 25 and 50 microM. Conclusion: This study provides an effective structure-based pharmacophore virtual screening method to discover BChE inhibitors and provide new choices for the development of BChE inhibitors, which may be beneficial for AD patients.
ESTHER : Lu_2021_Future.Med.Chem_13_769
PubMedSearch : Lu_2021_Future.Med.Chem_13_769
PubMedID: 33759552

Title : Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach - Huang_2020_J.Med.Chem_63_7052
Author(s) : Huang F , Hu H , Wang K , Peng C , Xu W , Zhang Y , Gao J , Liu Y , Zhou H , Huang R , Li M , Shen J , Xu Y
Ref : Journal of Medicinal Chemistry , 63 :7052 , 2020
Abstract : Covalent ligands are of great interest as therapeutic drugs or biochemical tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound 8, which has a more than 130,000-fold and 3900-fold increase in potency and selectivity, respectively, compared to those of the covalent fragment. Furthermore, fluorescent probes with high selectivity and sensitivity are developed to characterize Lp-PLA2 and its enzymatic activity in vitro or even in living cells in a way more convenient than immunoblotting tests or immunofluorescence imaging. Overall, we provide a paradigm for application of the covalent fragment-based strategy in covalent ligand discovery and the advantage of enol-cyclocarbamate as a new warhead in designing covalent inhibitors of serine hydrolases.
ESTHER : Huang_2020_J.Med.Chem_63_7052
PubMedSearch : Huang_2020_J.Med.Chem_63_7052
PubMedID: 32459096
Gene_locus related to this paper: human-PLA2G7

Title : Endothelial Lipase Exerts its Anti-Atherogenic Effect through Increased Catabolism of beta-VLDLs - Yan_2020_J.Atheroscler.Thromb__
Author(s) : Yan H , Niimi M , Wang C , Chen Y , Zhou H , Matsuhisa F , Nishijima K , Kitajima S , Zhang B , Yokomichi H , Nakajima K , Murakami M , Zhang J , Chen YE , Fan J
Ref : J Atheroscler Thromb , : , 2020
Abstract : AIM: Endothelial lipase (EL) plays an important role in lipoprotein metabolism. Our recent study showed that increased hepatic expression of EL attenuates diet-induced hypercholesterolemia, thus subsequently reducing atherosclerosis in transgenic (Tg) rabbits. However, it is yet to be determined whether increased EL activity itself per se is anti-atherogenic or whether the anti-atherogenic effect of EL is exclusively dependent on its lipid-lowering effect. METHODS: To determine the mechanisms underlying EL-mediated anti-atherogenic effect, we fed Tg and non-Tg rabbits diets containing different amounts of cholesterol to make their plasma cholesterol levels similarly high. Sixteen weeks later, we examined their lipoprotein profiles and compared their susceptibility to atherosclerosis. RESULTS: With Tg and non-Tg rabbits having hypercholesterolemia, the plasma lipids and lipoprotein profiles were observed to be similar, while pathological examinations revealed that lesion areas of both aortic and coronary atherosclerosis of Tg rabbits were not significantly different from non-Tg rabbits. Moreover, Tg rabbits exhibited faster clearance of DiI-labeled beta-VLDLs than non-Tg rabbits. CONCLUSION: The results of our study suggest that the enhancement of beta-VLDL catabolism is the major mechanism for atheroprotective effects of EL in Tg rabbits.
ESTHER : Yan_2020_J.Atheroscler.Thromb__
PubMedSearch : Yan_2020_J.Atheroscler.Thromb__
PubMedID: 32448826

Title : Study on the Regulation of Earthworm Physiological Function under Cadmium Stress Based on a Compound Mathematical Model - Zhou_2020_Environ.Toxicol.Pharmacol__103499
Author(s) : Zhou H , Zhang T , Zhuang J , Xu M , Liu X , Shi Q , Zhou D
Ref : Environ Toxicol Pharmacol , :103499 , 2020
Abstract : A cadmium (Cd) stress test was carried out on Eisenia fetida in artificial soil. Six Cd concentration gradient solutions (0, 50, 100, 125, 250 and 500 mg/kg) were prepared. Two treatment groups, short-term stress and long-term stress, were established. The former lasted for 10 days, and the latter lasted for 30 days. The Biolog ECO-microplate culture method was used to determine the utilization of the 31 carbon sources by the microbes in earthworm homogenate. The total protein content (TP), peroxidase activity (POD), catalase activity (CAT), superoxide dismutase activity (SOD), glutathione peroxidase activity (GPX), glutathione-S-transferase activity (GST), malondialdehyde content (MDA) and acetylcholinesterase activity (AChE) in earthworm were determined in order to investigate the regulation of oxidative stress and the functional diversity of microbial communities in earthworms under Cd stress. By combining the entropy weight method (EW) and the technique for order preference by similarity to an ideal solution model (TOPSIS), the physiological functional indices of earthworms were assessed objectively and scientifically, and the physiological changes under the different stress periods were evaluated. The results showed that a Cd-tolerant dominant population appeared in the microbial community under Cd stress. In the short-term test, oxidative stress were more effective in coping with Cd stress than the microbial community, and oxidative stress regulated the microbial community functional diversity. Under long-term Cd stress, the regulatory effect was weak or non-existent. In this study, a new evaluation model was established to explore the regulation process of earthworm on its oxidation stress and the functional diversity of microbial communities under Cd stress, and provide a theoretical basis for revealing the detoxification mechanism of earthworms.
ESTHER : Zhou_2020_Environ.Toxicol.Pharmacol__103499
PubMedSearch : Zhou_2020_Environ.Toxicol.Pharmacol__103499
PubMedID: 32956818

Title : The rs1051931 G>A Polymorphism in the PLA2G7 Gene Confers Resistance to Immunoglobulin Therapy in Kawasaki Disease in a Southern Chinese Population - Gu_2020_Front.Pediatr_8_338
Author(s) : Gu X , Lin W , Xu Y , Che D , Tan Y , Lu Z , Pi L , Fu L , Zhou H , Jiang Z
Ref : Front Pediatr , 8 :338 , 2020
Abstract : Background: Kawasaki disease (KD) is a common cardiovascular disease in infants and young children, with fever, rash, and conjunctivitis as the main clinical manifestations, which can lead to the occurrence of coronary aneurysms. Intravenous immunoglobulin (IVIG) is the preferred treatment for KD patients, but 10-20% of patients are resistant to IVIG. Lipoprotein-associated phospholipase A 2 (Lp-PLA2) is a potential therapeutic target for coronary atherosclerotic heart disease, and the polymorphism of Phospholipase A2 Group VII (PLA2G7) is closely related to the activity of Lp-PLA2, of which rs1051931 is the strongest. Therefore, the rs1051931 polymorphism may be a predictor of IVIG resistance in KD patients. Methods: A total of 760 KD cases, including 148 IVIG-resistant patients and 612 IVIG-responsive patients, were genotyped for rs1051931 in PLA2G7, we compared the effects of rs1051931 on IVIG treatment in KD patients by odds ratios (OR) and 95% confidence interval (CI). Results: The homozygous mutation AA may be a protective factor for IVIG resistance in KD patients (adjusted OR = 3.47, 95% CI = 1.14-10.57, P = 0.0284) and is more evident in patients with KD aged <60 months (adjusted OR = 3.68, 95% CI = 1.10-12.28, P = 0.0399). Conclusions: The PLA2G7 rs1051931 G>A polymorphism may be suitable as a biomarker for the diagnosis or prognosis of IVIG resistance in KD in a southern Chinese population.
ESTHER : Gu_2020_Front.Pediatr_8_338
PubMedSearch : Gu_2020_Front.Pediatr_8_338
PubMedID: 32656171
Gene_locus related to this paper: human-PLA2G7

Title : The Trp183 is essential in lactonohydrolase ZHD detoxifying zearalenone and zearalenols - Zhou_2020_Biochem.Biophys.Res.Commun_522_986
Author(s) : Zhou H , Li L , Zhan B , Wang S , Li J , Hu XJ
Ref : Biochemical & Biophysical Research Communications , 522 :986 , 2020
Abstract : Lactonohydrolase ZHD can detoxify oestrogenic mycotoxin zearalenone and zearalenols through hydrolysis and decarboxylation. The detail mechanism, especially the role of Trp183, which interacts with substrate through p-pi interaction and one hydrogen bond, is still unknown. The Trp183 mutants abolished activity to ZEN, alpha-ZOL and beta-ZOL, except that W183F mutant retained about 40% activity against alpha-ZOL. In two W183F-reactant complex structures the reactants still bind at the active position and it suggested that this p-pi interaction takes responsible for the reactants recognization and allocation. Further, the ZHD-productant complex structures showed that the resorcinol ring of hydrolysed alpha-ZOL and hydrolysed beta-ZOL move a distance of one ring as compare to the resorcinol ring of reactant alpha-ZOL and beta-ZOL. The same movement also found in comparison of hydrolysed ZEN and ZEN. In the structure of W183F complex with hydrolysed alpha-ZOL the resorcinol ring of hydrolysed alpha-ZOL doesn't move as compare to the resorcinol ring of reactant alpha-ZOL. It suggested the Trp183 coordinated hydrogen bond takes responsible for the movement of the hydrolysed product. These functional and structural results suggested that Trp183 is essential for ZHD detoxifying zearalenone and zearalenols.
ESTHER : Zhou_2020_Biochem.Biophys.Res.Commun_522_986
PubMedSearch : Zhou_2020_Biochem.Biophys.Res.Commun_522_986
PubMedID: 31810602
Gene_locus related to this paper: biooc-ZHD101

Title : Self-assembly of lipase hybrid nanoflowers with bifunctional Ca(2+) for improved activity and stability - Zhang_2020_Enzyme.Microb.Technol_132_109408
Author(s) : Zhang Y , Sun W , Elfeky NM , Wang Y , Zhao D , Zhou H , Wang J , Bao Y
Ref : Enzyme Microb Technol , 132 :109408 , 2020
Abstract : Lipase ZC12, a cold-adapted lipase derived from Psychrobacter sp. ZY124, can be effectively activated by Ca(2+). Inspired by this significant property, we developed a novel immobilized lipase ZC12/Ca3(PO4)2 hybrid nanoflowers (LHNs). The LHNs have been characterized as a regular hierarchical flowerlike structure nanoflowers by scanning electron microscopy (SEM). Compared with free lipase ZC12, the LHNs exerted enhanced enzymatic activity of 206% and 2.31-fold in kcat/Km value, especially high specific activity at low temperature. After 7 successive cycles, the LHNs could still maintain its initial activity, demonstrating superior durability than the free lipase ZC12. Meanwhile, its stability basically kept unchanged in a wide range of temperature and pH. Finally, fructose laurate was transformed by the LHNs with 57.39% conversion rate which is twice as much as the free lipase. To sum up, these results validated that LHNs could emerge as an efficient immobilized lipase and possess the promising potential for practical applications.
ESTHER : Zhang_2020_Enzyme.Microb.Technol_132_109408
PubMedSearch : Zhang_2020_Enzyme.Microb.Technol_132_109408
PubMedID: 31731973
Gene_locus related to this paper: 9gamm-a0a1b1ijp3

Title : Inducing secondary metabolite production from Daldinia eschscholzii JC-15 by red ginseng medium - Wang_2019_Nat.Prod.Res__1
Author(s) : Wang BY , Yang YB , Yang XQ , Zhu CH , Yang S , Xu TT , Wang XY , Tan NH , Zhou H , Ding ZT
Ref : Nat Prod Res , :1 , 2019
Abstract : Red ginseng (RG) is one of the most popular herbal medicines and used as a dietary supplement in recent years. The bioactive ingredient in RG can induce the production of novel microbial metabolite from fermented RG. Using the one strain-many compounds strategy, the reinvestigation of the metabolites from Daldinia eschscholzii JC-15 cultured in red ginseng medium led to the isolation of an unprecedented benzopyran-naphthalene hybrid, daldinsin (1) and a new lactone (2). In this research, a new lactone, 8-hydroxylhelicascolide A (2) instead of helicascolide A was produced by the D. eschscholzii JC-15 induced by the red ginseng medium. Compound 1 showed anti-acetylcholinesterase activity with the inhibition ratio of 38.8% at 50 muM. Compound 2 indicated antimicrobial activities against Fusarium Solani, F. oxysporum, and Escherichia coli with MICs at 128 mug/mL. RG is therefore a promising activator in production of novel microbial metabolite.
ESTHER : Wang_2019_Nat.Prod.Res__1
PubMedSearch : Wang_2019_Nat.Prod.Res__1
PubMedID: 31111733

Title : Vicagrel enhances aspirin-induced inhibition of both platelet aggregation and thrombus formation in rodents due to its decreased metabolic inactivation - Jia_2019_Biomed.Pharmacother_115_108906
Author(s) : Jia YM , Ge PX , Zhou H , Ji JZ , Tai T , Gu TT , Zhu T , Li YF , Mi QY , Huang BB , Xie HG
Ref : Biomed Pharmacother , 115 :108906 , 2019
Abstract : Both aspirin and vicagrel are effective antiplatelet drugs, with the potential for concomitant use as another dual-antiplatelet therapy for the prevention of recurrent thrombotic or ischemic events. Because they both are the substrates of carboxylesterase 2 (CES2), aspirin attenuated the metabolic activation of and platelet response to vicagrel in mice treated with the two drugs concomitantly. In this study, we sought to clarify whether vicagrel could affect platelet responses to aspirin and their underlying mechanisms. Plasma levels of aspirin and salicylic acid were determined by liquid chromatography-tandem mass spectrometry, inhibition of arachidonic acid (AA)-induced whole-blood platelet aggregation by aspirin was assessed with an aggregometer, and their antithrombotic effects were evaluated by arteriovenous shunt thrombosis model. The results showed that concomitant use of vicagrel (5, 10, or 20 mg/kg) led to an average of 55% and 77% increases in systemic exposure of aspirin (Cmax and AUC0-t) and 2.8-fold increase in suppression of AA-induced platelet aggregation in mice when compared with use of aspirin alone. In the rat thrombus formation model, vicagrel (1 mg/kg) enhanced inhibition of thrombosis formation by aspirin (5 mg/kg), but not vice versa. We conclude that vicagrel increases platelet responses to aspirin and also enhances inhibition of thrombus formation of aspirin due to decreased CES2-catalyzed aspirin inactivation in rodents, and that an integrated net effect on thrombus formation in vivo is superior to inhibition of AA- or ADP-induced platelet aggregation ex vivo by either of the two drugs if taken concomitantly.
ESTHER : Jia_2019_Biomed.Pharmacother_115_108906
PubMedSearch : Jia_2019_Biomed.Pharmacother_115_108906
PubMedID: 31060007

Title : Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein - Zhou_2019_Nat.Commun_10_3068
Author(s) : Zhou H , Chen Y , Zhang S , Niu P , Qin K , Jia W , Huang B , Lan J , Zhang L , Tan W , Wang X
Ref : Nat Commun , 10 :3068 , 2019
Abstract : Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.
ESTHER : Zhou_2019_Nat.Commun_10_3068
PubMedSearch : Zhou_2019_Nat.Commun_10_3068
PubMedID: 31296843

Title : Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection - Jia_2019_Emerg.Microbes.Infect_8_760
Author(s) : Jia W , Channappanavar R , Zhang C , Li M , Zhou H , Zhang S , Zhou P , Xu J , Shan S , Shi X , Wang X , Zhao J , Zhou D , Perlman S , Zhang L
Ref : Emerg Microbes Infect , 8 :760 , 2019
Abstract : The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naive hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
ESTHER : Jia_2019_Emerg.Microbes.Infect_8_760
PubMedSearch : Jia_2019_Emerg.Microbes.Infect_8_760
PubMedID: 31130102

Title : Protoilludane-type sesquiterpenoids from Armillaria sp. by co-culture with the endophytic fungus Epicoccumsp. associated with Gastrodia elata - Li_2019_Bioorg.Chem_95_103503
Author(s) : Li HT , Tang LH , Liu T , Yang RN , Yang YB , Zhou H , Ding ZT
Ref : Bioorg Chem , 95 :103503 , 2019
Abstract : An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of eight new compounds, including five protoilludane-type sesquiterpenes (1-5) and three aryl esters (6-8), together with six known analogues (9-14). The assignments of their structures were conducted via extensive analyses of the spectroscopic data and comparison of experimental and calculatedelectronic circular dichroism(ECD)data. Notably, these new compounds were not present in the pure culture controls and were only detected in the co-cultures. Compound 4 is the first example of an ent-protoilludane sesquiterpenoid scaffold bearing a five-membered lactone. Compound 6 exhibited moderate in vitro cytotoxic activities against five human cancer cell lines (HL-60, A549, MCF-7, SMMC-7721, and SW480) with IC50 values ranging from 15.80 to 23.03 muM. Moreover, 6 showed weak acetylcholinesterase inhibitory activity (IC50 value of 23.85 muM).
ESTHER : Li_2019_Bioorg.Chem_95_103503
PubMedSearch : Li_2019_Bioorg.Chem_95_103503
PubMedID: 31855825

Title : New azaphilones and tremulane sesquiterpene from endophytic Nigrospora oryzae cocultured with Irpex lacteus - Zhou_2018_Fitoterapia_130_26
Author(s) : Zhou QY , Yang XQ , Zhang ZX , Wang BY , Hu M , Yang YB , Zhou H , Ding ZT
Ref : Fitoterapia , 130 :26 , 2018
Abstract : Five new metabolites belonging to two backbones of pulvilloric acid-type azaphilone and tremulane sesquiterpene were obtained and their structures were determined by spectral analysis. Based on the biogenesis analysis, tremulane sesquiterpenes were obtained from Irpex lacteus by the stimulation of mixed-culture. The antifungal selectivities of metabolites produced by fungus against their co-culture fungus and common pathogens, exhibited competitive interaction of this mix-culture. The tremulane sesquiterpene conocenol B produced by I. lacteus through the induction of Nigrospora oryzae showed selectivity of anti-fungal activity against its co-culture fungus, N. oryzae, with MICs at 16 mug/mL and 128 mug/mL against I. lacteus. The fungus can metabolize these new compounds to inhibit the growth of co-culture fungus while not inhibiting its own growth. Compound 5 was active against acetylcholinesterase (AChE) with a ratio of 35% at the concentration of 50 muM.
ESTHER : Zhou_2018_Fitoterapia_130_26
PubMedSearch : Zhou_2018_Fitoterapia_130_26
PubMedID: 30076888

Title : NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma - Jing_2018_Biosci.Rep_38_
Author(s) : Jing JS , Li H , Wang SC , Ma JM , Yu LQ , Zhou H
Ref : Bioscience Reports , 38 : , 2018
Abstract : N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan-Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan-Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.
ESTHER : Jing_2018_Biosci.Rep_38_
PubMedSearch : Jing_2018_Biosci.Rep_38_
PubMedID: 30413609
Gene_locus related to this paper: human-NDRG3

Title : ( R)- N-(1-Methyl-2-hydroxyethyl)-13-( S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes - Liu_2018_J.Med.Chem_61_8639
Author(s) : Liu Y , Ji L , Eno M , Kudalkar S , Li AL , Schimpgen M , Benchama O , Morales P , Xu S , Hurst D , Wu S , Mohammad KA , Wood JT , Zvonok N , Papahatjis DP , Zhou H , Honrao C , Mackie K , Reggio P , Hohmann AG , Marnett LJ , Makriyannis A , Nikas SP
Ref : Journal of Medicinal Chemistry , 61 :8639 , 2018
Abstract : The synthesis of potent metabolically stable endocannabinoids is challenging. Here we report a chiral arachidonoyl ethanolamide (AEA) analogue, namely, (13 S,1' R)-dimethylanandamide (AMG315, 3a), a high affinity ligand for the CB1 receptor ( Ki of 7.8 +/- 1.4 nM) that behaves as a potent CB1 agonist in vitro (EC50 = 0.6 +/- 0.2 nM). (13 S,1' R)-dimethylanandamide is the first potent AEA analogue with significant stability for all endocannabinoid hydrolyzing enzymes as well as the oxidative enzymes COX-2. When tested in vivo using the CFA-induced inflammatory pain model, 3a behaved as a more potent analgesic when compared to endogenous AEA or its hydrolytically stable analogue AM356. This novel analogue will serve as a very useful endocannabinoid probe.
ESTHER : Liu_2018_J.Med.Chem_61_8639
PubMedSearch : Liu_2018_J.Med.Chem_61_8639
PubMedID: 30196704

Title : Human UGT2B7 is the major isoform responsible for the glucuronidation of clopidogrel carboxylate - Ji_2018_Biopharm.Drug.Dispos_39_88
Author(s) : Ji JZ , Huang BB , Gu TT , Tai T , Zhou H , Jia YM , Mi QY , Zhang MR , Xie HG
Ref : Biopharmaceutics & Drug Disposition , 39 :88 , 2018
Abstract : Clopidogrel is predominantly hydrolyzed to clopidogrel carboxylic acid (CCA) by carboxylesterase 1, and subsequently CCA is glucuronidated to clopidogrel acyl glucuronide (CAG) by uridine diphosphate-glucuronosyltransferases (UGTs); however, the UGT isoenzymes glucuronidating CCA remain unidentified to date. In this study, the glucuronidation of CCA was screened with pooled human liver microsomes (HLMs) and 7 human recombinant UGT (rUGT) isoforms. Results indicated that rUGT2B7 exhibited the highest catalytical activity for the CCA glucuronidation as measured with a mean Vmax value of 120.9 pmol/min/mg protein, 3- to 12-fold higher than that of the other rUGT isoforms tested. According to relative activity factor approach, the relative contribution of rUGT2B7 to CCA glucuronidation was estimated to be 58.6%, with the minor contributions (3%) from rUGT1A9. Moreover, the glucuronidation of CCA followed Michaelis-Menten kinetics with a mean Km value of 372.9 muM and 296.4 muM for pooled HLMs and rUGT2B7, respectively, showing similar affinity for both. The formation of CAG was significantly inhibited by azidothymidine and gemfibrozil (well-characterized UGT2B7 substrates) in a concentration-dependent manner, or by fluconazole (a typical UGT2B7-selective inhibitor) in a time-dependent manner, for both HLMs and rUGT2B7, respectively. In addition, CCA inhibited azidothymidine glucuronidation (catalyzed almost exclusively by UGT2B7) by HLMs and rUGT2B7 in a concentration-dependent manner, indicating that CCA is a substrate of UGT2B7. These results reveal that UGT2B7 is the major enzyme catalyzing clopidogrel glucuronidation in the human liver, and that there is the potential for drug-drug interactions between clopidogrel and the other substrate drugs of UGT2B7.
ESTHER : Ji_2018_Biopharm.Drug.Dispos_39_88
PubMedSearch : Ji_2018_Biopharm.Drug.Dispos_39_88
PubMedID: 29240983

Title : Controlled synthesis of polydopamine: A new strategy for highly sensitive fluorescence turn-on detection of acetylcholinesterase activity - Yang_2018_Mikrochim.Acta_185_132
Author(s) : Yang M , Zhou H , Zhang Y , Hu Z , Niu N , Yu C
Ref : Mikrochim Acta , 185 :132 , 2018
Abstract : A new water soluble fluorescent coronene probe (CTCA) was synthesized and is shown to display strong fluorescence (with excitation/emission maxima at 313/450 nm) in aqueous solution. Dopamine was oxidized under air to form polydopamine (PDA) which quenches the fluorescence of CTCA. The enzyme acetylcholinesterase (AChE) is known catalyze the hydrolysis of acetylthiocholine to produce thiocholine. Thiocholine inhibits the polymerization of DA, and this leads to recovery in CTCA fluorescence. These findings form the basis for a new method for detection of AChE activity. The assay has a detection limit as low as 0.05 mU.mL(-1) of AChE. It is highly selective, and other enzymes do no noticeably interfere. It was applied to the determination of AChE activity in (spiked) human serum, and of AChE inhibitors in (spiked) lake water samples. Graphical abstract Controlled synthesis of polydopamine for the highly sensitive and selective sensing of AChE activity is reported for the first time.
ESTHER : Yang_2018_Mikrochim.Acta_185_132
PubMedSearch : Yang_2018_Mikrochim.Acta_185_132
PubMedID: 29594716

Title : Aspirin Attenuates the Bioactivation of and Platelet Response to Vicagrel in Mice - Jia_2018_J.Cardiovasc.Pharmacol_72_252
Author(s) : Jia YM , Gu TT , Ji JZ , Tai T , Zhang MR , Huang BB , Zhou H , Mi QY , Xie HG
Ref : J Cardiovasc Pharmacol , 72 :252 , 2018
Abstract : Vicagrel, a novel acetate analogue of clopidogrel, exerts more potent antiplatelet effect than clopidogrel in rodents. Relevant evidence indicated that aspirin and vicagrel are the drug substrate for carboxylesterase 2. Accordingly, it is deduced that concomitant use of aspirin could attenuate the bioactivation of and platelet response to vicagrel. To clarify whether there could be such an important drug-drug interaction, the differences in both the formation of vicagrel active metabolite H4 and the inhibition of adenosine diphosphate-induced platelet aggregation by vicagrel were measured and compared between mice treated with vicagrel alone or in combination with aspirin. The plasma H4 concentration was determined by liquid chromatography-tandem mass spectrometry, and the inhibition of platelet aggregation by vicagrel was assessed by whole-blood platelet aggregation. Compared with vicagrel (2.5 mg.kg) alone, concurrent use of aspirin (5, 10, or 20 mg.kg) significantly decreased systemic exposure of H4, an average of 38% and 41% decrease in Cmax and AUC0-infinity in mice when in combination with aspirin at 10 mg.kg, respectively. Furthermore, concomitant use of aspirin (10 mg.kg) and vicagrel (2.5 mg.kg) resulted in an average of 66% reduction in the inhibition of adenosine diphosphate-induced platelet aggregation by vicagrel. We conclude that aspirin significantly attenuates the formation of vicagrel active metabolite H4 and platelet response to vicagrel in mice, and that such an important drug-drug interaction would appear in clinical settings if vicagrel is taken with aspirin concomitantly when marketed in the future.
ESTHER : Jia_2018_J.Cardiovasc.Pharmacol_72_252
PubMedSearch : Jia_2018_J.Cardiovasc.Pharmacol_72_252
PubMedID: 30358688

Title : Effects of soil acidification on the toxicity of organophosphorus pesticide on Eisenia fetida and its mechanism - Zou_2018_J.Hazard.Mater_359_365
Author(s) : Zou X , Xiao X , Zhou H , Chen F , Zeng J , Wang W , Feng G , Huang X
Ref : J Hazard Mater , 359 :365 , 2018
Abstract : Organophosphorus pesticides (OPs) have been widely used to control agricultural insects. Soil acidification is a major problem in soil of intensive agricultural systems, especially in red soil with a low pH buffer capacity. However, the effects of soil acidification on the toxicity of pesticides are still unclear. In the present study, the toxicity of three OPs on E. fetida was determined at individual (14-day lethal test) and biochemical levels (antioxidative defence enzymes) by using acidified soils (pH=5.5, 4.3 and 3.1). The results showed that the toxicity of tested OPs was slightly increased with the decrease of soil pH. To interpret the phenomena, an optimum Quantitative Structure Activity Relationship (QSAR) model was developed based on the toxicity mechanism and the partial least squares regression (PLS) method. The model indicated bioavailability and toxicodynamics are key factors of soil acidification affecting the toxicity of the OPs. Further results revealed the bioavailability of the OPs was strongly related to their hydrolysis and biodegradation character, whereas the effects of soil acidification on toxicodynamics were mainly caused by the interaction between the acetylcholinesterase (AchE) and the OPs. Results will increase understanding of the effects of soil acidification on the toxicity of pesticides and its mechanism.
ESTHER : Zou_2018_J.Hazard.Mater_359_365
PubMedSearch : Zou_2018_J.Hazard.Mater_359_365
PubMedID: 30048951

Title : A new method to characterize the kinetics of cholinesterases inhibited by carbamates - Xiao_2017_J.Pharm.Biomed.Anal_144_175
Author(s) : Xiao Q , Zhou H , Wei H , Du H , Tan W , Zhan Y , Pistolozzi M
Ref : J Pharm Biomed Anal , 144 :175 , 2017
Abstract : The inhibition of cholinesterases (ChEs) by carbamates includes a carbamylation (inhibition) step, in which the drug transfers its carbamate moiety to the active site of the enzyme and a decarbamylation (activity recovery) step, in which the carbamyl group is hydrolyzed from the enzyme. The carbamylation and decarbamylation kinetics decide the extent and the duration of the inhibition, thus the full characterization of candidate carbamate inhibitors requires the measurement of the kinetic constants describing both steps. Carbamylation and decarbamylation rate constants are traditionally measured by two separate set of experiments, thus making the full characterization of candidate inhibitors time-consuming. In this communication we show that by the analysis of the area under the inhibition-time curve of cholinesterases inhibited by carbamates it is possible to calculate the decarbamylation rate constant from the same data traditionally used to characterize only the carbamylation kinetics, therefore it is possible to obtain a full characterization of the inhibition with a single set of experiments. The characterization of the inhibition kinetics of human and dog plasma butyrylcholinesterase and of human acetylcholinesterase by bambuterol and bambuterol monocarbamate enantiomers was used to demonstrate the validity of the approach. The results showed that the proposed method provides reliable estimations of carbamylation and decarbamylation rate constants thus representing a simple and useful approach to reduce the time required for the characterization of carbamate inhibitors.
ESTHER : Xiao_2017_J.Pharm.Biomed.Anal_144_175
PubMedSearch : Xiao_2017_J.Pharm.Biomed.Anal_144_175
PubMedID: 28483282

Title : Discovery of the leinamycin family of natural products by mining actinobacterial genomes - Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
Author(s) : Pan G , Xu Z , Guo Z , Hindra , Ma M , Yang D , Zhou H , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Cheng J , Van Nieuwerburgh F , Suh JW , Duan Y , Shen B
Ref : Proc Natl Acad Sci U S A , 114 :E11131 , 2017
Abstract : Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.
ESTHER : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedSearch : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedID: 29229819
Gene_locus related to this paper: 9actn-a0a2m9jcs9 , 9actn-a0a2m9ijf7 , 9actn-a0a2m9iy91 , 9actn-a0a2m9k146 , 9actn-a0a2m9m5n6 , 9actn-a0a2m9ifq0 , 9actn-a0a1c4rpf7

Title : Quantitative estimation of cholinesterase-specific drug metabolism of carbamate inhibitors provided by the analysis of the area under the inhibition-time curve - Zhou_2017_J.Pharm.Biomed.Anal_144_167
Author(s) : Zhou H , Xiao Q , Tan W , Zhan Y , Pistolozzi M
Ref : J Pharm Biomed Anal , 144 :167 , 2017
Abstract : Several molecules containing carbamate groups are metabolized by cholinesterases. This metabolism includes a time-dependent catalytic step which temporary inhibits the enzymes. In this paper we demonstrate that the analysis of the area under the inhibition versus time curve (AUIC) can be used to obtain a quantitative estimation of the amount of carbamate metabolized by the enzyme. (R)-bambuterol monocarbamate and plasma butyrylcholinesterase were used as model carbamate-cholinesterase system. The inhibition of different concentrations of the enzyme was monitored for 5h upon incubation with different concentrations of carbamate and the resulting AUICs were analyzed. The amount of carbamate metabolized could be estimated with <15% accuracy (RE%) and <=23% precision (RSD%). Since the knowledge of the inhibition kinetics is not required for the analysis, this approach could be used to determine the amount of drug metabolized by cholinesterases in a selected compartment in which the cholinesterase is confined (e.g. in vitro solutions, tissues or body fluids), either in vitro or in vivo.
ESTHER : Zhou_2017_J.Pharm.Biomed.Anal_144_167
PubMedSearch : Zhou_2017_J.Pharm.Biomed.Anal_144_167
PubMedID: 28468728

Title : Novel Isochroman Dimers from Stachybotrys sp. PH30583: Fermentation, Isolation, Structural Elucidation and Biological Activities - Li_2017_Planta.Med_83_654
Author(s) : Li W , Yang YB , Yang XQ , Xie HD , Shao ZH , Zhou H , Miao CP , Zhao LX , Ding ZT
Ref : Planta Med , 83 :654 , 2017
Abstract : The rare anishidiol and five new isochromans, including three novel dimers with unprecedented skeletons, were isolated from Stachybotrys sp. PH30583. Their structures were determined by spectral analyses. The bioactivities of these compounds were also investigated. The dimers (6-10) inhibited acetylcholinesterase at 50 microM, but the monomers did not. To investigate the biogenesis of the novel dimers, a time-course investigation of metabolite production was undertaken.
ESTHER : Li_2017_Planta.Med_83_654
PubMedSearch : Li_2017_Planta.Med_83_654
PubMedID: 27806408

Title : Benzopyran derivatives from endophytic Daldinia eschscholzii JC-15 in Dendrobium chrysotoxum and their bioactivities - Hu_2017_Nat.Prod.Res__1
Author(s) : Hu M , Yang XQ , Zhou QY , Li SQ , Wang BY , Ruan BH , Yang YB , Zhang ZX , Zhou H , Ding ZT
Ref : Nat Prod Res , :1 , 2017
Abstract : Five new benzopyran derivatives (2-6) and a new natural product (1) were isolated from endophytic Daldinia eschscholzii in Dendrobium chrysotoxum and determined as (R)-2,3-dihydro-2,5-dihydroxy-2-methylchromen-4-one (1), (2R, 4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol (2), (R)-3-methoxyl-1-(2,6-dihydroxy phenyl)-butan-1-one (3), 7-O-alpha-d-ribosyl-5-hydroxy-2-methyl-4H-chromen-4-one (4), 7-O-alpha-d-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one (5), daldinium A (6). These compounds were evaluated for their antimicrobial activity, anti-acetylcholinesterase, nitric oxide inhibition, anticoagulant, photodynamic antimicrobial activities and glucose uptake of adipocytes. Some compounds showed photoactive antimicrobial activities and glucose uptake stimulating activities.
ESTHER : Hu_2017_Nat.Prod.Res__1
PubMedSearch : Hu_2017_Nat.Prod.Res__1
PubMedID: 29272956

Title : New bioactive compounds from aquatic endophyte Chaetomium globosum - Ruan_2017_Nat.Prod.Res__1
Author(s) : Ruan BH , Yu ZF , Yang XQ , Yang YB , Hu M , Zhang ZX , Zhou QY , Zhou H , Ding ZT
Ref : Nat Prod Res , :1 , 2017
Abstract : Two new oxidation products-related aureonitol and cytochalasan were isolated from Chaetomium globosum fermented in Chinese yam (Dioscorea opposita) and determined as 10,11-dihydroxyl- aureonitol (1) and yamchaetoglobosin A (2). Compound 2 indicated significant inhibitory effect on nitric oxide production in LPS-activated macrophages, anti-acetylcholinesterase activity with the inhibition ratios of 92.5, 38.2% at 50 muM, and cytotoxicity to HL-60, A-549, SMMC-7721, MCF-7 and SW480 with the range of inhibition ratio at 51-96% for a concentration of 40 muM. Compounds 1, 2 showed weak anticoagulant activity with PT at 16.8 s. Few work was reported on the anti-acetylcholinesterase, and anticoagulant activities of aureonitol, and cytochalasan derivatives. The preliminary structure-activity relationship stated that the oxidation ring-opening in yamchaetoglobosin A can retain the inhibitory effect against NO production and tumor cell.
ESTHER : Ruan_2017_Nat.Prod.Res__1
PubMedSearch : Ruan_2017_Nat.Prod.Res__1
PubMedID: 28927295

Title : Synthesis of furo[3,2-c]coumarin derivatives using visible-light-promoted radical alkyne insertion with bromocoumarins - Zhou_2016_Org.Biomol.Chem_14_6065
Author(s) : Zhou H , Deng X , Ma Z , Zhang A , Qin Q , Tan RX , Yu S
Ref : Org Biomol Chem , 14 :6065 , 2016
Abstract : The synthesis of privileged structures, which are potent drug candidates, is an impetus for drug discovery. The construction of heterocyclic framework furo[3,2-c]coumarins using a visible-light promoted photoredox neutral coupling of 3-bromo-4-hydroxycoumarins with commercially available alkynes has been reported. These reactions can be carried out at room temperature under visible light irradiation with good chemical yields. This work presents 17 furocoumarins, 12 of which are new. Three of the newly synthesized compounds show potent cytotoxicity, and one shows moderate acetylcholinesterase inhibitory activity with IC50 values of 2.16 +/- 0.13 muM.
ESTHER : Zhou_2016_Org.Biomol.Chem_14_6065
PubMedSearch : Zhou_2016_Org.Biomol.Chem_14_6065
PubMedID: 27241337

Title : Characterization of the methemoglobin forming metabolites of benzocaine and lidocaine - Hartman_2016_Xenobiotica__1
Author(s) : Hartman N , Zhou H , Mao J , Mans D , Boyne M, 2nd , Patel V , Colatsky T
Ref : Xenobiotica , :1 , 2016
Abstract : 1. Topical anesthesia with benzocaine or lidocaine occasionally causes methemoglobinemia, an uncommon but potentially fatal disorder where the blood has a reduced ability to transport oxygen. Previous in vitro studies using human whole blood have shown that benzocaine causes more methemoglobin (MetHb) formation than lidocaine, and that both compounds require metabolic transformation to form the MetHb producing species. In the current investigation, the active species of benzocaine forming the MetHb was investigated. 2. HPLC analysis of benzocaine samples incubated with human hepatic S9 showed the formation of a peak with the same UV spectrum and retention time as benzocaine hydroxylamine (BenzNOH). To confirm the activity of BenzNOH, MetHb production following exposure to the compound was determined in whole human blood using an Avoximeter 4000 CO-oximeter. 3. BenzNOH produced MetHb in a concentration dependent manner without the need for metabolic activation. Benzocaine in the presence of metabolic activation required a concentration of 500 muM to produce a similar degree of MetHb formation as 20 muM BenzNOH without activation. Previous work suggested that two metabolites of lidocaine may also form MetHb; N-hydroxyxylidine and 4-hydroxyxylidine. Of these two metabolites 4-hydroxyxylidine produced the most MetHb in whole blood in vitro in the absence of metabolic activation, however BenzNOH produced up to 14.2 times more MetHb than 4-hydroxyxylidine at a similar concentration. 4. These results suggest that the ability of benzocaine to form MetHb is likely to be mediated through its hydroxylamine metabolite and that this metabolite is inherently more active than the potentially MetHb-forming metabolites of lidocaine.
ESTHER : Hartman_2016_Xenobiotica__1
PubMedSearch : Hartman_2016_Xenobiotica__1
PubMedID: 27321253

Title : Obesity associated Lyplal1 gene is regulated in diet induced obesity but not required for adipocyte differentiation - Lei_2015_Mol.Cell.Endocrinol_411_207
Author(s) : Lei X , Callaway M , Zhou H , Yang Y , Chen W
Ref : Mol Cell Endocrinol , 411 :207 , 2015
Abstract : Obesity and its associated morbidities represent one of the major and most rapidly expanding health epidemics in the world. Recent genome-wide association studies (GWAS) have identified several variants in LYPLAL1 gene that are significantly associated with central obesity preferentially in females. However, the exact function of this gene in adipose tissue development and obesity remains completely uncharacterized. We found murine Lyplal1 gene demonstrated a depot and sex-specific expression profile in white adipose tissues (WAT), and was significantly reduced in the epididymal and retroperitoneal fats in a murine model of high fat diet induced obesity (DIO). Lyplal1 mRNA was mildly up-regulated during adipogenesis and enriched in mature adipocytes through a PPARgamma-independent mechanism. However, overexpression and knockdown of Lyplal1 did not significantly perturb adipocyte differentiation, triacylglycerol accumulation and/or insulin signaling. These data highlight a depot-specific marked reduction of Lyplal1 transcripts in diet induced obesity but a dispensable role of Lyplal1 in adipose tissue development.
ESTHER : Lei_2015_Mol.Cell.Endocrinol_411_207
PubMedSearch : Lei_2015_Mol.Cell.Endocrinol_411_207
PubMedID: 25958046
Gene_locus related to this paper: human-LYPLAL1 , mouse-lypl1

Title : Genetic variation in aryl N-acetyltransferase results in significant differences in the pharmacokinetic and safety profiles of amifampridine (3,4-diaminopyridine) phosphate - Haroldsen_2015_Pharmacol.Res.Perspect_3_e00099
Author(s) : Haroldsen PE , Garovoy MR , Musson DG , Zhou H , Tsuruda L , Hanson B , O'Neill CA
Ref : Pharmacol Res Perspect , 3 :e00099 , 2015
Abstract : The clinical use of amifampridine phosphate for neuromuscular junction disorders is increasing. The metabolism of amifampridine occurs via polymorphic aryl N-acetyltransferase (NAT), yet its pharmacokinetic (PK) and safety profiles, as influenced by this enzyme system, have not been investigated. The objective of this study was to assess the effect of NAT phenotype and genotype on the PK and safety profiles of amifampridine in healthy volunteers (N = 26). A caffeine challenge test and NAT2 genotyping were used to delineate subjects into slow and fast acetylators for PK and tolerability assessment of single, escalating doses of amifampridine (up to 30 mg) and in multiple daily doses (20 mg QID) of amifampridine. The results showed that fast acetylator phenotypes displayed significantly lower C max, AUC, and shorter t 1/2 for amifampridine than slow acetylators. Plasma concentrations of the N-acetyl metabolite were approximately twofold higher in fast acetylators. Gender differences were not observed. Single doses of amifampridine demonstrated dose linear PKs. Amifampridine achieved steady state plasma levels within 1 day of dosing four times daily. No accumulation or time-dependent changes in amifampridine PK parameters occurred. Overall, slow acetylators reported 73 drug-related treatment-emergent adverse events versus 6 in fast acetylators. Variations in polymorphic NAT corresponding with fast and slow acetylator phenotypes significantly affects the PK and safety profiles of amifampridine.
ESTHER : Haroldsen_2015_Pharmacol.Res.Perspect_3_e00099
PubMedSearch : Haroldsen_2015_Pharmacol.Res.Perspect_3_e00099
PubMedID: 25692017

Title : Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle - Chen_2014_Nat.Genet_46_253
Author(s) : Chen S , Zhang G , Shao C , Huang Q , Liu G , Zhang P , Song W , An N , Chalopin D , Volff JN , Hong Y , Li Q , Sha Z , Zhou H , Xie M , Yu Q , Liu Y , Xiang H , Wang N , Wu K , Yang C , Zhou Q , Liao X , Yang L , Hu Q , Zhang J , Meng L , Jin L , Tian Y , Lian J , Yang J , Miao G , Liu S , Liang Z , Yan F , Li Y , Sun B , Zhang H , Zhu Y , Du M , Zhao Y , Schartl M , Tang Q , Wang J
Ref : Nat Genet , 46 :253 , 2014
Abstract : Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
ESTHER : Chen_2014_Nat.Genet_46_253
PubMedSearch : Chen_2014_Nat.Genet_46_253
PubMedID: 24487278
Gene_locus related to this paper: cynse-a0a3p8wch2 , cynse-a0a3p8vd14 , cynse-a0a3p8w747 , cynse-a0a3p8wq40 , cynse-a0a3p8wul3 , cynse-a0a3p8vqr4 , cynse-a0a3p8vmz4

Title : A mechanism regulating G protein-coupled receptor signaling that requires cycles of protein palmitoylation and depalmitoylation - Jia_2014_J.Biol.Chem_289_6249
Author(s) : Jia L , Chisari M , Maktabi MH , Sobieski C , Zhou H , Konopko AM , Martin BR , Mennerick SJ , Blumer KJ
Ref : Journal of Biological Chemistry , 289 :6249 , 2014
Abstract : Reversible attachment and removal of palmitate or other long-chain fatty acids on proteins has been hypothesized, like phosphorylation, to control diverse biological processes. Indeed, palmitate turnover regulates Ras trafficking and signaling. Beyond this example, however, the functions of palmitate turnover on specific proteins remain poorly understood. Here, we show that a mechanism regulating G protein-coupled receptor signaling in neuronal cells requires palmitate turnover. We used hexadecyl fluorophosphonate or palmostatin B to inhibit enzymes in the serine hydrolase family that depalmitoylate proteins, and we studied R7 regulator of G protein signaling (RGS)-binding protein (R7BP), a palmitoylated allosteric modulator of R7 RGS proteins that accelerate deactivation of Gi/o class G proteins. Depalmitoylation inhibition caused R7BP to redistribute from the plasma membrane to endomembrane compartments, dissociated R7BP-bound R7 RGS complexes from Gi/o-gated G protein-regulated inwardly rectifying K(+) (GIRK) channels and delayed GIRK channel closure. In contrast, targeting R7BP to the plasma membrane with a polybasic domain and an irreversibly attached lipid instead of palmitate rendered GIRK channel closure insensitive to depalmitoylation inhibitors. Palmitate turnover therefore is required for localizing R7BP to the plasma membrane and facilitating Gi/o deactivation by R7 RGS proteins on GIRK channels. Our findings broaden the scope of biological processes regulated by palmitate turnover on specific target proteins. Inhibiting R7BP depalmitoylation may provide a means of enhancing GIRK activity in neurological disorders.
ESTHER : Jia_2014_J.Biol.Chem_289_6249
PubMedSearch : Jia_2014_J.Biol.Chem_289_6249
PubMedID: 24385443

Title : Genome sequence of Anopheles sinensis provides insight into genetics basis of mosquito competence for malaria parasites - Zhou_2014_BMC.Genomics_15_42
Author(s) : Zhou D , Zhang D , Ding G , Shi L , Hou Q , Ye Y , Xu Y , Zhou H , Xiong C , Li S , Yu J , Hong S , Yu X , Zou P , Chen C , Chang X , Wang W , Lv Y , Sun Y , Ma L , Shen B , Zhu C
Ref : BMC Genomics , 15 :42 , 2014
Abstract : BACKGROUND: Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan.
RESULTS: We performed 454 next-generation sequencing and obtained a draft sequence of A. sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of this genome sequence, we observed expansion and contraction of several immune-related gene families in anopheline relative to culicine mosquito species. These differences suggest that species-specific immune responses to Plasmodium invasion underpin the biological differences in susceptibility to Plasmodium infection that characterize these two mosquito subfamilies.
CONCLUSIONS: The A. sinensis genome produced in this study, provides an important resource for analyzing the genetic basis of susceptibility and resistance of mosquitoes to Plasmodium parasites research which will ultimately facilitate the design of urgently needed interventions against this debilitating mosquito-borne disease.
ESTHER : Zhou_2014_BMC.Genomics_15_42
PubMedSearch : Zhou_2014_BMC.Genomics_15_42
PubMedID: 24438588
Gene_locus related to this paper: anoga-Q7PVF9 , 9dipt-a0a084vlt1 , 9dipt-a0a084vdq2 , 9dipt-sime3xf.a , 9dipt-sime3xf.b , 9dipt-a0a084vbj8 , 9dipt-a0a084wan7 , 9dipt-a0a084wik4 , 9dipt-a0a084wk64 , 9dipt-a0a084wez8 , 9dipt-a0a084vji7 , 9dipt-a0a084vlc2 , 9dipt-a0a084vsa5 , 9dipt-a0a084wlk0 , 9dipt-a0a084wah8 , 9dipt-a0a084wln4 , 9dipt-a0a084we78 , 9dipt-a0a084wjm6 , 9dipt-a0a084wjm7 , 9dipt-a0a084we77 , 9dipt-a0a084wlk1 , 9dipt-a0a084we80 , 9dipt-a0a084wjm4 , 9dipt-a0a084w1n7 , 9dipt-a0a084we79 , 9dipt-a0a084wev9 , 9dipt-a0a084vlc3 , 9dipt-a0a084vdq4 , 9dipt-a0a084vdq5 , 9dipt-a0a084vdq1 , 9dipt-a0a084wah9 , 9dipt-a0a084wan6 , 9dipt-a0a084wlj8 , 9dipt-a0a084wk45 , 9dipt-a0a084wk46 , 9dipt-a0a084wlj9 , 9dipt-a0a084vsa4 , 9dipt-a0a084vs93 , 9dipt-a0a084wl93 , anosi-a0a0f7kyf5 , anosi-a0a0f7l1f2 , anosi-a0a084wum0 , anost-a0a182xxz0 , anosi-a0a084vn28 , anosi-a0a084vpt0 , anoga-q7q887

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo - Sun_2013_Neurosci.Bull_29_83
Author(s) : Sun C , Wang Q , Zhou H , Yu S , Simard AR , Kang C , Li Y , Kong Y , An T , Wen Y , Shi F , Hao J
Ref : Neurosci Bull , 29 :83 , 2013
Abstract : The matrix-degrading metalloproteinases (MMPs), particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA (pcDNA-ASMMP9), which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4- to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex (AS-MMP-9-treated group), subcutaneous injection of endostatin (endostatin-treated group), or both (combined therapy group). Mice treated with pcDNA (empty vector)-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.
ESTHER : Sun_2013_Neurosci.Bull_29_83
PubMedSearch : Sun_2013_Neurosci.Bull_29_83
PubMedID: 23307113

Title : The key role of a non-active-site residue Met148 on the catalytic efficiency of meta-cleavage product hydrolase BphD - Zhou_2013_Appl.Microbiol.Biotechnol_97_10399
Author(s) : Zhou H , Qu Y , Kong C , Shen E , Wang J , Zhang X , Ma Q , Zhou J
Ref : Applied Microbiology & Biotechnology , 97 :10399 , 2013
Abstract : meta-Cleavage product (MCP) hydrolases (EC 3.7.1.9) can catalyze a specific C-C bond fission during the microbial aerobic degradation of aromatics. The previous studies on structure-function relationship of MCP hydrolases mainly focus on the active site residues by site-directed mutagenesis. However, the information about the role of the non-active-site residues is still unclear. In this study, a non-active-site residue Met148 of MCP hydrolase BphD was selected as the mutagenesis site according to the sequence alignments, structure superimpose and the tunnel analysis, which underwent the saturation mutagenesis resulting 19 mutants. The catalytic efficiencies of the mutants on 6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) were all decreased compared with the wild-type one except for the M148D mutant. Especially, the M148P mutant exhibited 290-fold lower k cat/K m than that of the wild-type BphD. Transient kinetic analyses of M148P showed the reciprocal relaxation time corresponded to C-C bond cleavage and product release steps (9.6 s(-1)) was 4.08-fold lower than BphD WT (39.2 s(-1)). Tunnel cluster analysis of BphD WT, M148P and M148W demonstrated that only the bulky Trp148 could block tunnel T2 in the BphD WT, but it exhibited slight effects on the catalytic efficiency (0.94-fold of BphD WT). Therefore, product release was not the main reason for the efficiency decrease of M148P. On the other hand, molecular dynamics simulations on the BphD WT and BphD M148P in complex with HOPDA indicated that the dramatic decrease of the catalytic efficiencies of BphD M148P should be due to the unproductive binding of HOPDA. The study demonstrated the catalytic efficiency of MCP hydrolase can be engineered by modification of non-active site residue.
ESTHER : Zhou_2013_Appl.Microbiol.Biotechnol_97_10399
PubMedSearch : Zhou_2013_Appl.Microbiol.Biotechnol_97_10399
PubMedID: 23494625

Title : In situ formation of metal coordination polymer: a strategy for fluorescence turn-on assay of acetylcholinesterase activity and inhibitor screening - Liao_2013_Anal.Chem_85_2667
Author(s) : Liao D , Chen J , Zhou H , Wang Y , Li Y , Yu C
Ref : Analytical Chemistry , 85 :2667 , 2013
Abstract : A novel method for the sensing of acetylcholinesterase (AChE) activity and inhibitor screening based on the formation of metal coordination polymer has been developed. Acetylthiocholine (ATCh) was selected as the substrate. In the presence of AChE, ATCh was hydrolyzed to thiocholine and acetate. Thiocholine interacted with Ag(I) to form a metal coordination polymer. A positively charged perylene probe (probe 1) was employed. The fluorescence of probe 1 was very efficiently quenched by a polyanion [PVS, poly(vinyl sulfonate)]. In the presence of acetylcholinesterase, the positively charged metal coordination polymer newly formed in situ would interact with PVS, probe 1 monomer molecules were released, and a turn on fluorescence signal was detected. The assay is highly sensitive, a limit of detection of 0.04 mU/mL AChE was obtained. The assay is also highly selective, a number of potential interference proteins (enzymes) were tested, and none of them show noticeable interference. Sensing of AChE inhibitor was also demonstrated. Our assay is fairly simple and inexpensive. We envision that it could be used for the sensitive detection of other hydrolytic enzyme activities with properly selected substrates and for the screening of potential inhibitor drugs.
ESTHER : Liao_2013_Anal.Chem_85_2667
PubMedSearch : Liao_2013_Anal.Chem_85_2667
PubMedID: 23379662

Title : mTORC2 controls actin polymerization required for consolidation of long-term memory - Huang_2013_Nat.Neurosci_16_441
Author(s) : Huang W , Zhu PJ , Zhang S , Zhou H , Stoica L , Galiano M , Krnjevic K , Roman G , Costa-Mattioli M
Ref : Nat Neurosci , 16 :441 , 2013
Abstract : A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.
ESTHER : Huang_2013_Nat.Neurosci_16_441
PubMedSearch : Huang_2013_Nat.Neurosci_16_441
PubMedID: 23455608

Title : Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution - Chen_2013_Nat.Commun_4_1595
Author(s) : Chen J , Huang Q , Gao D , Wang J , Lang Y , Liu T , Li B , Bai Z , Luis Goicoechea J , Liang C , Chen C , Zhang W , Sun S , Liao Y , Zhang X , Yang L , Song C , Wang M , Shi J , Liu G , Liu J , Zhou H , Zhou W , Yu Q , An N , Chen Y , Cai Q , Wang B , Liu B , Min J , Huang Y , Wu H , Li Z , Zhang Y , Yin Y , Song W , Jiang J , Jackson SA , Wing RA , Chen M
Ref : Nat Commun , 4 :1595 , 2013
Abstract : The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.
ESTHER : Chen_2013_Nat.Commun_4_1595
PubMedSearch : Chen_2013_Nat.Commun_4_1595
PubMedID: 23481403
Gene_locus related to this paper: orysa-Q6ZDG3 , orysa-q6h415 , orysj-q6yse8 , orysa-q33aq0 , orybr-j3l7k2 , orybr-j3m138 , orybr-j3l6m8 , orybr-j3m3b3 , orybr-j3l8d1 , orybr-j3kza5 , orybr-j3mnb5 , orybr-j3n4p4 , orybr-j3lg73 , orybr-j3l342 , orybr-j3msi2 , orybr-j3nb83 , orybr-j3mpc5

Title : Genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from a patient before and after treatment with tigecycline - Hua_2012_J.Bacteriol_194_6979
Author(s) : Hua X , Zhou H , Jiang Y , Feng Y , Chen Q , Ruan Z , Yu Y
Ref : Journal of Bacteriology , 194 :6979 , 2012
Abstract : Acinetobacter baumannii is a Gram-negative bacterium which emerged as a significant nosocomial pathogen worldwide. To investigate the molecular basis of the tigecycline-resistant mechanism, we determined the genome sequences of two multidrug-resistant A. baumannii strains isolated from a patient before and after treatment with tigecycline.
ESTHER : Hua_2012_J.Bacteriol_194_6979
PubMedSearch : Hua_2012_J.Bacteriol_194_6979
PubMedID: 23209232
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : Enhanced performance of lipase-catalyzed kinetic resolution of secondary alcohols in monoether-functionalized ionic liquids - Zhou_2011_Bioresour.Technol_102_5562
Author(s) : Zhou H , Chen J , Ye L , Lin H , Yuan Y
Ref : Bioresour Technol , 102 :5562 , 2011
Abstract : Several cationic monoether-functionalized ionic liquids (MEF-ILs) with different substituents were synthesized and used as media for kinetic resolution of secondary alcohols catalyzed by several lipases. The results indicate that Novozym 435 (an immobilized Candida antarctica Lipase B) had higher efficiency compared to other lipases in deracemization. The alkyl substituents at the 2- and 3-positions in the imidazolium ring of MEF-ILs were found to contribute to the increased enantioselectivity and enhancement of the reaction rate, respectively, while the higher stereo-hindrance of ether bonds decreased the activity. An enantioselectivity higher than 99% with 50% conversion of rac-1-phenylethanol was achieved using the catalyst system comprised of Novozym 435 and the MEF-IL 1-(3-ethoxypropyl)-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide. The catalytic system could be separated and reused without considerable activity loss. MEF-ILs can be a new class of enzyme-benign media suitable for lipase-catalyzed kinetic resolution of secondary alcohols.
ESTHER : Zhou_2011_Bioresour.Technol_102_5562
PubMedSearch : Zhou_2011_Bioresour.Technol_102_5562
PubMedID: 21388804

Title : Suppression of PKR promotes network excitability and enhanced cognition by interferon-gamma-mediated disinhibition - Zhu_2011_Cell_147_1384
Author(s) : Zhu PJ , Huang W , Kalikulov D , Yoo JW , Placzek AN , Stoica L , Zhou H , Bell JC , Friedlander MJ , Krnjevic K , Noebels JL , Costa-Mattioli M
Ref : Cell , 147 :1384 , 2011
Abstract : The double-stranded RNA-activated protein kinase (PKR) was originally identified as a sensor of virus infection, but its function in the brain remains unknown. Here, we report that the lack of PKR enhances learning and memory in several behavioral tasks while increasing network excitability. In addition, loss of PKR increases the late phase of long-lasting synaptic potentiation (L-LTP) in hippocampal slices. These effects are caused by an interferon-gamma (IFN-gamma)-mediated selective reduction in GABAergic synaptic action. Together, our results reveal that PKR finely tunes the network activity that must be maintained while storing a given episode during learning. Because PKR activity is altered in several neurological disorders, this kinase presents a promising new target for the treatment of cognitive dysfunction. As a first step in this direction, we show that a selective PKR inhibitor replicates the Pkr(-/-) phenotype in WT mice, enhancing long-term memory storage and L-LTP.
ESTHER : Zhu_2011_Cell_147_1384
PubMedSearch : Zhu_2011_Cell_147_1384
PubMedID: 22153080

Title : Genomic analysis of the multidrug-resistant Acinetobacter baumannii strain MDR-ZJ06 widely spread in China - Zhou_2011_Antimicrob.Agents.Chemother_55_4506
Author(s) : Zhou H , Zhang T , Yu D , Pi B , Yang Q , Zhou J , Hu S , Yu Y
Ref : Antimicrobial Agents & Chemotherapy , 55 :4506 , 2011
Abstract : We previously reported that the multidrug-resistant (MDR) Acinetobacter baumannii strain MDR-ZJ06, belonging to European clone II, was widely spread in China. In this study, we report the whole-genome sequence of this clinically important strain. A 38.6-kb AbaR-type genomic resistance island (AbaR22) was identified in MDR-ZJ06. AbaR22 has a structure similar to those of the resistance islands found in A. baumannii strains AYE and AB0057, but it contained only a few antibiotic resistance genes. The region of resistant gene accumulation as previously described was not found in AbaR22. In the chromosome of the strain MDR-ZJ06, we identified the gene bla(oxa-23) in a composite transposon (Tn2009). Tn2009 shared the backbone with other A. baumannii transponsons that harbor bla(oxa-23), but it was bracketed by two ISAba1 elements which were transcribed in the same orientation. MDR-ZJ06 also expressed the armA gene on its plasmid pZJ06, and this gene has the same genetic environment as the armA gene of the Enterobacteriaceae. These results suggest variability of resistance acquisition even in closely related A. baumannii strains.
ESTHER : Zhou_2011_Antimicrob.Agents.Chemother_55_4506
PubMedSearch : Zhou_2011_Antimicrob.Agents.Chemother_55_4506
PubMedID: 21788470
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : The genome of the mesopolyploid crop species Brassica rapa - Wang_2011_Nat.Genet_43_1035
Author(s) : Wang X , Wang H , Wang J , Sun R , Wu J , Liu S , Bai Y , Mun JH , Bancroft I , Cheng F , Huang S , Li X , Hua W , Freeling M , Pires JC , Paterson AH , Chalhoub B , Wang B , Hayward A , Sharpe AG , Park BS , Weisshaar B , Liu B , Li B , Tong C , Song C , Duran C , Peng C , Geng C , Koh C , Lin C , Edwards D , Mu D , Shen D , Soumpourou E , Li F , Fraser F , Conant G , Lassalle G , King GJ , Bonnema G , Tang H , Belcram H , Zhou H , Hirakawa H , Abe H , Guo H , Jin H , Parkin IA , Batley J , Kim JS , Just J , Li J , Xu J , Deng J , Kim JA , Yu J , Meng J , Min J , Poulain J , Hatakeyama K , Wu K , Wang L , Fang L , Trick M , Links MG , Zhao M , Jin M , Ramchiary N , Drou N , Berkman PJ , Cai Q , Huang Q , Li R , Tabata S , Cheng S , Zhang S , Sato S , Sun S , Kwon SJ , Choi SR , Lee TH , Fan W , Zhao X , Tan X , Xu X , Wang Y , Qiu Y , Yin Y , Li Y , Du Y , Liao Y , Lim Y , Narusaka Y , Wang Z , Li Z , Xiong Z , Zhang Z
Ref : Nat Genet , 43 :1035 , 2011
Abstract : We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.
ESTHER : Wang_2011_Nat.Genet_43_1035
PubMedSearch : Wang_2011_Nat.Genet_43_1035
PubMedID: 21873998
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brarp-m4ei94 , brarp-m4c988 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brarp-m4dwa6 , brana-a0a078j4f0 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078dfa9 , brana-a0a078ic91 , brarp-m4ctw3 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078jx23 , brarp-m4da84 , brarp-m4dwr7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , brarp-m4cwq4 , brarp-m4dcj8 , brarp-m4eh17 , brarp-m4eey4 , brarp-m4dnj8 , brarp-m4ey83 , brarp-m4ey84

Title : [Selective isolation and diversity of cold-adapted lipase-producing strains from permafrost soil at the terminus of a glacier in the Tianshan Mountains] - Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
Author(s) : Xu Y , Wang D , Shi X , Zheng X , Zhou H , Liu Y , Ni Y
Ref : Wei Sheng Wu Xue Bao , 51 :233 , 2011
Abstract : OBJECTIVE: The diversity of culturable lipase-producing bacterial strains from permafrost soils at the terminus of a glacier in the Tianshan Mountains was investigated. Isolation and molecular phylogenetic analysis were performed to expand our knowledge on diversity of psychrotrophic and psychrophilic bacteria. In addition, efforts were made focusing on screening for cold active lipases. METHODS: Lipase-producing bacterial strains were detected on tween 80 and olive oil plates, respectively. Identity and genetic diversity of strains isolated were determined by spatial 16S rRNA gene sequences and rep-PCR fingerprint. The physiological tests were carried out to determine the phonotypic differences between strains showing high similarity of 16S rRNA gene sequences. RESULTS: Of the total 17 bacterial stains exhibiting cold-adapted lipase activity, we found that only 8 stains were able to hydrolyze olive oil. Based on 16S rRNA gene sequences, the lipase-producing bacterial isolates fell in five phylogenetic groups: subclasses (, ( and ( of Proteobacteria, Actinobacteria, and the Cytophaga-Flexibacter-Bacteroides (CFB) phylum. Nearly 59% of the isolates were affiliated with the genus Pseudomonas. CONCLUSION: The results enrich our knowledge on the psychrotrophic bacterial diversity and biogeographic distribution of cold active lipases-producing bacteria in cold environments.
ESTHER : Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
PubMedSearch : Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
PubMedID: 21574385

Title : Enzymatic synthesis of resorcylic acid lactones by cooperation of fungal iterative polyketide synthases involved in hypothemycin biosynthesis - Zhou_2010_J.Am.Chem.Soc_132_4530
Author(s) : Zhou H , Qiao K , Gao Z , Meehan MJ , Li JW , Zhao X , Dorrestein PC , Vederas JC , Tang Y
Ref : Journal of the American Chemical Society , 132 :4530 , 2010
Abstract : Hypothemycin is a macrolide protein kinase inhibitor from the fungus Hypomyces subiculosus. During biosynthesis, its carbon framework is assembled by two iterative polyketide synthases (PKSs), Hpm8 (highly reducing) and Hpm3 (nonreducing). These were heterologously expressed in Saccharomyces cerevisiae BJ5464-NpgA, purified to near homogeneity, and reconstituted in vitro to produce (6'S,10'S)-trans-7',8'-dehydrozearalenol (1) from malonyl-CoA and NADPH. The structure of 1 was determined by X-ray crystallographic analysis. In the absence of functional Hpm3, the reducing PKS Hpm8 produces and offloads truncated pyrone products instead of the expected hexaketide. The nonreducing Hpm3 is able to accept an N-acetylcysteamine thioester of a correctly functionalized hexaketide to form 1, but it is unable to initiate polyketide formation from malonyl-CoA. We show that the starter-unit:ACP transacylase (SAT) of Hpm3 is critical for crosstalk between the two enzymes and that the rate of biosynthesis of 1 is determined by the rate of hexaketide formation by Hpm8.
ESTHER : Zhou_2010_J.Am.Chem.Soc_132_4530
PubMedSearch : Zhou_2010_J.Am.Chem.Soc_132_4530
PubMedID: 20222707
Gene_locus related to this paper: hypsb-hpm3

Title : Clinicopathologic features between multicentric occurence and intrahepatic metastasis of multiple hepatocellular carcinomas related to HBV - Wang_2009_Surg.Oncol_18_25
Author(s) : Wang J , Li Q , Sun Y , Zheng H , Cui Y , Li H , Zhou H , Hao X
Ref : Surg Oncol , 18 :25 , 2009
Abstract : AIMS: To clarify the incidence of multicentric occurrence (MO) and intrahepatic metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) in China and to identify the differences between them. PATIENTS AND METHODS: Histopathologic features of multiple tumors in 82 cases with HCC were analyzed. The two groups, the origin was determinable as of multicentric occurrence or as of intrahepatic metastasis, were analyzed for their survival rate, disease-free survival and clinicopathologic differences. RESULTS: According to histological findings, 19.5% and 69.5% patients were considered to be MO and IM, respectively. In total 73 cases from the histopathological method were selected and divided into group MO (16 cases) and the group IM (57 cases). Analysis of stepwise regression identified that: Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) were the most important discriminating factors between MO and IM (p<0.05). As for their prognosis, Kaplan-Meier and Log rank test showed the survival rate in group MO was significantly better than that in the group IM (p=0.003). No statistical significance was found between the disease-free survival in group MO and that in group IM (p=0.141). The analysis of Cox's proportional hazards model showed that tumor type (MO or IM) and Child's stage were the important prognostic factors (p=0.002 and 0.014, respectively). CONCLUSIONS: The incidence of MO in patients with multiple HCCs related to HBV is only about 20%, which is lower than that of Japan. Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) are the most important discriminating factors between MO and IM. The prognosis of patients with MO compared to IM is significantly better and tumor type (MO or IM) and Child's stage are important prognostic factors.
ESTHER : Wang_2009_Surg.Oncol_18_25
PubMedSearch : Wang_2009_Surg.Oncol_18_25
PubMedID: 18640032

Title : RanBPM is an acetylcholinesterase-interacting protein that translocates into the nucleus during apoptosis - Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
Author(s) : Gong X , Ye W , Zhou H , Ren X , Li Z , Zhou W , Wu J , Gong Y , Ouyang Q , Zhao X , Zhang X
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :883 , 2009
Abstract : Acetylcholinesterase (AChE) expression may be induced during apoptosis in various cell types. Here, we used the C-terminal of AChE to screen the human fetal brain library and found that it interacted with Ran-binding protein in the microtubule-organizing center (RanBPM). This interaction was further confirmed by coimmunoprecipitation analysis. In HEK293T cells, RanBPM and AChE were heterogeneously expressed in the cisplatin-untreated cytoplasmic extracts and in the cisplatin-treated cytoplasmic or nuclear extracts. Our previous studies performed using morphologic methods have shown that AChE translocates from the cytoplasm to the nucleus during apoptosis. Taken together, these results suggest that RanBPM is an AChE-interacting protein that is translocated from the cytoplasm into the nucleus during apoptosis, similar to the translocation observed in case of AChE.
ESTHER : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedSearch : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedID: 19902122

Title : Analyses of associations between three positionally cloned asthma candidate genes and asthma or asthma-related phenotypes in a Chinese population - Zhou_2009_BMC.Med.Genet_10_123
Author(s) : Zhou H , Hong X , Jiang S , Dong H , Xu X
Ref : BMC Med Genet , 10 :123 , 2009
Abstract : BACKGROUND: Six asthma candidate genes, ADAM33, NPSR1, PHF11, DPP10, HLA-G, and CYFIP2, located at different chromosome regions have been positionally cloned following the reported linkage studies. For ADAM33, NPSR1, and CYFIP2, the associations with asthma or asthma-related phenotypes have been studied in East Asian populations such as Chinese and Japanese. However, for PHF11, DPP10, and HLA-G, none of the association studies have been conducted in Asian populations. Therefore, the aim of the present study is to test the associations between these three positionally cloned genes and asthma or asthma-related phenotypes in a Chinese population.
METHODS: Two, five, and two single nucleotide polymorphisms (SNPs) in the identified top regions of PHF11, DPP10, and HLA-G, respectively, were genotyped in 1183 independent samples. The study samples were selected based on asthma affectation status and extreme values in at least one of the following three asthma-related phenotypes: total serum immunoglobulin E levels, bronchial responsiveness test, and skin prick test. Both single SNP and haplotype analyses were performed.
RESULTS: We found that DPP10 was significantly associated with bronchial hyperresponsiveness (BHR) and BHR asthma after the adjustment for multiple testing; while the associations of PHF11 with positive skin reactions to antigens and the associations of HLA-G with BHR asthma were only nominally significant. CONCLUSION: Our study is the first one to provide additional evidence that supports the roles of DPP10 in influencing asthma or BHR in a Chinese population.
ESTHER : Zhou_2009_BMC.Med.Genet_10_123
PubMedSearch : Zhou_2009_BMC.Med.Genet_10_123
PubMedID: 19951440
Gene_locus related to this paper: human-DPP10

Title : Characterization of the polyoxin biosynthetic gene cluster from Streptomyces cacaoi and engineered production of polyoxin H - Chen_2009_J.Biol.Chem_284_10627
Author(s) : Chen W , Huang T , He X , Meng Q , You D , Bai L , Li J , Wu M , Li R , Xie Z , Zhou H , Zhou X , Tan H , Deng Z
Ref : Journal of Biological Chemistry , 284 :10627 , 2009
Abstract : A gene cluster (pol) essential for the biosynthesis of polyoxin, a nucleoside antibiotic widely used for the control of phytopathogenic fungi, was cloned from Streptomyces cacaoi. A 46,066-bp region was sequenced, and 20 of 39 of the putative open reading frames were defined as necessary for polyoxin biosynthesis as evidenced by its production in a heterologous host, Streptomyces lividans TK24. The role of PolO and PolA in polyoxin synthesis was demonstrated by in vivo experiments, and their functions were unambiguously characterized as O-carbamoyltransferase and UMP-enolpyruvyltransferase, respectively, by in vitro experiments, which enabled the production of a modified compound differing slightly from that proposed earlier. These studies should provide a solid foundation for the elucidation of the molecular mechanisms for polyoxin biosynthesis, and set the stage for combinatorial biosynthesis using genes encoding different pathways for nucleoside antibiotics.
ESTHER : Chen_2009_J.Biol.Chem_284_10627
PubMedSearch : Chen_2009_J.Biol.Chem_284_10627
PubMedID: 19233844
Gene_locus related to this paper: strci-c1ic18

Title : A multidimensional chromatography technology for in-depth phosphoproteome analysis - Albuquerque_2008_Mol.Cell.Proteomics_7_1389
Author(s) : Albuquerque CP , Smolka MB , Payne SH , Bafna V , Eng J , Zhou H
Ref : Mol Cell Proteomics , 7 :1389 , 2008
Abstract : Protein phosphorylation is a post-translational modification widely used to regulate cellular responses. Recent studies showed that global phosphorylation analysis could be used to study signaling pathways and to identify targets of protein kinases in cells. A key objective of global phosphorylation analysis is to obtain an in-depth mapping of low abundance protein phosphorylation in cells; this necessitates the use of suitable separation techniques because of the complexity of the phosphoproteome. Here we developed a multidimensional chromatography technology, combining IMAC, hydrophilic interaction chromatography, and reverse phase LC, for phosphopeptide purification and fractionation. Its application to the yeast Saccharomyces cerevisiae after DNA damage led to the identification of 8764 unique phosphopeptides from 2278 phosphoproteins using tandem MS. Analysis of two low abundance proteins, Rad9 and Mrc1, revealed that approximately 50% of their phosphorylation was identified via this global phosphorylation analysis. Thus, this technology is suited for in-depth phosphoproteome studies.
ESTHER : Albuquerque_2008_Mol.Cell.Proteomics_7_1389
PubMedSearch : Albuquerque_2008_Mol.Cell.Proteomics_7_1389
PubMedID: 18407956
Gene_locus related to this paper: yeast-YDR428C , yeast-YDR444W , yeast-yfd4

Title : Prolylcarboxypeptidase gene, chronic hypertension, and risk of preeclampsia - Wang_2006_Am.J.Obstet.Gynecol_195_162
Author(s) : Wang L , Feng Y , Zhang Y , Zhou H , Jiang S , Niu T , Wei LJ , Xu X , Wang X
Ref : Am J Obstet Gynecol , 195 :162 , 2006
Abstract : OBJECTIVE: Renin-angiotensin System is essential for the homeostasis of blood pressure in humans. The roles of renin-angiotensin system gene polymorphisms including angiotensinogen, angiotensin-converting enzyme, renin and angiotensin II receptor, type 1 genes in the pathogenesis of preeclampsia have been extensively studied, but most association studies produced either negative or inconsistent results. Prolylcarboxypeptidase encodes a lysosomal enzyme and is a regulator for both renin-angiotensin system and the kallikrein-kinin system. There is no published study on prolylcarboxypeptidase gene and preeclampsia. STUDY DESIGN: We investigated the independent and joint association of five polymorphisms in angiotensinogen, angiotensin-converting enzyme, and prolylcarboxypeptidase gene and chronic hypertension with the risk of preeclampsia in 125 preeclamptic and 1040 non-preeclamptic black women enrolled at the Boston Medical Center. We used logistic regression models to estimate the odds ratios of risk for preeclampsia associated with each gene polymorphism and its joint association with chronic hypertension. RESULTS: No association was found in four polymorphisms in angiotensinogen and angiotensin-converting enzyme. Prolylcarboxypeptidase E112D (rs2298668) D allele along and jointly with chronic hypertension were associated with a significantly increased risk of preeclampsia. Compared to women with homozygous EE genotype and without chronic hypertension, higher risks of preeclampsia were observed in DD women without chronic hypertension (OR = 3.7, 95% CI, 1.2 - 12.4) and EE women with chronic hypertension (OR = 9.1, 95% CI: 4.7 - 17.6). Women with both D allele and chronic hypertension had the highest risk (OR = 158, 95% CI, 25-infinite). This finding was validated in an independent sample of 1,015 non-black women. We further compared the prolylcarboxypeptidase transcript levels in peripheral blood cells of 23 preeclamptic (30% with chronic hypertension) and 51 non-preeclamptic (6% with chronic hypertension) women 2 - 3 days after delivery. The PRCP transcript levels were lower in ED/DD women than in EE woman (P = .03) and lower in preeclamptic women than in non-preeclamptic women (P = .007). CONCLUSION: Our data showed that prolylcarboxypeptidase D allele coupled with chronic hypertension was associated with a significantly increased risk of preeclampsia in both black and non-black women. Gene expression assays lent further support for the functional significance of prolylcarboxypeptidase in the etiology of preeclampsia.
ESTHER : Wang_2006_Am.J.Obstet.Gynecol_195_162
PubMedSearch : Wang_2006_Am.J.Obstet.Gynecol_195_162
PubMedID: 16681991
Gene_locus related to this paper: human-PRCP

Title : Adipose tissue-specific CETP expression in mice: impact on plasma lipoprotein metabolism - Zhou_2006_J.Lipid.Res_47_2011
Author(s) : Zhou H , Li Z , Hojjati MR , Jang D , Beyer TP , Cao G , Tall AR , Jiang XC
Ref : J Lipid Res , 47 :2011 , 2006
Abstract : Adipose tissue appears to be a highly conserved site of cholesteryl ester transfer protein (CETP) expression across species. To investigate the impact of adipose CETP expression on lipid metabolism, we created adipose tissue-specific CETP transgenic (CETPTg) mice. CETP mRNA is predominantly expressed in adipose tissue. Plasma CETP mass and activity are readily detectable in CETPTg mice but not in controls. Plasma lipoprotein analysis shows marked reductions in HDL cholesterol and phospholipids, increases non-HDL lipids, decreases apolipoprotein A-I (apoA-I), and increases apoB. Unexpectedly, CETPTg adipocytes are significantly smaller than those in control mice (44%), triglyceride and cholesterol in adipose tissue were significantly decreased compared with controls (50% and 37%, respectively), and phospholipids showed no significant changes. To study the mechanism, we measured peroxisome proliferator-activated receptor gamma, sterol-regulatory element binding protein-1c, LPL, and hormone-sensitive lipase (HSL) in aP2-CETPTg adipose tissue and controls and found that, except for HSL, all mRNA levels are significantly decreased in the transgenic mice compared with controls (26, 33, and 22%). In conclusion, adipose tissue CETP makes a major contribution to CETP in the circulation, reduces HDL, and increases non-HDL cholesterol levels. Moreover, adipose tissue CETP expression changes triglyceride and cholesterol content and the size of adipocytes.
ESTHER : Zhou_2006_J.Lipid.Res_47_2011
PubMedSearch : Zhou_2006_J.Lipid.Res_47_2011
PubMedID: 16751623

Title : [Pathological changes and apoptosis of brain cells in rat embryo suffering from intrauterine hypoxia-ischemic injury] - Yu_2004_Sichuan.Da.Xue.Xue.Bao.Yi.Xue.Ban_35_354
Author(s) : Yu D , Mao M , Zhou H , Wang ZL
Ref : Sichuan Da Xue Xue Bao Yi Xue Ban , 35 :354 , 2004
Abstract : OBJECTIVE: To observe the pathological changes of fetal rat brain cells caused by transient intrauterine ischemia in pregnant rats.
METHODS: The uterine arteries of the pregnant rats at 17 days of gestation were clamped for 30 min in the experimental group, the samples were collected 24, 48 and 72 hours respectively after the clamping of artery, respectively. In control group, the pregnant rat's abdomens were cut open and closed but the uterine arteries were kept intact; the samples were collected 24, 48 and 72 hours after the sham operation, respectively. The pathological changes of brain tissues were observed under light microscope by HE, Nissl, cholinesterase staining, sequential TUNEL technique, and by electron microscopy as well.
RESULTS: The edema, degeneration of neural cells and the hemorrhage of brain were observed in experimental group. The Nissl bodies and the activity of cholinesterase decreased. The apoptosis cells appeared 24 hours after hypoxia-ischemia injury and increased progressively with time. CONCLUSION: Uterine hypoxia and ischemia can cause severe damage to neural cells of fetal rat.
ESTHER : Yu_2004_Sichuan.Da.Xue.Xue.Bao.Yi.Xue.Ban_35_354
PubMedSearch : Yu_2004_Sichuan.Da.Xue.Xue.Bao.Yi.Xue.Ban_35_354
PubMedID: 15181834

Title : Differential signalling by muscarinic receptors in smooth muscle: m2-mediated inactivation of myosin light chain kinase via Gi3, Cdc42\/Rac1 and p21-activated kinase 1 pathway, and m3-mediated MLC20 (20 kDa regulatory light chain of myosin II) phosphorylation via Rho-associated kinase\/myosin phosphatase targeting subunit 1 and protein kinase C\/CPI-17 pathway - Murthy_2003_Biochem.J_374_145
Author(s) : Murthy KS , Zhou H , Grider JR , Brautigan DL , Eto M , Makhlouf GM
Ref : Biochemical Journal , 374 :145 , 2003
Abstract : Signalling via m3 and m2 receptors in smooth muscles involved activation of two G-protein-dependent pathways by each receptor. m2 receptors were coupled via Gbetagammai3 with activation of phospholipase C-beta3, phosphoinositide 3-kinase and Cdc42/Rac1 (where Cdc stands for cell division cycle) and p21-activated kinase 1 (PAK1), resulting in phosphorylation and inactivation of myosin light chain kinase (MLCK). Each step was inhibited by methoctramine and pertussis toxin. PAK1 activity was abolished in cells expressing both Cdc42-DN (where DN stands for dominant negative) and Rac1-DN. MLCK phosphorylation was inhibited by PAK1 antibody, and in cells expressing Cdc42-DN and Rac1-DN. m3 receptors were coupled via Galpha(q/11) with activation of phospholipase C-beta1 and via RhoA with activation of Rho-associated kinase (Rho kinase), phospholipase D and protein kinase C (PKC). Rho kinase and phospholipase D activities were inhibited by C3 exoenzyme and in cells expressing RhoA-DN. PKC activity was inhibited by bisindolylmaleimide, and in cells expressing RhoA-DN; PKC activity was also inhibited partly by Y27632 (44+/-5%). PKC-induced phosphorylation of PKC-activated 17 kDa inhibitor protein of type 1 phosphatase (CPI-17) at Thr38 was abolished by bisindolylmaleimide and inhibited partly by Y27632 (28+/-3%). Rho-kinase-induced phosphorylation of myosin phosphatase targeting subunit (MYPT1) and was abolished by Y27632. Sustained phosphorylation of 20 kDa regulatory light chain of myosin II (MLC20) and contraction were abolished by bisindolylmaleimide Y27632 and C3 exoenzyme and in cells expressing RhoA-DN. The results suggest that Rho-kinase-dependent phosphorylation of MYPT1 and PKC-dependent phosphorylation and enhancement of CPI-17 binding to the catalytic subunit of MLC phosphatase (MLCP) act co-operatively to inhibit MLCP activity, leading to sustained stimulation of MLC20 phosphorylation and contraction. Because Y27632 inhibited both Rho kinase and PKC activities, it could not be used to ascertain the contribution of MYPT1 to inhibition of MLCP activity. m2-dependent phosphorylation and inactivation of MLCK precluded its involvement in sustained MLC20 phosphorylation and contraction.
ESTHER : Murthy_2003_Biochem.J_374_145
PubMedSearch : Murthy_2003_Biochem.J_374_145
PubMedID: 12733988

Title : Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA - Murthy_2003_Am.J.Physiol.Gastrointest.Liver.Physiol_284_G1006
Author(s) : Murthy KS , Zhou H , Grider JR , Makhlouf GM
Ref : American Journal of Physiology Gastrointest Liver Physiol , 284 :G1006 , 2003
Abstract : The role of RhoA in myosin light-chain (MLC)(20) dephosphorylation and smooth muscle relaxation by PKA and PKG was examined in freshly dispersed and cultured smooth muscle cells expressing wild-type RhoA, constitutively active Rho(V14), and phosphorylation site-deficient Rho(A188). Activators of PKA (5,6-dichloro-1-beta-ribofuranosyl benzimidazole 3',5'-cyclic monophosphothionate, Sp-isomer; cBIMPS) or PKG [8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), sodium nitroprusside (SNP)] or both PKA and PKG (VIP) induced phosphorylation of constitutively active Rho(V14) and agonist (ACh)- or GTPgammaS-stimulated wild-type RhoA but not Rho(A188). Phosphorylation was accompanied by translocation of membrane-bound wild-type RhoA and Rho(V14) to the cytosol and complete inhibition of ACh-stimulated Rho kinase and phospholipase D activities, RhoA/Rho kinase association, MLC(20) phosphorylation, and sustained muscle contraction. Each of these events was blocked depending on the agent used, by the PKG inhibitor KT5823 or the PKA inhibitor myristoylated PKI. Inhibitors were used at a concentration (1 microM) previously shown by direct measurement of kinase activity to selectively inhibit the corresponding kinase. In muscle cells overexpressing the active phosphorylation site-deficient mutant Rho(A188), MLC(20) phosphorylation was partly inhibited by SNP, VIP, cBIMPS, and 8-pCPT-cGMP, suggesting the existence of an independent inhibitory mechanism downstream of RhoA. Results demonstrate that dephosphorylation of MLC(20) and smooth muscle relaxation are preferentially mediated by PKG- and PKA-dependent phosphorylation and inactivation of RhoA.
ESTHER : Murthy_2003_Am.J.Physiol.Gastrointest.Liver.Physiol_284_G1006
PubMedSearch : Murthy_2003_Am.J.Physiol.Gastrointest.Liver.Physiol_284_G1006
PubMedID: 12736149

Title : Heterogeneity of presynaptic muscarinic receptors mediating inhibition of sympathetic transmitter release: a study with M2- and M4-receptor-deficient mice - Trendelenburg_2003_Br.J.Pharmacol_138_469
Author(s) : Trendelenburg AU , Gomeza J , Klebroff W , Zhou H , Wess J
Ref : British Journal of Pharmacology , 138 :469 , 2003
Abstract : 1 Presynaptic muscarinic receptors modulate sympathetic transmitter release. The goal of the present study was to identify the muscarinic receptor subtype(s) mediating inhibition of sympathetic transmitter release in mouse atria, urinary bladder and vas deferens. To address this question, electrically evoked noradrenaline release was assessed using tissue preparations from NMRI, M(2)- and M(4)-knockout, and the corresponding M(2)- and M(4)-wildtype mice, after preincubation with (3)H-noradrenaline. 2 The muscarinic agonist carbachol decreased evoked tritium overflow (20 pulses/50 Hz) in each tissue and strain investigated. After deletion of the M(2)-receptor the maximal inhibition by carbachol was significantly reduced (by 41-72%), but not abolished, in all tissues. After deletion of the M(4)-receptor a moderate and significant reduction of the maximal inhibition by carbachol (by 28%) was observed only in the vas deferens. 3 Experiments with the muscarinic antagonists methoctramine and pirenzepine confirmed that the presynaptic muscarinic receptors were predominantly M(2) in atria and bladder and probably a mixture of M(2) and M(4) in the vas deferens. 4 Experiments in the urinary bladder with the cholinesterase inhibitor physostigmine and the muscarinic antagonist ipratropium demonstrated that endogenously released acetylcholine predominantly acted through M(2)-receptors to inhibit noradrenaline release. However, the results do not exclude a minor contribution of M(4)-receptors to this endogenous inhibition. 5 In conclusion, our results clearly indicate that the release-inhibiting muscarinic receptors on postganglionic sympathetic axons in mouse atria, bladder and vas deferens represent mixtures of M(2)- and non-M(2)-receptors. The non-M(2)-receptors remain unknown in atria and the bladder, and may represent primarily M(4)-receptors in the vas deferens. These results reveal an unexpected heterogeneity among the muscarinic receptors mediating inhibition of noradrenaline release.
ESTHER : Trendelenburg_2003_Br.J.Pharmacol_138_469
PubMedSearch : Trendelenburg_2003_Br.J.Pharmacol_138_469
PubMedID: 12569072

Title : Heterogeneity of release-inhibiting muscarinic autoreceptors in heart atria and urinary bladder: a study with M(2)- and M(4)-receptor-deficient mice - Zhou_2002_Naunyn.Schmiedebergs.Arch.Pharmacol_365_112
Author(s) : Zhou H , Meyer A , Starke K , Gomeza J , Wess J , Trendelenburg AU
Ref : Naunyn Schmiedebergs Arch Pharmacol , 365 :112 , 2002
Abstract : Release-inhibiting muscarinic autoreceptors were studied in heart atria and the urinary bladder of NMRI mice, M(2)-receptor-deficient mice, M(4)-receptor-deficient mice, and wildtype mice sharing the genetic background of the knockout animals. Segments of the tissues were preincubated with (3)H-choline and then superfused and stimulated electrically. In atrial segments taken from adult mice and stimulated with 120 pulses at 1 Hz, the muscarinic receptor agonist oxotremorine-M reduced the evoked overflow of tritium. Its concentration-response curves in atria from NMRI, M(2)-wildtype, M(4)-wildtype and M(2)-knockout mice were similar, with maximal inhibition by about 75%. In atria from M(4)-knockout mice, the maximal inhibitory effect of oxotremorine-M was reduced to 57%. The concentration-response curves of oxotremorine-M were shifted to the right by ipratropium, methoctramine and pirenzepine. Methoctramine and pirenzepine were approximately equipotent antagonists in all strains except in M(4)-knockout atria in which methoctramine was more potent than pirenzepine. When atria from adult NMRI mice were stimulated by 360 pulses at 3 Hz, ipratropium increased the evoked overflow of tritium both in the absence and in the presence of physostigmine (0.1 microM). In atria taken from 1-day-old NMRI mice, oxotremorine-M failed to reduce the evoked overflow of tritium. In bladder segments taken from adult mice, superfused with medium containing oxotremorine-M (1 microM), and stimulated by 360 pulses at 3 Hz, ipratropium increased the evoked overflow of tritium. Its concentration-response curves in preparations from NMRI, M(2)-wildtype, M(4)-wildtype and M(2)-knockout mice were similar. There was one exception: ipratropium failed to cause an increase in bladder pieces from M(4)-knockout mice. Methoctramine and pirenzepine also increased the evoked overflow of tritium in all strains except the M(4)-knockout. The two antagonists were approximately equipotent in NMRI, M(4)-wildtype and M(2)-knockout preparations but methoctramine was less potent than pirenzepine in M(2)-wildtype preparations. When bladder pieces from adult NMRI mice were superfused with oxotremorine-M-free medium and stimulated by 360 pulses at 3 Hz, ipratropium increased the evoked overflow of tritium in the presence of physostigmine (0.1 microM) but not in its absence. In bladder segments taken from 1-day-old NMRI mice and superfused with medium containing oxotremorine-M (1 microM), ipratropium increased the evoked overflow of tritium in the same way as in adult tissue. It is concluded that NMRI mice and the two wildtype strains are similar in their muscarinic autoreceptors. In atria, the autoreceptors are heterogeneous. Some are M(4). The non-M(4)-autoreceptors probably are M(2). In the bladder, the autoreceptors are exclusively M(4). In both tissues, the autoreceptors are activated by previously released acetylcholine under appropriate conditions.
ESTHER : Zhou_2002_Naunyn.Schmiedebergs.Arch.Pharmacol_365_112
PubMedSearch : Zhou_2002_Naunyn.Schmiedebergs.Arch.Pharmacol_365_112
PubMedID: 11819029

Title : Functional interaction of calcium-\/calmodulin-dependent protein kinase II and cytosolic phospholipase A(2) - Muthalif_2001_J.Biol.Chem_276_39653
Author(s) : Muthalif MM , Hefner Y , Canaan S , Harper J , Zhou H , Parmentier JH , Aebersold R , Gelb MH , Malik KU
Ref : Journal of Biological Chemistry , 276 :39653 , 2001
Abstract : Calcium-/calmodulin-dependent protein kinase II (CaM kinase II), a decoder of Ca(2+) signals, and cytosolic phospholipase A(2) (cPLA(2)), an enzyme involved in arachidonate release, are involved in many physiological and pathophysiological processes. Activation of CaM kinase II in norepinephrine-stimulated vascular smooth muscle cells leads to activation of cPLA(2) and arachidonic acid release. Surface plasmon resonance, mass spectrometry, and kinetic studies show that CaM kinase II binds to cPLA(2) resulting in cPLA(2) phosphorylation on Ser-515 and an increase in its enzymatic activity. Phosphopeptide mapping studies with cPLA(2) from norepinephrine-stimulated smooth muscle cells indicates that phosphorylation of cPLA(2) on Ser-515, but not on Ser-505 or Ser-727, occurs in vivo. This novel signaling pathway for arachidonate release is shown to be cPLA(2)-dependent by use of a recently described and highly selective inhibitor of this enzyme.
ESTHER : Muthalif_2001_J.Biol.Chem_276_39653
PubMedSearch : Muthalif_2001_J.Biol.Chem_276_39653
PubMedID: 11479288

Title : A cysteine-rich form of Xenopus neuregulin induces the expression of acetylcholine receptors in cultured myotubes - Yang_1999_Mol.Cell.Neurosci_13_415
Author(s) : Yang JF , Zhou H , Choi RC , Ip NY , Peng HB , Tsim KWK
Ref : Molecular & Cellular Neurosciences , 13 :415 , 1999
Abstract : Neuregulin-1 (NRG-1) has diverse functions in neural development, and one of them is to up regulate the expression of acetylcholine receptors (AChRs) at muscle fibers during the formation of neuromuscular junctions. NRG-1 has two prominent alternative splicing sites at the N-terminus; it could be an immunoglobulin (Ig)-like domain named Ig-NRG-1 or an apolar cysteine-rich domain (CRD) named CRD-NRG-1. cDNAs encoding Xenopus CRD-NRG-1 were isolated by cross-hybridization with Xenopus Ig-NRG-1 cDNA fragment. The amino acid sequence of Xenopus CRD-NRG-1 is 45 to 70% identical to the human, rat, and chick homologs. Similar to Ig-NRG-1, two variation sites within CRD-NRG-1 were identified at the spacer domain with 0 or 43 amino acids inserted and at the C-terminus of the EGF-like domain to derive either alpha or beta isoform. Two transcripts encoding CRD-NRG-1, approximately 7.5 and approximately 9.0 kb, were revealed in adult brain and spinal cord, but the expression in muscle was below the detectable level. The recombinant Xenopus CRD-NRG-1 when applied onto cultured myotubes was able to induce the tyrosine phosphorylation of ErbB receptors and the expression of AChR. The AChR-inducing activity of CRD-NRG-1 was precipitated by anti-NRG-1 antibody but not by heparin. In situ hybridization showed a strong expression of CRD-NRG-1 mRNA in developing brain, spinal cord, and myotomal muscles of Xenopus embryo. Similar to the results in other species, both CRD-NRG-1 and Ig-NRG-1 may play a role in the developing Xenopus neuromuscular junctions.
ESTHER : Yang_1999_Mol.Cell.Neurosci_13_415
PubMedSearch : Yang_1999_Mol.Cell.Neurosci_13_415
PubMedID: 10383827

Title : Development of the neuromuscular junction: genetic analysis in mice - Sanes_1998_J.Physiol.Paris_92_167
Author(s) : Sanes JR , Apel ED , Burgess RW , Emerson RB , Feng G , Gautam M , Glass D , Grady RM , Krejci E , Lichtman JW , Lu JT , Massoulie J , Miner JH , Moscoso LM , Nguyen Q , Nichol M , Noakes PG , Patton BL , Son YJ , Yancopoulos GD , Zhou H
Ref : Journal de Physiologie (Paris) , 92 :167 , 1998
Abstract : Formation of the skeletal neuromuscular junction is a multi-step process that requires communication between the nerve and muscle. Studies in many laboratories have led to identification of factors that seem likely to mediate these interactions. 'Knock-out' mice have now been generated with mutations in several genes that encode candidate transsynaptic messengers and components of their effector mechanisms. Using these mice, it is possible to test hypotheses about the control of synaptogenesis. Here, we review our studies on neuromuscular development in mutant mice lacking agrin alpha CGRP, rapsyn, MuSK, dystrophin, dystrobrevin, utrophin, laminin alpha 5, laminin beta 2, collagen alpha 3 (IV), the acetylcholine receptor epsilon subunit, the collagenous tail of acetylcholinesterase, fibroblast growth factor-5, the neural cell adhesion molecule, and tenascin-C.
ESTHER : Sanes_1998_J.Physiol.Paris_92_167
PubMedSearch : Sanes_1998_J.Physiol.Paris_92_167
PubMedID: 9789802

Title : Cloning of cDNAs encoding xenopus neuregulin: expression in myotomal muscle during embryo development - Yang_1998_Brain.Res.Mol.Brain.Res_58_59
Author(s) : Yang JF , Zhou H , Pun S , Ip NY , Peng HB , Tsim KWK
Ref : Brain Research Mol Brain Res , 58 :59 , 1998
Abstract : Neuregulin has diverse functions in neural development, and one of them is the up regulation of acetylcholine receptors (AChRs) at the muscle fiber during the formation of neuromuscular junctions. Although the primary source of neuregulin is derived from motor neuron, the expression in muscle has also been demonstrated. The precise role of neuron-derived and muscle-derived neuregulin during the early stages of development is not known. In order to study the role of neuregulin during early embryo development, we isolated the cDNAs encoding Xenopus neuregulin by cross-hybridization with its chick homologue. The amino acid sequence of Xenopus protein is 50 to 70% identical to members of the neuregulin family. The cDNAs encoding different isoforms of Xenopus neuregulin were identified, and these isoforms have two variation sites: (i) the spacer domain with either 0 or 43 amino acid insertion; and (ii) the C-terminus of EGF-like domain to derive either alpha or beta isoform. When the EGF-like domain of Xenopus neuregulin was expressed in mammalian cells, the recombinant protein was able to induce the expression of AChR and the tyrosine phosphorylation of erbB receptors in cultured myotubes. An approximately 6.5 kb transcript corresponding to neuregulin was detected in RNA isolated from brain and muscle. Various splicing variants were expressed in different Xenopus tissues. In situ hybridization showed a strong expression of neuregulin in developing brain and spinal cord of Xenopus embryo. In addition, it was also prominently expressed in the myotomal muscle. These data suggest that in addition to motor neurons, the postsynaptic muscle cells can also contribute neuregulin for synaptogenesis.
ESTHER : Yang_1998_Brain.Res.Mol.Brain.Res_58_59
PubMedSearch : Yang_1998_Brain.Res.Mol.Brain.Res_58_59
PubMedID: 9685585

Title : A role of midkine in the development of the neuromuscular junction - Zhou_1997_Mol.Cell.Neurosci_10_56
Author(s) : Zhou H , Muramatsu T , Halfter W , Tsim KWK , Peng HB
Ref : Molecular & Cellular Neurosciences , 10 :56 , 1997
Abstract : Midkine (MK) is a member of a family of developmentally regulated neurotrophic and heparin-binding growth factors. It is expressed during the midgestation period in a retinoid-acid dependent manner during embryogenesis in the mouse. In vitro, it promotes neurite outgrowth from spinal cord neurons and cell migration. It expression is strongest in the central nervous system, thus suggesting a function for this protein in neural development. In this study, the role of MK in synaptogenesis was examined in the Xenopus system. A Xenopus MK cDNA was cloned from an embryonic library encompassing neurulation and synaptogenesis stages. By Northern blot analysis, MK mRNA was detected from the onset of neurulation and throughout the stages of synaptogenesis in the Xenopus embryo. This suggests that MK is also an important growth regulator in Xenopus embryogenesis. To study the function of MK in the development of the neuromuscular junction (NMJ), fusion proteins were made and their ability to induce the formation of acetylcholine receptor (AChR) clusters in cultured muscle cells was studied. Beads coated with MK strongly induce AChR clustering. When nerve-muscle cocultures were labeled with antibodies made against the MK fusion protein, MK immunoreactivity was detected at the NMJ. Unlike heparin-binding growth-associated molecule (HB-GAM), another member of this growth factor family, MK expression cannot be detected in the muscle but is present in spinal cord neurites. Consistent with these in vitro data is the observation that MK mRNA is only localized in the central nervous system but the protein is deposited at the intersomitic junction where the NMJ is located in vivo. Exogenously applied MK does bind to the heparan sulfate proteoglycan on the surface of Xenopus muscle cells. Agrin, a heparan-sulfate proteoglycan that induces the formation of AChR clusters in cultured muscle cells, binds strongly to MK. Bath application of MK in conjunction with agrin results in a change in the pattern of AChR clustering induced by agrin alone. These data suggest that MK is a neuron-derived factor that participates in the signal transduction process during NMJ development.
ESTHER : Zhou_1997_Mol.Cell.Neurosci_10_56
PubMedSearch : Zhou_1997_Mol.Cell.Neurosci_10_56
PubMedID: 9361288

Title : Role of m1 receptor-G protein coupling in cell proliferation in the prostate - Luthin_1997_Life.Sci_60(13-14)_963
Author(s) : Luthin GR , Wang P , Zhou H , Dhanasekaran D , Ruggieri MR
Ref : Life Sciences , 60 :963 , 1997
Abstract : The prostate gland from several animal species contains variable levels of muscarinic subtypes, but only the human prostate expresses significant levels of the m1 subtype. We studied muscarinic receptor activity in human benign prostatic hypertrophy (BPH) as well as several cell lines derived from prostate cancer. The BPH we studied expresses approximately 75% of the m1 receptor and undetectable levels of the other receptor subtypes whereas PC3 cells express only the m3 receptor subtype. DU145 and LnCaP cells express approximately equal levels of m1 and m3 receptor subtypes. Only the PC3 cells responded to carbachol with an increase in turnover of polyphosphoinositides, and none of the cell lines responded with effects on cAMP metabolism. Co-precipitation of receptors with heterotrimeric guanine nucleotide-binding regulatory proteins demonstrated interactions of the m1 receptors with Gi, Gq and G16 in BPH tissue and of the m1 and m3 receptors with Gi, Gq and G12 in PC3 and DU145 cells. Mitogen activated protein kinase (ERK) activity was seen in response to carbachol in PC3 and DU145 but not LnCaP cells. Finally, carbachol promoted cell proliferation in all three cell lines. Thus, there appears to be no consistent relationship between ERK activity, cell proliferation, and the subtype mediating the proliferative response, amongst these prostate cancer cell lines.
ESTHER : Luthin_1997_Life.Sci_60(13-14)_963
PubMedSearch : Luthin_1997_Life.Sci_60(13-14)_963
PubMedID: 9121362

Title : [Twenty-years health surveillance of workers in dipterex packaging] - Sun_1996_Chung.Hua.Yu.Fang.I.Hsueh.Tsa.Chih_30_273
Author(s) : Sun D , Zhou H , Huang J
Ref : Chinese Journal of Preventive Medicine , 30 :273 , 1996
Abstract : Data of health surveillance from 1970 to 1989 for the workers employed in dipterex packaging were collected and statistically analyzed with a microcomputer by scoring their whole blood choline esterase activities and symptoms and signs. Results showed working environment improved and air pollution and absorption of pollutants via skin decreased with technology innovation and longterm hygienic supervision, monitoring and health surveillance in the factory. Incidence of dipterex poisoning in workers employed in the department of pesticide packaging lowered significantly, from 25.26% in the early 1970's to 5.17% in late 1970's and to 1.85% during 1980's, with periodical physical examinations for them, and timely management of the patients with poisoning and the cases at high risk.
ESTHER : Sun_1996_Chung.Hua.Yu.Fang.I.Hsueh.Tsa.Chih_30_273
PubMedSearch : Sun_1996_Chung.Hua.Yu.Fang.I.Hsueh.Tsa.Chih_30_273
PubMedID: 9388884

Title : Neurotoxins from Agkistrodon halys (pallas) and Bungarus fasciatus venom -
Author(s) : Heilbronn E , Jiang MS , Zhou H , Haggblad J , Rydqvist B
Ref : Prog Clin Biol Res , 253 :265 , 1987
PubMedID: 3432290