Zhang Q

References (171)

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 : Characterization and validation of fatty acid metabolism-related genes predicting prognosis, immune infiltration, and drug sensitivity in endometrial cancer - Li_2024_Biotechnol.Appl.Biochem__
Author(s) : Li H , Zhou T , Zhang Q , Yao Y , Hua T , Zhang J , Wang H
Ref : Biotechnol Appl Biochem , : , 2024
Abstract : Endometrial cancer is considered to be the second most common tumor of the female reproductive system, and patients diagnosed with advanced endometrial cancer have a poor prognosis. The influence of fatty acid metabolism in the prognosis of patients with endometrial cancer remains unclear. We constructed a prognostic risk model using transcriptome sequencing data of endometrial cancer and clinical information of patients from The Cancer Genome Atlas (TCGA) database via least absolute shrinkage and selection operator regression analysis. The tumor immune microenvironment was analyzed using the CIBERSORT algorithm, followed by functional analysis and immunotherapy efficacy prediction by gene set variation analysis. The role of model genes in regulating endometrial cancer in vitro was verified by CCK-8, colony formation, wound healing, and transabdominal invasion assays, and verified in vivo by subcutaneous tumor transplantation in nude mice. A prognostic model containing 14 genes was constructed and validated in 3 cohorts and clinical samples. The results showed differences in the infiltration of immune cells between the high-risk and low-risk groups, and that the high-risk group may respond better to immunotherapy. Experiments in vitro confirmed that knockdown of epoxide hydrolase 2 (EPHX2) and acyl-CoA oxidase like (ACOXL) had an inhibitory effect on EC cells, as did overexpression of hematopoietic prostaglandin D synthase (HPGDS). The same results were obtained in experiments in vivo. Prognostic models related to fatty acid metabolism can be used for the risk assessment of endometrial cancer patients. Experiments in vitro and in vivo confirmed that the key genes HPGDS, EPHX2, and ACOXL in the prognostic model may affect the development of endometrial cancer.
ESTHER : Li_2024_Biotechnol.Appl.Biochem__
PubMedSearch : Li_2024_Biotechnol.Appl.Biochem__
PubMedID: 38616327

Title : Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity - Zhang_2024_Sci.Immunol_9_eadh2334
Author(s) : Zhang T , Yu W , Cheng X , Yeung J , Ahumada V , Norris PC , Pearson MJ , Yang X , van Deursen W , Halcovich C , Nassar A , Vesely MD , Zhang Y , Zhang J , Ji L , Flies DB , Liu L , Langermann S , LaRochelle WJ , Humphrey R , Zhao D , Zhang Q , Gu R , Schalper KA , Sanmamed MF , Chen L
Ref : Sci Immunol , 9 :eadh2334 , 2024
Abstract : T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.
ESTHER : Zhang_2024_Sci.Immunol_9_eadh2334
PubMedSearch : Zhang_2024_Sci.Immunol_9_eadh2334
PubMedID: 38669316

Title : Traditional uses, phytochemistry, pharmacology, toxicity and clinical application of traditional Chinese medicine Cynoglossum amabile: a review - Fan_2024_Front.Pharmacol_15_1325283
Author(s) : Fan Y , Wang M , Zhang Q , Ouyang S , Mao W , Xu C , Long C
Ref : Front Pharmacol , 15 :1325283 , 2024
Abstract : Cynoglossum amabile, a member of the Boraginaceae family, is a well-known traditional Chinese medicine and ethnomedicine known as Daotihu. Despite several studies confirming the presence of bioactive pyrrolizidine alkaloids such as amabiline, ambelline, echinatine, europine, and others in C. amabile, there has been no comprehensive review of its traditional uses, phytochemistry, and pharmacology thus far. This review was conducted by thoroughly examining the literature and analyzing network databases. It covers various aspects of C. amabile, including botanical characteristics, geographical distribution, traditional applications, phytochemistry, pharmacological activities, toxicology, and clinical applications. The results have shown that C. amabile has been traditionally used for medicinal, edible, and ornamental purposes in China for many centuries. The whole plant, root, and leaf of C. amabile are used by different ethnic groups, such as Lisu, Bai, Naxi, Yi, Jinuo, and Han, to treat malaria, hepatitis, dysentery, leucorrhea, tuberculosis cough, fracture, joint dislocation, trauma bleeding, and skin carbuncle abscess. A total of 47 chemical components, including alkaloids (pyrrolizidine alkaloids, PAs), sterols, organic acids, and saccharides, were isolated from C. amabile. Pharmacological studies show that the chemical extracts of C. amabile possess various biological activities, such as anti-inflammatory, anti-tumor, anti-microbial, cardiovascular effects, ganglionic action, and acetylcholinesterase inhibition. However, it is important to note that C. amabile exhibits hepatotoxicity, with its toxicity being linked to its primary PAs components. Although preliminary studies suggest potential applications in the treatment of prostate diseases and alopecia, further research is needed to validate these clinical uses. Our review highlights the traditional uses, phytochemistry, biological activity, toxicity, and clinical applications of C. amabile. It emphasizes the essential guiding role of the indigenous medicinal knowledge system in developing new drugs. Previous studies have shown that the phytochemical and pharmacological characteristics of C. amabile are significantly related to its traditional medicinal practices. Cynoglossum amabile has excellent market potential and can be further analyzed in terms of phytochemistry, pharmacology, and toxicology, which are critical for its clinical drug safety, quality evaluation, and resource development.
ESTHER : Fan_2024_Front.Pharmacol_15_1325283
PubMedSearch : Fan_2024_Front.Pharmacol_15_1325283
PubMedID: 38655180

Title : Role of soluble epoxide hydrolase in pain and depression comorbidity - Bu_2024_Neurobiol.Dis_193_106443
Author(s) : Bu Y , Yang S , Wang D , Hu S , Zhang Q , Wu Z , Yang C
Ref : Neurobiol Dis , 193 :106443 , 2024
Abstract : The coexistence of chronic pain and depression in clinical practice places a substantial social burden and profoundly impacts in patients. Although a clear correlation exists, the underlying mechanism of comorbidity between chronic pain and depression remains elusive. Research conducted in recent decades has uncovered that soluble epoxide hydrolase, a pivotal enzyme in the metabolism of polyunsaturated fatty acids, plays a crucial role in inflammation. Interestingly, this enzyme is intricately linked to the development of both pain and depression. With this understanding, this review aims to summarize the roles of soluble epoxide hydrolase in pain, depression, and their comorbidity. Simultaneously, we will also explore the underlying mechanisms, providing guidance for future research and drug development.
ESTHER : Bu_2024_Neurobiol.Dis_193_106443
PubMedSearch : Bu_2024_Neurobiol.Dis_193_106443
PubMedID: 38395315

Title : Astaxanthin activates the Nrf2\/Keap1\/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity - Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
Author(s) : Zhang Q , Luo C , Li Z , Huang W , Zheng S , Liu C , Shi X , Ma Y , Ni Q , Tan W , Peng J , Chen Y , Wu W , Li J , Wu K
Ref : Ecotoxicology & Environmental Safety , 271 :115960 , 2024
Abstract : Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe(2+) content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe(2+) metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
ESTHER : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedSearch : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedID: 38219622

Title : Long-term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-based Study - Cai_2024_Neuroepidemiology__
Author(s) : Cai Q , Batista AE , Borsum J , Zhang Q , Isheden G , Kunovszki P , Gandhi K , Heerlein K , Brauner S
Ref : Neuroepidemiology , : , 2024
Abstract : INTRODUCTION: Health care costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and pre-existing (PE) MG in Sweden. METHODS: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having <= 24-month follow-up during the period 1/1/2010 to 12/31/2017 were included. RESULTS: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (+/-SD) age was 61.3 (+/-17.4) years and 52.3% were female. In first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs 83.9%), corticosteroids (59.6% vs 45.8%), thymectomy (12.1% vs 0.7%) and plasma exchange (3.8% vs 0.6%); had higher all-cause (70.9% vs 35.8%) and MG-related (62.5% vs 18.4%) hospitalization rates with 11 more hospitalization days (all p<0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred 7302 (p<0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p<0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ~55% for ND MG from year 1 and were comparable with PE MG. CONCLUSION: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.
ESTHER : Cai_2024_Neuroepidemiology__
PubMedSearch : Cai_2024_Neuroepidemiology__
PubMedID: 38631321

Title : Lead induced cerebellar toxicology of developmental Japanese quail (Coturnix japonica) via oxidative stress-based Nrf2\/Keap1 pathway inhibition and glutathione-mediated apoptosis signaling activation - Zhang_2024_Environ.Pollut_352_124114
Author(s) : Zhang Y , Pei X , Jing L , Zhang Q , Zhao H
Ref : Environ Pollut , 352 :124114 , 2024
Abstract : Lead (Pb) is a heavy metal that has been recognized as a neurotoxin, meaning it can cause harmful effects on the nervous system. However, the neurotoxicology of Pb to birds still needs further study. In this study, we examined the neurotoxic effects of Pb exposure on avian cerebellum by using an animal model-Japanese quail (Coturnix japonica). The one-week old male chicks were exposed to 50, 200 and 500 mg/kg Pb of environmental relevance in the feed for five weeks. The results showed Pb caused cerebellar microstructural damages charactered by deformation of neuroglia cells, granule cells and Purkinje cells with Nissl body changes. Moreover, cerebellar neurotransmission was disturbed by Pb with increasing acetylcholine (ACh) and decreasing acetylcholinesterase (AChE), dopamine (DA), gamma-Aminobutyric Acid (GABA) and Na(+)/K(+) ATPase. Meanwhile, cerebellar oxidative stress was caused by Pb exposure represented by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) as well as decreasing catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH) and superoxide dismutase (SOD). Moreover, RNA-Seq analysis showed that molecular signaling pathways in the cerebellum were disrupted by Pb exposure. In particular, the disruption of nuclear factor erythroid-2-related factor 2 (Nfr2)/kelch-like ECH-associated protein 1 (Keap1) pathway and glutathione metabolism pathway indicated increasing cell apoptosis and functional disorder in the cerebellum. The present study revealed that Pb induced cerebellar toxicology through structural injury, oxidative stress, neurotransmission interference and abnormal apoptosis.
ESTHER : Zhang_2024_Environ.Pollut_352_124114
PubMedSearch : Zhang_2024_Environ.Pollut_352_124114
PubMedID: 38718965

Title : Metabolic engineering of Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids - Dong_2024_Metab.Eng__
Author(s) : Dong G , Zhao Y , Ding W , Xu S , Zhang Q , Zhao H , Shi S
Ref : Metab Eng , : , 2024
Abstract : Odd-numbered fatty acids (FAs) have been widely used in nutrition, agriculture, and chemical industries. Recently, some studies showed that they could be produced from bacteria or yeast, but the products are almost exclusively odd-numbered long-chain FAs. Here we report the design and construction of two biosynthetic pathways in Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids (OMFAs) via ricinoleic acid and 10-hydroxystearic acid, respectively. The production of OMFAs was enabled by introducing a hydroxy fatty acid cleavage pathway, including an alcohol dehydrogenase from Micrococcus luteus, a Baeyer-Villiger monooxygenase from Pseudomonas putida, and a lipase from Pseudomonas fluorescens. These OMFA biosynthetic pathways were optimized by eliminating the rate-limiting step, generating heptanoic acid, 11-hydroxyundec-9-enoic acid, nonanoic acid, and 9-hydroxynonanoic acid at 7.83 mg/L, 9.68 mg/L, 9.43 mg/L and 13.48 mg/L, respectively. This work demonstrates the biological production of OMFAs in a sustainable manner in S. cerevisiae.
ESTHER : Dong_2024_Metab.Eng__
PubMedSearch : Dong_2024_Metab.Eng__
PubMedID: 38325640

Title : SLC25A28 Overexpression Promotes Adipogenesis by Reducing ATGL - Guan_2024_J.Diabetes.Res_2024_5511454
Author(s) : Guan H , Xiao L , Hao K , Zhang Q , Wu D , Geng Z , Duan B , Dai H , Xu R , Feng X
Ref : J Diabetes Res , 2024 :5511454 , 2024
Abstract : Adipose tissue dysfunction is seen among obese and type 2 diabetic individuals. Adipocyte proliferation and hypertrophy are the root causes of adipose tissue expansion. Solute carrier family 25 member 28 (SLC25A28) is an iron transporter in the inner mitochondrial membrane. This study is aimed at validating the involvement of SLC25A28 in adipose accumulation by tail vein injection of adenovirus (Ad)-SLC25A28 and Ad-green fluorescent protein viral particles into C57BL/6J mice. After 16 weeks, the body weight of the mice was measured. Subsequently, morphological analysis was performed to establish a high-fat diet (HFD)-induced model. SLC25A28 overexpression accelerated lipid accumulation in white and brown adipose tissue (BAT), enhanced body weight, reduced serum triglyceride (TG), and impaired serum glucose tolerance. The protein expression level of lipogenesis, lipolysis, and serum adipose secretion hormone was evaluated by western blotting. The results showed that adipose TG lipase (ATGL) protein expression was reduced significantly in white and BAT after overexpression SLC25A28 compared to the control group. Moreover, SLC25A28 overexpression inhibited the BAT formation by downregulating UCP-1 and the mitochondrial biosynthesis marker PGC-1alpha. Serum adiponectin protein expression was unregulated, which was consistent with the expression in inguinal white adipose tissue (iWAT). Remarkably, serum fibroblast growth factor (FGF21) protein expression was negatively related to the expansion of adipose tissue after administrated by Ad-SLC25A28. Data from the current study indicate that SLC25A28 overexpression promotes diet-induced obesity and accelerates lipid accumulation by regulating hormone secretion and inhibiting lipolysis in adipose tissue.
ESTHER : Guan_2024_J.Diabetes.Res_2024_5511454
PubMedSearch : Guan_2024_J.Diabetes.Res_2024_5511454
PubMedID: 38736904

Title : Discovery of 1,2,4-Oxadiazole Derivatives Containing Haloalkyl as Potential Acetylcholine Receptor Nematicides - Luo_2023_Int.J.Mol.Sci_24_
Author(s) : Luo L , Ou Y , Zhang Q , Gan X
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Plant-parasitic nematodes pose a serious threat to crops and cause substantial financial losses due to control difficulties. Tioxazafen (3-phenyl-5-thiophen-2-yl-1,2,4-oxadiazole) is a novel broad-spectrum nematicide developed by the Monsanto Company, which shows good prevention effects on many kinds of nematodes. To discover compounds with high nematocidal activities, 48 derivatives of 1,2,4-oxadiazole were obtained by introducing haloalkyl at the 5-position of tioxazafen, and their nematocidal activities were systematically evaluated. The bioassays revealed that most of 1,2,4-oxadiazole derivatives showed remarkable nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci. Notably, compound A1 showed excellent nematocidal activity against B. xylophilus with LC(50) values of 2.4 microg/mL, which was superior to that of avermectin (335.5 microg/mL), tioxazafen (>300 microg/mL), and fosthiazate (436.9 microg/mL). The transcriptome and enzyme activity results indicate that the nematocidal activity of compound A1 was mainly related to the compound which affected the acetylcholine receptor of B. xylophilus.
ESTHER : Luo_2023_Int.J.Mol.Sci_24_
PubMedSearch : Luo_2023_Int.J.Mol.Sci_24_
PubMedID: 36982843

Title : Dendrobium nobile Lindl ameliorates learning and memory deficits in scopolamine-treated mice - Zhang_2023_J.Ethnopharmacol__117416
Author(s) : Zhang Q , Li Y , Fan B , Wang F , Li Z , Carlos Pires Dias A , Liu X , Wang Q
Ref : J Ethnopharmacol , :117416 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl (DNL), a valued time-honored herb, possesses immune-boosting and age-delaying properties, has been widely used to treat hyperglycemia and neurological diseases, and is probably a potential drug for improving learning and memory. Scopolamine (Scop), an antagonist for muscarinic receptors, potentially impairing intelligence and memory. AIM OF THE STUDY: This investigation aimed to assess the efficacy of DNL in alleviating scopolamine-induced cognitive deficits in mice and its mechanisms. MATERIALS AND METHODS: We utilized the open-field test, novel object recognition test (NOR), and Morris water maze test (MWM) to assess the potential of DNL in ameliorating learning and memory dysfunction caused by scopolamine in mice. Enzyme-linked immunosorbent assay (ELISA) was employed to measure Choline acetyltransferase (ChAT) content and Acetylcholinesterase (AChE) activities in the brain, and oxidative stress-related factors in the serum, including Malondialdehyde (MDA), Superoxide dismutase (SOD), and glutathione (GSH) content. RESULTS: Scopolamine injection significantly reduced the discrimination index of mice in the NOR test and impaired their performance in the MWM test, as demonstrated by longer escape latency, fewer target crossings, and less time spent in the target quadrant in the MWM. After 25 days of administration, DNL increased the discrimination index of the scopolamine-treated mice in the NOR test. DNL reduced the escape latency in the MWM test in the model mice. DNL increased the target crossing number and the percentage of time spent in the target quadrant in the MWM test. ELISA experiments indicated that DNL decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress makers (GSH, SOD, and MDA) in scopolamine-induced mice. CONCLUSIONS: DNL may improve the learning and memory in mice treated with scopolamine, possibly by modulating oxidative stress and impaired cholinergic function.
ESTHER : Zhang_2023_J.Ethnopharmacol__117416
PubMedSearch : Zhang_2023_J.Ethnopharmacol__117416
PubMedID: 37981114

Title : Acaricidal activities of paeonol from Moutan Cortex, dried bark of Paeonia suffruticosa, against the grain pest mite Aleuroglyphus ovatus (Acari: Acaridae) - Zou_2023_Exp.Appl.Acarol__
Author(s) : Zou M , Xue Q , Teng Q , Zhang Q , Liu T , Li Y , Zhao J
Ref : Exp Appl Acarol , : , 2023
Abstract : Aleuroglyphus ovatus (Acari: Acaridae) is a major pest mite of stored grains that is distributed worldwide. Paeonol, a phenolic component of the essential oil extracted from the Chinese herb Paeonia moutan, possesses a range of biological activities, including antiviral, antifungal and acaricidal activity. This study investigated the bioactivity of paeonol against A. ovatus and its effect on the activity of detoxification enzymes. The bioactivity of paeonol against A. ovatus was determined by contact, fumigation and repellency bioassays, and the mechanism was preliminarily explored via morphological observation of the color changes of mite epidermis and determination of the changing trend of some important enzymes associated with acaricidal efficacy in the mites. The results showed that the median lethal concentration (LC(50)) in the contact and fumigation bioassays was 9.832 microg/cm(2) and 14.827 microg/cm(3), respectively, and the acaricidal activity of paeonol was higher under direct contact than under fumigation. Dynamic symptomatology studies registered typical neurotoxicity symptoms including excitation, convulsion and paralysis in A. ovatus treated with paeonol. The enzyme activity of catalase (CAT), nitric oxide synthase (NOS) and glutathione-S-transferase (GST) was higher, whereas the activity of superoxide dismutase (SOD) and acetylcholinesterase (AChE) was lower, compared to the control group. CAT, NOS and GST were activated, whereas SOD and AChE activities were inhibited after paeonol intervention. Our findings suggest paeonol has potent acaricidal activity against A. ovatus and thus may be used as an agent to control the stored-product mite A. ovatus.
ESTHER : Zou_2023_Exp.Appl.Acarol__
PubMedSearch : Zou_2023_Exp.Appl.Acarol__
PubMedID: 37979065

Title : Complete bio-degradation of poly(butylene adipate-co-terephthalate) via engineered cutinases - Yang_2023_Nat.Commun_14_1645
Author(s) : Yang Y , Min J , Xue T , Jiang P , Liu X , Peng R , Huang JW , Qu Y , Li X , Ma N , Tsai FC , Dai L , Zhang Q , Liu Y , Chen CC , Guo RT
Ref : Nat Commun , 14 :1645 , 2023
Abstract : Poly(butylene adipate-co-terephthalate) (PBAT), a polyester made of terephthalic acid (TPA), 1,4-butanediol, and adipic acid, is extensively utilized in plastic production and has accumulated globally as environmental waste. Biodegradation is an attractive strategy to manage PBAT, but an effective PBAT-degrading enzyme is required. Here, we demonstrate that cutinases are highly potent enzymes that can completely decompose PBAT films in 48 h. We further show that the engineered cutinases, by applying a double mutation strategy to render a more flexible substrate-binding pocket exhibit higher decomposition rates. Notably, these variants produce TPA as a major end-product, which is beneficial feature for the future recycling economy. The crystal structures of wild type and double mutation of a cutinase from Thermobifida fusca in complex with a substrate analogue are also solved, elucidating their substrate-binding modes. These structural and biochemical analyses enable us to propose the mechanism of cutinase-mediated PBAT degradation.
ESTHER : Yang_2023_Nat.Commun_14_1645
PubMedSearch : Yang_2023_Nat.Commun_14_1645
PubMedID: 36964144
Gene_locus related to this paper: idesa-peth , thefu-q6a0i4

Title : Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis - Guo_2023_Front.Neurol_14_1129470
Author(s) : Guo W , Gou X , Yu L , Zhang Q , Yang P , Pang M , Pang X , Pang C , Wei Y , Zhang X
Ref : Front Neurol , 14 :1129470 , 2023
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease that primarily occurs in elderly individuals with cognitive impairment. Although extracellular beta-amyloid (Abeta) accumulation and tau protein hyperphosphorylation are considered to be leading causes of AD, the molecular mechanism of AD remains unknown. Therefore, in this study, we aimed to explore potential biomarkers of AD. Next-generation sequencing (NGS) datasets, GSE173955 and GSE203206, were collected from the Gene Expression Omnibus (GEO) database. Analysis of differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein networks were performed to identify genes that are potentially associated with AD. Analysis of the DEG based protein-protein interaction (PPI) network using Cytoscape indicated that neuroinflammation and T-cell antigen receptor (TCR)-associated genes (LCK, ZAP70, and CD44) were the top three hub genes. Next, we validated these three hub genes in the AD database and utilized two machine learning models from different AD datasets (GSE15222) to observe their general relationship with AD. Analysis using the random forest classifier indicated that accuracy (78%) observed using the top three genes as inputs differed only slightly from that (84%) observed using all genes as inputs. Furthermore, another data set, GSE97760, which was analyzed using our novel eigenvalue decomposition method, indicated that the top three hub genes may be involved in tauopathies associated with AD, rather than Abeta pathology. In addition, protein-protein docking simulation revealed that the top hub genes could form stable binding sites with acetylcholinesterase (ACHE). This suggests a potential interaction between hub genes and ACHE, which plays an essential role in the development of anti-AD drug design. Overall, the findings of this study, which systematically analyzed several AD datasets, illustrated that LCK, ZAP70, and CD44 may be used as AD biomarkers. We also established a robust prediction model for classifying patients with AD.
ESTHER : Guo_2023_Front.Neurol_14_1129470
PubMedSearch : Guo_2023_Front.Neurol_14_1129470
PubMedID: 37056359

Title : Enantioselectivity and origin of enhanced efficiency in polyethylene terephthalate hydrolases catalyzed depolymerization - Zheng_2023_J.Hazard.Mater_452_131295
Author(s) : Zheng M , Li Y , Dong W , Zhang Q , Wang W
Ref : J Hazard Mater , 452 :131295 , 2023
Abstract : Biotechnology is one of the most promising strategies to resolve the global crisis of plastic pollution. A clear understanding of the core enzyme mechanisms in the biotransformation process is critical for rational enzyme engineering and for practical, industrial-scale applications. Herein, we systematically examined and evidenced a largely unexplored piece in the depolymerization mechanism catalyzed by polyethylene terephthalate (PET) hydrolases: their enantioselectivity. We found that all the short-lived tetrahedron intermediates (IM3 and IM8) possess S-type chirality in six representative PET hydrolases. For instance, the binding percentage ratio of pro-S:pro-R is 57:21 in FAST-PETase, while pro-S binding leads to a much lower average energy barrier (5.2 kcal/mol) than pro-R binding (33.1 kcal/mol). Key structural features (e.g. the angle for Ser@H1-His@N1-PET@O2 and distance for His@N1-PET@O2) that significantly modulate the enantioselectivity were identified. The origin of the energy landscape variation between wild-type IsPETase and mutant FAST-PETase was also unveiled via analysis of key features, the distortion/interaction energy, and non-covalent bond interactions. This study supplies the missing piece in the mechanism for depolymerization catalyzed by PET hydrolases, and will aid in the rational design of enzymes for industrial recycling of PET plastic waste.
ESTHER : Zheng_2023_J.Hazard.Mater_452_131295
PubMedSearch : Zheng_2023_J.Hazard.Mater_452_131295
PubMedID: 36989777

Title : An in vitro evaluation of kratom (Mitragyna speciosa) on the catalytic activity of carboxylesterase 1 (CES1) - Melchert_2023_Chem.Biol.Interact__110715
Author(s) : Melchert PW , Zhang Q , Mukhopadhyay S , Kanumuri SRR , McCurdy CR , Markowitz JS
Ref : Chemico-Biological Interactions , :110715 , 2023
Abstract : Kratom, (Mitragyna Speciosa Korth.) is a plant indigenous to Southeast Asia whose leaves are cultivated for a variety of medicinal purposes and mostly consumed as powders or tea in the United States. Kratom use has surged in popularity with the lay public and is currently being investigated for possible therapeutic benefits including as a treatment for opioid withdrawal due to the pharmacologic effects of its indole alkaloids. A wide array of psychoactive compounds are found in kratom, with mitragynine being the most abundant alkaloid. The drug-drug interaction (DDI) potential of mitragynine and related alkaloids have been evaluated for effects on the major cytochrome P450s (CYPs) via in vitro assays and limited clinical investigations. However, no thorough assessment of their potential to inhibit the major hepatic hydrolase, carboxylesterase 1 (CES1), exists. The purpose of this study was to evaluate the in vitro inhibitory potential of kratom extracts and its individual major alkaloids using an established CES1 assay and incubation system. Three separate kratom extracts and the major kratom alkaloids mitragynine, speciogynine, speciociliatine, paynantheine, and corynantheidine displayed a concentration-dependent reversible inhibition of CES1. The experimental K(i) values were determined as follows for mitragynine, speciociliatine, paynantheine, and corynantheidine: 20.6, 8.6, 26.1, and 12.5 microM respectively. Speciociliatine, paynantheine, and corynantheidine were all determined to be mixed-type reversible inhibitors of CES1, while mitragynine was a purely competitive inhibitor. Based on available pharmacokinetic data, determined Ki values, and a physiologically based inhibition screen mimicking alkaloid exposures in humans, a DDI mediated via CES1 inhibition appears unlikely across a spectrum of doses (i.e., 2-20g per dose). However, further clinical studies need to be conducted to exclude the possibility of a DDI at higher and extreme doses of kratom and those who are chronic users.
ESTHER : Melchert_2023_Chem.Biol.Interact__110715
PubMedSearch : Melchert_2023_Chem.Biol.Interact__110715
PubMedID: 37716419

Title : Parkinson's disease and comorbid myasthenia gravis: a case report and literature review - Zhang_2023_Front.Neurol_14_1303434
Author(s) : Zhang Q , Xu E , Li HF , Chan P , Zhao Z , Ma J
Ref : Front Neurol , 14 :1303434 , 2023
Abstract : BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Myasthenia gravis (MG) is a rare autoimmune disease caused by antibodies against the neuromuscular junction. PD and comorbid MG are rarely seen. CASE PRESENTATION: Here we report on a patient who was diagnosed with PD and MG. A 74-year-old man had a 4-year history of bradykinesia and was diagnosed with PD. He subsequently developed incomplete palpebral ptosis, apparent dropped head, and shuffling of gait. The results of neostigmine tests were positive. Repetitive nerve stimulation (RNS) showed significant decremental responses at 3 and 5 Hz in the orbicularis oculi. The patient's anti-acetylcholine receptor (anti-AchR) antibody serum level was also elevated. Meanwhile, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine positron emission tomography-computed tomography ((18)F-AV133 PET-CT) scan revealed a significant decrease in uptake in the bilateral putamen. After addition of cholinesterase inhibitors, his symptoms of palpebral ptosis and head drop improved greatly and he showed a good response to levodopa. CONCLUSION: Although PD with MG is rare, we still need to notice the possibility that a PD patient may have comorbid MG. The underlying mechanism of PD and comorbid MG remains unknown, but an imbalance between the neurotransmitters dopamine and acetylcholine and the immune system are likely to play significant roles in the pathogenesis. In this article, we present our case and a literature review on the co-occurrence of PD and MG, reviewing their clinical features, and discuss the underlying pathogenic mechanism of this comorbidity.
ESTHER : Zhang_2023_Front.Neurol_14_1303434
PubMedSearch : Zhang_2023_Front.Neurol_14_1303434
PubMedID: 38259657

Title : The primary neurotoxic factor, Lansamide I, from Clausena lansium fruits and metabolic dysfunction invoked - Chen_2023_Food.Chem.Toxicol_181_114087
Author(s) : Chen J , Zhang X , Zhang Y , Zhang H , Zhang Q
Ref : Food & Chemical Toxicology , 181 :114087 , 2023
Abstract : Wampee (Clausena lansium) is a common fruit in South Asia. The pulp is a tasty food, and the seed is a typical traditional herb in China. However, we identified a primary toxic compound, Lansamide I, by NMR and X-ray diffraction of single-crystal. The compound occurred at 4.17 +/- 0.16 mg/kg of dried seed and 0.08 +/- 0.01 g/kg of fresh fruit. In our phenotype-based toxicity investigation, the compound caused decreased hatchability of zebrafish eggs, increased malformations such as enlarged yolk sacs and pericardial edema, and delayed body length development. Moreover, the compound also caused nerve cell damage and decreased locomotor activity. The compound caused an increase in peroxidation levels in vivo, with increases in both malondialdehyde and superoxide dismutase levels, but did not interfere with acetylcholinesterase levels. Metabolomic studies found that the compound caused significant up-regulation of 16 metabolites, mainly amino acids and peptides, which were involved in the nucleotide metabolism pathway and the betaine biosynthesis module. The qRT-PCR revealed that the substance interfered with the mRNA expression of tat and dctpp. These discoveries offer fresh perspectives on the toxicity mechanisms and metabolic response to the primary harmful molecules in wampee, which could inform the rational usage of wampee resources.
ESTHER : Chen_2023_Food.Chem.Toxicol_181_114087
PubMedSearch : Chen_2023_Food.Chem.Toxicol_181_114087
PubMedID: 37804914

Title : A Systematic Review of Clinical Practice Guidelines for Alzheimer's Disease and Strategies for Future Advancements - Tahami_2023_Neurol.Ther__
Author(s) : Tahami Monfared AA , Phan NTN , Pearson I , Mauskopf J , Cho M , Zhang Q , Hampel H
Ref : Neurol Ther , : , 2023
Abstract : INTRODUCTION: Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and managing patients is evolving. METHODS: A systematic literature review (SLR) of practice guidelines for mild cognitive impairment (MCI) and AD dementia was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic literature review (SLR) aimed to summarize current clinical practice guidelines for screening, testing, diagnosis, treatment and monitoring in the AD continuum. The results of this SLR were used to propose a way forward for practice guidelines given the possible introduction of biomarker-guided technology using blood- or plasma-based assays and disease-modifying treatments (DMTs) targeted for early disease. RESULTS: 53 clinical practice guidelines were identified, 15 of which were published since 2018. Screening for asymptomatic populations was not recommended. Biomarker testing was not included in routine diagnostic practice. There was no consensus on which neurocognitive tests to use to diagnose and monitor MCI or AD dementia. Pharmacologic therapies were not recommended for MCI, while cholinesterase inhibitors and memantine were recommended for AD treatment. DISCUSSION: The pre-2018 and post-2018 practice guidelines share similar recommendations for screening, diagnosis and treatment. However, once DMTs are approved, clinicians will require guidance on the appropriate use of DMTs in a clinical setting. This guidance should include strategies for identifying eligible patients and evaluating the DMT benefit-to-risk profile to facilitate shared decision-making among physicians, patients and care partners. CONCLUSION: Regular evidence-based updates of existing guidelines for the AD continuum are required over the coming decades to integrate rapidly evolving technologic and medical scientific advances and bring emerging approaches for management of early disease into clinical practice. This will pave the way toward biomarker-guided identification and targeted treatment and the realization of precision medicine for AD.
ESTHER : Tahami_2023_Neurol.Ther__
PubMedSearch : Tahami_2023_Neurol.Ther__
PubMedID: 37261607

Title : Glimepiride, a novel soluble epoxide hydrolase inhibitor, protects against heart failure via increasing epoxyeicosatrienoic acids - Zhao_2023_J.Mol.Cell.Cardiol_185_13
Author(s) : Zhao C , Jiang X , Peng L , Zhang Y , Li H , Zhang Q , Wang Y , Yang F , Wu J , Wen Z , He Z , Shen J , Chen C , Wang DW
Ref : Journal of Molecular & Cellular Cardiology , 185 :13 , 2023
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs), which exert multiple endogenous protective effects, are hydrolyzed into less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). However, commercial drugs related to EETs or sEH are not yet in clinical use. METHODS: Firstly, the plasma concentration of EETs and DHETs of 316 patients with heart failure (HF) were detected and quantitated by liquid chromatography-tandem mass spectrometry. Then, transverse aortic constriction (TAC)-induced HF was introduced in cardiomyocyte-specific Ephx2(-/-) mice. Moreover, Western blot, real-time PCR, luciferase reporter, ChIP assays were employed to explore the underlying mechanism. Finally, multiple sEH inhibitors were designed, synthesized, and validated in vitro and in vivo. RESULTS: The ratios of DHETs/EETs were increased in the plasma from patients with HF. Meanwhile, the expression of sEH was upregulated in the heart of patients and mice with HF, especially in cardiomyocytes. Cardiomyocyte-specific Ephx2(-/-) mice ameliorated cardiac dysfunction induced by TAC. Consistently, Ephx2 knockdown protected Angiotensin II (AngII)-treated cardiomyocytes via increasing EETs in vitro. Mechanistically, AngII could enhance the expression of transcript factor Krppel-like factor 15 (KLF15), which in turn upregulated sEH. Importantly, glimepiride was identified as a novel sEH inhibitor, which benefited from the elevated EETs during HF. CONCLUSIONS: Glimepiride attenuates HF in mice in part by increasing EETs. CLINICAL TRIAL IDENTIFIER: NCT03461107 (https://clinicaltrials.gov).
ESTHER : Zhao_2023_J.Mol.Cell.Cardiol_185_13
PubMedSearch : Zhao_2023_J.Mol.Cell.Cardiol_185_13
PubMedID: 37871528

Title : Rapid detection of carbamate nerve agent analogues using dually functionalized gold nanoclusters - Zhang_2023_Anal.Bioanal.Chem_415_3275
Author(s) : Zhang Q , Lv J , Xia J , Wang L , Qu G , Yang Y , Liu S
Ref : Anal Bioanal Chem , 415 :3275 , 2023
Abstract : Carbamate nerve agents (CMNAs) are a type of lethal cholinesterase inhibitor with one or more quaternary amine centres and aromatic rings. CMNAs have been recently added to the Annex on Chemicals of the Chemical Weapons Convention (CWC) and Schedules of Controlled Chemicals of China. In this study, a rapid, sensitive and selective method was developed for the fluorescence detection of ambenonium chloride (AC) through host-guest and electrostatic dual interactions between AC and cyclodextrin/11-mercaptoundecanoic acid (CD/MUA) dually functionalized gold nanoclusters (AuNCs). Through this method, AC was detected with a limit of detection of 10.0 ng/mL. Method evaluation showed high selectivity towards AC over other related compounds. The practical applicability was verified, as satisfactory recoveries were obtained for AC spiked in river water and urine, as well as Proficiency Test samples from Organisation for the Prohibition of Chemical Weapons (OPCW). In addition, a fluorescence sensing array comprising four AuNCs was designed to distinguish six carbamates and structurally similar compounds. This method provides a potential approach for the rapid, sensitive and selective recognition and detection of CMNAs.
ESTHER : Zhang_2023_Anal.Bioanal.Chem_415_3275
PubMedSearch : Zhang_2023_Anal.Bioanal.Chem_415_3275
PubMedID: 37266687

Title : Electrochemiluminescence enhanced by isolating ACQphores in imine-linked covalent organic framework for organophosphorus pesticide assay - Song_2023_Talanta_266_124964
Author(s) : Song L , Zhang Q , Min L , Guo X , Gao W , Cui L , Zhang CY
Ref : Talanta , 266 :124964 , 2023
Abstract : Most of covalent organic frameworks (COFs) are non or weakly emissive due to either the molecular thermal motion-mediated energy dissipation or the aggregation-caused quenching (ACQ) effect. Herein, we synthesize an imine-linked COF (TFPPy-TPh-COF) with high electrochemiluminescence (ECL) emission and the capability of eliminating the ACQ effect and further construct an ECL sensor for malathion detection. The imine-linked COF is obtained by the condensation reaction of (1,1':3',1''-terphenyl)-4,4''-diamine (TPh) and 1,3,6,8-tetrakis(p-formylphenyl)pyrene (TFPPy), and it has higher ECL efficiency than TFPPy aggregates due to the separation of ACQ luminophores (i.e., TFPPy) from each other by TPh and the restriction of intramolecular motions of TFPPy and TPh to reduce the nonradiative decay. The efficient quenching of ECL is achieved by electrochemiluminescence resonance energy transfer (ERET) from the excited state of the TFPPy-TPh-COF to zeolite imidazolate framework-8 (ZIF-8) and the steric hindrance of ZIF-8. Acetylcholinesterase (AChE) can enzymatically hydrolyze acetylcholine (ACh) to generate acetic acid. The resultant acetic acid can trigger the dissolution of ZIF-8 to produce an enhanced ECL signal. Malathion as an organophosphorus pesticide serves as an AChE inhibitor to prevent the production of acetic acid, inducing the decrease of ECL signal. This sensor displays a limit of detection (LOD) of 2.44 pg/mL and a wide dynamic detection range of 0.01-1000 ng/mL. Furthermore, it can be used to detect other organophosphates pesticides (e.g., methidathion, chlorpyrifos, and paraoxon) and measure malathion in real samples (i.e., pakchoi, lettuce, and apples).
ESTHER : Song_2023_Talanta_266_124964
PubMedSearch : Song_2023_Talanta_266_124964
PubMedID: 37481885

Title : A Multi-Enzyme Cascade Response for the Colorimetric Recognition of Organophosphorus Pesticides Utilizing Core-Shell Pd@Pt Nanoparticles with High Peroxidase-like Activity - Majid_2023_Foods_12_
Author(s) : Majid Z , Zhang Q , Yang Z , Che H , Cheng N
Ref : Foods , 12 : , 2023
Abstract : In modern agricultural practices, organophosphorus pesticides or insecticides (OPs) are regularly used to restrain pests. Their limits are closely monitored since their residual hinders the capability of acetylcholinesterase (AChE) and brings out a threatening accumulation of the neurotransmitter acetylcholine (ACh), which affects human well-being. Therefore, spotting OPs in food and the environment is compulsory to prevent human health. Several techniques are available to identify OPs but encounter shortcomings like time-consuming, operating costs, and slow results achievement, which calls for further solutions. Herein, we present a rapid colorimetric sensor for quantifying OPs in foods using TMB as a substrate, a multi-enzyme cascade system, and the synergistic property of core-shell Palladinum@Platinum (Pd@Pt) nanoparticles. The multi-enzyme cascade response framework is a straightforward and effective strategy for OPs recognition and can resolve the previously mentioned concerns. Numerous OPs, including Carbofuran, Malathion, Parathion, Phoxim, Rojor, and Phosmet, were successfully quantified at different concentrations. The cascade method established using Pd@Pt had a simple and easy operation, a lower detection limit range of (1-2.5 ng/mL), and a short detection time of about 50 min. With an R(2) value of over 0.93, OPs showed a linear range of 10-200 ng/mL, portraying its achievement in quantifying pesticide residue. Lastly, the approach was utilized in food samples and recovered more than 80% of the residual OPs.
ESTHER : Majid_2023_Foods_12_
PubMedSearch : Majid_2023_Foods_12_
PubMedID: 37685251

Title : Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis - Pu_2023_Clin.Immunol__109850
Author(s) : Pu Y , Cheng R , Zhang Q , Huang T , Lu C , Tang Z , Zhong Y , Wu L , Hammock BD , Hashimoto K , Luo Y , Liu Y
Ref : Clin Immunol , :109850 , 2023
Abstract : Rheumatoid arthritis (RA) is an autoimmune disease characterized by enigmatic pathogenesis. Polyunsaturated fatty acids (PUFAs) are implicated in RA's development and progression, yet their exact mechanisms of influence are not fully understood. Soluble epoxide hydrolase (sEH) is an enzyme that metabolizes anti-inflammatory epoxy fatty acids (EpFAs), derivatives of PUFAs. In this study, we report elevated sEH expression in the joints of CIA (collagen-induced arthritis) rats, concomitant with diminished levels of two significant EpFAs. Additionally, increased sEH expression was detected in both the synovium of CIA rats and in the synovium and fibroblast-like synoviocytes (FLS) of RA patients. The sEH inhibitor TPPU attenuated the migration and invasion capabilities of FLS derived from RA patients and to reduce the secretion of inflammatory factors by these cells. Our findings indicate a pivotal role for sEH in RA pathogenesis and suggest that sEH inhibitors offer a promising new therapeutic strategy for managing RA.
ESTHER : Pu_2023_Clin.Immunol__109850
PubMedSearch : Pu_2023_Clin.Immunol__109850
PubMedID: 38013165

Title : Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery - Qu_2023_Int.J.Gen.Med_16_1567
Author(s) : Qu W , Yao Y , Liu Y , Jo H , Zhang Q , Zhao H
Ref : Int J Gen Med , 16 :1567 , 2023
Abstract : PURPOSE: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA. PATIENTS AND METHODS: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays. RESULTS: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models. CONCLUSION: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.
ESTHER : Qu_2023_Int.J.Gen.Med_16_1567
PubMedSearch : Qu_2023_Int.J.Gen.Med_16_1567
PubMedID: 37139258
Gene_locus related to this paper: human-CES2

Title : Near-infrared ratiometric fluorescent strategy for butyrylcholinesterase activity and its application in the detection of pesticide residue in food samples and biological imaging - Yuan_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_297_122719
Author(s) : Yuan W , Wan C , Zhang J , Li Q , Zhang P , Zheng K , Zhang Q , Ding C
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 297 :122719 , 2023
Abstract : Butyrylcholinesterase (BChE) is an essential esterase synthesized by the liver, and its level is considered as a vital index for health evaluation. Therefore, it is of great need to develop a highly sensitive and selective tool to monitor BChE activity, which remains a considerable challenge on account of its usage in complex biological systems. A near-infrared (NIR) fluorescent probe was elaborated in this work, employing cyanine backbone to provide the intrinsic NIR fluorescence and avoid interference from bioluminescence. There presented an intriguing structural transformation upon the sensing event to shrink the conjugation in this protocol, leading to an eye-catching fluorescence change from NIR (816 nm) to red (637 nm) region, which gave rise to the proposed ratiometric assay. After an overall investigation, this receptor was verified to be applicable in a wide bio-area with ratiometric pattern, including the cellular level and slice platform. It was worth mentioning that this receptor was also discovered to be capable of monitoring pesticide dichlorvos (DDVP) residue in food samples with high sensitivity and accuracy, with significant potential to be developed as an alternative candidate for monitoring environmental pollution.
ESTHER : Yuan_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_297_122719
PubMedSearch : Yuan_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_297_122719
PubMedID: 37043836

Title : Soluble DPP4 can act as a diagnostic biomarker in Hashimoto's thyroiditis with thyroid papillary carcinoma - Zhang_2023_J.Cancer.Res.Ther_19_1048
Author(s) : Zhang Y , Zhang Q , Zheng Y , Chen J , Liu N , Liu K , Song W
Ref : J Cancer Research Ther , 19 :1048 , 2023
Abstract : BACKGROUND: Hashimoto's thyroiditis (HT) is an independent risk factor for papillary thyroid carcinoma (PTC), but the underlying mechanism remains unknown. The incidence of PTC in patients with HT is significantly elevated, and the presence of both HT and PTC contributes to a higher rate of misdiagnosis. MATERIALS AND METHODS: Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the thyroid nodule gene chip dataset from GEO Datasets. Serum and clinical data from 191 patients with thyroid nodules at the affiliated hospital were collected for analysis. Experimental techniques, including real-time quantitative PCR, ELISA, immunohistochemistry (IHC), and enzyme activity detection, were used to measure the level of dipeptidyl peptidase 4 (DPP4) in thyroid nodule tissues and serum. RESULTS: Thyroid nodules in patients with HT and PTC exhibit high levels of DPP4, along with elevated concentrations of soluble DPP4 in the serum. These findings demonstrate the potential predictive value of soluble DPP4 for PTC diagnosis. CONCLUSIONS: The concentration and enzymatic activity of soluble DPP4 in serum can serve as diagnostic biomarkers for patients with HT-associated PTC.
ESTHER : Zhang_2023_J.Cancer.Res.Ther_19_1048
PubMedSearch : Zhang_2023_J.Cancer.Res.Ther_19_1048
PubMedID: 37675735

Title : Impacts of QM region sizes and conformation numbers on modelling enzyme reactions: a case study of polyethylene terephthalate hydrolase - Zheng_2023_Phys.Chem.Chem.Phys__
Author(s) : Zheng M , Li Y , Zhang Q , Wang W
Ref : Phys Chem Chem Phys , : , 2023
Abstract : A quantum mechanics/molecular mechanics (QM/MM) approach is a broadly used tool in computational enzymology. Treating the QM region with a high-level DFT method is one of the important branches. Here, taking leaf-branch compost cutinase-catalyzed polyethylene terephthalate depolymerization as an example, the convergence behavior of energy barriers as well as key structural and charge features with respect to the size of the QM region (up to 1000 atoms) is systematically investigated. BP86/6-31G(d)//CHARMM and M06-2X/6-311G(d,p)//CHARMM level of theories were applied for geometry optimizations and single-point energy calculations, respectively. Six independent enzyme conformations for all the four catalytic steps (steps (i)-(iv)) were considered. Most of the twenty-four cases show that at least 500 QM atoms are needed while only two rare cases show that -100 QM atoms are sufficient for convergence when only a single conformation was considered. This explains why most previous studies showed that 500 or more QM atoms are required while a few others showed that -100 QM atoms are sufficient for DFT/MM calculations. More importantly, average energy barriers and key structural/charge features from six conformations show an accelerated convergence than that in a single conformation. For instance, to reach energy barrier convergence (within 2.0 kcal mol(-1)) for step (ii), only -100 QM atoms are required if six conformations are considered while 500 or more QM atoms are needed with a single conformation. The convergence is accelerated to be more rapid if hundreds and thousands of conformations were considered, which aligns with previous findings that only several dozens of QM atoms are required for convergence with semi-empirical QM/MM MD simulations.
ESTHER : Zheng_2023_Phys.Chem.Chem.Phys__
PubMedSearch : Zheng_2023_Phys.Chem.Chem.Phys__
PubMedID: 37917137

Title : Highly stable acetylcholinesterase electrochemical biosensor based on polymerized ionic liquids microgel for pesticides detection - Wan_2022_Mikrochim.Acta_189_300
Author(s) : Wan Y , Wang H , Zhang L , Chen Y , Li S , Zhou J , Zhang Q , Xia L
Ref : Mikrochim Acta , 189 :300 , 2022
Abstract : A highly stable electrochemical biosensor for pesticide detection was developed. For the first time polymeric ionic liquids (PILs) were introduced to construct an acetylcholinesterase (AChE) biosensor . AChE was entrapped in PILs microspheres through an emulsion polymerization reaction, where negatively charged Au nanoparticles (Au NPs) can be immobilized by the positively charged PILs, leading to improved catalytic performance. The results suggest that the positively charged PILs not only provide a biocompatible microenvironment around the enzyme molecule, stabilizing its biological activity and preventing its leakage, but also act as a modifiable interface allowing other components with electron transport properties to be loaded onto the polymer substrate, thus providing an efficient electron transport channel for the entrapped enzyme. More notably, when AChE was immobilized in a positively charged environment, the active site is closer to the electrode, promoting faster electron transfer. The detection limits of the constructed electrochemical biosensor AChE@PILs@Au NPs/GCE toward carbaryl and dichlorvos (DDVP) were 5.0 x 10(-2) ng ml(-1) and 3.9 x 10(-2) ng ml(-1), in a wide linear range of 6.3 x 10(-2)-8.8 x 10(2) ng ml(-1) and 1.3 x 10(-1)-1.4 x 10(3) ng ml(-1), respectively. More importantly, the biosensor has high thermal and storage stability, which facilitates rapid field analysis of fruits and vegetables in a variety of climates. In addition, the biosensor reported has good repeatability and selectivity and has high accuracy in the analysis of peaches, tap water, and other types of samples.
ESTHER : Wan_2022_Mikrochim.Acta_189_300
PubMedSearch : Wan_2022_Mikrochim.Acta_189_300
PubMedID: 35904635

Title : Dynamics of allosteric regulation of the phospholipase C-gamma isozymes upon recruitment to membranes - Siraliev-Perez_2022_Elife_11_
Author(s) : Siraliev-Perez E , Stariha JTB , Hoffmann RM , Temple BRS , Zhang Q , Hajicek N , Jenkins ML , Burke JE , Sondek J
Ref : Elife , 11 : , 2022
Abstract : Numerous receptor tyrosine kinases and immune receptors activate phospholipase C-gamma (PLC-gamma) isozymes at membranes to control diverse cellular processes including phagocytosis, migration, proliferation, and differentiation. The molecular details of this process are not well understood. Using hydrogen-deuterium exchange mass spectrometry, we show that PLC-gamma1 is relatively inert to lipid vesicles that contain its substrate, phosphatidylinositol 4,5-bisphosphate (PIP(2)), unless first bound to the kinase domain of the fibroblast growth factor receptor (FGFR1). Exchange occurs throughout PLC-gamma1 and is exaggerated in PLC-gamma1 containing an oncogenic substitution (D1165H) that allosterically activates the lipase. These data support a model whereby initial complex formation shifts the conformational equilibrium of PLC-gamma1 to favor activation. This receptor-induced priming of PLC-gamma1 also explains the capacity of a kinase-inactive fragment of FGFR1 to modestly enhance the lipase activity of PLC-gamma1 operating on lipid vesicles but not a soluble analog of PIP(2) and highlights potential cooperativity between receptor engagement and membrane proximity. Priming is expected to be greatly enhanced for receptors embedded in membranes and nearly universal for the myriad of receptors and co-receptors that bind the PLC-gamma isozymes.
ESTHER : Siraliev-Perez_2022_Elife_11_
PubMedSearch : Siraliev-Perez_2022_Elife_11_
PubMedID: 35708309

Title : Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women - Zhang_2022_Food.Sci.Nutr_10_3
Author(s) : Zhang B , Yu L , Cheng M , Zhang Q , Wu J , Yang J , Liu Q , Lu S , Zhao X , Deng K , Liu Y , Wang J , Zhao P
Ref : Food Sci Nutr , 10 :3 , 2022
Abstract : To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_3
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_3
PubMedID: 35035905

Title : Construction of a Novel Lipase Catalytic System Based on Hybrid Membranes with Interwoven Electrospun Polyacrylic Acid and Polyvinyl Pyrrolidone Gel Fibers - Wang_2022_Gels_8_
Author(s) : Wang Z , Lin S , Zhang Q , Li J , Yin S
Ref : Gels , 8 : , 2022
Abstract : Efficient lipase catalysis requires sufficient oil-water interface engineered through structural design. Inspired by the architectural features of fabrics, a novel lipase-membrane catalytic system with interwoven polyacrylic acid (PAA) gel fibers and polyvinyl pyrrolidone (PVP) gel fibers was developed in this study by using double-needle electrospinning and gelation. It has been demonstrated that PAA/PVP hybrid gel fiber membranes (HGFMs) have a high swelling capacity for both water and oil phases, which created numerous discontinuous oil-water contact surface units in limited space of HGFMs, consequently forming effective interfacial catalytic systems. Volume competition between the water and oil phases suggests that balancing the proportions of these phases is very important for effective construction of oil-water interfaces and conditioning catalysis. Regulation of multiple factors of PAA/PVP HGFMs resulted in a catalytic efficiency of up to 2.1 times that of a macroscopic 'oil-up/water-down' system (room temperature, pH = 7), and 2.9 times when three membranes are superimposed, as well as excellent pH and temperature stability. HGFMs were stacked to build a high-performing catalytic performance reactor. We expect that this study will be a beneficial exploration for expanding the lipase catalytic system.
ESTHER : Wang_2022_Gels_8_
PubMedSearch : Wang_2022_Gels_8_
PubMedID: 36547336

Title : Identification of Novel Organophosphate Esters in Hydroponic Lettuces (Lactuca sativa L.): Biotransformation and Acropetal Translocation - Li_2022_Environ.Sci.Technol__
Author(s) : Li X , Yao Y , Chen H , Zhang Q , Li C , Zhao L , Guo S , Cheng Z , Wang Y , Wang L , Sun H
Ref : Environ Sci Technol , : , 2022
Abstract : The absorption, translocation, and biotransformation behaviors of organophosphate esters (OPEs) and diesters (OPdEs) in a hydroponic system were investigated. The lateral root was found as the main accumulation and biotransformation place of OPEs and OPdEs in lettuce. The nontarget analysis using high-resolution mass spectrometry revealed five hydroxylated metabolites and five conjugating metabolites in the OPE exposure group, among which methylation, acetylation, and palmitoyl conjugating OPEs were reported as metabolites for the first time. Particularly, methylation on phosphate can be a significant process for plant metabolism, and methyl diphenyl phosphate (MDPP) accounted for the majority of metabolites. The translocation factor values of most identified OPE metabolites are negatively associated with their predicted logarithmic octanol-water partitioning coefficient (log K(ow)) values (0.75-2.45), indicating that hydrophilicity is a dominant factor in the translocation of OPE metabolites in lettuce. In contrast, palmitoyl conjugation may lead to an enhanced acropetal translocation and those with log K(ow) values < 0 may have limited translocation potential. Additionally, OPE diesters produced from the biotransformation of OPEs in lettuce showed a higher acropetal translocation potential than those exposed directly. These results further emphasize the necessity to consider biotransformation as an utmost important factor in the accumulation and acropetal translocation potential of OPEs in plants.
ESTHER : Li_2022_Environ.Sci.Technol__
PubMedSearch : Li_2022_Environ.Sci.Technol__
PubMedID: 35849551

Title : PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma - Li_2022_Med.Oncol_39_250
Author(s) : Li H , Wu Z , Zhong R , Zhang Q , Chen Q , Shen Y
Ref : Med Oncol , 39 :250 , 2022
Abstract : Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC.
ESTHER : Li_2022_Med.Oncol_39_250
PubMedSearch : Li_2022_Med.Oncol_39_250
PubMedID: 36209344

Title : Effect of transcutaneous auricular vagus nerve stimulation on delayed neurocognitive recovery in elderly patients - Zhou_2022_Aging.Clin.Exp.Res__
Author(s) : Zhou Q , Yu L , Yin C , Zhang Q , Wang X , Kang K , Shao D , Wang Q
Ref : Aging Clin Exp Res , : , 2022
Abstract : BACKGROUND: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could decrease the incidence of delayed neurocognitive recovery (dNCR) in elderly adults after total joint arthroplasty (TJA). METHODS: A prospective, randomized, double-blind, sham-controlled trial was designed. In total, 124 elderly patients undergoing TJA were enrolled and randomly assigned to taVNS group (n = 62), who received taVNS at 1 h before anesthetic induction until the end of surgery, or sham stimulation (SS) group (n = 62), who received SS in the same manner. Neuropsychological batteries were performed before and at 1 week after surgery to assess the incidence of dNCR. Blood samples were collected before surgery and at 1 day after surgery to detect the activity of cholinesterase (AChE and BChE), as well as the levels of inflammatory factors (TNF-alpha, IL-1beta, IL-6, and HMGB1) and brain damage factor S100beta. RESULTS: Of 124 patients, 119 completed 1 week neuropsychological tests. The incidence of dNCR was significantly decreased in taVNS group [10% (6/60)] compared with the SS group [27.1% (16/59)] (P < 0.05). Patients who received taVNS had lower blood levels of AChE, BChE, IL-6, HMGB1, and S100beta after surgery (P < 0.05), as compared with those in the SS group. There was no difference in TNF-alpha between the two groups. CONCLUSION: The taVNS can decrease the incidence of dNCR after TJA in elderly patients, which may be related to the inhibition of inflammatory cytokine production and the reduction of cholinesterase activity.
ESTHER : Zhou_2022_Aging.Clin.Exp.Res__
PubMedSearch : Zhou_2022_Aging.Clin.Exp.Res__
PubMedID: 35809206

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

Title : Hydrolysis Mechanism of Carbamate Methomyl by a Novel Esterase PestE: A QM\/MM Approach - Wang_2022_Int.J.Mol.Sci_24_
Author(s) : Wang Z , Zhang Q , Wang G , Wang W , Wang Q
Ref : Int J Mol Sci , 24 : , 2022
Abstract : Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: () serine-initiated nucleophilic attack and () C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps and , respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based k(cat) prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein-substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases.
ESTHER : Wang_2022_Int.J.Mol.Sci_24_
PubMedSearch : Wang_2022_Int.J.Mol.Sci_24_
PubMedID: 36613879

Title : Cirrhosinones A-H, 24-hydroxy cevanine-type alkaloids from Fritillariacirrhosa - Dong_2022_Phytochemistry_197_113129
Author(s) : Dong H , Zhang Y , Wai Ming T , Wang S , Li J , Fu S , Zhang Q , Zeng K , Tu P , Liang H
Ref : Phytochemistry , 197 :113129 , 2022
Abstract : Eight undescribed isosteroidal alkaloids cirrhosinones A-H (1-8), along with six known isosteroidal alkaloids (9-14), were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were determined by HRESIMS and 2D NMR analysis, and their absolute configurations were established by X-ray analysis. Compounds 1-8 possessed a typical cevanine-type alkaloid skeleton with a hydroxyl group rarely substituted at C-24 and compounds 4-8 possessed rare 7alpha or 7beta-hydroxyl groups. This was the first report of both C-7 and C-24 hydroxyl groups substituted cevanine-type alkaloids. In addition, an approach for distinguishing D/E cis and trans conformations of cevanine-type alkaloids by (1)H NMR data was developed. Moreover, the correlations between the relative configurations of 3-OH, 7-OH, 22-C, 24-OH, and 25-Me and the (1)H NMR and (13)C NMR data were also summarized. Compounds 1-9 exhibited moderate NO inhibitory activities in LPS-stimulated BV-2 cells at the concentration of 40 microM. The acetylcholinesterase inhibitory activities of compounds 1-7 and 9-10 were also evaluated and none of them showed acetylcholinesterase inhibitory activities at the concentrations of 20-80 microM.
ESTHER : Dong_2022_Phytochemistry_197_113129
PubMedSearch : Dong_2022_Phytochemistry_197_113129
PubMedID: 35176308

Title : Whole genome sequencing and analysis of fenvalerate degrading bacteria Citrobacter freundii CD-9 - Zhou_2022_AMB.Express_12_51
Author(s) : Zhou X , Lei D , Tang J , Wu M , Ye H , Zhang Q
Ref : AMB Express , 12 :51 , 2022
Abstract : Citrobacter freundii CD-9 is a Gram-negative bacteria sourced from factory sludge that can use fenvalerate as its sole carbon source and has a broad degradation spectrum for pyrethroid pesticides. The whole genome of CD-9 sequenced using Illumina HiSeq PE150 was reported in this study. The CD-9 genome size was 5.33 Mb and the G + C content was 51.55%. A total of 5291 coding genes, 9 5s-rRNA, and 79 tRNA were predicted bioinformatically. 3586 genes annotated to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database that can be involved in 173 metabolic pathways, including various microbial metabolic pathways that degrade exogenous chemicals, especially those that degrade aromatic compounds, and also produce a variety of bioactive substances. Fifty genes related to pyrethroid degradation were identified in the C. freundii CD-9 genome, including 9 dioxygenase, 25 hydrolase, and 16 esterase genes. Notably, RT-qPCR results showed that from the predicted 13 genes related to fenvalerate degradation, the expression of six genes, including esterase, HAD family hydrolase, lipolytic enzyme, and gentisic acid dioxygenase, was induced in the presence of fenvalerate. In this study, the key genes and degradation mechanism of C. freundii CD-9 were analyzed and the results provide scientific evidence to support its application in environmental bioremediation. It can establish application models for different environmental pollution management by constructing genetically engineered bacteria for efficient fenvalerate or developing enzyme formulations that can be industrially produced.
ESTHER : Zhou_2022_AMB.Express_12_51
PubMedSearch : Zhou_2022_AMB.Express_12_51
PubMedID: 35523901

Title : Integrative assessment of biomarker responses in Mytilus galloprovincialis exposed to seawater acidification and copper ions - Qu_2022_Sci.Total.Environ_851_158146
Author(s) : Qu Y , Zhang T , Zhang R , Wang X , Zhang Q , Wang Q , Dong Z , Zhao J
Ref : Sci Total Environ , 851 :158146 , 2022
Abstract : The interactive effects of ocean acidification (OA) and copper (Cu) ions on the mussel Mytilus galloprovincialis are not well understood. The underlying mechanisms also remain obscure. In this study, individuals of M. galloprovincialis were exposed for 28 days to 25 microg/L and 50 microg/L Cu ions at two pH levels (ambient level - pH 8.1; acidified level - pH 7.6). The mussels were then monitored for 56 days to determine their recovery ability. Physiological parameters (clearance rate and respiration rate), oxidative stress and neurotoxicity biomarkers (activities of superoxide dismutase, lipid peroxidation, catalase, and acetylcholinesterase), as well as the recovery ability of these parameters, were investigated in two typical tissues (i.e., gills and digestive glands). Results showed that (1) OA affected the bioconcentration of Cu in the gills and digestive glands of the mussels; (2) both OA and Cu can lead to physiological disturbance, oxidative stress, cellular damage, energy metabolism disturbance, and neurotoxicity on M. galloprovincialis; (3) gill is more sensitive to OA and Cu than digestive gland; (4) Most of the biochemical and physiological alternations caused by Cu and OA exposures in M. galloprovincialis can be repaired by the recovery experiments; (5) integrated biomarker response (IBR) analysis demonstrated that both OA and Cu ions exposure caused survival stresses to the mussels, with the highest effect shown in the co-exposure treatment. This study highlights the necessity to include OA along with pollutants in future studies to better elucidate the risks of ecological perturbations. The work also sheds light on the recovery of marine animals after short-term environmental stresses when the natural environment has recovered.
ESTHER : Qu_2022_Sci.Total.Environ_851_158146
PubMedSearch : Qu_2022_Sci.Total.Environ_851_158146
PubMedID: 35987231

Title : In vitro inhibition of carboxylesterase 1 by Kava (Piper methysticum) Kavalactones - Melchert_2022_Chem.Biol.Interact__109883
Author(s) : Melchert PW , Qian Y , Zhang Q , Klee BO , Xing C , Markowitz JS
Ref : Chemico-Biological Interactions , :109883 , 2022
Abstract : Kava refers to the extracts from the rhizome of the plant Piper methysticum which is of particular significance to various indigenous cultures in the South Pacific region. Kavalactones are the active constituents of kava products and are associated with sedative and anxiolytic effects. Kavalactones have been evaluated in vitro for their potential to alter the activity of various CYP450 enzymes but have undergone little systematic investigation as to their potential influence on esterases. This study investigated the inhibition effects of kava and its kavalactones on carboxylesterase 1 (CES1) in an in vitro system and established associated kinetic parameters. Kava and its kavalactones were found to produce reversible inhibition of CES1 to varying degrees. Kavain, dihydrokavain, and desmethoxyyangonin displayed competitive type inhibition, while methysticin, dihydromethysticin, and yangonin displayed a mixed competitive-noncompetitive type inhibition. The inhibition constants (K(i)) values for each of the kavalactones were as follows: methysticin (35.2 microM), dihydromethysticin (68.2 microM), kavain (81.6 microM), dihydrokavain (105.3 microM), yangonin (24.9 microM), and desmethoxyyangonin (25.2 microM). With consideration to the in vitro K(i) for each evaluated kavalactone as well as available clinical kavalactone concentrations in blood circulation, co-administration of CES1 substrate medications and kava products at the recommended daily dose is generally free of drug interaction concerns. However, uncertainty around kavalactone exposure in humans has been noted and a clinically relevant CES1 inhibition by kavain, dihydrokavain, and dihydromethysticin is indeed possible if the kavalactone consumption is higher than 1000 mg in the context of over-the-counter usage. Further clinical studies would be required to assess the possibility of clinically significant kava drug-drug interactions with CES1 substrate medications.
ESTHER : Melchert_2022_Chem.Biol.Interact__109883
PubMedSearch : Melchert_2022_Chem.Biol.Interact__109883
PubMedID: 35278473

Title : Knockdown of hepatocyte Perilipin-3 mitigates hepatic steatosis and steatohepatitis caused by hepatocyte CGI-58 deletion in mice - Bao_2022_J.Mol.Cell.Biol__
Author(s) : Bao X , Ma X , Huang R , Chen J , Xin H , Zhou M , Li L , Tong S , Zhang Q , Shui G , Deng F , Yu L , Li MD , Zhang Z
Ref : J Molecular & Cellular Biology , : , 2022
Abstract : Comparative gene identification-58 (CGI-58), also known as alpha/beta hydrolase domain containing 5 (ABHD5), is the co-activator of adipose triglyceride lipase that hydrolyzes triglycerides stored in the cytosolic lipid droplets. Mutations in CGI-58 gene cause Chanarin-Dorfman syndrome (CDS), an autosomal recessive neutral lipid storage disease with ichthyosis. The liver pathology of CDS manifests as steatosis and steatohepatitis, which currently has no effective treatments. Perilipin-3 (Plin3) is a member of the Perilipin-ADRP-TIP47 (PAT) protein family that is essential for lipid droplet biogenesis. The objective of this study was to test a hypothesis that deletion of a major lipid droplet protein alleviates fatty liver pathogenesis caused by CGI-58 deficiency in hepatocytes. Adult CGI-58-floxed mice were injected with adeno-associated vectors simultaneously expressing the Cre recombinase and microRNA against Plin3 under the control of a hepatocyte-specific promoter, followed by high-fat diet (HFD) feeding for 6 weeks. Liver and blood samples were then collected from these animals for histological and biochemical analysis. Plin3 knockdown in hepatocytes prevented steatosis, steatohepatitis, and necroptosis caused by hepatocyte CGI-58 deficiency. Our work is the first to show that inhibiting Plin3 in hepatocytes is sufficient to mitigate hepatocyte CGI-58 deficiency-induced hepatic steatosis and steatohepatitis in mice.
ESTHER : Bao_2022_J.Mol.Cell.Biol__
PubMedSearch : Bao_2022_J.Mol.Cell.Biol__
PubMedID: 36107452

Title : Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis - Lang_2022_BMC.Pediatr_22_295
Author(s) : Lang B , Han L , Zeng L , Zhang Q , Chen S , Huang L , Jia Z , Yu Q , Zhang L
Ref : BMC Pediatr , 22 :295 , 2022
Abstract : BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.
ESTHER : Lang_2022_BMC.Pediatr_22_295
PubMedSearch : Lang_2022_BMC.Pediatr_22_295
PubMedID: 35590273

Title : Phytochemical composition, antimicrobial activities, and cholinesterase inhibitory properties of the lichen Usnea diffracta Vain - Hao_2022_Front.Chem_10_1063645
Author(s) : Hao YM , Yan YC , Zhang Q , Liu BQ , Wu CS , Wang LN
Ref : Front Chem , 10 :1063645 , 2022
Abstract : Lichens are important sources of versatile bioactive compounds. Two new dibenzofurans (1-2), a multi-substituted single benzene ring (3), and two organic acid compounds (4-5) along with 25 known compounds (6-30) were isolated from the lichen Usnea diffracta Vain. Their structures were identified by physicochemical properties and spectral analyses. Compounds 1-30 were tested for inhibitory activities against Staphylococcus aureus, Escherichia coli, and Candida albicans by the disk diffusion method and microdilution assay respectively. Compound 3 showed moderate inhibitory activities against S. aureus and E. coli with the inhibition zone (IZ) of 6.2smm and 6.3smm, respectively. Depside 10 exhibited good activity against S.aureus and C. albicans with 6.6smm and 32 microg/ml, respectively. The acetylcholinesterase inhibitory activities of compounds 1, 2, and 6-8 with the characteristic dibenzofuran scaffold were evaluated var anti-AChE assay and a molecular docking study. Compound 2 could better inhibit AChE at the concentration of 0.3smicromol/ml with a value of 61.07 +/- 0.85%. The molecular docking study also demonstrated that compound 2 had the strongest binding affinity among the five dibenzofurans, and the '-CDOCKER Energy' value was 14.4513skcal/mol.
ESTHER : Hao_2022_Front.Chem_10_1063645
PubMedSearch : Hao_2022_Front.Chem_10_1063645
PubMedID: 36688056

Title : Discovering monoacylglycerol lipase inhibitors by a combination of fluorogenic substrate assay and activity-based protein profiling - Deng_2022_Front.Pharmacol_13_941522
Author(s) : Deng H , Zhang Q , Lei Q , Yang N , Yang K , Jiang J , Yu Z
Ref : Front Pharmacol , 13 :941522 , 2022
Abstract : The endocannabinoid 2-arachidonoylglycerol (2-AG) is predominantly metabolized by monoacylglycerol lipase (MAGL) in the brain. Selective inhibitors of MAGL provide valuable insights into the role of 2-AG in a variety of (patho)physiological processes and are potential therapeutics for the treatment of diseases such as neurodegenerative disease and inflammation, pain, as well as cancer. Despite a number of MAGL inhibitors been reported, inhibitors with new chemotypes are still required. Here, we developed a substrate-based fluorescence assay by using a new fluorogenic probe AA-HNA and successfully screened a focused library containing 320 natural organic compounds. Furthermore, we applied activity-based protein profiling (ABPP) as an orthogonal method to confirm the inhibitory activity against MAGL in the primary substrate-based screening. Our investigations culminated in the identification of two major compound classes, including quinoid diterpene (23, cryptotanshinone) and beta-carbolines (82 and 93, cis- and trans-isomers), with significant potency towards MAGL and good selectivity over other 2-AG hydrolases (ABHD6 and ABHD12). Moreover, these compounds also showed antiproliferative activities against multiple cancer cells, including A431, H1975, B16-F10, OVCAR-3, and A549. Remarkably, 23 achieved complete inhibition towards endogenous MAGL in most cancer cells determined by ABPP. Our results demonstrate the potential utility of the substrate-based fluorescence assay in combination with ABPP for rapidly discovering MAGL inhibitors, as well as providing an effective approach to identify potential targets for compounds with significant biological activities.
ESTHER : Deng_2022_Front.Pharmacol_13_941522
PubMedSearch : Deng_2022_Front.Pharmacol_13_941522
PubMedID: 36105202

Title : Ferulic acid regulates miR-17\/PTEN axis to inhibit LPS-induced pulmonary microvascular endothelial cells apoptosis through activation of PI3K\/Akt pathway - Zhang_2022_J.Toxicol.Sci_47_61
Author(s) : Zhang Q , Wang Z , Zhu J , Peng Z , Tang C
Ref : Journal of Toxicological Sciences , 47 :61 , 2022
Abstract : Acute lung injury (ALI) is mainly mediated by the damage of pulmonary microvascular endothelial cells (PMVECs). LPS is one of the pathogenic factors leading to microcirculatory abnormalities of ALI. Ferulic acid (FA) exhibits therapeutic eects against various diseases. During lipopolysaccharide-induced acute respiratory distress syndrome, FA, when given beforehand, could depress inflammation and oxidative stress. However, the concrete role and underlying mechanism of FA in ALI have not been well characterized. Ten microg/mL Lipopolysaccharide (LPS) was used to treat rat PMVECs for 24 hr. qRT-PCR was used to detect the level of miR-17 and phosphatase and tensin homolog deleted on chromosome ten (PTEN). Western blot was used to analyze the associated proteins in the PI3K/Akt pathway, and the apoptosis-related proteins. Flow cytometric analysis was performed to detect the apoptosis of PMVECs. MTT assay was constructed to detect the cell viability. Luciferase assay was conducted to detect the target gene of miR-17 and PTEN. A cell model for in vitro studying the role of FA in ALI was established using PMVECs. Our data demonstrate that FA up-regulates miR-17 and declines apoptosis induced by LPS. FA inhibits apoptosis mediated by up-regulating miR-17. Furthermore, we found miR-17 targeted PTEN negatively. FA inhibits cleaved caspase-3 and Bax expression through the PI3K/Akt pathway mediated by up-regulating miR-17. Over-expression of PTEN could contribute to the similar expression trend of the PI3K/Akt signal pathway protein compared to miR-17 inhibitor transfected cells. FA inhibits PMVECs apoptosis induced by LPS via miR-17/PTEN to further regulate the activation of the PI3K/Akt pathway in ALI. We anticipate that our data will provoke additional studies for ALI clinical therapy.
ESTHER : Zhang_2022_J.Toxicol.Sci_47_61
PubMedSearch : Zhang_2022_J.Toxicol.Sci_47_61
PubMedID: 35110471

Title : Inhibition of Dipeptidyl Peptidase-4 by Flavonoids: Structure-Activity Relationship, Kinetics and Interaction Mechanism - Pan_2022_Front.Nutr_9_892426
Author(s) : Pan J , Zhang Q , Zhang C , Yang W , Liu H , Lv Z , Liu J , Jiao Z
Ref : Front Nutr , 9 :892426 , 2022
Abstract : With the aim to establish a structure-inhibitory activity relationship of flavonoids against dipeptidyl peptidase-4 (DPP-4) and elucidate the interaction mechanisms between them, a pannel of 70 structurally diverse flavonoids was used to evaluate their inhibitory activities against DPP-4, among which myricetin, hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin showed higher inhibitory activities in a concentration-dependent manner. Structure-activity relationship analysis revealed that introducing hydroxyl groups to C3', C4', and C6 of the flavonoid structure was beneficial to improving the inhibitory efficacy against DPP-4, whereas the hydroxylation at position 3 of ring C in the flavonoid structure was unfavorable for the inhibition. Besides, the methylation of the hydroxyl groups at C3', C4', and C7 of the flavonoid structure tended to lower the inhibitory activity against DPP-4, and the 2,3-double bond and 4-carbonyl group on ring C of the flavonoid structure was essential for the inhibition. Glycosylation affected the inhibitory activity diversely, depending on the structure of flavonoid aglycone, type of glycoside, as well as the position of substitution. Inhibition kinetic analysis suggested that myricetin reversibly inhibited DPP-4 in a non-competitive mode, whereas hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin all reversibly inhibited DPP-4 in a mixed type. Moreover, the fluorescence quenching analysis indicated that all the five flavonoid compounds could effectively quench the intrinsic fluorescence of DPP-4 by spontaneously binding with it to form an unstable complex. Hydrogen bonds and van der Waals were the predominant forces to maintain the complex of myricetin with DPP-4, and electrostatic forces might play an important role in stabilizing the complexes of the remaining four flavonoids with DPP-4. The binding of the tested flavonoids to DPP-4 could also induce the conformation change of DPP-4 and thus led to inhibition on the enzyme. Molecular docking simulation further ascertained the binding interactions between DPP-4 and the selected five flavonoids, among which hyperoside, narcissoside, cyaniding 3-O-glucoside, and isoliquiritigenin inserted into the active site cavity of DPP-4 and interacted with the key amino acid residues of the active site, whereas the binding site of myricetin was located in a minor cavity close to the active pockets of DPP-4.
ESTHER : Pan_2022_Front.Nutr_9_892426
PubMedSearch : Pan_2022_Front.Nutr_9_892426
PubMedID: 35634373

Title : A carboxylesterase-activatable near-infrared phototheranostic probe for tumor fluorescence imaging and photodynamic therapy - Li_2022_RSC.Adv_12_35477
Author(s) : Li L , Zhang Q , Li J , Tian Y , Liu W , Diao H
Ref : RSC Adv , 12 :35477 , 2022
Abstract : Phototheranostic probes have been proven to be a promising option for cancer diagnosis and treatment. However, near-infrared phototheranostic probes with specific tumor microenvironment responsiveness are still in demand. In this paper, a carboxylesterase (CES)-responsive near-infrared phototheranostic probe was developed by incorporating 6-acetamidohexanoic acid into a hemicyanine dye through an ester bond. The probe exhibits highly sensitive and selective fluorescence enhancement towards CES because CES-catalyzed cleavage of the ester bond leads to the release of the fluorophore. By virtue of its near-infrared analytical wavelengths and high sensitivity, the probe has been employed for endogenous CES activatable fluorescence imaging of tumor cells. Moreover, under 660 nm laser irradiation, the probe can generate toxic reactive oxygen species and efficiently kill tumor cells, with low cytotoxicity in dark. As far as we know, the probe was the first CES-responsive phototheranostic probe with both near-infrared analytical wavelengths and photosensitive capacity, which may be useful in the real-time and in situ imaging of CES as well as imaging-guided photodynamic therapy of tumors. Therefore, the proposed probe may have wide application prospect in cancer theranostics.
ESTHER : Li_2022_RSC.Adv_12_35477
PubMedSearch : Li_2022_RSC.Adv_12_35477
PubMedID: 36540215

Title : Genetic manipulation of the interconversion between diacylglycerols and triacylglycerols in Rhodosporidium toruloides - Zhang_2022_Front.Bioeng.Biotechnol_10_1034972
Author(s) : Zhang Y , Zhang S , Chu Y , Zhang Q , Zhou R , Yu D , Wang S , Lyu L , Xu G , Zhao ZK
Ref : Front Bioeng Biotechnol , 10 :1034972 , 2022
Abstract : The basidiomycetous yeast Rhodosporidium toruloides (R. toruloides) is an excellent producer for neutral lipids, including triacylglycerols (TAG). Partially because genetic tools for this yeast were less developed, limited efforts were shown to explore its capacity for the production of higher-value lipids such as diacylglycerols (DAG). Here, four genes linked to the interconversion between DAG and TAG were manipulated to promote the production of DAG and free fatty acids (FFA). Among them, three TAG synthesis-related genes, DGA1, LRO1, and ARE1, were down-regulated successively via the RNA interference technology, and an endogenous TAG lipase encoded by TGL5 was fused with LDP1 and over-expressed to convert TAG into DAG and FFA. Results showed that those engineered R. toruloides strains grew normally under nutrient-rich conditions but notably slower than the parental strain NP11 in the lipid production stage. When cultivated in nitrogen-limited media, engineered strains were able to produce total lipids with improved contents of DAG and FFA by up to two-fold and three-fold, respectively. Further correlation analysis between lipid composition and cell density indicated that the formation of TAG correlated positively with cell growth; however, other lipids including DAG did negatively. This study offered valuable information and strains to engineer R. toruloides for advanced production of fatty acid derivatives.
ESTHER : Zhang_2022_Front.Bioeng.Biotechnol_10_1034972
PubMedSearch : Zhang_2022_Front.Bioeng.Biotechnol_10_1034972
PubMedID: 36394004

Title : In vitro evaluation of the impact of Covid-19 therapeutic agents on the hydrolysis of the antiviral prodrug remdesivir - Zhang_2022_Chem.Biol.Interact_365_110097
Author(s) : Zhang Q , Melchert PW , Markowitz JS
Ref : Chemico-Biological Interactions , 365 :110097 , 2022
Abstract : Remdesivir (RDV, Veklury(a)) is an FDA-approved prodrug for the treatment of hospitalized patients with COVID-19. Recent in vitro studies have indicated that human carboxylesterase 1 (CES1) is the major metabolic enzyme catalyzing RDV activation. COVID-19 treatment for hospitalized patients typically also involves a number of antibiotics and anti-inflammatory drugs. Further, individuals who are carriers of a CES1 variant (polymorphism in exon 4 codon 143 [G143E]) may experience impairment in their ability to metabolize therapeutic agents which are CES1 substrates. The present study assessed the potential influence of nine therapeutic agents (hydroxychloroquine, ivermectin, erythromycin, clarithromycin, roxithromycin, trimethoprim, ciprofloxacin, vancomycin, and dexamethasone) commonly used in treating COVID-19 and 5 known CES1 inhibitors on the metabolism of RDV. Additionally, we further analyzed the mechanism of inhibition of cannabidiol (CBD), as well as the impact of the G143E polymorphism on RDV metabolism. An in vitro S9 fraction incubation method and in vitro to in vivo pharmacokinetic scaling were utilized. None of the nine therapeutic agents evaluated produced significant inhibition of RDV hydrolysis; CBD was found to inhibit RDV hydrolysis by a mixed type of competitive and noncompetitive partial inhibition mechanism. In vitro to in vivo modeling suggested a possible reduction of RDV clearance and increase of AUC when coadministration with CBD. The same scaling method also suggested a potentially lower clearance and higher AUC in the presence of the G143E variant. In conclusion, a potential CES1-mediated DDI between RDV and the nine assessed medications appears unlikely. However, a potential CES1-mediated DDI between RDV and CBD may be possible with sufficient exposure to the cannabinoid. Patients carrying the CES1 G143E variant may exhibit a slower biotransformation and clearance of RDV. Further clinical studies would be required to evaluate and characterize the clinical significance of a CBD-RDV interaction.
ESTHER : Zhang_2022_Chem.Biol.Interact_365_110097
PubMedSearch : Zhang_2022_Chem.Biol.Interact_365_110097
PubMedID: 35964681

Title : The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects - Markowitz_2022_Med.Cannabis.Cannabinoids_5_199
Author(s) : Markowitz JS , De Faria L , Zhang Q , Melchert PW , Frye RF , Klee BO , Qian Y
Ref : Med Cannabis Cannabinoids , 5 :199 , 2022
Abstract : INTRODUCTION: Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as an over-the-counter supplement, a component of medical cannabis, and a prescriptive treatment of childhood epilepsies. In vitro studies suggest CBD may inhibit a number of drug-metabolizing enzymes, including carboxylesterase 1 (CES1). The aim of this study was to evaluate effect of CBD on the disposition of the CES1 substrate methylphenidate (MPH). METHODS: In a randomized, placebo-controlled, crossover study, 12 subjects ingested 750 mg of CBD solution, or alternatively, a placebo solution twice daily for a 3-day run-in period followed by an additional CBD dose (or placebo) and a single 10 mg dose of MPH and completed serial blood sampling for pharmacokinetic analysis. MPH and CBD concentrations were measured by liquid chromatography with tandem mass spectrometry. RESULTS: The C(max) (mean +/- CV) for the CBD group and placebo group was 13.5 +/- 43.7% ng/mL and 12.2 +/- 36.4% ng/mL, respectively. AUC(inf) (ng/mL*h) for the CBD group and placebo group was 70.7 +/- 32.5% and 63.6 +/- 25.4%, respectively. The CBD AUC(0-8h) (mean +/- CV) was 1,542.2 +/- 32% ng/mL*h, and C(max) was 389.2 +/- 39% ng/mL. When compared to MPH only, the geometric mean ratio (CBD/control, 90% CI) for AUC(inf) and C(max) with CBD co-administration was 1.09 (0.89, 1.32) and 1.08 (0.85, 1.37), respectively. DISCUSSION/CONCLUSION: Although the upper bound of bioequivalence was not met, the mean estimates of AUC and C(max) ratios were generally small and unlikely to be of clinical significance.
ESTHER : Markowitz_2022_Med.Cannabis.Cannabinoids_5_199
PubMedSearch : Markowitz_2022_Med.Cannabis.Cannabinoids_5_199
PubMedID: 36467779

Title : AND-Logic Strategy for Accurate Analysis of Alzheimer's Disease via Fluorescent Probe Lighted Up by Two Specific Biomarkers - Zhang_2021_Anal.Chem__
Author(s) : Zhang P , Fu C , Liu H , Guo X , Zhang Q , Gao J , Chen W , Yuan W , Ding C
Ref : Analytical Chemistry , : , 2021
Abstract : Alzheimer's disease (AD) has become a global threat to the elderly health with a short survival time after diagnosis. Due to the asymptomatic stage during the early development, patients are usually diagnosed at the middle or late stage. Therefore, an efficient tool for AD early diagnosis deserves considerable attention, which could make a significant contribution to the treatment intervention. A fluorescent probe has been widely applied for detecting and visualizing species of interest in vitro and in vivo, and the proper reaction between the probe and analytes is responsible for the fluorescence change to provide a lighting-on or ratiometric responsive pattern with satisfactory sensing behavior. In this work, we report the first attempt to build up an AND-logic probe P2 for AD accuracy diagnosis taking butyrylcholinesterase (BChE) and reactive oxygen species (ROSs) as dual targets. Upon the co-stimulation by these two factors through enzymatic hydrolysis and redox reaction, the NIR emission could be readily turned on. This AND sensing pattern avoided the false-positive response effectively, and other diseases sharing one biomarker could hardly induce a NIR fluorescence response. The sensing assay has also been confirmed to be feasible in vitro and in vivo with good sensibility and selectivity. It is worth mentioning that the probe structure has been optimized in terms of the linkage length. This study shows that probe P2 with a connecting arm of medium length (one methylene, n = 1) has superior sensing performance, promising to provide a reference for the relative structure design.
ESTHER : Zhang_2021_Anal.Chem__
PubMedSearch : Zhang_2021_Anal.Chem__
PubMedID: 34353021

Title : Evaluation of the effect of high protein supply on diaphragm atrophy in critically ill patients receiving prolonged mechanical ventilation - Zhang_2021_Nutr.Clin.Pract__
Author(s) : Zhang Q , Zhou J , Zhu D , Zhou S
Ref : Nutr Clin Pract , : , 2021
Abstract : BACKGROUND: Our aim was to evaluate the effect of high protein to the target of 2.0 g/kg/d on diaphragm atrophy and clinical prognosis of patients receiving prolonged mechanical ventilation (MV). METHODS: This prospective, randomized, controlled, single-center study included 41 patients who were treated with <=7 days' MV. The patients were randomly divided into a standard nutrition treatment (SNT) group and intensive nutrition treatment (INT) group, followed by evaluation of computer tomography-analyzed diaphragm volume, the level of butyrylcholinesterase (BChE) as a muscle mass indicator, and respiratory mechanics indices weekly to observe and compare the differences between the groups. RESULTS: In the INT group, the actual protein (1.70 +/- 0.21 vs 1.06 +/- 0.21 g/kg/d, P < .001) and calorie intake (33.46 +/- 2.78 vs 25.75 +/- 4.81 kcal/kg/d, P < .001) were significantly different from those of the SNT group. Compared with the SNT group, the INT group's diaphragm atrophy improved in the fourth and fifth weeks (all P < .05). The BChE after the third week was higher (all P < .05). No significant differences in respiratory mechanical indices and clinical outcomes were found in the surviving patients between the groups. CONCLUSION: INT improved the diaphragm atrophy and muscle mass of critically ill patients receiving prolonged MV. There was no evidence that increasing protein to the target amount of 2.0 g/kg/d is related to improvement in clinical prognosis for patients receiving prolonged MV.
ESTHER : Zhang_2021_Nutr.Clin.Pract__
PubMedSearch : Zhang_2021_Nutr.Clin.Pract__
PubMedID: 34101252

Title : Absolute protein assay for the simultaneous quantification of two epoxide hydrolases in rats by mass spectrometry-based targeted proteomics - Wu_2021_J.Sep.Sci__
Author(s) : Wu T , Xi X , Chen Y , Jiang C , Zhang Q , Dai G , Bai Y , Zhang W , Ni T , Zou J , Ju W , Xu M
Ref : J Sep Sci , : , 2021
Abstract : Epoxide hydrolases catalyze the hydrolysis of both exogenous and endogenous epoxides to the corresponding vicinal diols by adding water. Microsomal and soluble epoxide hydrolase are two main mammalian enzymes that have been intensely characterized. The purpose of this investigation was to develop and validate a proteomics assay allowing the simultaneous quantification of microsomal and soluble epoxide hydrolase in rats. Protein quantification was realized through targeted proteomics, using liquid chromatography with tandem mass spectrometry for the determination of trypsin-specific surrogate peptides after digestion. Stable isotope-labeled peptides were used as the internal standards. The chromatography of the surrogate peptides was performed on an Agilent SB C(18) column (100 mm x 4.6 mm, 1.8 microm) with gradient elution. Acetonitrile containing 0.1% formic acid and 0.1% formic acid aqueous solution were used as mobile phases. A multiple reaction monitoring method in a positive ionization mode was used for the simultaneous detection of the peptides. The method was validated concerning the specificity, linearity, within-day and between-day accuracy and precision, matrix effect, stability, and digestion efficiency. The developed assay was successfully used to quantify the protein levels of microsomal and soluble epoxide hydrolase in rat liver, kidney, and heart S9 samples. This article is protected by copyright. All rights reserved.
ESTHER : Wu_2021_J.Sep.Sci__
PubMedSearch : Wu_2021_J.Sep.Sci__
PubMedID: 34008891

Title : Insights into mechanisms involved in the uptake, translocation, and metabolism of phthalate esters in Chinese cabbage (Brassica rapa var. chinensis) - Cheng_2021_Sci.Total.Environ_768_144945
Author(s) : Cheng Z , Wang Y , Qiao B , Zhang Q , Sun H
Ref : Sci Total Environ , 768 :144945 , 2021
Abstract : In the present study, the uptake and translocation mechanisms of phthalate esters (PAEs) and their primary mono esters metabolites (mPAEs), and the mechanisms of PAEs metabolism in plants were elucidated. The objectives of this study were to: (i) elucidate the fractionation of PAEs and mPAEs in Chinese cabbage (Brassica rapa var. chinensis) by hydroponic experiment, (ii) investigate the PAEs and mPAEs uptake mechanisms in root by inhibitor experiments, (iii) explain the molecular mechanisms of PAE interactions with the plant macromolecules by proteomics analysis and molecular docking, and (iv) reveal the involvement of carboxylesterase in the plant metabolism of PAEs. The results demonstrated that both the apoplastic and symplastic pathways contributed to the uptake of di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP) by vacuum-infiltration-centrifugation method. The energy-dependent active process was involved for the uptake of DnBP, DEHP, MnBP, and MEHP. The passive uptake pathways of anion mPAEs and neutral PAEs differ. Aquaporins contributed to the uptake of anion MnBP and MEHP, and slow-type anion channel was also responsible for the uptake of anion MEHP. Molecular interactions of PAEs and macromolecules were further characterized by proteomic analysis and molecular docking. PAEs were transferred via non-specific lipid transfer protein by binding hydroponic amino acid residues. The carboxylesterase enzyme was attributed to the metabolism of PAEs to form mPAEs by using crude enzyme extract and commercial pure enzyme. This study provides both experimental and theoretical evidence for uptake, accumulation, and metabolism of PAEs in plants.
ESTHER : Cheng_2021_Sci.Total.Environ_768_144945
PubMedSearch : Cheng_2021_Sci.Total.Environ_768_144945
PubMedID: 33736326

Title : Fluorescent Determination of Butyrylcholinesterase Activity and Its Application in Biological Imaging and Pesticide Residue Detection - Zhang_2021_ACS.Sens__
Author(s) : Zhang Q , Fu C , Guo X , Gao J , Zhang P , Ding C
Ref : ACS Sens , : , 2021
Abstract : Butyrylcholinesterase (BChE) is an essential human cholinesterase relevant to liver conditions and neurodegenerative diseases, which makes it a pivotal biomarker of health. It therefore remains challenging and highly desired to elaborate efficient chemical tools for BChE with simple operations and satisfactory working performance. In this work, a background-free detection strategy was built by virtue of the judicious coupling of a specific BChE-enzymatic reaction and in situ cyclization. High sensitivity with a low limit of detection (LOD) of 0.075 microg/mL could be readily achieved from the blank background and the as-produced emissive indicators, and the specific reaction site contributed to the high selectivity over other bio-species even acetylcholinesterase (AChE). In addition to the multifaceted spectral experiments to verify the sensing mechanism, this work assumed comprehensive studies on the application. The bio-investigation ranged from cells to an organism, declaring a noteworthy prospect in disease diagnosis, especially for Alzheimer's disease (AD), a common neurodegenerative disease with over-expressed BChE. Moreover, its excellent work for inhibition efficacy elucidation was also proved with the accuracy IC(50) of tacrine for BChE (8.6 nM), giving rise to an expanded application for trace pesticide determination.
ESTHER : Zhang_2021_ACS.Sens__
PubMedSearch : Zhang_2021_ACS.Sens__
PubMedID: 33503372

Title : Smart nanozyme of silver hexacyanoferrate with versatile bio-regulated activities for probing different targets - Zhang_2021_Talanta_228_122268
Author(s) : Zhang L , Zhang Q , Liu Q , Wu X , Dong Y , Wang GL
Ref : Talanta , 228 :122268 , 2021
Abstract : Smart nanozymes that can be facile and rapidly produced, while with efficiently bio-regulated activity, are attractive for biosensing applications. Herein, a smart nanozyme, silver hexacyanoferrate (Ag(4)[Fe(CN)(6)]), was constructed in situ via the rapid, direct reaction between silver(I) and K(4)[Fe(CN)(6)]. And the activity of the nanozyme can be rationally modulated by different enzymatic reactions including the glucose oxidase (GOx, taken as a model oxidoreductase), alkaline phosphatase (ALP), and acetylcholinesterase (AChE). On the basis of which, a multiple function platform for the highly sensitive detection of glucose, ALP and AChE were developed through colorimetry. Corresponding detection limits for the above three targets were found to be as low as 0.32 microM, 3.3 U/L and 0.083 U/L (S/N = 3), respectively. The present study provides a novel nanozyme that can be produced in situ, which rules out the harsh, cumbersome, and time-consuming synthesis/purification procedures. In addition, it establishes a multiple function platform for the amplified detection of versatile targets by the aid of the developed nanozyme, whose detection has the advantages of low cost, ease-of-use, high sensitivity, and good selectivity.
ESTHER : Zhang_2021_Talanta_228_122268
PubMedSearch : Zhang_2021_Talanta_228_122268
PubMedID: 33773716

Title : Antibodies to Full-Length Agrin Protein in Chinese Patients With Myasthenia Gravis - Wang_2021_Front.Immunol_12_753247
Author(s) : Wang S , Yang H , Guo R , Wang L , Zhang Y , Lv J , Zhao X , Zhang J , Fang H , Zhang Q , Yang J , Cui X , Gao P , Chang T , Gao F
Ref : Front Immunol , 12 :753247 , 2021
Abstract : This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.
ESTHER : Wang_2021_Front.Immunol_12_753247
PubMedSearch : Wang_2021_Front.Immunol_12_753247
PubMedID: 34956185

Title : Computational biotransformation of polyethylene terephthalate by depolymerase: A QM\/MM approach - Zheng_2021_J.Hazard.Mater_423_127017
Author(s) : Zheng M , Li Y , Dong W , Feng S , Zhang Q , Wang W
Ref : J Hazard Mater , 423 :127017 , 2021
Abstract : Despite increasing environmental concerns on ever-lasting Polyethylene Terephthalate (PET), its global production is continuously growing. Effective strategies that can completely remove PET from environment are urgently desired. Here biotransformation processes of PET by one of the most effective enzymes, leaf-branch compost cutinase (LCC), were systematically explored with Molecular Dynamics and Quantum Mechanics/Molecular Mechanics approaches. We found that four concerted steps are required to complete the whole catalytic cycle. The last concerted step, deacylation, was determined as the rate-determining step with Boltzmann-weighted average barrier of 13.6 kcal/mol and arithmetic average of 16.1 +/- 2.9 kcal/mol. Interestingly, unprecedented fluctuations of hydrogen bond length during LCC catalyzed transformation process toward PET were found. This fluctuation was also observed in enzyme IsPETase, indicating that it may widely exist in other catalytic triad (Ser-His-Asp) containing enzymes as well. In addition, possible features (bond, angle, dihedral angle and charge) that influence the catalytic reaction were identified and correlations between activation energies and key features were established. Our results present new insights into catalytic mechanism of hydrolases and shed light on the efficient recycling of the ever-lasting PET.
ESTHER : Zheng_2021_J.Hazard.Mater_423_127017
PubMedSearch : Zheng_2021_J.Hazard.Mater_423_127017
PubMedID: 34464862
Gene_locus related to this paper: 9bact-g9by57

Title : ((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Abeta(1-42)-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis - Ding_2021_ACS.Chem.Neurosci__
Author(s) : Ding Y , Wang X , Ji J , Zhang X , Chen M , Li S , Zhang Q , Liu P
Ref : ACS Chem Neurosci , : , 2021
Abstract : Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3beta (GSK-3beta) inhibitor, on the learning and memory function of rats with amyloid-beta(1-42) (Abeta(1-42))-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Abeta, donepezil, and low-dose and high-dose 9b groups. The rats in the Abeta, donepezil, and two 9b intervention groups received a single microinjection of 10 microg of Abeta(1-42) into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Abeta(1-42), phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Abeta group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Abeta(1-42). The novel GSK-3beta inhibitor 9b could improve learning and memory dysfunction caused by Abeta(1-42) through its antioxidant and antiapoptotic effects.
ESTHER : Ding_2021_ACS.Chem.Neurosci__
PubMedSearch : Ding_2021_ACS.Chem.Neurosci__
PubMedID: 33517657

Title : Copper(II) complex as a turn on fluorescent sensing platform for acetylcholinesterase activity with high sensitivity - Zhang_2020_Talanta_208_120406
Author(s) : Zhang P , Fu C , Xiao Y , Zhang Q , Ding C
Ref : Talanta , 208 :120406 , 2020
Abstract : Acetylcholinesterase (AChE) is an important enzyme associated with many nervous diseases, demonstrating the great need for smarter sensing platform with improved sensitivity, selectivity and simplified operation. A "turn on" fluorometric assay is described herein for AChE activity detection, according to the specific enzyme catalyzed reaction of acetylcholine (ATCh) by AChE, which generates thiocholine (TCh) as the product. The well-designed fluorescent probe HBTP possesses ESIPT (Excited State Intramolecular Proton Transfer) nature, leading to a larger Stokes shift, which could be quenched upon coordination with Cu(2+). The fluorescence-silent HBTP-Cu(2+) complex could be broken by TCh generated from reaction of ATCh with AChE, giving rise to HBTP release which originates from competitive coordination of TCh with Cu(2+). This complex probe HBTP-Cu(2+) offers a limit detection as low as 0.02 mUmL(-1), which is lower than most reported literatures. Furthermore, both HBTP-Cu(2+) and HBTP show little toxicity to live cells and is available in visualizing cellular AChE activity.
ESTHER : Zhang_2020_Talanta_208_120406
PubMedSearch : Zhang_2020_Talanta_208_120406
PubMedID: 31816742

Title : Preparation of Lipase-Electrospun SiO(2) Nanofiber Membrane Bioreactors and Their Targeted Catalytic Ability at the Macroscopic Oil-Water Interface - Kuang_2020_J.Agric.Food.Chem_68_8362
Author(s) : Kuang L , Zhang Q , Li J , Tian H
Ref : Journal of Agricultural and Food Chemistry , 68 :8362 , 2020
Abstract : Lipase is one of the most widely used enzymes in biocatalysis. Because of the special structure of the catalytic active center, lipases show high catalytic activity at oil-water interfaces. Hence, the interface plays a key role in activating and modulating lipase biocatalysis. Compared with traditional catalytic systems that offer interfaces, such as emulsions, a lipase-membrane bioreactor exhibits many obvious advantages when at the macroscopic oil-water system. In our current research, a series of new Burkholderia cepacia lipase (BCL)-SiO(2) nanofiber membrane (NFM) bioreactors prepared via combined electrospinning and immobilization strategies were reported. These SiO(2) NFMs assisted BCL in reaching the oil-water interface for efficient catalysis. The enzyme loading capacity and catalytic efficiency of BCL-SiO(2) NFMs varied with the surface hydrophobicity of the electrospun NFMs. As the hydrophobicity increased, the activity decreased from 2.43-fold to 0.74-fold that of free BCL. However, the lipase-loading capacity increased obviously when the hydrophobicity of the SiO(2) NFMs increased from 0 to 143 degrees, and no significant change was observed when the hydrophobicity of the SiO(2) NFMs increased from 143 to 153 degrees. The gel trapping technique proved that the hydrolytic activity of the different BCL-SiO(2) NFM bioreactors depends on the contact area of the membrane at the oil-water interface. BCL-SiO(2) NFM, BCL-SiO(2) NFM-C(12), and BCL-SiO(2) NFM-C(18) retained 32, 83, and 42% of activity, respectively, after five cycles of reuse. The current work was a useful exploration of the construction and modification of lipase-membrane reactors based on electrospun inorganic silicon.
ESTHER : Kuang_2020_J.Agric.Food.Chem_68_8362
PubMedSearch : Kuang_2020_J.Agric.Food.Chem_68_8362
PubMedID: 32649192

Title : Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease - Wei_2020_Circ.Res_127_249
Author(s) : Wei X , Adak S , Zayed M , Yin L , Feng C , Speck SL , Kathayat RS , Zhang Q , Dickinson BC , Semenkovich CF
Ref : Circulation Research , 127 :249 , 2020
Abstract : RATIONALE: Peripheral artery disease, common in metabolic syndrome and diabetes mellitus, responds poorly to medical interventions and is characterized by chronic vessel immaturity leading to lower extremity amputations. OBJECTIVE: To define the role of reversible palmitoylation at the endothelium in the maintenance of vascular maturity. METHODS AND RESULTS: Endothelial knockout of the depalmitoylation enzyme APT-1 (acyl-protein thioesterase 1) in mice impaired recovery from chronic hindlimb ischemia, a model of peripheral artery disease. Endothelial APT-1 deficiency decreased fibronectin processing, disrupted adherens junctions, and inhibited in vitro lumen formation. In an unbiased palmitoylation proteomic screen of endothelial cells from genetically modified mice, R-Ras, known to promote vessel maturation, was preferentially affected by APT-1 deficiency. R-Ras was validated as an APT-1 substrate, and click chemistry analyses demonstrated increased R-Ras palmitoylation in cells with APT-1 deficiency. APT-1 enzyme activity was decreased in endothelial cells from db/db mice. Hyperglycemia decreased APT-1 activity in human umbilical vein endothelial cells, due, in part, to altered acetylation of the APT-1 protein. Click chemistry analyses demonstrated increased R-Ras palmitoylation in the setting of hyperglycemia. Altered R-Ras trafficking, increased R-Ras palmitoylation, and fibronectin retention were found in diabetes mellitus models. Loss of R-Ras depalmitoylation caused by APT-1 deficiency constrained R-Ras membrane trafficking, as shown by total internal reflection fluorescence imaging. To rescue cellular phenotypes, we generated an R-Ras molecule with an inserted hydrophilic domain to circumvent membrane rigidity caused by defective palmitoylation turnover. This modification corrected R-Ras membrane trafficking, restored fibronectin processing, increased adherens junctions, and rescued defective lumen formation induced by APT-1 deficiency. CONCLUSIONS: These results suggest that endothelial depalmitoylation is regulated by the metabolic milieu and controls plasma membrane partitioning to maintain vascular homeostasis.
ESTHER : Wei_2020_Circ.Res_127_249
PubMedSearch : Wei_2020_Circ.Res_127_249
PubMedID: 32233916

Title : A Comparison of the Resolution of Selective (+\/-)-Glycidyl Butyrate by Using Free and Nano-SiO(2) Immobilized Porcine Pancreatic Lipase - Zhang_2020_J.Nanosci.Nanotechnol_20_6168
Author(s) : Zhang Q , Qian J , Guo H , Zhang W , Kuang C
Ref : J Nanosci Nanotechnol , 20 :6168 , 2020
Abstract : To explore the hydrolyzed properties of nano-SiO(2) immobilized porcine pancreatic lipase, the selective hydrolysis of immobilized lipase for glycidyl butyrate was compared with the free enzyme. The hydrolysis selectivity of the immobilized biocatalyst was evaluated and compared with the free enzyme using the enantiomeric excess (ee) of resolving racemic glycidyl butyrate as the indicator. The enantiomeric excess of the immobilized biocatalyst could be increased by 4.5%-10.0% which compared with the free enzyme under every single technological condition. The ee was improved from 84.7% for free enzyme to 91.6% for the immobilized enzyme with 61.2% conversion. Compared with free enzyme, the conversion rate of the immobilized enzyme was increased slightly, but the % enantiomeric excess of the immobilized enzyme was increased greatly.
ESTHER : Zhang_2020_J.Nanosci.Nanotechnol_20_6168
PubMedSearch : Zhang_2020_J.Nanosci.Nanotechnol_20_6168
PubMedID: 32384967

Title : In situ and real-time insight into Rhizopus chinensis lipase under high pressure and temperature: Conformational traits and biobehavioural analysis - Chen_2020_Int.J.Biol.Macromol_154_1314
Author(s) : Chen G , Zhang Q , Chen H , Lu Q , Miao M , Campanella OH , Feng B
Ref : Int J Biol Macromol , 154 :1314 , 2020
Abstract : An in situ and real-time investigation was performed using an optical cell system and in-silico analysis to reveal the impacts of pressure and temperature on the conformational state and behaviours of Rhizopus chinensis lipase (RCL). The fluorescence intensity (FI) of RCL increased remarkably under high pressure, and part of this increase was recovered after depressurization. This result displayed the partially reversible conformational change of RCL, which may be associated with the local change of Trp224 near the catalytic centre. High temperature caused a significant loss of secondary structure, whereas the alpha-helical segments including the lid were preserved by high pressure even at temperatures over 60 degreesC. The parameters of enzymatic reaction monitored by UV showed that the hydrolysis rate was remarkably enhanced by the pressure of 200 MPa. In the pressure range of 0.1-200 MPa, the active volume measured by the in situ system decreased from -2.85 to -6.73 mL/mol with the temperature increasing from 20 degreesC to 40 degreesC. The high catalytic capacity of the lipase under high pressure and high temperature was primarily attributed to pressure protection on RCL.
ESTHER : Chen_2020_Int.J.Biol.Macromol_154_1314
PubMedSearch : Chen_2020_Int.J.Biol.Macromol_154_1314
PubMedID: 31733249

Title : The influence mechanism of temperature on solid phase denitrification based on denitrification performance, carbon balance, and microbial analysis - Shen_2020_Sci.Total.Environ_732_139333
Author(s) : Shen Q , Ji F , Wei J , Fang D , Zhang Q , Jiang L , Cai A , Kuang L
Ref : Sci Total Environ , 732 :139333 , 2020
Abstract : In this work, the influence mechanism of temperature on solid phase denitrification (SPD) was investigated using a pilot-scale reactor supported with polycaprolactone (PCL). The results showed that under nitrate loads of ~31.5 mg N/(L.h), as temperature decreased from 30 degrees C to 13 degrees C, the nitrate removal efficiency declined from 94% to 57%. Furthermore, denitrification rate constants were input into Arrhenius equation and the resulting temperature coefficient was 1.04. Significantly nitrite accumulation and less effluent COD residue occurred at low-temperatures. Via stoichiometry, the sludge yield coefficient and COD demand for nitrate removal both increased as a function of increasing temperature; and were calculated at 20 degrees C as 0.069 g MLVSS/(g COD.d) and 3.265 g COD/g N, respectively. Carbon balance analysis indicated that the COD release rate (upsilon) at 30 degrees C was twice that at 13 degrees C. LEfSe analysis demonstrated that Desulfomicrobium, Desulfovibrio, and Meganema were abundant at low-temperature, while Simplicispira, Aquabacterium, and Acidovorax were enriched at high-temperature. Besides, carboxylesterase (PCL depolymerase) was more abundant at high-temperature, implying an association with a fast upsilon. Moreover, nar was enriched at low-temperature, while nir was depleted, which led to nitrite accumulation. These results provide reference for SPD design parameter estimation and/or optimal operation strategy.
ESTHER : Shen_2020_Sci.Total.Environ_732_139333
PubMedSearch : Shen_2020_Sci.Total.Environ_732_139333
PubMedID: 32438161

Title : Biodegradation mechanism of polycaprolactone by a novel esterase MGS0156: a QM\/MM approach - Feng_2020_Environ.Sci.Process.Impacts_22_2332
Author(s) : Feng S , Yue Y , Chen J , Zhou J , Li Y , Zhang Q
Ref : Environ Sci Process Impacts , 22 :2332 , 2020
Abstract : Nowadays micro-plastic pollution has become one of the most serious global environmental problems. A potential strategy in managing micro-plastic waste is enzyme-catalyzed degradation. MGS0156 is a hydrolase screened from environmental metagenomes, which can efficiently degrade commercial plastics such as polycaprolactone, polylactide, etc. Here a combined molecular dynamics, molecular mechanics Poisson-Boltzmann surface area, and quantum mechanics/molecular mechanism method was used to reveal the enzymatic depolymerization mechanism. By systematically analyzing the binding processes of nine oligomers (from a monomer to tetramer), we found that longer oligomers have relatively stronger binding energy. The degradation process involves two concerted elementary steps: triad-assisted nucleophilic attack and C-O bond cleavage. C-O bond cleavage is the rate determining step with an average barrier of 15.7 kcal mol-1, which is consistent with the experimentally determined kcat (1101 s-1, corresponds to 13.3 kcal mol-1). The electrostatic influence analysis of twenty amino acids highlights His231 and Asp237 as potential mutation targets for designing more efficient MGS0156 mutants.
ESTHER : Feng_2020_Environ.Sci.Process.Impacts_22_2332
PubMedSearch : Feng_2020_Environ.Sci.Process.Impacts_22_2332
PubMedID: 33146659
Gene_locus related to this paper: 9zzzz-A0A0G3FEJ8

Title : Degradation mechanism for Zearalenone ring-cleavage by Zearalenone hydrolase RmZHD: A QM\/MM study - Zhou_2020_Sci.Total.Environ_709_135897
Author(s) : Zhou J , Zhu L , Chen J , Wang W , Zhang R , Li Y , Zhang Q
Ref : Sci Total Environ , 709 :135897 , 2020
Abstract : The danger of zearalenone (ZEN) as an endocrine disruptor to humans and the environment has aroused increasing attention. In this study, we implemented the quantum mechanics/molecular mechanics (QM/MM) method to investigate the degradation mechanism of ZEN hydrolase (RmZHD) toward ZEN at the atomic level. The degradation process involves two concerted reaction pathways, where the active site contains a Ser-His-Glu triplet as a proton donor. With the Boltzmann-weighted average potential barriers of 18.1 and 21.5 kcal/mol, the process undergoes proton transfer and nucleophilic-substituted ring opening to form a hydroxyl product. Non-covalent interaction analyses elucidated hydrogen bonding between key amino acids with ZEN. The electrostatic influence analysis of 16 amino acids proposes residues Asp34 and His128 as the possible mutation target for future mutation design of enzyme RmZHD. An in-depth investigation of the protein environment of RmZHD can improve the bioremediation efficiency of endocrine disrupting chemicals.
ESTHER : Zhou_2020_Sci.Total.Environ_709_135897
PubMedSearch : Zhou_2020_Sci.Total.Environ_709_135897
PubMedID: 31887512
Gene_locus related to this paper: 9euro-a0a0d2ilk1

Title : Gene cloning, expression, purification and characterization of a sn-1,3 extracellular lipase from Aspergillus niger GZUF36 - Xing_2020_J.Food.Sci.Technol_57_2669
Author(s) : Xing S , Zhu R , Li C , He L , Zeng X , Zhang Q
Ref : J Food Sci Technol , 57 :2669 , 2020
Abstract : Sn-1,3 extracellular Aspergillus niger GZUF36 lipase (EXANL1) has wide application potential in the food industry. However, the A. niger strain has defects such as easy degradation and instability in the expression of sn-1,3 lipase. To obtain a stable expression of this lipase and its subsequent enzymatic properties, the gene encoding EXANL1 was cloned and expressed in Escherichia coli BL21 (DE3) cells using pET-28a as the expression vector. The temperature-induced conditions were optimized, and we successfully achieved its active expression in E. coli. These conditions significantly influenced the active expression of EXANL1 (P < 0.05), and the highest enzyme activity of the supernatant of lysis cells expressed at 20 degreesC was at 7.02 +/- 0.05 U/mL. The expressed recombinant EXANL1 was purified using Ni-NTA, showing an estimated relative molecular mass of 35 kDa. The recombinant EXANL1 exhibited maximum activity at 35 degreesC and pH 4.0, with a wide acid pH range. Thin-layer chromatography analysis showed that the enzyme displayed sn-1,3 positional selectivity toward triolein. The recombinant EXANL1 could maintain its relative activities (> 80%) after 24 h of incubation at pH 3-10, suggesting its suitability for a wide range of industrial applications. After comparing these properties with those of the other A. niger lipases, we found that some key amino acids may play a decisive role in enzymology. This work laid a foundation for the stable expression of the EXANL1 gene and its potential industrial application.
ESTHER : Xing_2020_J.Food.Sci.Technol_57_2669
PubMedSearch : Xing_2020_J.Food.Sci.Technol_57_2669
PubMedID: 32549617
Gene_locus related to this paper: aspng-EXANL1

Title : Rationally design and chemical modification: Getting a new and efficient biocatalyst for Henry reaction - Yu_2020_Enzyme.Microb.Technol_142_109695
Author(s) : Yu Z , Zhang Q , Tang H , Xu G
Ref : Enzyme Microb Technol , 142 :109695 , 2020
Abstract : A robust biocatalyst for green Henry reaction was achieved. Based on the fact that Henry reaction requires a base for proton transfer, we firstly proposed that the catalytic triad of lipase could play this role. The distance between the substrate and the catalytic center and the surrounding amino acid interaction network were used as the criterion. Benzaldehyde and nitromethane were used as the model reaction, RNL (Lipase from Rhizopus niveus) was considered to be the best Henry reaction catalyst via a molecular dynamics simulation. Then experiments demonstrated that RNL has a yield of 48 % using model substrate in water. Further, in order to increase product yield, the chemical modifier 1, 2-cyclohexanedione (CHD) was used to modify Arg on RNL. As a result, RNL (CHD) increased the activity of catalyzing Henry reaction and had a broad spectrum of substrates, the yield of the product was as high as 67-99 %.
ESTHER : Yu_2020_Enzyme.Microb.Technol_142_109695
PubMedSearch : Yu_2020_Enzyme.Microb.Technol_142_109695
PubMedID: 33220873
Gene_locus related to this paper: rhidl-lipas

Title : Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties - Zhang_2020_Nat.Commun_11_3719
Author(s) : Zhang W , Zhang Y , Qiu H , Guo Y , Wan H , Zhang X , Scossa F , Alseekh S , Zhang Q , Wang P , Xu L , Schmidt MH , Jia X , Li D , Zhu A , Guo F , Chen W , Ni D , Usadel B , Fernie AR , Wen W
Ref : Nat Commun , 11 :3719 , 2020
Abstract : Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3'5'H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds.
ESTHER : Zhang_2020_Nat.Commun_11_3719
PubMedSearch : Zhang_2020_Nat.Commun_11_3719
PubMedID: 32709943
Gene_locus related to this paper: camsi-a0a7j7g2i2 , camsi-a0a7j7hil4

Title : The genome evolution and low-phosphorus adaptation in white lupin - Xu_2020_Nat.Commun_11_1069
Author(s) : Xu W , Zhang Q , Yuan W , Xu F , Muhammad Aslam M , Miao R , Li Y , Wang Q , Li X , Zhang X , Zhang K , Xia T , Cheng F
Ref : Nat Commun , 11 :1069 , 2020
Abstract : White lupin (Lupinus albus) is a legume crop that develops cluster roots and has high phosphorus (P)-use efficiency (PUE) in low-P soils. Here, we assemble the genome of white lupin and find that it has evolved from a whole-genome triplication (WGT) event. We then decipher its diploid ancestral genome and reconstruct the three sub-genomes. Based on the results, we further reveal the sub-genome dominance and the genic expression of the different sub-genomes varying in relation to their transposable element (TE) density. The PUE genes in white lupin have been expanded through WGT as well as tandem and dispersed duplications. Furthermore, we characterize four main pathways for high PUE, which include carbon fixation, cluster root formation, soil-P remobilization, and cellular-P reuse. Among these, auxin modulation may be important for cluster root formation through involvement of potential genes LaABCG36s and LaABCG37s. These findings provide insights into the genome evolution and low-P adaptation of white lupin.
ESTHER : Xu_2020_Nat.Commun_11_1069
PubMedSearch : Xu_2020_Nat.Commun_11_1069
PubMedID: 32103018
Gene_locus related to this paper: lupal-a0a6a5lz53 , lupal-a0a6a5mjk3

Title : PREPL Deficiency: A Homozygous Splice Site PREPL Mutation in a Patient With Congenital Myasthenic Syndrome and Absence of Ovaries and Hypoplasia of Uterus - Yang_2020_Front.Genet_11_198
Author(s) : Yang Q , Hua R , Qian J , Yi S , Shen F , Zhang Q , Li M , Luo J , Fan X
Ref : Front Genet , 11 :198 , 2020
Abstract : Prolyl endopeptidase-like (PREPL) deficiency (MIM 616224) is a very rare congenital disorder characterized by neonatal hypotonia and feeding difficulties, ptosis, neuromuscular symptoms, cognitive impairments, growth hormone deficiency, short stature, and hypergonadotropic hypogonadism. This syndrome is an autosomal recessive disease resulting from mutations in the PREPL gene. Previous reports have associated PREPL deficiency with only one nucleotide substitution, the deletion of four nucleotides, and eight small microdeletions in the PREPL gene In this study, we used whole exome sequencing (WES) to identify a novel homozygous splicing mutation (c.616 + 1G > T) in a 14-year-old Chinese girl with PREPL deficiency. Sequencing of the RT-PCR products from the patient's blood sample revealed that the c.616 + 1G > T variant disrupted normal splicing in intron 4 leading to an aberrant inclusion of 43 nucleotides in intron, a frameshift, and premature termination codon. Our patient exhibited several of the common phenotypes, including severe neonatal hypotonia, growth impairment and cognitive problems. However, we also observed several unusual phenotypic characteristics: absence of the ovaries, hypoplasia of the uterus, microcephaly and a short neck in patient is alsoobserved. These results provide further evidence for the involvement of PREPL development of the ovaries and uterus. Our findings may provide further insight into the relationship between the genotype and phenotype in collagen-associated diseases and improve the clinical diagnosis of Prolyl endopeptidase-like deficiency.
ESTHER : Yang_2020_Front.Genet_11_198
PubMedSearch : Yang_2020_Front.Genet_11_198
PubMedID: 32218803
Gene_locus related to this paper: human-PREPL

Title : Approach to Cognitive Impairment in Parkinson's Disease - Zhang_2020_Neurotherapeutics_17_1495
Author(s) : Zhang Q , Aldridge GM , Narayanan NS , Anderson SW , Uc EY
Ref : Neurotherapeutics , 17 :1495 , 2020
Abstract : Cognitive dysfunction is common in Parkinson's disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvement of memory and other domains. Subtle symptoms in the premotor and early phases of PD progress to mild cognitive impairment (MCI) which may be present at the time of diagnosis. Eventually, a large majority of PD patients develop dementia with advancing age and longer disease duration, which is usually accompanied by immobility, hallucinations/psychosis, and dysautonomia. Dopaminergic medications and deep brain stimulation help motor dysfunction, but may have potential cognitive side effects. Central acetylcholinesterase inhibitors, and possibly memantine, provide modest and temporary symptomatic relief for dementia, although there is no evidence-based treatment for MCI. There is no proven disease-modifying treatment for cognitive impairment in PD. The symptomatic and disease-modifying role of physical exercise, cognitive training, and neuromodulation on cognitive impairment in PD is under investigation. Multidisciplinary approaches to cognitive impairment with effective treatment of comorbidities, proper rehabilitation, and maintenance of good support systems in addition to pharmaceutical treatment may improve the quality of life of the patients and caregivers.
ESTHER : Zhang_2020_Neurotherapeutics_17_1495
PubMedSearch : Zhang_2020_Neurotherapeutics_17_1495
PubMedID: 33205381

Title : Structures and esterolytic reactivity of novel binuclear copper(ii) complexes with reduced l-serine Schiff bases as mimic carboxylesterases - Zhang_2020_Dalton.Trans_49_10261
Author(s) : Zhang Q , Shu J , Zhang Y , Xu Z , Yue J , Liu X , Xu B , Chen Z , Jiang W
Ref : Dalton Trans , 49 :10261 , 2020
Abstract : Three novel binuclear copper(ii) complexes with reduced l-serine Schiff bases were synthesized and their structures were analyzed with single-crystal X-ray diffraction and DFT calculations. The crystal data revealed that all of these binuclear complexes are chiral. Both 5-halogenated (bromo- and chloro-) binuclear complexes exhibit right-handed helix structural character. Interestingly, the 5-methyl-containing analogue has a two-dimensional pore structure. In this paper, the esterolysis reactivity of the as-prepared complexes shows that in the hydrolysis of p-nitrophenyl acetate (PNPA) these three complexes provide 26, 18, 40-fold rate acceleration as compared to the spontaneous hydrolysis of PNPA at pH 7.0, respectively. Under selected conditions, in excess buffered aqueous solution a rate enhancement by three orders of magnitude was observed for the catalytic hydrolysis of another carboxylic ester, p-nitrophenyl picolinate (PNPP). These complexes efficiently promoted PNPP hydrolysis in a micellar solution of cetyltrimethylammonium bromide (CTAB), giving rise to a rate enhancement in excess of four orders of magnitude, which is approximately 2.0-3.2 times higher than that in the buffer.
ESTHER : Zhang_2020_Dalton.Trans_49_10261
PubMedSearch : Zhang_2020_Dalton.Trans_49_10261
PubMedID: 32672259

Title : Cascade Reaction System Integrating Single-Atom Nanozymes with Abundant Cu Sites for Enhanced Biosensing - Wu_2020_Anal.Chem__
Author(s) : Wu Y , Wu J , Jiao L , Xu W , Wang H , Wei X , Gu W , Ren G , Zhang N , Zhang Q , Huang L , Gu L , Zhu C
Ref : Analytical Chemistry , : , 2020
Abstract : Single-atom nanozymes (SAzymes), as novel nanozymes with atomically dispersed active sites, are of great importance in the de-velopment of nanozymes for their high catalytic activities, the maximum utilization efficiency of metal atoms, and the simple mod-el of active sites. Herein, the peroxidase-like SAzymes with high-concentration Cu sites on carbon nanosheets (Cu-N-C) were syn-thesized through a salt-template strategy. With the densely distributed active Cu atoms (~5.1 wt%), the Cu-N-C SAzymes exhibit remarkable activity to mimic natural peroxidase. Integrating Cu-N-C SAzymes with natural acetylcholinesterase and choline oxi-dase, three-enzyme-based cascade reaction system was constructed for the colorimetric detection of acetylcholine and organo-phosphorus pesticides. This work not only provides a strategy to synthesize SAzymes with abundant active sites but also gives some new insights for robust nanozyme biosensing systems.
ESTHER : Wu_2020_Anal.Chem__
PubMedSearch : Wu_2020_Anal.Chem__
PubMedID: 31941278

Title : Enantioselective Hydrolysis of Styrene Oxide and Benzyl Glycidyl Ether by a Variant of Epoxide Hydrolase from Agromyces mediolanus - Jin_2019_Mar.Drugs_17_
Author(s) : Jin H , Li Y , Zhang Q , Lin S , Yang Z , Ding G
Ref : Mar Drugs , 17 : , 2019
Abstract : Enantiopure epoxides are versatile synthetic intermediates for producing optically active pharmaceuticals. In an effort to provide more options for the preparation of enantiopure epoxides, a variant of the epoxide hydrolase (vEH-Am) gene from a marine microorganism Agromyces mediolanus was synthesized and expressed in Escherichia coli. Recombiant vEH-Am displayed a molecular weight of 43 kDa and showed high stability with a half-life of 51.1 h at 30 degrees C. The purified vEH-Am exhibited high enantioselectivity towards styrene oxide (SO) and benzyl glycidyl ether (BGE). The vEH-Am preferentially converted (S)-SO, leaving (R)-SO with the enantiomeric excess (ee) >99%. However, (R)-BGE was preferentially hydrolyzed by vEH-Am, resulting in (S)-BGE with >99% ee. To investigate the origin of regioselectivity, the interactions between vEH-Am and enantiomers of SO and BGE were analyzed by molecular docking simulation. In addition, it was observed that the yields of (R)-SO and (S)-BGE decreased with the increase of substrate concentrations. The yield of (R)-SO was significantly increased by adding 2% (v/v) Tween-20 or intermittent supplementation of the substrate. To our knowledge, vEH-Am displayed the highest enantioselectivity for the kinetic resolution of racemic BGE among the known EHs, suggesting promising applications of vEH-Am in the preparation of optically active BGE.
ESTHER : Jin_2019_Mar.Drugs_17_
PubMedSearch : Jin_2019_Mar.Drugs_17_
PubMedID: 31226863
Gene_locus related to this paper: agrme-a0a088b180

Title : Glucoconjugated Monoterpene Indole Alkaloids from Uncaria rhynchophylla - Guo_2019_J.Nat.Prod_82_3288
Author(s) : Guo Q , Si X , Shi Y , Yang H , Liu X , Liang H , Tu P , Zhang Q
Ref : Journal of Natural Products , 82 :3288 , 2019
Abstract : Twenty-six glucoconjugated monoterpene indole alkaloids, including 12 new compounds, rhynchophyllosides A-L (1-12), and 14 known ones, 13-26, were obtained from the hook-bearing stems of Uncaria rhynchophylla (Miq.) Miq. ex Havil. Their structures were unambiguously elucidated by analyses of UV, MS, NMR, ECD, and single-crystal X-ray diffraction data. The ESI-MS(n) behavior of the new glucoalkaloids was also elucidated. Although comprising the same glucosyl moiety, the aglycone skeletons and glucosidic numbers and linkage varied greatly, implying the diversity in biosynthetic pathways. This is the first report of such structurally diverse glucoconjugated monoterpene indole alkaloids from U. rhynchophylla. Compound 1 represents a new subtype of oxindole alkaloid with a seven-membered D-ring, 10 is a rare monoterpene indole alkaloid with the glucosyl moiety located at C-9, 4 and 5 are the first two oxindole alkaloid diglycosides, and 11 and 12 represent the first two examples of alkaloids with a quinolone nucleus from the genus Uncaria. Compound 10 exhibited moderate acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 10.5 muM. Molecular docking was performed to explore the binding mode of inhibitor 10 at the active site of AChE.
ESTHER : Guo_2019_J.Nat.Prod_82_3288
PubMedSearch : Guo_2019_J.Nat.Prod_82_3288
PubMedID: 31804070

Title : Clinical analysis of Chinese anti-low-density-lipoprotein-receptor-associated protein 4 antibodies in patients with myasthenia gravis - Li_2019_Eur.J.Neurol_26_1296
Author(s) : Li M , Han J , Zhang Y , Lv J , Zhang J , Zhao X , Ren L , Fang H , Yang J , Cui X , Zhang Q , Li Q , Du Y , Gao F
Ref : Eur Journal of Neurology , 26 :1296 , 2019
Abstract : BACKGROUND AND PURPOSE: Low-density-lipoprotein-receptor-associated protein 4 (LRP4) autoantibodies have recently been detected in myasthenia gravis (MG), but little is known about the clinical characteristics associated with this serological type. In this study, the clinical features of Chinese patients with anti-LRP4 antibody-positive MG were characterized. METHODS: A total of 2172 MG serum samples were collected from patients in various parts of China. An enzyme-linked immunosorbent assay was used to detect acetylcholine receptor (AChR) antibody and titin antibody, and cell-based assays were used to detect muscle-specific kinase antibody and LRP4 antibody. Clinical data for patients with MG were collected from different provinces in China. RESULTS: In total, 16 (0.8%) patients with LRP4-MG were found amongst 2172 total patients, including three patients with AChR/LRP4-MG. Additionally, 13 (2.9%) patients with LRP4-MG were found amongst 455 patients with double seronegative MG. The ratio of males to females for these 13 patients was 1:1.6, and 53.8% patients were children. A total of 91.7% of cases exhibited initial ocular involvement, and 58.3% of cases exhibited simple eye muscle involvement. Responses to acetylcholinesterase inhibitors and prednisone were observed. CONCLUSION: The expanded sample confirmed that the positive rate of LRP4 antibodies in China is lower than that in western countries. Our results highlighted the differences between LRP4-MG and other antibody groups. Children and female patients with LRP4-MG have a higher prevalence, often involving the ocular muscles and limb muscles. The clinical symptoms are mild, and satisfactory responses to treatment are often achieved.
ESTHER : Li_2019_Eur.J.Neurol_26_1296
PubMedSearch : Li_2019_Eur.J.Neurol_26_1296
PubMedID: 31050101

Title : Hydroxy-alpha-sanshool isolated from Zanthoxylum bungeanum attenuates learning and memory impairments in scopolamine-treated mice - Zhang_2019_Food.Funct_10_7315
Author(s) : Zhang M , Xie M , Wei D , Wang L , Hu M , Zhang Q , He Z , Peng W , Wu C
Ref : Food Funct , 10 :7315 , 2019
Abstract : Learning and memory impairments are common symptoms of dementia in neurodegenerative disorders. Occasionally, we found that Zanthoxylum bungeanum pericarps (ZBP) significantly activated the spontaneous activity of the hippocampus (HIPP) and paraHIPP (P < 0.001, uncorrected), implying the potential ability of ZBP to improve cognitive impairments. Thus, this study aimed to investigate the improving effect of hydroxy-alpha-sanshool (HAS), a characteristic ingredient of ZBP, against scopolamine (1 mg kg(-1), i.p.)-induced learning and memory deficits. HAS (5 mg kg(-1), p.o.) markedly reversed scopolamine-induced cognitive impairments, as indicated by its performance in the passive avoidance test and Morris water maze test (P < 0.01). Furthermore, HAS (2.5 and 5.0 mg kg(-1), p.o.) also dose-dependently prevented changes in hippocampal neuronal morphology and apoptosis, inhibited acetylcholinesterase (AChE) activity, increased the acetylcholine (ACh) content, and increased the protein and mRNA expression of brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding (p-CREB) compared with those in the model group (P < 0.05 & P < 0.01). These findings demonstrated that HAS attenuated scopolamine-induced cognitive impairments mainly by enhancing the activity of the cholinergic system and increasing the CREB/BDNF signalling pathway.
ESTHER : Zhang_2019_Food.Funct_10_7315
PubMedSearch : Zhang_2019_Food.Funct_10_7315
PubMedID: 31637395

Title : Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease - Bai_2019_Eur.J.Med.Chem_183_111737
Author(s) : Bai P , Wang K , Zhang P , Shi J , Cheng X , Zhang Q , Zheng C , Cheng Y , Yang J , Lu X , Sang Z
Ref : Eur Journal of Medicinal Chemistry , 183 :111737 , 2019
Abstract : A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50=1.3+/-0.01muM) and butyrylcholinesterase (IC50=1.2+/-0.09muM). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57+/-0.01muM. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced Abeta1-42 aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu(2+)-induced Abeta1-42 aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, Abeta1-42 and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD.
ESTHER : Bai_2019_Eur.J.Med.Chem_183_111737
PubMedSearch : Bai_2019_Eur.J.Med.Chem_183_111737
PubMedID: 31581002

Title : Prognostic Impact of Carboxylesterase 2 in Cholangiocarcinoma - Goeppert_2019_Sci.Rep_9_4338
Author(s) : Goeppert B , Renner M , Singer S , Albrecht T , Zhang Q , Mehrabi A , Pathil A , Springfeld C , Kohler B , Rupp C , Weiss KH , Kuhl AA , Arsenic R , Pape UF , Vogel A , Schirmacher P , Roessler S , Utku N
Ref : Sci Rep , 9 :4338 , 2019
Abstract : Carboxylesterase 2 (CES2) is instrumental for conversion of ester-containing prodrugs in cancer treatment. Novel treatment strategies are exceedingly needed for cholangiocarcinoma (CCA) patients. Here, we assessed CES2 expression by immunohistochemistry in a CCA cohort comprising 171 non-liver fluke associated, intrahepatic (n = 72) and extrahepatic (perihilar: n = 56; distal: n = 43) CCAs. Additionally, 80 samples of high-grade biliary intraepithelial neoplastic tissues and 158 corresponding samples of histological normal, non-neoplastic biliary tract tissues were included. CES2 expression was highest in non-neoplastic biliary tissue and significantly decreased in CCA. Patients showing any CES2 expression in tumor cells had a significantly better overall survival compared to negative cases (p = 0.008). This survival benefit was also maintained after stratification of CES2-positive cases, by comparing low, medium and high CES2 expression levels (p-trend = 0.0006). Evaluation of CCA subtypes showed the survival difference to be restricted to extrahepatic tumors. Correlation of CES2 expression with data of tumor-infiltrating immune cells showed that particularly CD8+ T cells were more frequently detected in CES2-positive CCAs. Furthermore, treatment of CCA cell lines with the prodrug Irinotecan reduced cell viability, increased cytotoxicity and modulated inflammatory gene expression. In conclusion, reduced CES2 expression is associated with poor outcome and low CD8+ T cell infiltration in CCA patients. Further clinical studies could show, whether CES2 expression may serve as a predictive marker in patients treated with prodrugs converted by CES2.
ESTHER : Goeppert_2019_Sci.Rep_9_4338
PubMedSearch : Goeppert_2019_Sci.Rep_9_4338
PubMedID: 30867471
Gene_locus related to this paper: human-CES2

Title : A Flexible Acetylcholinesterase-Modified Graphene for Chiral Pesticide Sensor - Zhang_2019_J.Am.Chem.Soc_141_14643
Author(s) : Zhang Y , Liu X , Qiu S , Zhang Q , Tang W , Liu H , Guo Y , Ma Y , Guo X , Liu Y
Ref : Journal of the American Chemical Society , 141 :14643 , 2019
Abstract : Sensors based on graphene are promising devices for chemical and biological detection owing to their high sensitivity, biocompatibility, and low costs. However, for chiral recognition, which is very important in biological systems, graphene sensors remain unable to discriminate enantiomers. Here, using chiral pesticide molecules as an example, we realized a highly sensitive graphene chiral sensor by modification with acetylcholinesterase (AChE). Quantum chemical simulations indicate that the inhibition effect of the enantiomer on AChE was transferred to graphene, which allowed for the electrical detection of chiral molecules. Under an operating voltage of 1 V, the sensitivity of the device reached 0.34 mug/L and 0.32 mug/L for (+)/(-)-methamidophos, respectively, which is much higher than by circular dichroism (6.90 mg/L and 5.16 mg/L, respectively). Furthermore, real-time, rapid detection was realized by combining with smartphones and wireless transmission.
ESTHER : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedSearch : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedID: 31448915

Title : Molluscicidal activity and physiological toxicity of quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits on Oncomelania hupensis - Ke_2019_PLoS.Negl.Trop.Dis_13_e0007740
Author(s) : Ke W , Tu C , Cao D , Lin X , Sun Q , Zhang Q
Ref : PLoS Negl Trop Dis , 13 :e0007740 , 2019
Abstract : Schistosomiasis is a serious worldwide parasitic disease. One of the best ways to control schistosomiasis is to control the population of Oncomelania hupensis snails. We sought to identify a high-efficiency biogenic molluscicide against Oncomelania with low toxicity, to avoid chemical molluscicide contamination and toxicity in aquatic organisms. We extracted quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits. Molluscicidal activity of the QBAs against Oncomelania was determined using bioassay. Our results showed that the extracted QBAs had a strong molluscicidal effect. In treatment of O. hupensis with QBAs for 48 h and 72 h, the lethal concentration (LC50) was 2.89 mg/L and 1.29 mg/L, respectively. The molluscicidal activity of QBAs was close to that of niclosamide (ethanolamine salt), indicating that QBAs have potential development value as novel biogenic molluscicides. We also analyzed physiological toxicity mechanisms by examining the activity of several important detoxification enzymes. We measured the effect of the extracted QBAs on the activities of glutathione S-transferase (GST), carboxylesterase (CarE), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the liver of O. hupensis. We found that the effects of QBAs on detoxification metabolism in O. hupensis were time and concentration dependent. The activities of GST, CarE, AKP, and ACP in the liver of snails increased significantly in the early stage of treatment (24 h), but decreased sharply in later stages (120 h), compared with these activities in controls. GST, CarE, AKP, and ACP activity in the liver of snails treated with LC50 QBAs for 120 h decreased by 62.3%, 78.1%, 59.2%, and 68.6%, respectively. Our results indicate that these enzymes were seriously inhibited by the extracted QBAs and the detoxification and metabolic functions of the liver gradually weakened, leading to poisoning, which could be the main cause of death in O. hupensis snails.
ESTHER : Ke_2019_PLoS.Negl.Trop.Dis_13_e0007740
PubMedSearch : Ke_2019_PLoS.Negl.Trop.Dis_13_e0007740
PubMedID: 31603908

Title : Selenepezil, a Selenium-Containing Compound, Exerts Neuroprotective Effect via Modulation of the Keap1-Nrf2-ARE Pathway and Attenuates Abeta-Induced Cognitive Impairment in Vivo - Yan_2019_ACS.Chem.Neurosci_10_2903
Author(s) : Yan J , Pang Y , Zhuang J , Lin H , Zhang Q , Han L , Ke P , Huang X
Ref : ACS Chem Neurosci , 10 :2903 , 2019
Abstract : Oxidative stress is a major risk factor for neurodegenerative disease. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is one of the most potent defensive systems against oxidative stress. Selenepezil, a selenium-based compound, was previously found to exhibit excellent acetylcholinesterase (AChE) inhibition, to mimic endogenous glutathione peroxidase (GPx) activity, and to exhibit scavenging activity for hydrogen peroxide in vitro. However, none of these activities have been evaluated in a cellular model, and detailed molecular mechanisms are not elucidated. Moreover, whether selenepezil ameliorates memory deficits in vivo remains unknown. This study validated the cytoprotective effect of selenepezil against 6-hydroxydopamine (6-OHDA)- or H2O2-induced SH-SY5Y cell damage via alleviation or neutralization of intracellular microtubule disorder, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and cell apoptosis. Our study clearly demonstrated that selenepezil pretreatment exhibited remarkable cytoprotective effect in a Nrf2-dependent manner via activating the Keap1-Nrf2-ARE pathway and stimulating the transcription of Nrf2-ARE-regulated cytoprotective genes. Moreover, selenepezil.HCl exerts neuroprotective effect via attenuating Abeta-induced cognitive impairment in Alzheimer's disease (AD) rat and was more active than the reference drug donepezil. In summary, selenepezil deserves further consideration for AD therapy.
ESTHER : Yan_2019_ACS.Chem.Neurosci_10_2903
PubMedSearch : Yan_2019_ACS.Chem.Neurosci_10_2903
PubMedID: 31035749

Title : Protection effect of polyols on Rhizopus chinensis lipase counteracting the deactivation from high pressure and high temperature treatment - Chen_2019_Int.J.Biol.Macromol_127_555
Author(s) : Chen G , Zhang Q , Lu Q , Feng B
Ref : Int J Biol Macromol , 127 :555 , 2019
Abstract : The influence of polyols on Rhizopus chinensis lipase (RCL) was investigated under high pressure. The poor stability of RCL was observed at 500MPa at 60 degrees C without polyols which protected RCL against the loss of activity. The lipase is more stable in phosphate buffer than in tris buffer despite the protection of polyols. The activity was maintained 63% by the sorbitol of 2mol/L in Tris-HCl buffer but 73% in phosphate buffer after the treatment at 500MPa and 60 degrees C for 25min. The same protective effects could be observed at 1mol/L of sorbitol, erythritol, xylitol, and mannitol. However, further increase of hydroxyl group number could not significantly improve the enzyme stability. The protection of polyols on RCL appears to depend on both of the polyol nature and the hydroxyl group number. Together with fluorescence spectra, circular dichroism spectra indicated that the chaotic conformation of RCL under high pressure became more ordered with 1mol/L sorbitol. The results showed that sorbitol effectively stabilized the lipase conformation including the hydrophobic core under extreme conditions. It might be attributed to the interaction of polyols with RCL surface to modify intra-/intermolecular hydrogen bonds, maintaining the hydrophobic interactions within RCL.
ESTHER : Chen_2019_Int.J.Biol.Macromol_127_555
PubMedSearch : Chen_2019_Int.J.Biol.Macromol_127_555
PubMedID: 30664969

Title : Screening and determination for potential acetylcholinesterase inhibitory constituents from ginseng stem-leaf saponins using ultrafiltration (UF)-LC-ESI-MS(2) - Yang_2019_Phytochem.Anal_30_26
Author(s) : Yang Y , Liang X , Jin P , Li N , Zhang Q , Yan W , Zhang H , Sun J
Ref : Phytochem Anal , 30 :26 , 2019
Abstract : INTRODUCTION: Previous studies have demonstrated that several ginsenosides have remarkable inhibitory effect on acetylcholinesterase (AChE). In the present study, ginseng stem-leaf saponins (GSLS) can improve learning and memory of Alzheimer's disease patients. However, much comprehensive information regarding AChE inhibition of GSLS and its metabolites is yet unknown. OBJECTIVE: The present study aims to screen and determine the potential of AChE inhibitors (AChEIs) from GSLS. METHODOLOGY: The active fraction of the GSLS detected in vitro AChE inhibition assays was selected as a starting material for the screening of the potential of AChEIs using ultrafiltration liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (UF-LC-ESI-MS(2) ). RESULTS: The results showed that 31 ginsenosides were identified with analysis using rapid resolution liquid chromatography with a diode array detector combined with electrospray ionisation tandem mass spectrometry (RRLC-DAD-ESI-MS(2) ) from the active fraction, and there are 27 compounds with AChE binding activity. Among them, 11 ginsenosides were evaluated and confirmed using in vitro enzymatic assay, and ginsenosides F1 , Rd, Rk3 , 20(S)-Rg3 , F2 and Rb2 were found to possess strong AChE inhibitory activities. CONCLUSION: The proposed UF-LC-ESI-MS(2) method was a powerful tool for the discovery of AChEIs from traditional Chinese medicine (TCM).
ESTHER : Yang_2019_Phytochem.Anal_30_26
PubMedSearch : Yang_2019_Phytochem.Anal_30_26
PubMedID: 30159954

Title : Lipase member H is a downstream molecular target of hypoxia inducible factor-1alpha and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines - Li_2019_Cancer.Manag.Res_11_931
Author(s) : Li Y , Zhou X , Zhang Q , Chen E , Sun Y , Ye D , Wang O , Zhang X , Lyu J
Ref : Cancer Manag Res , 11 :931 , 2019
Abstract : Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. Materials and methods: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. Results: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial-mesenchymal transition pathway in PTC. Conclusion: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future.
ESTHER : Li_2019_Cancer.Manag.Res_11_931
PubMedSearch : Li_2019_Cancer.Manag.Res_11_931
PubMedID: 30774423

Title : Effects of acute and chronic exposures of fluoxetine on the Chinese fish, topmouth gudgeon Pseudorasbora parva - Chen_2018_Ecotoxicol.Environ.Saf_160_104
Author(s) : Chen H , Zeng X , Mu L , Hou L , Yang B , Zhao J , Schlenk D , Dong W , Xie L , Zhang Q
Ref : Ecotoxicology & Environmental Safety , 160 :104 , 2018
Abstract : Fluoxetine is a selective serotonin reuptake inhibitor used as an antidepressant and has been frequently detected in aquatic environments. However, its effects in fish from Asia remain relatively less studied. In this study, the topmouth gudgeon Pseudorasbora parva was exposed to 0, 50, and 200microg/L of fluoxetine for 4h and 42 d. The effects of fluoxetine on biometrics were compared to biochemical endpoints indicative of stress in different fish tissues (brain, liver, gills and intestine) following exposures. In fish exposed for 42 d, lipid peroxidation endpoints were enhanced 80% in the liver and gills. Acetylcholinesterase (AChE) activity was increased 40% after exposure to 50microg/L and 55% at 200microg/L following 4h exposure. In contrast AChE was increased 26% (at 50microg/L) after 42 d of exposures. Enhanced ethoxyresorufin-O-deethylase activity (EROD) was detected only in fish exposed to 50microg/L of fluoxetine for 4h. The activity of alpha-glucosidase (alpha-Glu) was also induced (at 200microg/L) after 4h of exposure. After 4h of exposure, the activities of proteases in the intestine were generally inhibited at 200microg/L. Both 4h and 42 d exposures resulted in an increased hepatosomatic index (HSI) but did not affect the condition factor (CF). Our results demonstrate that fluoxetine significantly altered biochemical endpoints in P. parva after acute exposure and the morphological changes in liver size were not observed until 42d of exposure.
ESTHER : Chen_2018_Ecotoxicol.Environ.Saf_160_104
PubMedSearch : Chen_2018_Ecotoxicol.Environ.Saf_160_104
PubMedID: 29793199

Title : A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3 - Zhang_2018_Biomed.Res.Int_2018_3109251
Author(s) : Zhang Q , Xiao X , Zheng J , Li M , Yu M , Ping F , Wang T , Wang X
Ref : Biomed Res Int , 2018 :3109251 , 2018
Abstract : The collected data have revealed the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the vascular endothelium, including vildagliptin. However, the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats were randomly divided into the following four groups: control, diabetic, diabetic + low-dose vildagliptin (10 mg/kg/d), and diabetic + high-dose vildagliptin (20 mg/kg/d). The diabetic model was created by feeding a high-fat diet for four weeks and injection of streptozotocin. Then, vildagliptin groups were given oral vildagliptin for twelve weeks, and the control and diabetic groups were given the same volume of saline. The metabolic parameters, endothelial function, and whole genome expression in the aorta were examined. After 12 weeks of treatment, vildagliptin groups showed significantly reduced blood glucose, blood total cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may inhibit angiopoietin-like 3 (Angptl3) and betaine-homocysteine S-methyltransferase (Bhmt) expression and activated paraoxonase-1 (Pon1) in the aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway of vildagliptin in vivo.
ESTHER : Zhang_2018_Biomed.Res.Int_2018_3109251
PubMedSearch : Zhang_2018_Biomed.Res.Int_2018_3109251
PubMedID: 29951533

Title : Insecticidal Mechanism of Wintergreen Oil Against the Health Pest Paederus fuscipes (Coleoptera: Staphylinidae) - Liu_2018_J.Med.Entomol_55_155
Author(s) : Liu Z , Zhang Q , Wu X , Yu W , Guo S
Ref : Journal of Medical Entomology , 55 :155 , 2018
Abstract : Paederus fuscipes, a health pest, causes dermatitis linearis in humans. Wintergreen oil exhibits optimal insecticidal activity against P. fuscipes. However, the insecticidal mechanism remains unclear not only in P. fuscipes but also in other pests. In this study, we explored the insecticidal mechanism of wintergreen oil in terms of its effect on the activity of acetylcholinesterase (AChE) enzyme and detoxifying enzymes (carboxylesterase, glutathione-S-transferase, and mixed function oxidase); such effect was studied by fumigation both in vivo and in vitro in P. fuscipes male and female adults. In the in vivo and in vitro experiments on male and female adults, wintergreen oil did not significantly affect the activities of the three detoxifying enzymes. Hence, the mode of action of wintergreen oil may be unrelated to the three detoxifying enzymes. Wintergreen oil significantly inhibited AChE activity. When wintergreen oil was tested at different times in vivo, the highest inhibition rates were 41.99% (male) and 40.91% (female). When different doses of wintergreen oil were used for in vivo treatment, the highest inhibition rates were 33.78% (male) and 43.33% (female). When wintergreen oil was tested in vitro, the highest inhibition rates were 31.06% (male) and 35.57% (female). In vitro with chlorpyrifos as a positive control, the AChE activity of 3-mul wintergreen oil treatment was significantly lower than that of 10 mg/liter chlorpyrifos in both P. fuscipes male and female adults. The results demonstrated that AChE is a potential key factor, maybe a target enzyme, in the mechanism of wintergreen oil against P. fuscipes.
ESTHER : Liu_2018_J.Med.Entomol_55_155
PubMedSearch : Liu_2018_J.Med.Entomol_55_155
PubMedID: 29029320

Title : Characterization, in vitro binding properties, and inhibitory activity on pancreatic lipase of beta-glucans from different Qingke (Tibetan hulless barley) cultivars - Guo_2018_Int.J.Biol.Macromol_120_2517
Author(s) : Guo H , Lin S , Lu M , Gong JDB , Wang L , Zhang Q , Lin DR , Qin W , Wu DT
Ref : Int J Biol Macromol , 120 :2517 , 2018
Abstract : In order to explore Qingke beta-glucans as functional food ingredients for prevention of obesity, the physicochemical structures, in vitro binding properties, and inhibitory activities on pancreatic lipase of beta-glucans from three different Qingke cultivars, including Ganyucang (black), Dingqing (blue), and Zangqing 320 (white), were investigated and compared. Results showed that molecular weights, particle sizes, and intrinsic viscosities of beta-glucans from colored (black and blue) Qingke cultivars were much higher than those of white Qingke beta-glucans, respectively. In addition, the constituent monosaccharides of beta-glucans from colored Qingke cultivars were determined as arabinose, xylose, glucose, and galactose, and glucose was the dominant monosaccharide. Furthermore, colored Qingke beta-glucans exerted strong fat binding, cholesterol binding, and bile-acid binding capacities, as well as inhibitory activities on pancreatic lipase, which were much higher than those of white Qingke beta-glucans. Indeed, the fat binding, cholesterol binding, and bile-acid binding capacities, as well as the inhibitory activities on pancreatic lipase of Qingke beta-glucans were positively associated with their molecular weights and intrinsic viscosities. Results are beneficial for better understanding of the structure-function relationship of Qingke beta-glucans, and beta-glucans from colored Qingke cultivars (Ganyucang and Dingqing) could be further explored as functional food ingredients for prevention of obesity.
ESTHER : Guo_2018_Int.J.Biol.Macromol_120_2517
PubMedSearch : Guo_2018_Int.J.Biol.Macromol_120_2517
PubMedID: 30195000

Title : Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum - Guo_2018_Org.Biomol.Chem_16_8130
Author(s) : Guo Y , Zhang N , Sun W , Duan X , Zhang Q , Zhou Q , Chen C , Zhu H , Luo Z , Liu J , Li XN , Xue Y , Zhang Y
Ref : Org Biomol Chem , 16 :8130 , 2018
Abstract : Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 muM) and simultaneously inhibited BACE1 (at a concentration of 5 muM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed.
ESTHER : Guo_2018_Org.Biomol.Chem_16_8130
PubMedSearch : Guo_2018_Org.Biomol.Chem_16_8130
PubMedID: 30334059

Title : Arabidopsis phospholipase Dalpha1 and Ddelta oppositely modulate EDS1- and SA-independent basal resistance against adapted powdery mildew - Zhang_2018_J.Exp.Bot_69_3675
Author(s) : Zhang Q , Berkey R , Blakeslee JJ , Lin J , Ma X , King H , Liddle A , Guo L , Munnik T , Wang X , Xiao S
Ref : J Exp Bot , 69 :3675 , 2018
Abstract : Plants use a tightly regulated immune system to fight off various pathogens. Phospholipase D (PLD) and its product, phosphatidic acid, have been shown to influence plant immunity; however, the underlying mechanisms remain unclear. Here, we show that the Arabidopsis mutants pldalpha1 and plddelta, respectively, exhibited enhanced resistance and enhanced susceptibility to both well-adapted and poorly adapted powdery mildew pathogens, and a virulent oomycete pathogen, indicating that PLDalpha1 negatively while PLDdelta positively modulates post-penetration resistance. The pldalpha1delta double mutant showed a similar infection phenotype to pldalpha1, genetically placing PLDalpha1 downstream of PLDdelta. Detailed genetic analyses of plddelta with mutations in genes for salicylic acid (SA) synthesis (SID2) and/or signaling (EDS1 and PAD4), measurement of SA and jasmonic acid (JA) levels, and expression of their respective reporter genes indicate that PLDdelta contributes to basal resistance independent of EDS1/PAD4, SA, and JAsignaling. Interestingly, while PLDalpha1-enhanced green fluorescent protein (eGFP) was mainly found in the tonoplast before and after haustorium invasion, PLDdelta-eGFP's focal accumulation to the plasma membrane around the fungal penetration site appeared to be suppressed by adapted powdery mildew. Together, our results demonstrate that PLDalpha1 and PLDdelta oppositely modulate basal, post-penetration resistance against powdery mildew through a non-canonical mechanism that is independent of EDS1/PAD4, SA, and JA.
ESTHER : Zhang_2018_J.Exp.Bot_69_3675
PubMedSearch : Zhang_2018_J.Exp.Bot_69_3675
PubMedID: 29912376

Title : VHL and Hypoxia Signaling: Beyond HIF in Cancer - Zhang_2018_Biomedicines_6_
Author(s) : Zhang J , Zhang Q
Ref : Biomedicines , 6 : , 2018
Abstract : Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor alpha (including HIF1alpha and HIF2alpha) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-kappaB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer.
ESTHER : Zhang_2018_Biomedicines_6_
PubMedSearch : Zhang_2018_Biomedicines_6_
PubMedID: 29562667

Title : A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants - Pilkington_2018_BMC.Genomics_19_257
Author(s) : Pilkington SM , Crowhurst R , Hilario E , Nardozza S , Fraser L , Peng Y , Gunaseelan K , Simpson R , Tahir J , Deroles SC , Templeton K , Luo Z , Davy M , Cheng C , McNeilage M , Scaglione D , Liu Y , Zhang Q , Datson P , De Silva N , Gardiner SE , Bassett H , Chagne D , McCallum J , Dzierzon H , Deng C , Wang YY , Barron L , Manako K , Bowen J , Foster TM , Erridge ZA , Tiffin H , Waite CN , Davies KM , Grierson EP , Laing WA , Kirk R , Chen X , Wood M , Montefiori M , Brummell DA , Schwinn KE , Catanach A , Fullerton C , Li D , Meiyalaghan S , Nieuwenhuizen N , Read N , Prakash R , Hunter D , Zhang H , McKenzie M , Knabel M , Harris A , Allan AC , Gleave A , Chen A , Janssen BJ , Plunkett B , Ampomah-Dwamena C , Voogd C , Leif D , Lafferty D , Souleyre EJF , Varkonyi-Gasic E , Gambi F , Hanley J , Yao JL , Cheung J , David KM , Warren B , Marsh K , Snowden KC , Lin-Wang K , Brian L , Martinez-Sanchez M , Wang M , Ileperuma N , Macnee N , Campin R , McAtee P , Drummond RSM , Espley RV , Ireland HS , Wu R , Atkinson RG , Karunairetnam S , Bulley S , Chunkath S , Hanley Z , Storey R , Thrimawithana AH , Thomson S , David C , Testolin R , Huang H , Hellens RP , Schaffer RJ
Ref : BMC Genomics , 19 :257 , 2018
Abstract : BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.
ESTHER : Pilkington_2018_BMC.Genomics_19_257
PubMedSearch : Pilkington_2018_BMC.Genomics_19_257
PubMedID: 29661190
Gene_locus related to this paper: actde-CXE3 , actde-CXE5 , actch-a0a2r6p9v4 , actch-a0a2r6phk8 , actch-a0a2r6pty2 , actch-q0zpu6 , actcc-a0a2r6q553 , actcc-a0a2r6quq2 , actcc-a0a2r6q2m9 , actcc-a0a2r6q2n7 , actcc-a0a2r6ru97 , actcc-a0a2r6r3e8 , actcc-a0a2r6qy24 , actcc-a0a2r6pzy5 , actcc-a0a2r6p5n3 , actcc-a0a2r6qdp0 , actcc-a0a2r6qgs9

Title : Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane - Wang_2018_Phys.Chem.Chem.Phys_20_20540
Author(s) : Wang J , Tang X , Li Y , Zhang R , Zhu L , Chen J , Sun Y , Zhang Q , Wang W
Ref : Phys Chem Chem Phys , 20 :20540 , 2018
Abstract : The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts.
ESTHER : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedSearch : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedID: 30051124

Title : Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing acetylcholinesterase activity and its inhibitors - Zhang_2018_Talanta_183_258
Author(s) : Zhang Q , Hu Y , Wu D , Ma S , Wang J , Rao J , Xu L , Xu H , Shao H , Guo Z , Wang S
Ref : Talanta , 183 :258 , 2018
Abstract : A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine-Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking nanowire, was constructed to detect acetylcholinesterase (AChE) activity and screen its inhibitors. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce hydrogen peroxide (H2O2), thus L-Cys-Ag(I) CP possesses the electro-catalytic property to H2O2 reduction. Herein, the protein-mimicking nanowire-based platform was capable of investigating successive of H2O2 effectively by amperometric i-t (current-time) response, and was further applied for the turn-on electrochemical detection of AChE activity. The proposed sensor is highly sensitive (limit of detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The model for AChE inhibition was further established and two traditional AChE inhibitors (donepezil and tacrine) were employed to verify the feasibility of the system. The IC50 of donepezil and tacrine were estimated to be 1.4nM and 3.5nM, respectively. The developed protocol provides a new and promising platform for probing AChE activity and screening its inhibitors with low cost, high sensitivity and selectivity.
ESTHER : Zhang_2018_Talanta_183_258
PubMedSearch : Zhang_2018_Talanta_183_258
PubMedID: 29567174

Title : Duplication of a Pks gene cluster and subsequent functional diversification facilitate environmental adaptation in Metarhizium species - Zeng_2018_PLoS.Genet_14_e1007472
Author(s) : Zeng G , Zhang P , Zhang Q , Zhao H , Li Z , Zhang X , Wang C , Yin WB , Fang W
Ref : PLoS Genet , 14 :e1007472 , 2018
Abstract : The ecological importance of the duplication and diversification of gene clusters that synthesize secondary metabolites in fungi remains poorly understood. Here, we demonstrated that the duplication and subsequent diversification of a gene cluster produced two polyketide synthase gene clusters in the cosmopolitan fungal genus Metarhizium. Diversification occurred in the promoter regions and the exon-intron structures of the two Pks paralogs (Pks1 and Pks2). These two Pks genes have distinct expression patterns, with Pks1 highly expressed during conidiation and Pks2 highly expressed during infection. Different upstream signaling pathways were found to regulate the two Pks genes. Pks1 is positively regulated by Hog1-MAPK, Slt2-MAPK and Mr-OPY2, while Pks2 is positively regulated by Fus3-MAPK and negatively regulated by Mr-OPY2. Pks1 and Pks2 have been subjected to positive selection and synthesize different secondary metabolites. PKS1 is involved in synthesis of an anthraquinone derivative, and contributes to conidial pigmentation, which plays an important role in fungal tolerance to UV radiation and extreme temperatures. Disruption of the Pks2 gene delayed formation of infectious structures and increased the time taken to kill insects, indicating that Pks2 contributes to pathogenesis. Thus, the duplication of a Pks gene cluster and its subsequent functional diversification has increased the adaptive flexibility of Metarhizium species.
ESTHER : Zeng_2018_PLoS.Genet_14_e1007472
PubMedSearch : Zeng_2018_PLoS.Genet_14_e1007472
PubMedID: 29958281
Gene_locus related to this paper: metaq-pks1 , metra-pks2 , metmf-pks2 , metaf-pks1 , metbs-pks2 , metas-pks1 , metaq-pks2

Title : Enzymatic synthesis of lysophosphatidylcholine with n-3 polyunsaturated fatty acid from sn-glycero-3-phosphatidylcholine in a solvent-free system - Liu_2017_Food.Chem_226_165
Author(s) : Liu Y , Zhang Q , Guo Y , Liu J , Xu J , Li Z , Wang J , Wang Y , Xue C
Ref : Food Chem , 226 :165 , 2017
Abstract : The n-3 polyunsaturated fatty acids (PUFA)-rich lysophosphatidylcholine (LPC) was successfully synthesized by Thermomyces lanuginosus lipase (TL IM)-catalyzed esterification of glycerylphosphorylcholine (GPC) and n-3 PUFA-rich fatty acids in a solvent-free system. Effects of reaction temperature, enzyme loading and substrate mole ratio on the yield of LPC and incorporation of n-3 PUFA were evaluated. The acyl-specificities of five enzymes were tested for direct esterification of n-3 PUFA, and Lipozyme TL IM was found to be more effective than others for production of LPC with n-3 PUFA. Substrate mole ratio and reaction temperature, however, had no significant effect on the incorporation. The maximal yield of LPC was obtained under the following conditions: temperature 45 degC, enzyme loading 15% by weight and substrate mole ratio (GPC/n-3 PUFA) 1:20. Furthermore, the composition of products were further investigated in the study. The 1-acyl-sn-glycero-3-lysophosphatidylcholine (2-LPC) was predominant in the mixtures at early stages of reaction, whereas less increment of 2-acyl-sn-glycero-3-lysophosphatidylcholine (1-LPC) and PC was observed at later stages.
ESTHER : Liu_2017_Food.Chem_226_165
PubMedSearch : Liu_2017_Food.Chem_226_165
PubMedID: 28254008

Title : Enantioselectivity of haloalkane dehalogenase LinB on the degradation of 1,2-dichloropropane: A QM\/MM study - Tang_2017_Bioorg.Chem_73_16
Author(s) : Tang X , Zhang R , Li Y , Zhang Q , Wang W
Ref : Bioorg Chem , 73 :16 , 2017
Abstract : The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8kcal/mol for the (R)-isomer and 24.0kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP.
ESTHER : Tang_2017_Bioorg.Chem_73_16
PubMedSearch : Tang_2017_Bioorg.Chem_73_16
PubMedID: 28527381

Title : Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells - Yang_2017_Mol.Neurobiol_54_788
Author(s) : Yang H , Liu C , Chen B , An J , Zhang R , Zhang Q , Zhao J , He B , Hao DJ
Ref : Molecular Neurobiology , 54 :788 , 2017
Abstract : Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration medicine. Therefore, it is essential to establish a suitable cell reservoir as an issue-free alternative. Here, we demonstrate that spermatogonial stem cells (SSCs) derived from rat testis robustly give rise to terminally differentiated, functionally mature spinal cord neurons by using an optimized differentiation protocol. After performing a 3-week in vitro differentiation procedure, most cells exhibited neural morphological features and were Tuj-1 positive. Of note, approximately 60 % of the obtained cells coexpressed choline acetyltransferase (CHAT), acetylcholinesterase (AchE), and calcitonin gene-related peptide (CGRP). More importantly, apart from acquisition of neural antigenic and biochemical properties, nearly all neurons efficiently exhibited in vitro functionality similar to wild-type neurons, such as synapse formation, increased neuronal calcium influx, and electrophysiology. This is the first report revealing consistent and reproducible generation of large amounts of functional neurons from SSCs. Collectively, this system is suitable for studies of SSC transdifferentiation into neuronal cells and can provide sufficient neurons for the treatment of spinal cord injury as well as for genetic and small molecule screenings.
ESTHER : Yang_2017_Mol.Neurobiol_54_788
PubMedSearch : Yang_2017_Mol.Neurobiol_54_788
PubMedID: 27566610

Title : Genome-wide identification of pathogenicity, conidiation and colony sectorization genes in Metarhizium robertsii - Zeng_2017_Environ.Microbiol_19_3896
Author(s) : Zeng G , Chen X , Zhang X , Zhang Q , Xu C , Mi W , Guo N , Zhao H , You Y , Dryburgh FJ , Bidochka MJ , St Leger RJ , Zhang L , Fang W
Ref : Environ Microbiol , 19 :3896 , 2017
Abstract : Metarhizium robertsii occupies a wide array of ecological niches and has diverse lifestyle options (saprophyte, insect pathogen and plant symbiont), that renders it an unusually effective model for studying genetic mechanisms for fungal adaptation. Here over 20,000 M. robertsii T-DNA mutants were screened in order to elucidate genetic mechanism by which M. robertsii replicates and persists in diverse niches. About 287 conidiation, colony sectorization or pathogenicity loci, many of which have not been reported in other fungi were identified. By analysing a series of conidial pigmentation mutants, a new fungal pigmentation gene cluster, which contains Mr-Pks1, Mr-EthD and Mlac1 was identified. A conserved conidiation regulatory pathway containing Mr-BrlA, Mr-AbaA and Mr-WetA regulates expression of these pigmentation genes. During conidiation Mr-BlrA up-regulates Mr-AbaA, which in turn controls Mr-WetA. It was found that Hog1-MAPK regulates fungal conidiation by controlling the conidiation regulatory pathway, and that all three pigmentation genes exercise feedback regulation of conidiation. This work provided the foundation for deeper understanding of the genetic processes behind M. robertsii adaptive phenotypes, and advances our insights into conidiation and pigmentation in this fungus.
ESTHER : Zeng_2017_Environ.Microbiol_19_3896
PubMedSearch : Zeng_2017_Environ.Microbiol_19_3896
PubMedID: 28447400
Gene_locus related to this paper: metaf-pks1

Title : Neuroprotective Effects of Acetylcholinesterase Inhibitory Peptides from Anchovy (Coilia mystus) against Glutamate-Induced Toxicity in PC12 Cells - Zhao_2017_J.Agric.Food.Chem_65_11192
Author(s) : Zhao T , Su G , Wang S , Zhang Q , Zhang J , Zheng L , Sun B , Zhao M
Ref : Journal of Agricultural and Food Chemistry , 65 :11192 , 2017
Abstract : Ameliorations of cholinergic system dysfunction and oxidative stress in neurodegenerative diseases were main approaches to improve memory disorder. Our previous investigation showed that anchovy protein hydrolysate (APH) could attenuate scopolamine-induced memory deficits in mice by regulating acetylcholinesterase (AChE) activity. Therefore, peptides with AChE inhibitory activity in APH were explored and identified in this study, and their possible neuroprotective mechanisms on glutamate induced apoptosis in PC12 were also elucidated. Two peptides with strong AChE inhibitory capacity were identified as Pro-Ala-Tyr-Cys-Ser (PAYCS) and Cys-Val-Gly-Ser-Tyr (CVGSY) by ultraperformance liquid chromatography coupled with tandem mass spectrometry. The AChE inhibitory was 23.68 +/- 0.97% and 6.08 +/- 0.41%, respectively. Treatment with PAYCS and CVGSY could significantly (p < 0.05) increase cells viability, reduce lactate dehydrogenase release, reactive oxygen species (ROS) production, malondialdehyde content, and the ratio of Bax/Bcl-2 of glutamate-induced apoptosis PC12 cells (82.78 +/- 6.58 and 109.94 +/- 7.16% of control, respectively) as well as increase superoxide dismutase and GSH-px activities. In addition, both the peptides could inhibit Ca(2+) influx but have no effects on mitochondrial membrane potential. Results indicated that AChE inhibitory peptides (PAYCS and CVGSY) possibly protected the PC12 cells against glutamate-induced apoptosis via inhibiting ROS production and Ca(2+) influx. PAYCS and CVGSY might be considered as nutraceuticals for alleviating memory deficits.
ESTHER : Zhao_2017_J.Agric.Food.Chem_65_11192
PubMedSearch : Zhao_2017_J.Agric.Food.Chem_65_11192
PubMedID: 29190426

Title : Down-regulation of fibronectin and the correlated expression of neuroligin in hirschsprung disease - Zheng_2017_Neurogastroenterol.Motil_29_
Author(s) : Zheng Y , Lv X , Wang D , Gao N , Zhang Q , Li A
Ref : Neurogastroenterol Motil , 29 : , 2017
Abstract : AIM: The goal of this study was to investigate the expression of fibronectin (FN) and the correlated abundance of neuroligins (NLs) in the enteric nervous system (ENS) and to find a novel diagnostic marker in the serum of Hirschsprung disease (HSCR) patients. METHODS: The expression levels of FN, neuroligin-1 and neuroligin-2 were detected in 114 children with or without HSCR. The expression and localization of the NLs and FN were assessed morphologically by immunohistochemical staining. Western blot analysis and real-time fluorescence quantitative PCR (qPCR) were performed to examine the correlated expression of the NLs and FN in aganglionic, transitional, and normal ganglionic colon tissues. An enzyme-linked immunosorbent assay (ELISA) was performed to evaluate and compare serum FN levels between HSCR and non-HSCRand between long-type HSCR and short-type HSCR. RESULTS: These studies showed that both neuroligin-1 and neuroligin-2 were expressed at low levels in aganglionic segments and at intermediate levels in transitional segments compared to their high level of expression in normal tissue. In contrast, FN expression was negatively correlated, with expression in these three samples transitioning from highest to lowest. The serum FN level was higher in HSCR than in non-HSCR, but no significant difference between short-type HSCR and long-type HSCR was observed. CONCLUSION: FN affects the expression of both neuroligin-1 and neuroligin-2 in HSCR, which may lead to the hypoplasia of ganglion cells in the ENS. This correlation may play a key role in the pathogenesis, diagnosis, or classification of HSCR.
ESTHER : Zheng_2017_Neurogastroenterol.Motil_29_
PubMedSearch : Zheng_2017_Neurogastroenterol.Motil_29_
PubMedID: 28656720

Title : Organophosphate esters in sediment cores from coastal Laizhou Bay of the Bohai Sea, China - Wang_2017_Sci.Total.Environ_607-608_103
Author(s) : Wang Y , Wu X , Zhang Q , Hou M , Zhao H , Xie Q , Du J , Chen J
Ref : Sci Total Environ , 607-608 :103 , 2017
Abstract : Concentrations and vertical distributions of organophosphate esters (OPEs) were investigated in the sediment cores collected from the Laizhou Bay, Bohai Sea of China. The total concentrations of OPEs in the sediment core (CA) collected near the Yellow River Estuary were in the range of 11.8-102ng/g, while the total concentrations in the sediment core (CB) near a mariculture area were 6.65-41.5ng/g. Significantly high concentrations of OPEs were found in the sediments near the Yellow River Estuary than those in the mariculture area. Vertical distributions in the sediment cores demonstrated a recent increase of OPE emissions, especially for tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), and tris (2-chloroisopropyl) phosphate (TCPP). Generally, TCEP and TCPP were the dominant congeners in the sediment cores, while the profiles of TnBP were increase in the surface 0-20cm layers of the CA core. OPEs in the CA core may be remarkably influenced by the discharge of Yellow River, whereas OPEs in the CB core may originate from the transport through seawater. The remarkable increase of OPE flame retardants in the surface sediments raises the concern about their emissions and risks to the environment and indicates the need for further monitoring.
ESTHER : Wang_2017_Sci.Total.Environ_607-608_103
PubMedSearch : Wang_2017_Sci.Total.Environ_607-608_103
PubMedID: 28688252

Title : Abundance and Significance of Neuroligin-1 and Neurexin II in the Enteric Nervous System of Embryonic Rats - Wang_2017_Biomed.Res.Int_2017_1209360
Author(s) : Wang D , Pan J , Song G , Gao N , Zheng Y , Zhang Q , Li A
Ref : Biomed Res Int , 2017 :1209360 , 2017
Abstract : Aim. To investigate the abundance of neuroligin-1 and neurexin II in the enteric nervous system (ENS) of rats on different embryonic days and to explore their potential significance. Methods. The full-thickness colon specimens proximal to the ileocecal junction of rats on embryonic days 16, 18, and 20 and of newborns within 24 hours (E16, E18, E20, and Ep0) were studied, respectively. qRT-PCR was applied for detecting the expressions of neuroligin-1 and neurexin II on mRNA, and western blotting was employed for detecting their further expressions on the whole tissue. Finally, the histological appearance of neuroligin-1 and neurexin IIalpha was elucidated using immunohistochemical staining. Results. qRT-PCR showed that the neuroligin-1 and neurexin II mRNA expressions of groups E16, E18, E20, and Ep0 increased gradually with the growth of embryonic rats (P < 0.05). Western blotting confirmed the increasing tendency. In immunohistochemical staining, proteins neuroligin-1 and neurexin IIalpha positive cells concentrated mostly in the myenteric nerve plexus of the colon and their expressions depend on the embryonic time. Conclusion. Neuroligin-1 and neurexin II were both expressed in the ENS and have temporal correlation with the development of ENS, during which neuronal intestinal malformations (NIM) may occur due to their disruptions and consequent abnormal ENS development.
ESTHER : Wang_2017_Biomed.Res.Int_2017_1209360
PubMedSearch : Wang_2017_Biomed.Res.Int_2017_1209360
PubMedID: 28194405

Title : Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis - Xie_2017_J.Enzyme.Inhib.Med.Chem_32_659
Author(s) : Xie Q , Zheng Z , Shao B , Fu W , Xia Z , Li W , Sun J , Zheng W , Zhang W , Sheng W , Zhang Q , Chen H , Wang H , Qiu Z
Ref : J Enzyme Inhib Med Chem , 32 :659 , 2017
Abstract : Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer's disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (-)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC50 31.6 nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-beta (Abeta) lowering effects (51.9% decrease of Abeta42) superior to phenserine (31% decrease of total Abeta) in SH-SY5Y-APP695 cells at 50 microM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents.
ESTHER : Xie_2017_J.Enzyme.Inhib.Med.Chem_32_659
PubMedSearch : Xie_2017_J.Enzyme.Inhib.Med.Chem_32_659
PubMedID: 28274151

Title : MAPK cascade-mediated regulation of pathogenicity, conidiation and tolerance to abiotic stresses in the entomopathogenic fungus Metarhizium robertsii - Chen_2016_Environ.Microbiol_18_1048
Author(s) : Chen X , Xu C , Qian Y , Liu R , Zhang Q , Zeng G , Zhang X , Zhao H , Fang W
Ref : Environ Microbiol , 18 :1048 , 2016
Abstract : Metarhizium robertsii has been used as a model to study fungal pathogenesis in insects, and its pathogenicity has many parallels with plant and mammal pathogenic fungi. MAPK (Mitogen-activated protein kinase) cascades play pivotal roles in cellular regulation in fungi, but their functions have not been characterized in M. robertsii. In this study, we identified the full complement of MAPK cascade components in M. robertsii and dissected their regulatory roles in pathogenesis, conidiation and stress tolerance. The nine components of the Fus3, Hog1 and Slt2-MAPK cascades are all involved in conidiation. The Fus3- and Hog1-MAPK cascades are necessary for tolerance to hyperosmotic stress, and the Slt2- and Fus3-MAPK cascades both mediate cell wall integrity. The Hog1 and Slt2-MAPK cascades contribute to pathogenicity; the Fus3-MAPK cascade is indispensable for fungal pathogenesis. During its life cycle, M. robertsii experiences multiple microenvironments as it transverses the cuticle into the haemocoel. RNA-seq analysis revealed that MAPK cascades collectively play a major role in regulating the adaptation of M. robertsii to the microenvironmental change from the cuticle to the haemolymph. The three MAPKs each regulate their own distinctive subset of genes during penetration of the cuticle and haemocoel colonization, but they function redundantly to regulate adaptation to microenvironmental change.
ESTHER : Chen_2016_Environ.Microbiol_18_1048
PubMedSearch : Chen_2016_Environ.Microbiol_18_1048
PubMedID: 26714892
Gene_locus related to this paper: metra-pks2

Title : Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans - Wang_2016_Biopharm.Drug.Dispos_37_93
Author(s) : Wang H , Rangan VS , Sung MC , Passmore D , Kempe T , Wang X , Thevanayagam L , Pan C , Rao C , Srinivasan M , Zhang Q , Gangwar S , Deshpande S , Cardarelli P , Marathe P , Yang Z
Ref : Biopharmaceutics & Drug Disposition , 37 :93 , 2016
Abstract : CD70 is a tumor necrosis factor (TNF)-like type II integral membrane protein that is transiently expressed on activated T- and B-lymphocytes. Aberrant expression of CD70 was identified in both solid tumors and haematologic malignancies. BMS-936561 (alphaCD70_MED-A) is an antibody-drug conjugate composed of a fully human anti-CD70 monoclonal antibody (alphaCD70) conjugated with a duocarmycin derivative, MED-A, through a maleimide-containing citrulline-valine dipeptide linker. MED-A is a carbamate prodrug that is activated by carboxylesterase to its active form, MED-B, to exert its DNA alkylation activity. In vitro serum stability studies suggested the efficiencies of hydrolyzing the carbamate-protecting group in alphaCD70_MED-A followed a rank order of mouse > rat > > monkey > dog ~ human. Pharmacokinetics of alphaCD70_MED-A was evaluated in mice, monkeys, and dogs after single intravenous doses. In mice, alphaCD70_MED-A was cleared rapidly, with no detectable exposures after 15 min following dosing. In contrast, alphaCD70_MED-A was much more stable in monkeys and dogs. The clearance of alphaCD70_MED-A in monkeys was 58 mL/d/kg, ~2-fold faster than that in dogs (31 mL/d/kg). The human PK profiles of the total alphaCD70 and alphaCD70_MED-A were predicted using allometrically scaled monkeys PK parameters of alphaCD70 and the carbamate hydrolysis rate constant estimated in dogs. Comparing the predicted and observed human PK from the phase I study, the dose-normalized concentration-time profiles of alphaCD70_MED-A and the total alphaCD70 were largely within the 5(th) -95(th) percentile of the predicted profiles. Copyright (c) 2015 John Wiley & Sons, Ltd.
ESTHER : Wang_2016_Biopharm.Drug.Dispos_37_93
PubMedSearch : Wang_2016_Biopharm.Drug.Dispos_37_93
PubMedID: 25869904

Title : Artificial hydrolase based on carbon nanotubes conjugated with peptides - Zhang_2016_Nanoscale_8_16851
Author(s) : Zhang Q , He X , Han A , Tu Q , Fang G , Liu J , Wang S , Li H
Ref : Nanoscale , 8 :16851 , 2016
Abstract : An artificial enzyme was constructed by attaching short peptides with active sites (SHELKLKLKL, WLKLKLKL) onto carbon nanotubes (CNT). It was found that the combination of SHE amino acids was essential to form a catalytic triad. W was also incorporated into this artificial enzyme and acted as a substrate binding site, thus producing an enzyme model with synergism of 67.7% catalytic groups and 32.3% binding groups, CNT-(SHE/W)2:1-LKLKLKL. When the peptide SHELKLKLKL was attached with the catalytic triad site close to the surface of CNT, the composite had higher activity than a leucine-attached system terminated with the catalytic triad site, suggesting that CNT not only served as a platform for attaching active amino acids, but also created a hydrophobic microenvironment and facilitated the proton transfer process to enhance the catalytic activity. The artificial enzyme exhibited Michaelis-Menten behaviour, indicating that it was indeed a mimic of the corresponding natural enzyme. This work showed that a well-designed combination of CNT and short peptides containing active sites can mimic a natural enzyme.
ESTHER : Zhang_2016_Nanoscale_8_16851
PubMedSearch : Zhang_2016_Nanoscale_8_16851
PubMedID: 27714071

Title : Postconditioning with sevoflurane ameliorates spatial learning and memory deficit after hemorrhage shock and resuscitation in rats - Hu_2016_J.Surg.Res_206_307
Author(s) : Hu X , Wang J , Zhang Q , Duan X , Chen Z , Zhang Y
Ref : J Surg Res , 206 :307 , 2016
Abstract : BACKGROUND: Severe hemorrhage shock and resuscitation are a systemic ischemia-reperfusion phenomenon which can induce learning and memory deficit in human and rats. Sevoflurane postconditioning has been proved to offer neuroprotection under different setting of cerebral ischemia-reperfusion in rats. The aim of this study was to investigate whether sevoflurane postconditioning could improve spatial learning and memory ability after hemorrhage shock and resuscitation in rats.
METHODS: Thirty-five male rats were randomized into five groups: sham group, shock group, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%), and high concentration (sevo3, 3.6%) of sevoflurane postconditioning groups. The spatial learning and memory ability of rats were measured by Morris water maze 3 d after the operation. The expression of choline acetyltransferase (CHAT) and acetylcholinesterase (ACHE) in the hippocampus CA1 region was observed by immunohistochemistry method after the Morris water maze test.
RESULTS: The ability of spatial learning and memory of rats and the expression of CHAT was significantly declined, while the expression of ACHE increased in the shock group compared with the sham group (P < 0.05). Sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability and increased the expression of CHAT and decreased the expression of ACHE in hippocampal CA1 region when compared with shock group (P < 0.05).
CONCLUSIONS: Postconditioning with sevoflurane at the concentrations of 2.4% and 3.6% which improved the ability of spatial learning and memory after hemorrhage shock and resuscitation in rats may involve the protection of the cholinergic neurons in hippocampal CA1 region.
ESTHER : Hu_2016_J.Surg.Res_206_307
PubMedSearch : Hu_2016_J.Surg.Res_206_307
PubMedID: 27884324

Title : Optimization of Fermentation Medium for Extracellular Lipase Production from Aspergillus niger Using Response Surface Methodology - Jia_2015_Biomed.Res.Int_2015_497462
Author(s) : Jia J , Yang X , Wu Z , Zhang Q , Lin Z , Guo H , Lin CS , Wang J , Wang Y
Ref : Biomed Res Int , 2015 :497462 , 2015
Abstract : Lipase produced by Aspergillus niger is widely used in various industries. In this study, extracellular lipase production from an industrial producing strain of A. niger was improved by medium optimization. The secondary carbon source, nitrogen source, and lipid were found to be the three most influential factors for lipase production by single-factor experiments. According to the statistical approach, the optimum values of three most influential parameters were determined: 10.5 g/L corn starch, 35.4 g/L soybean meal, and 10.9 g/L soybean oil. Using this optimum medium, the best lipase activity was obtained at 2,171 U/mL, which was 16.4% higher than using the initial medium. All these results confirmed the validity of the model. Furthermore, results of the Box-Behnken Design and quadratic models analysis indicated that the carbon to nitrogen (C/N) ratio significantly influenced the enzyme production, which also suggested that more attention should be paid to the C/N ratio for the optimization of enzyme production.
ESTHER : Jia_2015_Biomed.Res.Int_2015_497462
PubMedSearch : Jia_2015_Biomed.Res.Int_2015_497462
PubMedID: 26366414

Title : Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis - He_2015_Clin.Sci.(Lond)_129_49
Author(s) : He T , Hu J , Yan G , Li L , Zhang D , Zhang Q , Chen B , Huang Y
Ref : Clinical Science (Lond) , 129 :49 , 2015
Abstract : The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis.
ESTHER : He_2015_Clin.Sci.(Lond)_129_49
PubMedSearch : He_2015_Clin.Sci.(Lond)_129_49
PubMedID: 25700221

Title : Surface display of the thermophilic lipase Tm1350 on the spore of Bacillus subtilis by the CotB anchor protein - Chen_2015_Extremophiles_19_799
Author(s) : Chen H , Tian R , Ni Z , Zhang Q , Zhang T , Chen Z , Chen K , Yang S
Ref : Extremophiles , 19 :799 , 2015
Abstract : Lipases expressed in microbial hosts have great commercial value, but their applications are restricted by the high costs of production and harsh conditions used in industrial processes, such as high temperature and alkaline environment. In this study, an Escherichia coli-Bacillus subtilis shuttle vector (pHS-cotB-Tm1350) was constructed for the spore surface display of the lipase Tm1350 from hyperthermophilic bacterium Thermotoga maritima MSB8. Successful display of the CotB-Tm1350 fusion protein on spore surface was confirmed by Western blot analysis and activity measurements. The optimal catalytic temperature and pH of the spore surface-displayed Tm1350 were 80 degreesC and 9, respectively, which were higher than non-immobilized Tm1350 (70 degreesC and pH 7.5). Analysis of thermal and pH stability showed that spore surface-displayed Tm1350 retained 81 or 70 % of its original activity after 8 h of incubation at pH 8 or pH 9 (70 degreesC), which were 18 % higher than the retained activity of the non-immobilized Tm1350 under the same conditions. Meanwhile, recycling experiments showed that the recombinant spores could be used for up to three reaction cycles without a significant decrease in the catalytic rate (84 %). These results suggested that enzyme display on the surface of the B. subtilis spore could serve as an effective approach for enzyme immobilization, which has potential applications in the harsh biochemical industry.
ESTHER : Chen_2015_Extremophiles_19_799
PubMedSearch : Chen_2015_Extremophiles_19_799
PubMedID: 26026992

Title : Effects of electroacupuncture on recovery of the electrophysiological properties of the rabbit gastrocnemius after contusion: an in vivo animal study - Liu_2015_BMC.Complement.Altern.Med_15_69
Author(s) : Liu S , Wang R , Luo D , Xu Q , Xiao C , Lin P , Yu Z , Zhao X , Cai R , Ma J , Zhang Q , Wang Y
Ref : BMC Complement Altern Med , 15 :69 , 2015
Abstract : BACKGROUND: Our preliminary studies indicated that electroacupuncture (EA) at the ST36 and Ashi acupoints could promote regeneration of the rabbit gastrocnemius (GM) by improving microcirculation perfusion, promoting the recovery of myofiber structures, and inhibiting excessive fibrosis. However, the effects of EA on recovery of the electrophysiological properties of the GM after contusion are not yet clear. Thus, the purpose of this study was to investigate the effects of EA at the Zusanli (ST36) and Ashi acupoints with regard to recovery of the electrophysiological properties of the rabbit GM after contusion.
METHODS: Forty-five rabbits were randomly divided into three groups: normal, contusion, and EA. After an acute GM contusion was produced (in rabbits in the contusion and EA groups), rabbits in the EA group were treated with electrostimulation at the ST36 and Ashi acupoints with 0.4 mA (2 Hz) for 15 min. The contusion group received no EA treatment. At different time points (7, 14, and 28 days) after contusion, we performed surface electromyography (EMG) and measured the nerve conduction velocity (NCV) of the GM and the GM branch of the tibial nerve. We also examined acetylcholinesterase (AchE) and Agrin expression in the neuromuscular junction (NMJ) via immunohistochemistry.
RESULTS: Compared with the contusion group, the EMG amplitude and NCV in rabbits in the EA group were significantly higher at all time points after contusion. AchE and Agrin expression in the EA group were significantly higher than those in the contusion group.
CONCLUSIONS: Our results showed that EA at the ST36 and Ashi acupoints effectively promoted recovery of the electrophysiological properties of the rabbit GM after contusion. The effects of EA were realized by promotion of the regeneration of myofibers and nerve fibers, as well as acceleration of NMJ reconstruction by upregulation of AchE and Agrin expression in the motor endplate area.
ESTHER : Liu_2015_BMC.Complement.Altern.Med_15_69
PubMedSearch : Liu_2015_BMC.Complement.Altern.Med_15_69
PubMedID: 25887510

Title : Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Abeta)-induced damage in vitro and in vivo - Zhang_2015_Neurosci_305_169
Author(s) : Zhang Q , Li J , Liu C , Song C , Li P , Yin F , Xiao Y , Jiang W , Zong A , Zhang X , Wang F
Ref : Neuroscience , 305 :169 , 2015
Abstract : In the present study, we investigated the effects of low molecular weight chondroitin sulfate (LMWCS) on amyloid beta (Abeta)-induced neurotoxicity in vitro and in vivo. The in vitro results showed that LMWCS blocked Abeta25-35-induced cell viability loss and apoptosis, decreased intracellular calcium concentration, reactive oxygen species (ROS) levels, the mitochondrial membrane potential (MMP) depolarization, and the protein expression of Caspase-3. During in vivo experiments, LMWCS improved the cognitive impairment induced by Abeta1-40, increased the level of choline acetyltransferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (AChE) in the mouse brain. Moreover, LMWCS decreased the density of pyramidal cells of CA1 regions, and suppressed the protein expression of Bax/Bcl-2 and Caspase-3, -9 in the hippocampus of mice. In conclusion, LMWCS possessed neuroprotective properties against toxic effects induced by Abeta peptides both in vitro and in vivo, which might be related to anti-apoptotic activity. LMWCS might be a useful preventive and therapeutic compound for Alzheimer's disease.
ESTHER : Zhang_2015_Neurosci_305_169
PubMedSearch : Zhang_2015_Neurosci_305_169
PubMedID: 26254241

Title : Expression and Characterization of a Novel Thermo-Alkalistable Lipase from Hyperthermophilic Bacterium Thermotoga maritima - Tian_2015_Appl.Biochem.Biotechnol_176_1482
Author(s) : Tian R , Chen H , Ni Z , Zhang Q , Zhang Z , Zhang T , Zhang C , Yang S
Ref : Appl Biochem Biotechnol , 176 :1482 , 2015
Abstract : A gene coding for lipase (Tm1350) from the hyperthermophilic bacterium Thermotoga maritima MSB8 was cloned and overexpressed by Escherichia coli. The enzyme can degrade substrates with both short and long acyl chain lengths. The apparent Km and Vmax values for p-nitrophenyl butyrate were 8 mM and 333 U/mg, respectively. The enzyme displayed optimal activity at pH 7.5 and 70 degrees C, maintained 66 % of the original activity after 8 h of incubation, and its half-lives at pHs 9 and 10 were 8 and 1 h. The activity of Tm1350 was stimulated up to 131 or 151 % of the original activity by incubating with 4 M urea or 20 % (v/v) methanol, and 90.1 or 70.2 % of the activity was maintained after 8 h incubation of the enzyme in 20 or 75 % (v/v) of the methanol, showing potential for biodiesel production. The activity of the enzyme without cysteine residue was stimulated up to 618 and 550 % of the original activity by incubating with dithiothreitol (DTT) and reduced glutathione (GSH) at a concentration of 1 mM. However, the circular dichroism spectra of the enzyme have no obvious change after DTT treatment. It is speculated that DTT interacts with potential residues in some key active sites without influence of structure.
ESTHER : Tian_2015_Appl.Biochem.Biotechnol_176_1482
PubMedSearch : Tian_2015_Appl.Biochem.Biotechnol_176_1482
PubMedID: 25957275

Title : Intranasal H102 Peptide-Loaded Liposomes for Brain Delivery to Treat Alzheimer's Disease - Zheng_2015_Pharm.Res_32_3837
Author(s) : Zheng X , Shao X , Zhang C , Tan Y , Liu Q , Wan X , Zhang Q , Xu S , Jiang X
Ref : Pharm Res , 32 :3837 , 2015
Abstract : PURPOSE: H102, a novel beta-sheet breaker peptide, was encapsulated into liposomes to reduce its degradation and increase its brain penetration through intranasal administration for the treatment of Alzheimer's disease (AD).
METHODS: The H102 liposomes were prepared using a modified thin film hydration method, and their transport characteristics were tested on Calu-3 cell monolayers. The pharmacokinetics in rats' blood and brains were also investigated. Behavioral experiments were performed to evaluate the improvements on AD rats' spatial memory impairment. The neuroprotective effects were tested by detecting acetylcholinesterase (AchE), choline acetyltransferase (ChAT) and insulin degrading enzyme (IDE) activity and conducting histological assays. The safety was evaluated on rats' nasal mucosa and cilia.
RESULTS: The liposomes prepared could penetrate Calu-3 cell monolayers consistently. After intranasal administration, H102 could be effectively delivered to the brain, and the AUC of H102 liposomes in the hippocampus was 2.92-fold larger than that of solution group. H102 liposomes could excellently ameliorate spatial memory impairment of AD model rats, increase the activities of ChAT and IDE and inhibit plaque deposition, even in a lower dosage compared with H102 intranasal solution. H102 nasal formulations showed no toxicity on nasal mucosa.
CONCLUSIONS: The H102-loaded liposome prepared in this study for nasal administration is stable, effective and safe, which has great potential for AD treatment.
ESTHER : Zheng_2015_Pharm.Res_32_3837
PubMedSearch : Zheng_2015_Pharm.Res_32_3837
PubMedID: 26113236

Title : Expression, purification and characterization of a functional, recombinant, cold-active lipase (LipA) from psychrotrophic Yersinia enterocolitica - Ji_2015_Protein.Expr.Purif_115_125
Author(s) : Ji X , Li S , Wang B , Zhang Q , Lin L , Dong Z , Wei Y
Ref : Protein Expr Purif , 115 :125 , 2015
Abstract : A novel cold-active lipase gene encoding 294 amino acid residues was obtained from the Yersinia enterocolitica strain KM1. Sequence alignment and phylogenetic analysis revealed that this novel lipase is a new member of the bacterial lipase family I.1. The lipase shares the conserved GXSXG motif and catalytic triad Ser85-Asp239-His261. The recombinant protein LipA was solubly and heterogeneously expressed in Escherichia coli, purified by Ni-affinity chromatography, and then characterized. LipA was active over a broad range spanning 15-60 degrees C with an optimum activity at 25 degrees C and across a wide pH range from 5.0 to 11.0 with an optimum activity at pH 7.5. The molecular weight was estimated to be 34.2KDa. The lipase could be activated by Mg(2+) and a low concentration (10%) of ethanol, dimethyl sulfoxide, methanol and acetonitrile, whereas it was strongly inhibited by Zn(2+), Cu(2+) and Mn(2+). This cold-active lipase may be a good candidate for detergents and biocatalysts at low temperature.
ESTHER : Ji_2015_Protein.Expr.Purif_115_125
PubMedSearch : Ji_2015_Protein.Expr.Purif_115_125
PubMedID: 26256062

Title : Purification and characterization of a hydrolysis-resistant lipase from Aspergillus terreus - Shi_2014_Biotechnol.Appl.Biochem_61_165
Author(s) : Shi H , Meng Y , Yang M , Zhang Q
Ref : Biotechnol Appl Biochem , 61 :165 , 2014
Abstract : Lipase from Aspergillus terreus was purified to homogeneity using ammonium sulfate precipitation and chromatographies with Q-Sepharose and Sephacryl S-200. It showed a single band on SDS-PAGE and IEF-PAGE with a relative molecular mass of 37.2 kDa and pI of 3.2. Its glycoprotein nature was confirmed with the percentage of saccharides of 5.02% and 3.88% determined by the phenol/sulfuric acid and anthrone/ sulfuric acid methods, respectively. The lipase hydrolyzed both plant oils and animal oils, with the K(m) value for substrate p-NPP of 16.42 mM at pH 6.0, 50 degrees C. The enzyme was tolerant in a wide range of pH (pH 3-12) with optimum activity at pH 4.0. It remained stable under the highest temperature of 65 degrees C, with maximal activity at 50 degrees C. Ca(2)(+), Co(2)(+), Mn(2)(+), and Ni(2)(+) stimulated enzyme activity, but Hg(2)(+) caused inhibition. Detected detergents had no obvious effect on enzyme activity, except SDS, which stimulated the activity at lower concentrations but inhibited the activity at higher concentrations. The inhibitory effect on enzyme activity of phenylmethanesulfonyl fluoride revealed that the Ser was involved in catalysis. Saccharides had no obvious effect on enzyme activity but could enhance its thermostability. Furthermore, the enzyme was resistant to trypsin digestion.
ESTHER : Shi_2014_Biotechnol.Appl.Biochem_61_165
PubMedSearch : Shi_2014_Biotechnol.Appl.Biochem_61_165
PubMedID: 23855368

Title : The coffee genome provides insight into the convergent evolution of caffeine biosynthesis - Denoeud_2014_Science_345_1181
Author(s) : Denoeud F , Carretero-Paulet L , Dereeper A , Droc G , Guyot R , Pietrella M , Zheng C , Alberti A , Anthony F , Aprea G , Aury JM , Bento P , Bernard M , Bocs S , Campa C , Cenci A , Combes MC , Crouzillat D , Da Silva C , Daddiego L , De Bellis F , Dussert S , Garsmeur O , Gayraud T , Guignon V , Jahn K , Jamilloux V , Joet T , Labadie K , Lan T , Leclercq J , Lepelley M , Leroy T , Li LT , Librado P , Lopez L , Munoz A , Noel B , Pallavicini A , Perrotta G , Poncet V , Pot D , Priyono , Rigoreau M , Rouard M , Rozas J , Tranchant-Dubreuil C , VanBuren R , Zhang Q , Andrade AC , Argout X , Bertrand B , de Kochko A , Graziosi G , Henry RJ , Jayarama , Ming R , Nagai C , Rounsley S , Sankoff D , Giuliano G , Albert VA , Wincker P , Lashermes P
Ref : Science , 345 :1181 , 2014
Abstract : Coffee is a valuable beverage crop due to its characteristic flavor, aroma, and the stimulating effects of caffeine. We generated a high-quality draft genome of the species Coffea canephora, which displays a conserved chromosomal gene order among asterid angiosperms. Although it shows no sign of the whole-genome triplication identified in Solanaceae species such as tomato, the genome includes several species-specific gene family expansions, among them N-methyltransferases (NMTs) involved in caffeine production, defense-related genes, and alkaloid and flavonoid enzymes involved in secondary compound synthesis. Comparative analyses of caffeine NMTs demonstrate that these genes expanded through sequential tandem duplications independently of genes from cacao and tea, suggesting that caffeine in eudicots is of polyphyletic origin.
ESTHER : Denoeud_2014_Science_345_1181
PubMedSearch : Denoeud_2014_Science_345_1181
PubMedID: 25190796
Gene_locus related to this paper: cofca-a0a068vi93 , cofca-a0a068uy77 , cofca-a0a068tzh7 , cofca-a0a068tuj7 , cofca-a0a068v983 , cofca-a0a068tnj0 , cofca-a0a068tyf7 , cofca-a0a068u1v4.1 , cofca-a0a068vks5 , cofar-a0a6p6xcv5

Title : Identification and characterization of a new erythromycin biosynthetic gene cluster in Actinopolyspora erythraea YIM90600, a novel erythronolide-producing halophilic actinomycete isolated from salt field - Chen_2014_PLoS.One_9_e108129
Author(s) : Chen D , Feng J , Huang L , Zhang Q , Wu J , Zhu X , Duan Y , Xu Z
Ref : PLoS ONE , 9 :e108129 , 2014
Abstract : Erythromycins (Ers) are clinically potent macrolide antibiotics in treating pathogenic bacterial infections. Microorganisms capable of producing Ers, represented by Saccharopolyspora erythraea, are mainly soil-dwelling actinomycetes. So far, Actinopolyspora erythraea YIM90600, a halophilic actinomycete isolated from Baicheng salt field, is the only known Er-producing extremophile. In this study, we have reported the draft genome sequence of Ac. erythraea YIM90600, genome mining of which has revealed a new Er biosynthetic gene cluster encoding several novel Er metabolites. This Er gene cluster shares high identity and similarity with the one of Sa. erythraea NRRL2338, except for two absent genes, eryBI and eryG. By correlating genotype and chemotype, the biosynthetic pathways of 3'-demethyl-erythromycin C, erythronolide H (EH) and erythronolide I have been proposed. The formation of EH is supposed to be sequentially biosynthesized via C-6/C-18 epoxidation and C-14 hydroxylation from 6-deoxyerythronolide B. Although an in vitro enzymatic activity assay has provided limited evidence for the involvement of the cytochrome P450 oxidase EryFAc (derived from Ac. erythraea YIM90600) in the catalysis of a two-step oxidation, resulting in an epoxy moiety, the attempt to construct an EH-producing Sa. erythraea mutant via gene complementation was not successful. Characterization of EryKAc (derived from Ac. erythraea YIM90600) in vitro has confirmed its unique role as a C-12 hydroxylase, rather than a C-14 hydroxylase of the erythronolide. Genomic characterization of the halophile Ac. erythraea YIM90600 will assist us to explore the great potential of extremophiles, and promote the understanding of EH formation, which will shed new insights into the biosynthesis of Er metabolites.
ESTHER : Chen_2014_PLoS.One_9_e108129
PubMedSearch : Chen_2014_PLoS.One_9_e108129
PubMedID: 25250723
Gene_locus related to this paper: 9acto-a0a099d7w4 , 9actn-a0a099d934

Title : The Down-Regulation of Neuroligin-2 and the Correlative Clinical Significance of Serum GABA Over-Expression in Hirschsprung's Disease - Yang_2014_Neurochem.Res_39_1451
Author(s) : Yang H , Niu J , Wang J , Zhang F , Zhang Q , Zhang W , Li A
Ref : Neurochem Res , 39 :1451 , 2014
Abstract : The goal of this study was to investigate the expression level of neuroligin-2 in different colon tissue segments of children with Hirschsprung's disease (HSCR) and the correlative clinical significance of serum Gamma-Aminobutyric Acid (serum GABA) in HSCR. Neuroligin-2 was assessed by Immunohistochemistry staining method on routine paraffin section from different colon tissue segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment). Western-blot analysis and real-time fluorescence quantitative PCR(qRT-PCR) were applied to compare and evaluate the expression levels of neuroligin-2 from three segments of HSCR, and we used Enzyme-linked Immunosorbent Assay (ELISA) method to detect and compare the serum GABA between HSCR and non-HSCR. Immunohistochemistry staining demonstrated that intensive neuroligin-2 staining was detected in the ganglion cells in the ganglionic colonic and transitional colonic segments from the HSCR children; however, neuroligin-2 staining was down-regulated significantly in the aganglionic colonic segments. The expression levels of neuroligin-2 mRNA and protein in the aganglionic colonic segment were decreased compared to the ganglionic colonic segment and transitional colonic segment (P < 0.05). And the level of serum GABA was significantly higher in HSCR than that in non-HSCR. The expression of neuroligin-2 varies from different segments of HSCR. The down-regulation of neuroligin-2 in aganglionic colonic segments may be correlated with the excessive intestine contraction and further result in HSCR. The over-expression of serum GABA may be considered as a new diagnostic method of HSCR.
ESTHER : Yang_2014_Neurochem.Res_39_1451
PubMedSearch : Yang_2014_Neurochem.Res_39_1451
PubMedID: 24842555

Title : Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease - Zhang_2013_Mol.Biol.Rep_40_2969
Author(s) : Zhang Q , Wang J , Li A , Liu H , Zhang W , Cui X , Wang K
Ref : Mol Biol Rep , 40 :2969 , 2013
Abstract : To investigate the expression levels of neurexins and neuroligins in the enteric nervous system (ENS) in Hirschsprung Disease (HSCR). Longitudinal muscles with adherent mesenteric plexus were obtained by dissection of the fresh gut wall of mice, guinea pigs, and humans. Double labeling of neurexin I and Hu (a neuron marker), neuroligin 1 and Hu, neurexin I and synaptophysin (a presynaptic marker), and neuroligin 1 and PSD95 (a postsynaptic marker) was performed by immunofluorescence staining. Images were merged to determine the relative localizations of the proteins. Expression levels of neurexin and neuroligin in different segments of the ENS in HSCR were investigated by immunohistochemistry. Neurexin and neuroligin were detected in the mesenteric plexus of mice, guinea pigs, and humans with HSCR. Neurexin was located in the presynapse, whereas neuroligin was located in the postsynapse. Expression levels of neurexin and neuroligin were significant in the ganglionic colonic segment of HSCR, moderate in the transitional segment, and negative in the aganglionic colonic segment. The expressions of neurexin and neuroligin in the transitional segments were significantly down-regulated compared with the levels in the normal segments (P < 0.05). Expression levels of neurexin and neuroligin in ENS are significantly down-regulated in HSCR, which may be involved in the pathogenesis of HSCR.
ESTHER : Zhang_2013_Mol.Biol.Rep_40_2969
PubMedSearch : Zhang_2013_Mol.Biol.Rep_40_2969
PubMedID: 23264101

Title : Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans - Zhang_2013_Genome.Announc_1_E00213
Author(s) : Zhang J , Cao G , Xu X , Jin H , Zhang Q , Chen J , Yang X , Pan H , Zhang X , Allard M , Brown E , Meng J
Ref : Genome Announc , 1 :E00213 , 2013
Abstract : Salmonellosis contributes significantly to the public health burden globally. Salmonella enterica serotype Newport is among Salmonella serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four S. Newport strains isolated from humans in China.
ESTHER : Zhang_2013_Genome.Announc_1_E00213
PubMedSearch : Zhang_2013_Genome.Announc_1_E00213
PubMedID: 23661485
Gene_locus related to this paper: salty-STY1441

Title : The interaction between OsMADS57 and OsTB1 modulates rice tillering via DWARF14 - Guo_2013_Nat.Commun_4_1566
Author(s) : Guo S , Xu Y , Liu H , Mao Z , Zhang C , Ma Y , Zhang Q , Meng Z , Chong K
Ref : Nat Commun , 4 :1566 , 2013
Abstract : Rice tillering is a multigenic trait that influences grain yield, but its regulation molecular module is poorly understood. Here we report that OsMADS57 interacts with OsTB1 (TEOSINTE BRANCHED1) and targets D14 (Dwarf14) to control the outgrowth of axillary buds in rice. An activation-tagged mutant osmads57-1 and OsMADS57-overexpression lines showed increased tillers, whereas OsMADS57 antisense lines had fewer tillers. OsMIR444a-overexpressing lines exhibited suppressed OsMADS57 expression and tillering. Furthermore, osmads57-1 was insensitive to strigolactone treatment to inhibit axillary bud outgrowth, and OsMADS57's function in tillering was dependent on D14. D14 expression was downregulated in osmads57-1, but upregulated in antisense and OsMIR444a-overexpressing lines. OsMADS57 bound to the CArG motif [C(A/T)TTAAAAAG] in the promoter and directly suppressed D14 expression. Interaction of OsMADS57 with OsTB1 reduced OsMADS57 inhibition of D14 transcription. Therefore, OsMIR444a-regulated OsMADS57, together with OsTB1, target D14 to control tillering. This regulation mechanism could have important application in rice molecular breeding programs focused on high grain yield.
ESTHER : Guo_2013_Nat.Commun_4_1566
PubMedSearch : Guo_2013_Nat.Commun_4_1566
PubMedID: 23463009

Title : Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) - Ming_2013_Genome.Biol_14_R41
Author(s) : Ming R , VanBuren R , Liu Y , Yang M , Han Y , Li LT , Zhang Q , Kim MJ , Schatz MC , Campbell M , Li J , Bowers JE , Tang H , Lyons E , Ferguson AA , Narzisi G , Nelson DR , Blaby-Haas CE , Gschwend AR , Jiao Y , Der JP , Zeng F , Han J , Min XJ , Hudson KA , Singh R , Grennan AK , Karpowicz SJ , Watling JR , Ito K , Robinson SA , Hudson ME , Yu Q , Mockler TC , Carroll A , Zheng Y , Sunkar R , Jia R , Chen N , Arro J , Wai CM , Wafula E , Spence A , Xu L , Zhang J , Peery R , Haus MJ , Xiong W , Walsh JA , Wu J , Wang ML , Zhu YJ , Paull RE , Britt AB , Du C , Downie SR , Schuler MA , Michael TP , Long SP , Ort DR , Schopf JW , Gang DR , Jiang N , Yandell M , dePamphilis CW , Merchant SS , Paterson AH , Buchanan BB , Li S , Shen-Miller J
Ref : Genome Biol , 14 :R41 , 2013
Abstract : BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.
ESTHER : Ming_2013_Genome.Biol_14_R41
PubMedSearch : Ming_2013_Genome.Biol_14_R41
PubMedID: 23663246
Gene_locus related to this paper: nelnu-a0a1u8aj84 , nelnu-a0a1u8bpe4 , nelnu-a0a1u7z9m9 , nelnu-a0a1u7ywy5 , nelnu-a0a1u8aik2 , nelnu-a0a1u7zmb5 , nelnu-a0a1u8a7m7 , nelnu-a0a1u8b0n9 , nelnu-a0a1u8b461 , nelnu-a0a1u7zzj3 , nelnu-a0a1u8ave7 , nelnu-a0a1u7yn26

Title : [Inhibitory effect of icariin on acetylcholinesterase] - Zhang_2012_Yao.Xue.Xue.Bao_47_1141
Author(s) : Zhang YD , Cai YN , Zhang Q , Qi ZL , Gao QQ
Ref : Yao Xue Xue Bao , 47 :1141 , 2012
Abstract : Acetylcholinesterase (AChE) inhibitors are mainly used in the treatment of Alzheimer's disease (AD). The inhibitory effect of icariin on the activity of AChE was investigated by inhibition kinetics. The binding interaction and binding sites between icariin and AChE were also studied by using fluorimetry and molecular docking, respectively. The results showed that icariin could potently inhibit the activity of AChE, the IC50 value was determined to be 3.50 x 10(-8) mol x L(-1), and the determined IC50 value to tacrine was 0.75 x 10(-8) mol x L(-1). Kinetic analyses showed that icariin is a reversible and mixed type AChE inhibitor. The inhibition constants K1 and K(IS) were determined to be 2.67 x 10(-8) and 4.43 x 10(-8) mol x L(-1), respectively. Icariin binds selectively to the AChE peripheral anionic site via hydrogen bonds and Van der Waals forces.
ESTHER : Zhang_2012_Yao.Xue.Xue.Bao_47_1141
PubMedSearch : Zhang_2012_Yao.Xue.Xue.Bao_47_1141
PubMedID: 23227542

Title : Affinity binding-guided fluorescent nanobiosensor for acetylcholinesterase inhibitors via distance modulation between the fluorophore and metallic nanoparticle - Zhang_2012_Anal.Chem_84_2830
Author(s) : Zhang Y , Hei T , Cai Y , Gao Q , Zhang Q
Ref : Analytical Chemistry , 84 :2830 , 2012
Abstract : The magnitude of fluorescence enhancement was found to depend strongly on the distance between fluorophores and metal nanostructures in metal-enhanced fluorescence (MEF). However, the precise placement of the particle in front of the molecule with nanometer accuracy and distance control is a great challenge. We describe a method using acetylcholinesterase (AChE) to modulate the distance between a gold nanoparticle (AuNP) and the fluorophore 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) (DDAO). We found that DDAO is a reversible mixed type-I AChE inhibitor. DDAO binds to the peripheral anionic site and penetrates into the active gorge site of AChE via inhibition kinetics test and molecular docking study. The affinity ligand DDAO bound to AChE which was immobilized onto AuNPs, and its fluorescence was sharply enhanced due to MEF. The fluorescence was reduced by distance variations between the AuNP and DDAO, which resulted from other inhibitors competitively binding with AChE and partly or completely displacing DDAO. Experimental results show that changes in fluorescence intensity are related to the concentration of inhibitors present in the solution. In addition, the nanobiosensor has high sensitivity, with detection limits as low as 0.4 muM for paraoxon and 10 nM for tacrine, and also exhibits different reduction efficiencies for the two types of inhibitor. Thus, instead of an inhibition test, a new type of affinity binding-guided fluorescent nanobiosensor was fabricated to detect AChE inhibitors, determine AChE inhibitor binding mode, and screen more potent AChE inhibitors. The proposed strategy may be applied to other proteins or protein domains via changes in the affinity ligand.
ESTHER : Zhang_2012_Anal.Chem_84_2830
PubMedSearch : Zhang_2012_Anal.Chem_84_2830
PubMedID: 22339669

Title : A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-beta(2)(5)(-)(3)(5)-treated rats following intranasal administration - Wu_2012_Eur.J.Pharm.Biopharm_80_368
Author(s) : Wu H , Li J , Zhang Q , Yan X , Guo L , Gao X , Qiu M , Jiang X , Lai R , Chen H
Ref : Eur J Pharm Biopharm , 80 :368 , 2012
Abstract : Because of the immunogenicity and toxicity in vivo of large molecules such as lectins, the application of these molecules is remarkably restricted in drug delivery systems. In this study, to improve the brain drug delivery and reduce the immunogenicity of traditional lectin modified delivery system, Odorranalectin (OL, 1700 Da), a novel non-immunogenic small peptide, was selected to establish an OL-modified cubosomes (Cubs) system. The streptavidin (SA)-conjugated Cubs were prepared by incorporating maleimide-PEG-oleate and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothiolane thiolated SA; mono-biotinylated OL was then coupled with the SA-modified Cubs. The OL-decorated Cubs (OL-Cubs) devised via a non-covalent SA-biotin "bridge" made it easy to conjugate OL and determine the number of ligands on the surface of the Cubs using sensitive chemiluminescent detection. Retention of the bio-recognitive activity of OL after covalent coupling was verified by hemagglutination testing. Nose-to-brain delivery characteristic of OL-Cubs was investigated by in vivo fluorescent biodistribution using coumarin-6 as a marker. The relative uptake of coumarin carried by OL-Cubs was 1.66- to 3.46-fold in brain tissues compared to that incorporated in the Cubs. Besides, Gly14-Humanin (S14G-HN) as a model peptide drug was loaded into cubosomes and evaluated for its pharmacodynamics on Alzheimer's disease (AD) rats following intranasal administration by Morris water maze test and acetylcholinesterase activity determination. The results suggested that OL functionalization enhanced the therapeutic effects of S14G-HN-loaded cubosomes on AD. Thus, OL-Cubs might offer a novel effective and noninvasive system for brain drug delivery, especially for peptides and proteins.
ESTHER : Wu_2012_Eur.J.Pharm.Biopharm_80_368
PubMedSearch : Wu_2012_Eur.J.Pharm.Biopharm_80_368
PubMedID: 22061263

Title : Intranasal administration of TAT-haFGF(14-154) attenuates disease progression in a mouse model of Alzheimer's disease - Lou_2012_Neurosci_223_225
Author(s) : Lou G , Zhang Q , Xiao F , Xiang Q , Su Z , Zhang L , Yang P , Yang Y , Zheng Q , Huang Y
Ref : Neuroscience , 223 :225 , 2012
Abstract : Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 ug/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced beta-amyloid protein(1-42) (Abeta(1-42)) deposits as well as the levels of Abeta soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Abeta pathology and oxidative stress.
ESTHER : Lou_2012_Neurosci_223_225
PubMedSearch : Lou_2012_Neurosci_223_225
PubMedID: 22885230

Title : Enhancement of nose-to-brain delivery of basic fibroblast growth factor for improving rat memory impairments induced by co-injection of beta-amyloid and ibotenic acid into the bilateral hippocampus - Feng_2012_Int.J.Pharm_423_226
Author(s) : Feng C , Zhang C , Shao X , Liu Q , Qian Y , Feng L , Chen J , Zha Y , Zhang Q , Jiang X
Ref : Int J Pharm , 423 :226 , 2012
Abstract : Basic fibroblast growth factor (bFGF) delivery to the brain of animals appears to be an emerging potential therapeutic approach to neurodegenerative diseases, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracerebroventricular infusion. A nasal spray of bFGF had been developed previously and the objective of the present study was to investigate whether bFGF nasal spray could enhance brain uptake of bFGF and ameliorate memory impairment induced by co-injection of beta-amyloid(25-35) and ibotenic acid into bilateral hippocampus of rats. The results of brain uptake study showed that the AUC(0-12h) of bFGF nasal spray in olfactory bulb, cerebrum, cerebellum and hippocampus was respectively 2.47, 2.38, 2.56 and 2.19 times that of intravenous bFGF solution, and 1.11, 1.95, 1.40 and 1.93 times that of intranasal bFGF solution, indicating that intranasal administration of bFGF nasal spray was an effective means of delivering bFGF to the brain, especially to cerebrum and hippocampus. In Morris water maze tasks, intravenous administration of bFGF solution at high dose (40 mug/kg) showed little improvement on spatial memory impairment. In contrast, bFGF solution of the same dose following intranasal administration could significantly ameliorate spatial memory impairment. bFGF nasal spray obviously improved spatial memory impairment even at a dose half (20 mug/kg) of bFGF solution, recovered their acetylcholinesterase and choline acetyltransferase activity to the sham control level, and alleviated neuronal degeneration in rat hippocampus, indicating neuroprotective effects on the central nerve system. In a word, bFGF nasal spray may be a new formulation of great potential for treating AD.
ESTHER : Feng_2012_Int.J.Pharm_423_226
PubMedSearch : Feng_2012_Int.J.Pharm_423_226
PubMedID: 22193058

Title : Genome sequencing reveals unique mutations in characteristic metabolic pathways and the transfer of virulence genes between V. mimicus and V. cholerae - Wang_2011_PLoS.One_6_e21299
Author(s) : Wang D , Wang H , Zhou Y , Zhang Q , Zhang F , Du P , Wang S , Chen C , Kan B
Ref : PLoS ONE , 6 :e21299 , 2011
Abstract : Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in the natural environmental and sometimes causes diarrhea and internal infections in humans. It shows similar phenotypes to V. cholerae but differs in some biochemical characteristics. The molecular mechanisms underlying the differences in biochemical metabolism between V. mimicus and V. cholerae are currently unclear. Several V. mimicus isolates have been found that carry cholera toxin genes (ctxAB) and cause cholera-like diarrhea in humans. Here, the genome of the V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and annotated. Analysis of its genome, together with those of other Vibrio species, revealed extensive differences within the Vibrionaceae. Common mutations in gene clusters involved in three biochemical metabolism pathways that are used for discrimination between V. mimicus and V. cholerae were found in V. mimicus strains. We also constructed detailed genomic structures and evolution maps for the general types of genomic drift associated with pathogenic characters in polysaccharides, CTX elements and toxin co-regulated pilus (TCP) gene clusters. Overall, the whole-genome sequencing of the V. mimicus strain carrying the cholera toxin gene provides detailed information for understanding genomic differences among Vibrio spp. V. mimicus has a large number of diverse gene and nucleotide differences from its nearest neighbor, V. cholerae. The observed mutations in the characteristic metabolism pathways may indicate different adaptations to different niches for these species and may be caused by ancient events in evolution before the divergence of V. cholerae and V. mimicus. Horizontal transfers of virulence-related genes from an uncommon clone of V. cholerae, rather than the seventh pandemic strains, have generated the pathogenic V. mimicus strain carrying cholera toxin genes.
ESTHER : Wang_2011_PLoS.One_6_e21299
PubMedSearch : Wang_2011_PLoS.One_6_e21299
PubMedID: 21731695
Gene_locus related to this paper: vibmi-d0gt41 , vibmi-u4zh77 , vibmi-g0sil5

Title : In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain - Liu_2011_Toxicol.Appl.Pharmacol_251_79
Author(s) : Liu Q , Shao X , Chen J , Shen Y , Feng C , Gao X , Zhao Y , Li J , Zhang Q , Jiang X
Ref : Toxicol Appl Pharmacol , 251 :79 , 2011
Abstract : Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-alpha level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.
ESTHER : Liu_2011_Toxicol.Appl.Pharmacol_251_79
PubMedSearch : Liu_2011_Toxicol.Appl.Pharmacol_251_79
PubMedID: 21163285

Title : Genome sequencing reveals insights into physiology and longevity of the naked mole rat - Kim_2011_Nature_479_223
Author(s) : Kim EB , Fang X , Fushan AA , Huang Z , Lobanov AV , Han L , Marino SM , Sun X , Turanov AA , Yang P , Yim SH , Zhao X , Kasaikina MV , Stoletzki N , Peng C , Polak P , Xiong Z , Kiezun A , Zhu Y , Chen Y , Kryukov GV , Zhang Q , Peshkin L , Yang L , Bronson RT , Buffenstein R , Wang B , Han C , Li Q , Chen L , Zhao W , Sunyaev SR , Park TJ , Zhang G , Wang J , Gladyshev VN
Ref : Nature , 479 :223 , 2011
Abstract : The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
ESTHER : Kim_2011_Nature_479_223
PubMedSearch : Kim_2011_Nature_479_223
PubMedID: 21993625
Gene_locus related to this paper: hetga-g5amh8 , hetga-g5an68 , hetga-g5anw7 , hetga-g5as32 , hetga-g5atg6 , hetga-g5b5b7 , hetga-g5b9m6 , hetga-g5bdh8 , hetga-g5bmv3 , hetga-g5bp66 , hetga-g5bp67 , hetga-g5bp68 , hetga-g5bpp3 , hetga-g5bsd4 , hetga-g5bul0 , hetga-g5bw29 , hetga-g5bze3 , hetga-g5c6q5 , hetga-g5bfw4 , hetga-g5b832 , hetga-g5c6q8 , hetga-g5bj87 , hetga-a0a0p6jix7 , hetga-g5c108 , hetga-g5c109 , hetga-g5c110 , hetga-g5arh0 , hetga-g5aua1 , hetga-g5are8 , hetga-g5ax31 , hetga-a0a0p6jud6 , hetga-g5b7v3 , hetga-a0a0p6jw61 , hetga-a0a0p6jdl4 , hetga-g5bg83 , hetga-g5bcu5 , hetga-g5bvp0 , hetga-g5b8m7 , hetga-g5b709 , hetga-g5bt99 , hetga-g5b4q4

Title : [Correlation research of isolated liver tissue pathology and clinical diagnosis in patients with chronic severe hepatitis B] - Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603
Author(s) : Sun J , Yu HW , Liu Z , Liu H , Zhang Q , Yao QW , Feng YM , Li J , Meng QH
Ref : Zhonghua Gan Zang Bing Za Zhi , 19 :603 , 2011
Abstract : To study the coincidence rate of clinical diagonisis with pathological diagnosis for chronic severe hepatitis, and to screen out clinical indicators consistent with pathological diagnosis. Fifty-one patients diagnosed as chronic severe hepatitis and underwent liver transplantation in Beijing You'an hospital from November 2004 to June 2009 participated in this study. The clinical data were selected as following: ALT, AST, urea nitrogen, creatinine, glucose, cholinesterase, total cholesterol, Glutamyl endopeptidase, alkaline phosphatase, serum potassium, serum sodium, prothrombin activity and blood ammonia level. The width of the portal vein and splenic vein thickness were measured by color Doppler ultrasound and were compared in different groups. Data were ananlyzed with independent sample t test and F test. The coincidence rate between clinical and pathological diagnoses in this study was 64.7%. ALT and AST levels for Chronic severe hepatitis and decompensated cirrhosis were 675.0+/-510.0 U/L, 67.00+/-45.0 U/L ( P is less than to 0.01) and 392.0 +/-370.0 U/L, 103.0+/-59.0 U/L (P is less than to 0.01) respectively, with statistically significant difference existed. The mean level of ALT in Chronic severe hepatitis group was significantly different in the situations of onset less than 30 days or more than 30 days (means were 761.0+/-743.0 U/L and 117.0+/-112.0 U/L, P is less than to 0.01). The rate of the phenomenon of enzyme isolated bile in the chronic severe hepatitis and decompensated cirrhosis group were 78.9% and 0 respectively. The coincidence rate of clinical with pathological diagnoses for Chronic Severe Hepatitis was low, increased ALT and AST levels would help improve the diagnostic accuracy.
ESTHER : Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603
PubMedSearch : Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603
PubMedID: 22152318

Title : Visual detection of organophosphorus pesticides represented by mathamidophos using Au nanoparticles as colorimetric probe - Li_2011_Talanta_87_93
Author(s) : Li H , Guo J , Ping H , Liu L , Zhang M , Guan F , Sun C , Zhang Q
Ref : Talanta , 87 :93 , 2011
Abstract : With citrate-coated Au nanoparticles as colorimetric probe, a novel visual method for rapid assay of organophosphorus pesticides has been developed. The assay principle is based on catalytic hydrolysis of acetylthiocholine into thiocholine by acetylcholinesterase, which induces the aggregation of Au nanoparticles and the color change from claret-red to purple or even grey. The original plasmon absorption of Au nanoparticles at 522 nm decreases, and simultaneously, a new absorption band appears at 675 nm. The irreversible inhibition of organophosphorus pesticides on acetylcholinesterase prevents aggregation of Au nanoparticles. Under optimum conditions, the absorbance at 522 nm of Au nanoparticles is related linearly to the concentration of mathamidophos in the range of 0.02-1.42 mug/mL with a detection limit of 1.40 ng/mL. This colorimetric method has been successfully utilized to detect mathamidophos in vegetables with satisfactory results. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for the analysis of organophosphorus pesticides.
ESTHER : Li_2011_Talanta_87_93
PubMedSearch : Li_2011_Talanta_87_93
PubMedID: 22099654

Title : Natural variation in GS5 plays an important role in regulating grain size and yield in rice - Li_2011_Nat.Genet_43_1266
Author(s) : Li Y , Fan C , Xing Y , Jiang Y , Luo L , Sun L , Shao D , Xu C , Li X , Xiao J , He Y , Zhang Q
Ref : Nat Genet , 43 :1266 , 2011
Abstract : Increasing crop yield is one of the most important goals of plant science research. Grain size is a major determinant of grain yield in cereals and is a target trait for both domestication and artificial breeding(1). We showed that the quantitative trait locus (QTL) GS5 in rice controls grain size by regulating grain width, filling and weight. GS5 encodes a putative serine carboxypeptidase and functions as a positive regulator of grain size, such that higher expression of GS5 is correlated with larger grain size. Sequencing of the promoter region in 51 rice accessions from a wide geographic range identified three haplotypes that seem to be associated with grain width. The results suggest that natural variation in GS5 contributes to grain size diversity in rice and may be useful in improving yield in rice and, potentially, other crops(2).
ESTHER : Li_2011_Nat.Genet_43_1266
PubMedSearch : Li_2011_Nat.Genet_43_1266
PubMedID: 22019783
Gene_locus related to this paper: orysa-q5w727

Title : Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase - Shen_2011_Mol.Biol.Rep_38_553
Author(s) : Shen LL , Liu H , Peng J , Gan L , Lu L , Zhang Q , Li L , He F , Jiang Y
Ref : Mol Biol Rep , 38 :553 , 2011
Abstract : The farnesoid X receptor (FXR) is a nuclear receptor that regulates gene expression in response to bile acids (BAs). FXR plays an important role in the homeostasis of bile acid, cholesterol, lipoprotein and triglyceride. In this report, we identified fatty acid synthase (FAS) and hepatic lipase (HL) genes as novel target genes of FXR. Human hepatoma HepG2 cells were treated with chenodeoxycholic acid, the natural FXR ligand, and the messenger RNA and protein levels of FAS and HL were determined by RT-PCR and Western blot analysis, respectively. Chenodeoxycholic acid (CDCA) down-regulated the expression of FAS and HL genes in a dose and time-dependent manner in human hepatoma HepG2 cells. In addition, treatment of mice with CDCA significantly decreased the expression of FAS and HL in mouse liver and the activity of HL. These results demonstrated that FAS and HL might be FXR-regulated genes in liver cells. In view of the role of FAS and HL in lipogenesis and plasma lipoprotein metabolism, our results further support the central role of FXR in the homeostasis of fatty acid and lipid.
ESTHER : Shen_2011_Mol.Biol.Rep_38_553
PubMedSearch : Shen_2011_Mol.Biol.Rep_38_553
PubMedID: 20373033

Title : Complete genome sequence of Bacillus thuringiensis mutant strain BMB171 - He_2010_J.Bacteriol_192_4074
Author(s) : He J , Shao X , Zheng H , Li M , Wang J , Zhang Q , Li L , Liu Z , Sun M , Wang S , Yu Z
Ref : Journal of Bacteriology , 192 :4074 , 2010
Abstract : Bacillus thuringiensis has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of B. thuringiensis mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory.
ESTHER : He_2010_J.Bacteriol_192_4074
PubMedSearch : He_2010_J.Bacteriol_192_4074
PubMedID: 20525827
Gene_locus related to this paper: bacan-BA3703 , bacan-DHBF , bacce-BC0192 , bacce-BC0968 , bacce-BC1677 , bacce-BC1788 , bacce-BC2141 , bacce-BC2171 , bacce-BC2456 , bacce-BC2458 , bacce-BC3133 , bacce-BC4102 , bacce-BC4854 , bacce-BC4862 , bacce-BC5130 , bacce-PHAC , baccr-pepx

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Nerve agent exposure elicits site-specific changes in protein phosphorylation in mouse brain - Zhu_2010_Brain.Res_1342_11
Author(s) : Zhu H , O'Brien JJ , O'Callaghan JP , Miller DB , Zhang Q , Rana M , Tsui T , Peng Y , Tomesch J , Hendrick JP , Wennogle LP , Snyder GL
Ref : Brain Research , 1342 :11 , 2010
Abstract : Organophosphorus (OP) compounds cause toxic symptoms, including convulsions, coma, and death, as the result of irreversible inhibition of acetylcholinesterase (AChE). The development of effective treatments to block these effects and attenuate long-term cognitive and motor disabilities that result from OP intoxication is hampered by a limited understanding of the CNS pathways responsible for these actions. We employed a candidate method (called CNSProfile) to identify changes in the phosphorylation state of key neuronal phosphoproteins evoked by the OP compound, diisopropyl fluorophosphate (DFP). Focused microwave fixation was used to preserve the phosphorylation state of phosphoproteins in brains of DFP-treated mice; hippocampus and striatum were analyzed by immunoblotting with a panel of phospho-specific antibodies. DFP exposure elicited comparable effects on phosphorylation of brain phosphoproteins in both C57BL/6 and FVB mice. DFP treatment significantly altered phosphorylation at regulatory residues on glutamate receptors, including Serine897 (S897) of the NR1 NMDA receptor. NR1 phosphorylation was bi-directionally regulated after DFP in striatum versus hippocampus. NR1 phosphorylation was reduced in striatum, but elevated in hippocampus, compared with controls. DARPP-32 phosphorylation in striatum was selectively increased at the Cdk5 kinase substrate, Threonine75 (T75). Phencynonate hydrochloride, a muscarinic cholinergic antagonist, prevented seizure-like behaviors and the observed changes in phosphorylation induced by DFP. The data reveal region-specific effects of nerve agent exposure on intracellular signaling pathways that correlate with seizure-like behavior and which are reversed by the muscarinic receptor blockade. This approach identifies specific targets for nerve agents, including substrates for Cdk5 kinase, which may be the basis for new anti-convulsant therapies.
ESTHER : Zhu_2010_Brain.Res_1342_11
PubMedSearch : Zhu_2010_Brain.Res_1342_11
PubMedID: 20423708

Title : Enantioselective interaction with acetylcholinesterase of an organophosphate insecticide fenamiphos - Wang_2010_Chirality_22_612
Author(s) : Wang C , Zhang N , Li L , Zhang Q , Zhao M , Liu W
Ref : Chirality , 22 :612 , 2010
Abstract : Enantioselectivity in the environmental behavior and ecotoxicity of chiral pesticide is widely observed. However, the investigation of the enantioselective mechanisms remains limited. In this study, we used fenamiphos (FAP), an organophosphorus insecticide, to study enantioselectivity in toxicity to arthropods and the inhibition potential towards acetylcholinesterase (AChE) in the rat pheochromocytoma 12 (PC 12) cell line. Furthermore, we carried out molecular docking to help explain the mechanisms of enantioselective toxicity of FAP. The two enantiomers of FAP were successfully separated and identified as R-(+)-FAP and S-(-)-FAP. Toxicological assays revealed that R-(+)-FAP was 2.4-fold more toxic than S-(-)-FAP to Daphnia magna and approximately threefold more to PC12 cells. Based on molecular docking results, dynamic simulation shows that strong hydrophobic interactions and a key hydrogen bond can only exist between R-(+)-FAP and AChE, which helps explain the preference of R-(+) binding to AChE over that of the S-(-)-enantiomer, and supports our biological results. Our present study considers the impact of stereochemistry on ecotoxicological effects and, ultimately, on development of environmentally safe, insecticidally efficient pesticides.
ESTHER : Wang_2010_Chirality_22_612
PubMedSearch : Wang_2010_Chirality_22_612
PubMedID: 19899158

Title : Discovery of novel alpha7 nicotinic receptor antagonists - Peng_2010_Bioorg.Med.Chem.Lett_20_4825
Author(s) : Peng Y , Zhang Q , Snyder GL , Zhu H , Yao W , Tomesch J , Papke RL , O'Callaghan JP , Welsh WJ , Wennogle LP
Ref : Bioorganic & Medicinal Chemistry Lett , 20 :4825 , 2010
Abstract : Two distinct families of small molecules were discovered as novel alpha7 nicotinic acetylcholine receptor (nAChR) antagonists by pharmacophore-based virtual screening. These novel antagonists exhibited selectivity for the neuronal alpha7 subtype over other nAChRs and good brain penetration. Neuroprotection was demonstrated by representative compounds 7i and 8 in a mouse seizure-like behavior model induced by the nerve agent diisopropylfluorophosphate (DFP). These novel nAChR antagonists have potential use as antidote for organophosphorus nerve agent intoxication.
ESTHER : Peng_2010_Bioorg.Med.Chem.Lett_20_4825
PubMedSearch : Peng_2010_Bioorg.Med.Chem.Lett_20_4825
PubMedID: 20638843

Title : Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications - Liao_2009_Chem.Biol_16_141
Author(s) : Liao R , Duan L , Lei C , Pan H , Ding Y , Zhang Q , Chen D , Shen B , Yu Y , Liu W
Ref : Chemical Biology , 16 :141 , 2009
Abstract : Thiopeptides, with potent activity against various drug-resistant pathogens, contain a characteristic macrocyclic core consisting of multiple thiazoles, dehydroamino acids, and a 6-membered nitrogen heterocycle. Their biosynthetic pathways remain elusive, in spite of great efforts by in vivo feeding experiments. Here, cloning, sequencing, and characterization of the thiostrepton and siomycin A gene clusters unveiled a biosynthetic paradigm for the thiopeptide specific core formation, featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. The paradigm generality for thiopeptide biosynthesis was supported by genome mining and ultimate confirmation of the thiocillin I production in Bacillus cereus ATCC 14579, a strain that was previously unknown as a thiopeptide producer. These findings set the stage to accelerate the discovery of thiopeptides by prediction at the genetic level and to generate structural diversity by applying combinatorial biosynthesis methods.
ESTHER : Liao_2009_Chem.Biol_16_141
PubMedSearch : Liao_2009_Chem.Biol_16_141
PubMedID: 19246004
Gene_locus related to this paper: 9acto-c0jrv0 , 9acto-c0jrv6 , strlu-c0jry1 , 9actn-c0jrw3 , strlu-c0l0l7

Title : Invasive mechanism and management strategy of Bemisia tabaci (Gennadius) biotype B: progress report of 973 Program on invasive alien species in China - Wan_2009_Sci.China.C.Life.Sci_52_88
Author(s) : Wan F , Zhang G , Liu S , Luo C , Chu D , Zhang Y , Zang L , Jiu M , Lu Z , Cui X , Zhang L , Zhang F , Zhang Q , Liu W , Liang P , Lei Z
Ref : Sci China C Life Sciences , 52 :88 , 2009
Abstract : Bemisia tabaci (Gennadius) biotype B, called a "superbug", is one of the most harmful biotypes of this species complex worldwide. In this report, the invasive mechanism and management of B. tabaci biotype B, based on our 5-year studies, are presented. Six B. tabaci biotypes, B, Q, ZHJ1, ZHJ2, ZHJ3 and FJ1, have been identified in China. Biotype B dominates the other biotypes in many regions of the country. Genetic diversity in biotype B might be induced by host plant, geographical conditions, and/or insecticidal application. The activities of CarE (carboxylesterase) and GSTs (glutathione-S-transferase) in biotype B reared on cucumber and squash were greater than on other host plants, which might have increased its resistance to insecticides. The higher activities of detoxification enzymes in biotype B might be induced by the secondary metabolites in host plants. Higher adaptive ability of biotype B adults to adverse conditions might be linked to the expression of heat shock protein genes. The indigenous B. tabaci biotypes were displaced by the biotype B within 225 d. The asymmetric mating interactions and mutualism between biotype B and begomoviruses via its host plants speed up widespread invasion and displacement of other biotypes. B. tabaci biotype B displaced Trialeurodes vaporariorum (Westwood) after 4-7 generations under glasshouse conditions. Greater adaptive ability of the biotype B to adverse conditions and its rapid population increase might be the reasons of its successful displacement of T. vaporariorum. Greater ability of the biotype B to switch to different host plants may enrich its host plants, which might enable it to better compete with T. vaporariorum. Native predatory natural enemies possess greater ability to suppress B. tabaci under field conditions. The kairomones in the 3rd and 4th instars of biotype B may provide an important stimulus in host searching and location by its parasitoids. The present results provide useful information in explaining the mechanisms of genetic diversity, evolution and molecular eco-adaptation of biotype B. Furthermore, it provides a base for sustainable management of B. tabaci using biological and ecological measures.
ESTHER : Wan_2009_Sci.China.C.Life.Sci_52_88
PubMedSearch : Wan_2009_Sci.China.C.Life.Sci_52_88
PubMedID: 19152088

Title : Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi - Akiyoshi_2009_PLoS.Pathog_5_e1000261
Author(s) : Akiyoshi DE , Morrison HG , Lei S , Feng X , Zhang Q , Corradi N , Mayanja H , Tumwine JK , Keeling PJ , Weiss LM , Tzipori S
Ref : PLoS Pathog , 5 :e1000261 , 2009
Abstract : Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence.
ESTHER : Akiyoshi_2009_PLoS.Pathog_5_e1000261
PubMedSearch : Akiyoshi_2009_PLoS.Pathog_5_e1000261
PubMedID: 19132089
Gene_locus related to this paper: entbh-b7xjm2

Title : Development, characterization, and evaluation of a fusion protein of a novel glucagon-like peptide-1 (GLP-1) analog and human serum albumin in Pichia pastoris - Gao_2009_Biosci.Biotechnol.Biochem_73_688
Author(s) : Gao Z , Bai G , Chen J , Zhang Q , Pan P , Bai F , Geng P
Ref : Biosci Biotechnol Biochem , 73 :688 , 2009
Abstract : Glucagon-like peptide-1 (GLP-1) has considerable potential as a possible therapeutic agent for type-2 diabetes. Unfortunately, this glucoincretin is short lived due to degradation by dipeptidyl-peptidase IV and rapid clearance by renal filtration. In this study, we attempted to extend GLP-1 action through the attachment of a lysine residue at the N-terminal of GLP-1 (named KGLP-1), and to make a fusion protein with human serum albumin (HSA) in Pichia pastoris. The protein, designated KGLP-1/HSA, was purified by an immunomagnetic separation technique. High performance liquid chromatography (HPLC) showed that the purified protein had an overall purity of 92.0%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the expected molecular mass of 70,297.8 Da. Additionally, the N-terminal sequence of KGLP-1/HSA was confirmed by N-terminal sequencing. The stability and biological activity of KGLP-1/HSA were then evaluated in vitro and in vivo. The findings indicated that fusion KGLP-1/HSA preserved the action of native GLP-1, and the active duration was greatly prolonged.
ESTHER : Gao_2009_Biosci.Biotechnol.Biochem_73_688
PubMedSearch : Gao_2009_Biosci.Biotechnol.Biochem_73_688
PubMedID: 19270384

Title : The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation - Zhang_2009_Mol.Genet.Genomics_282_417
Author(s) : Zhang Q , Liang C , Yu YA , Chen N , Dandekar T , Szalay AA
Ref : Mol Genet Genomics , 282 :417 , 2009
Abstract : As a new anticancer treatment option, vaccinia virus (VACV) has shown remarkable antitumor activities (oncolysis) in preclinical studies, but potential infection of other organs remains a safety concern. We present here genome comparisons between the de novo sequence of GLV-1h68, a recombinant VACV, and other VACVs. The identified differences in open reading frames (ORFs) include genes encoding host-range selection, virulence and immune modulation proteins, e.g., ankyrin-like proteins, serine proteinase inhibitor SPI-2/CrmA, tumor necrosis factor (TNF) receptor homolog CrmC, semaphorin-like and interleukin-1 receptor homolog proteins. Phylogenetic analyses indicate that GLV-1h68 is closest to Lister strains but has lost several ORFs present in its parental LIVP strain, including genes encoding CrmE and a viral Golgi anti-apoptotic protein, v-GAAP. The reduced pathogenicity of GLV-1h68 is confirmed in male mice bearing C6 rat glioma and in immunocompetent mice bearing B16-F10 murine melanoma. The contribution of foreign gene expression cassettes in the F14.5L, J2R and A56R loci is analyzed, in particular the contribution of F14.5L inactivation to the reduced virulence is demonstrated by comparing the virulence of GLV-1h68 with its F14.5L-null and revertant viruses. GLV-1h68 is a promising engineered VACV variant for anticancer therapy with tumor-specific replication, reduced pathogenicity and benign tissue tropism.
ESTHER : Zhang_2009_Mol.Genet.Genomics_282_417
PubMedSearch : Zhang_2009_Mol.Genet.Genomics_282_417
PubMedID: 19701652
Gene_locus related to this paper: cowvi-M5L

Title : Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework - Yu_2009_ACS.Chem.Biol_4_855
Author(s) : Yu Y , Duan L , Zhang Q , Liao R , Ding Y , Pan H , Wendt-Pienkowski E , Tang G , Shen B , Liu W
Ref : ACS Chemical Biology , 4 :855 , 2009
Abstract : Nosiheptide (NOS), belonging to the e series of thiopeptide antibiotics that exhibit potent activity against various bacterial pathogens, bears a unique indole side ring system and regiospecific hydroxyl groups on the characteristic macrocyclic core. Here, cloning, sequencing, and characterization of the nos gene cluster from Streptomyces actuosus ATCC 25421 as a model for this series of thiopeptides has unveiled new insights into their biosynthesis. Bioinformatics-based sequence analysis and in vivo investigation into the gene functions show that NOS biosynthesis shares a common strategy with recently characterized b or c series thiopeptides for forming the characteristic macrocyclic core, which features a ribosomally synthesized precursor peptide with conserved posttranslational modifications. However, it apparently proceeds via a different route for tailoring the thiopeptide framework, allowing the final product to exhibit the distinct structural characteristics of e series thiopeptides, such as the indole side ring system. Chemical complementation supports the notion that the S-adenosylmethionine-dependent protein NosL may play a central role in converting tryptophan to the key 3-methylindole moiety by an unusual carbon side chain rearrangement, most likely via a radical-initiated mechanism. Characterization of the indole side ring-opened analogue of NOS from the nosN mutant strain is consistent with the proposed methyltransferase activity of its encoded protein, shedding light into the timing of the individual steps for indole side ring biosynthesis. These results also suggest the feasibility of engineering novel thiopeptides for drug discovery by manipulating the NOS biosynthetic machinery.
ESTHER : Yu_2009_ACS.Chem.Biol_4_855
PubMedSearch : Yu_2009_ACS.Chem.Biol_4_855
PubMedID: 19678698
Gene_locus related to this paper: stras-c6fx50

Title : Cloning and characterization of the tetrocarcin A gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics - Fang_2008_J.Bacteriol_190_6014
Author(s) : Fang J , Zhang Y , Huang L , Jia X , Zhang Q , Zhang X , Tang G , Liu W
Ref : Journal of Bacteriology , 190 :6014 , 2008
Abstract : Tetrocarcin A (TCA), produced by Micromonospora chalcea NRRL 11289, is a spirotetronate antibiotic with potent antitumor activity and versatile modes of action. In this study, the biosynthetic gene cluster of TCA was cloned and localized to a 108-kb contiguous DNA region. In silico sequence analysis revealed 36 putative genes that constitute this cluster (including 11 for unusual sugar biosynthesis, 13 for aglycone formation, and 4 for glycosylations) and allowed us to propose the biosynthetic pathway of TCA. The formation of D-tetronitrose, L-amicetose, and L-digitoxose may begin with D-glucose-1-phosphate, share early enzymatic steps, and branch into different pathways by competitive actions of specific enzymes. Tetronolide biosynthesis involves the incorporation of a 3-C unit with a polyketide intermediate to form the characteristic spirotetronate moiety and trans-decalin system. Further substitution of tetronolide with five deoxysugars (one being a deoxynitrosugar) was likely due to the activities of four glycosyltransferases. In vitro characterization of the first enzymatic step by utilization of 1,3-biphosphoglycerate as the substrate and in vivo cross-complementation of the bifunctional fused gene tcaD3 (with the functions of chlD3 and chlD4) to Delta chlD3 and Delta chlD4 in chlorothricin biosynthesis supported the highly conserved tetronate biosynthetic strategy in the spirotetronate family. Deletion of a large DNA fragment encoding polyketide synthases resulted in a non-TCA-producing strain, providing a clear background for the identification of novel analogs. These findings provide insights into spirotetronate biosynthesis and demonstrate that combinatorial-biosynthesis methods can be applied to the TCA biosynthetic machinery to generate structural diversity.
ESTHER : Fang_2008_J.Bacteriol_190_6014
PubMedSearch : Fang_2008_J.Bacteriol_190_6014
PubMedID: 18586939
Gene_locus related to this paper: micch-b5l6l6

Title : Influences of Cu or Cd on the neurotoxicity induced by petroleum hydrocarbons in ragworm Perinereis aibuhitensis - Zhang_2008_J.Environ.Sci.(China)_20_364
Author(s) : Zhang Q , Zhou Q , Wang J , Sun S , Hua T , Ren L
Ref : J Environ Sci (China) , 20 :364 , 2008
Abstract : The ecotoxicological effects of heavy metals and petroleum hydrocarbons (PHCs) on ragworms are still vague. The relationships between toxicological indices (mortality and acetylcholinesterase (AChE) activity) and concentrations of toxicants (Cu, Cd, and PHCs) were examined in the estuary keystone species Perinereis aibuhitensis in laboratory conditions. The results of single toxicant indicated that three toxicants had potentially physiological toxicity to P. aibuhitensis. The estimated 4-d and 10-d LC50 for Cu, Cd, and PHCs was derived from the relationships between mortality and toxicants concentrations. Notable changes in the morphological signs and symptoms of P. aibuhitensis exposed to PHCs were observed. The AChE activity of P. aibuhitensis was more sensitive to the toxicity of PHCs than the others. The results of combined toxicants implied that the combined toxicity of Cu or Cd and PHCs to P. aibuhitensis was related to the concentration combination of toxicants. Compared to single PHCs treatment, the addition of Cu or Cd significantly mitigated the neurotoxicity of PHCs to AChE activity in P. aibuhitensis, which showed an antagonistic effect.
ESTHER : Zhang_2008_J.Environ.Sci.(China)_20_364
PubMedSearch : Zhang_2008_J.Environ.Sci.(China)_20_364
PubMedID: 18595406

Title : Response to pioglitazone treatment is associated with the lipoprotein lipase S447X variant in subjects with type 2 diabetes mellitus - Wang_2007_Int.J.Clin.Pract_61_552
Author(s) : Wang G , Wang X , Zhang Q , Ma Z
Ref : Int J Clin Pract , 61 :552 , 2007
Abstract : To investigate the influence of the S447X variant in lipoprotein lipase (LPL) gene on the response rate to therapy with the thiazolidinedione pioglitazone. A total of 113 diabetic patients were treated with pioglitazone 30 mg for 10 weeks. Response to the pioglitazone treatment was defined by either a >10% relative reduction in fasting blood glucose (FBG) or a more than 1% decrease in glycosylated haemoglobin (HbA1c) values after 10 weeks of pioglitazone treatment. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method. Using the criteria >10% relative reduction in FBG after 10 weeks of pioglitaone treatment, responder frequency to pioglitazone treatment in S447S genotype group is significantly higher than S447X genotype group. Meanwhile, the S447X genotype conferred a statistically significant 0.538-fold reduction in response rate to pioglitazone treatment relative to the S447S genotype. Moreover, pioglitazone treatment has significantly beneficial effects on serum lipid profile and blood pressure in S447S genotype carriers. The S447X variant in LPL gene may be a cause for therapy modification by pioglitazone.
ESTHER : Wang_2007_Int.J.Clin.Pract_61_552
PubMedSearch : Wang_2007_Int.J.Clin.Pract_61_552
PubMedID: 17394430

Title : Pancreatic lipase-inhibiting triterpenoid saponins from fruits of Acanthopanax senticosus - Li_2007_Chem.Pharm.Bull.(Tokyo)_55_1087
Author(s) : Li F , Li W , Fu H , Zhang Q , Koike K
Ref : Chem Pharm Bull (Tokyo) , 55 :1087 , 2007
Abstract : Sixteen triterpenoid saponins were isolated from the fruits of Acanthopanax senticosus, including a new compound, acanthopanaxoside E (1), which was established as 3-O-beta-D-glucuronopyranosyl echinocystic acid 28-O-beta-D-glucopyranoside on the basis of various spectroscopic analyses and chemical degradation. By using a pancreatic lipase-inhibiting assay system, the crude saponin fraction showed inhibitory activity on pancreatic lipase, which is a key enzyme in lipid digestion. Among the isolated compounds, silphioside F (2), copteroside B (3), hederagenin 3-O-beta-D-glucuronopyranoside 6'-O-methyl ester (4) and gypsogenin 3-O-beta-D-glucuronopyranoside (5) showed inhibitory activity toward pancreatic lipase with IC(50) values of 0.22, 0.25, 0.26 and 0.29 mM, respectively, and the free carboxylic acid groups in position 28 within their chemical structures were required for enhancement of pancreatic lipase inhibition.
ESTHER : Li_2007_Chem.Pharm.Bull.(Tokyo)_55_1087
PubMedSearch : Li_2007_Chem.Pharm.Bull.(Tokyo)_55_1087
PubMedID: 17603209

Title : One-step purification of a fusion protein of glucagon-like peptide-1 and human serum albumin expressed in pichia pastoris by an immunomagnetic separation technique - Chen_2007_Biosci.Biotechnol.Biochem_71_2655
Author(s) : Chen J , Bai G , Cao Y , Gao Z , Zhang Q , Zhu Y , Yang W
Ref : Biosci Biotechnol Biochem , 71 :2655 , 2007
Abstract : Glucagon-like peptide-1 (GLP-1) has great therapeutic potential to treat diabetes type 2, mainly due to its unique glucose-dependent stimulation of insulin secretion profiles, but its clinical application is limited by its short half-life in vivo, which resultes from degradation by dipeptidyl peptidase IV and/or renal clearance. Developing long-acting GLP-1 analogs is therefore an important step toward using them therapeutically. In this study, the GLP-1/human serum albumin (HSA) fusion protein gene was cloned into the secretor type expression vector pPIC9K and subsequently expressed in Pichia pastoris. The expression quantity reached 58.5 mg/l in small-scale incubation. After optimization and characterization, the GLP-1/HSA fusion protein was successfully purified from the supernatant of the broth using immunomagnetic cellulose microspheres. HPLC showed that the purified GLP-1/HSA had an overall purity of 93.9%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the fusion protein exhibited the expected molecular mass of 70 kDa. Furthermore, that analysis of in vivo activity indicated that GLP-1/HSA reduced the blood glucose level after intraperitoneal administration to Chinese Kunming mice in a dose-dependent manner, and the effects held significantly 4 h after administration. Overall, this study illustrates the development of a long-acting GLP-1/HSA fusion protein expressed in Pichia pastoris.
ESTHER : Chen_2007_Biosci.Biotechnol.Biochem_71_2655
PubMedSearch : Chen_2007_Biosci.Biotechnol.Biochem_71_2655
PubMedID: 17986790

Title : Effect of surface hydrophobicity\/hydrophilicity of mesoporous supports on the activity of immobilized lipase - He_2006_J.Colloid.Interface.Sci_298_780
Author(s) : He J , Xu Y , Ma H , Zhang Q , Evans DG , Duan X
Ref : J Colloid Interface Sci , 298 :780 , 2006
Abstract : Taking advantage of the virtue of hydrophilic surface, lipase was firstly immobilized on SBA-15 as a support. Then the surface of the SBA-15 with enzyme entrapped inside the channels was modified by grafting with organic moieties. It has been found that the silylation with n-decyltrimethoxysilane (DE) and 3-(trimethoxysilyl)propyl methacrylate (MA) following the lipase immobilization increases the surface hydrophobicity. But the surface modified by MA shows more hydrophilicity than that modified by DE. The activity assay indicates that the hydrolytic activity for the hydrolysis of insoluble or partly soluble substrates increases with enhanced surface hydrophobicity.
ESTHER : He_2006_J.Colloid.Interface.Sci_298_780
PubMedSearch : He_2006_J.Colloid.Interface.Sci_298_780
PubMedID: 16430912

Title : The complete genome sequence of Mycobacterium avium subspecies paratuberculosis - Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_12344
Author(s) : Li L , Bannantine JP , Zhang Q , Amonsin A , May BJ , Alt D , Banerji N , Kanjilal S , Kapur V
Ref : Proc Natl Acad Sci U S A , 102 :12344 , 2005
Abstract : We describe here the complete genome sequence of a common clone of Mycobacterium avium subspecies paratuberculosis (Map) strain K-10, the causative agent of Johne's disease in cattle and other ruminants. The K-10 genome is a single circular chromosome of 4,829,781 base pairs and encodes 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon. In silico analysis identified >3,000 genes with homologs to the human pathogen, M. tuberculosis (Mtb), and 161 unique genomic regions that encode 39 previously unknown Map genes. Analysis of nucleotide substitution rates with Mtb homologs suggest overall strong selection for a vast majority of these shared mycobacterial genes, with only 68 ORFs with a synonymous to nonsynonymous substitution ratio of >2. Comparative sequence analysis reveals several noteworthy features of the K-10 genome including: a relative paucity of the PE/PPE family of sequences that are implicated as virulence factors and known to be immunostimulatory during Mtb infection; truncation in the EntE domain of a salicyl-AMP ligase (MbtA), the first gene in the mycobactin biosynthesis gene cluster, providing a possible explanation for mycobactin dependence of Map; and Map-specific sequences that are likely to serve as potential targets for sensitive and specific molecular and immunologic diagnostic tests. Taken together, the availability of the complete genome sequence offers a foundation for the study of the genetic basis for virulence and physiology in Map and enables the development of new generations of diagnostic tests for bovine Johne's disease.
ESTHER : Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_12344
PubMedSearch : Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_12344
PubMedID: 16116077
Gene_locus related to this paper: mycpa-q73tc9 , mycpa-q73vt9 , mycpa-q73xs5 , mycpa-q741s1

Title : Design, synthesis, and biological evaluation of new territrem B analogues - Jiang_2005_Chem.Biodivers_2_557
Author(s) : Jiang X , Ao L , Zhou C , Yang L , Zhang Q , Li H , Sun L , Wu X , Bai H , Zhao Y
Ref : Chem Biodivers , 2 :557 , 2005
Abstract : Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined.
ESTHER : Jiang_2005_Chem.Biodivers_2_557
PubMedSearch : Jiang_2005_Chem.Biodivers_2_557
PubMedID: 17192004

Title : The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis - Salnikow_2003_Cancer.Res_63_3524
Author(s) : Salnikow K , Davidson T , Zhang Q , Chen LC , Su W , Costa M
Ref : Cancer Research , 63 :3524 , 2003
Abstract : Nickel is a potent environmental pollutant in industrial countries. Because nickel compounds are carcinogenic, exposure to nickel represents a serious hazard to human health. The understanding of how nickel exerts its toxic and carcinogenic effects at a molecular level may be important in risk assessment, as well as in the treatment and prevention of occupational diseases. Previously, using human and rodent cells in vitro, we showed that hypoxia-inducible signaling pathway was activated by carcinogenic nickel compounds. Acute exposure to nickel resulted in the accumulation of hypoxia-inducible transcription factor (HIF)-1, which strongly activated hypoxia-inducible genes, including the recently discovered tumor marker NDRG1 (Cap43). To further identify HIF-1-dependent nickel-inducible genes and to understand the role of the HIF-dependent signaling pathway in nickel-induced transformation, we used the Affymetrix GeneChip to compare the gene expression profiles in wild-type cells or in cells from HIF-1 alpha knockout mouse embryos exposed to nickel chloride. As expected, when we examined 12,000 genes for expression changes, we found that genes coding for glycolytic enzymes and glucose transporters, known to be regulated by HIF-1 transcription factor, were induced by nickel only in HIF-1 alpha-proficient cells. In addition, we found a number of other hypoxia-inducible genes up-regulated by nickel in a HIF-dependent manner including BCL-2-binding protein Nip3, EGLN1, hypoxia-inducible gene 1 (HIG1), and prolyl 4-hydroxylase. Additionally, we found a number of genes induced by nickel in a HIF-independent manner, suggesting that Ni activated other signaling pathways besides HIF-1. Finally, we found that in HIF-1 alpha knockout cells, nickel strongly induced the expression of the whole group of genes that were not expressed in the presence of HIF-1. Because the majority of modulated genes were induced or suppressed by nickel in a HIF-1-dependent manner, we elucidated the role of HIF-1 transcription factor in cell transformation. In HIF-1 alpha-proficient cells, nickel exposure increased soft agar growth, whereas it decreased soft agar growth in HIF-1 alpha-deficient cells. We hypothesize that the induction of HIF-1 transcription factor by nickel may be important during the nickel-induced carcinogenic process.
ESTHER : Salnikow_2003_Cancer.Res_63_3524
PubMedSearch : Salnikow_2003_Cancer.Res_63_3524
PubMedID: 12839937

Title : Schizosaccharomyces pombe cells deficient in triacylglycerols synthesis undergo apoptosis upon entry into the stationary phase. - Zhang_2003_J.Biol.Chem_278_47145
Author(s) : Zhang Q , Chieu HK , Low CP , Zhang S , Heng CK , Yang H
Ref : Journal of Biological Chemistry , 278 :47145\ , 2003
Abstract : Triacylglycerols (TAG) are important energy storage molecules for nearly all eukaryotic organisms. In this study, we found that two gene products (Plh1p and Dga1p) are responsible for the terminal step of TAG synthesis in the fission yeast Schizosaccharomyces pombe through two different mechanisms: Plh1p is a phospholipid diacylglycerol acyltransferase, whereas Dga1p is an acyl-CoA:diacylglycerol acyltransferase. Cells with both dga1+ and plh1+ deleted (DKO cells) lost viability upon entry into the stationary phase and demonstrated prominent apoptotic markers. Exponentially growing DKO cells also underwent dramatic apoptosis when briefly treated with diacylglycerols (DAGs) or free fatty acids. We provide strong evidence suggesting that DAG, not sphingolipids, mediates fatty acids-induced lipoapoptosis in yeast. Lastly, we show that generation of reactive oxygen species is essential to lipoapoptosis.
ESTHER : Zhang_2003_J.Biol.Chem_278_47145
PubMedSearch : Zhang_2003_J.Biol.Chem_278_47145
PubMedID: 12963726
Gene_locus related to this paper: schpo-pdat

Title : [Impact of aldicarb and its complex pollution on DNA of zebrafish embryo] - Li_2003_Ying.Yong.Sheng.Tai.Xue.Bao_14_982
Author(s) : Li Y , Zhang Q , Dai S
Ref : Ying Yong Sheng Tai Xue Bao , 14 :982 , 2003
Abstract : This paper deals with the impact of a complex pollution system composed of a very toxic carbamate pesticide, aldicarb and the widely used anionic surfactant, sodium dodecylbenzenesulfonate(SDBS), on DNA of zebrafish (Brachydanio rerio) embryo. The results indicated that DNA damage caused by aldicarb became more serious with its increasing concentration, but single-strand break caused by aldicarb in low concentration and short time could be repaired, and high concentration led to double-strand break which was difficult to repaire. SDBS in certain concentration (20 mg.L-1) could reduce the toxicity of aldicarb in the complex pollution system.
ESTHER : Li_2003_Ying.Yong.Sheng.Tai.Xue.Bao_14_982
PubMedSearch : Li_2003_Ying.Yong.Sheng.Tai.Xue.Bao_14_982
PubMedID: 12974010

Title : A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome - Mural_2002_Science_296_1661
Author(s) : Mural RJ , Adams MD , Myers EW , Smith HO , Miklos GL , Wides R , Halpern A , Li PW , Sutton GG , Nadeau J , Salzberg SL , Holt RA , Kodira CD , Lu F , Chen L , Deng Z , Evangelista CC , Gan W , Heiman TJ , Li J , Li Z , Merkulov GV , Milshina NV , Naik AK , Qi R , Shue BC , Wang A , Wang J , Wang X , Yan X , Ye J , Yooseph S , Zhao Q , Zheng L , Zhu SC , Biddick K , Bolanos R , Delcher AL , Dew IM , Fasulo D , Flanigan MJ , Huson DH , Kravitz SA , Miller JR , Mobarry CM , Reinert K , Remington KA , Zhang Q , Zheng XH , Nusskern DR , Lai Z , Lei Y , Zhong W , Yao A , Guan P , Ji RR , Gu Z , Wang ZY , Zhong F , Xiao C , Chiang CC , Yandell M , Wortman JR , Amanatides PG , Hladun SL , Pratts EC , Johnson JE , Dodson KL , Woodford KJ , Evans CA , Gropman B , Rusch DB , Venter E , Wang M , Smith TJ , Houck JT , Tompkins DE , Haynes C , Jacob D , Chin SH , Allen DR , Dahlke CE , Sanders R , Li K , Liu X , Levitsky AA , Majoros WH , Chen Q , Xia AC , Lopez JR , Donnelly MT , Newman MH , Glodek A , Kraft CL , Nodell M , Ali F , An HJ , Baldwin-Pitts D , Beeson KY , Cai S , Carnes M , Carver A , Caulk PM , Center A , Chen YH , Cheng ML , Coyne MD , Crowder M , Danaher S , Davenport LB , Desilets R , Dietz SM , Doup L , Dullaghan P , Ferriera S , Fosler CR , Gire HC , Gluecksmann A , Gocayne JD , Gray J , Hart B , Haynes J , Hoover J , Howland T , Ibegwam C , Jalali M , Johns D , Kline L , Ma DS , MacCawley S , Magoon A , Mann F , May D , McIntosh TC , Mehta S , Moy L , Moy MC , Murphy BJ , Murphy SD , Nelson KA , Nuri Z , Parker KA , Prudhomme AC , Puri VN , Qureshi H , Raley JC , Reardon MS , Regier MA , Rogers YH , Romblad DL , Schutz J , Scott JL , Scott R , Sitter CD , Smallwood M , Sprague AC , Stewart E , Strong RV , Suh E , Sylvester K , Thomas R , Tint NN , Tsonis C , Wang G , Williams MS , Williams SM , Windsor SM , Wolfe K , Wu MM , Zaveri J , Chaturvedi K , Gabrielian AE , Ke Z , Sun J , Subramanian G , Venter JC , Pfannkoch CM , Barnstead M , Stephenson LD
Ref : Science , 296 :1661 , 2002
Abstract : The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
ESTHER : Mural_2002_Science_296_1661
PubMedSearch : Mural_2002_Science_296_1661
PubMedID: 12040188
Gene_locus related to this paper: mouse-ABH15 , mouse-Ces3b , mouse-Ces4a , mouse-dpp4 , mouse-FAP , mouse-Lipg , mouse-Q8C1A9 , mouse-rbbp9 , mouse-SERHL , mouse-SPG21 , mouse-w4vsp6

Title : Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks - Smoot_2002_Proc.Natl.Acad.Sci.U.S.A_99_4668
Author(s) : Smoot JC , Barbian KD , Van Gompel JJ , Smoot LM , Chaussee MS , Sylva GL , Sturdevant DE , Ricklefs SM , Porcella SF , Parkins LD , Beres SB , Campbell DS , Smith TM , Zhang Q , Kapur V , Daly JA , Veasy LG , Musser JM
Ref : Proc Natl Acad Sci U S A , 99 :4668 , 2002
Abstract : Acute rheumatic fever (ARF), a sequelae of group A Streptococcus (GAS) infection, is the most common cause of preventable childhood heart disease worldwide. The molecular basis of ARF and the subsequent rheumatic heart disease are poorly understood. Serotype M18 GAS strains have been associated for decades with ARF outbreaks in the U.S. As a first step toward gaining new insight into ARF pathogenesis, we sequenced the genome of strain MGAS8232, a serotype M18 organism isolated from a patient with ARF. The genome is a circular chromosome of 1,895,017 bp, and it shares 1.7 Mb of closely related genetic material with strain SF370 (a sequenced serotype M1 strain). Strain MGAS8232 has 178 ORFs absent in SF370. Phages, phage-like elements, and insertion sequences are the major sources of variation between the genomes. The genomes of strain MGAS8232 and SF370 encode many of the same proven or putative virulence factors. Importantly, strain MGAS8232 has genes encoding many additional secreted proteins involved in human-GAS interactions, including streptococcal pyrogenic exotoxin A (scarlet fever toxin) and two uncharacterized pyrogenic exotoxin homologues, all phage-associated. DNA microarray analysis of 36 serotype M18 strains from diverse localities showed that most regions of variation were phages or phage-like elements. Two epidemics of ARF occurring 12 years apart in Salt Lake City, UT, were caused by serotype M18 strains that were genetically identical, or nearly so. Our analysis provides a critical foundation for accelerated research into ARF pathogenesis and a molecular framework to study the plasticity of GAS genomes.
ESTHER : Smoot_2002_Proc.Natl.Acad.Sci.U.S.A_99_4668
PubMedSearch : Smoot_2002_Proc.Natl.Acad.Sci.U.S.A_99_4668
PubMedID: 11917108
Gene_locus related to this paper: strpy-ESTA , strpy-PEPXP , strpy-SPY1308 , strpy-SPYM18.1727 , strpy-SPYM18.1957

Title : The sequence of the human genome - Venter_2001_Science_291_1304
Author(s) : Venter JC , Adams MD , Myers EW , Li PW , Mural RJ , Sutton GG , Smith HO , Yandell M , Evans CA , Holt RA , Gocayne JD , Amanatides P , Ballew RM , Huson DH , Wortman JR , Zhang Q , Kodira CD , Zheng XH , Chen L , Skupski M , Subramanian G , Thomas PD , Zhang J , Gabor Miklos GL , Nelson C , Broder S , Clark AG , Nadeau J , McKusick VA , Zinder N , Levine AJ , Roberts RJ , Simon M , Slayman C , Hunkapiller M , Bolanos R , Delcher A , Dew I , Fasulo D , Flanigan M , Florea L , Halpern A , Hannenhalli S , Kravitz S , Levy S , Mobarry C , Reinert K , Remington K , Abu-Threideh J , Beasley E , Biddick K , Bonazzi V , Brandon R , Cargill M , Chandramouliswaran I , Charlab R , Chaturvedi K , Deng Z , Di Francesco V , Dunn P , Eilbeck K , Evangelista C , Gabrielian AE , Gan W , Ge W , Gong F , Gu Z , Guan P , Heiman TJ , Higgins ME , Ji RR , Ke Z , Ketchum KA , Lai Z , Lei Y , Li Z , Li J , Liang Y , Lin X , Lu F , Merkulov GV , Milshina N , Moore HM , Naik AK , Narayan VA , Neelam B , Nusskern D , Rusch DB , Salzberg S , Shao W , Shue B , Sun J , Wang Z , Wang A , Wang X , Wang J , Wei M , Wides R , Xiao C , Yan C , Yao A , Ye J , Zhan M , Zhang W , Zhang H , Zhao Q , Zheng L , Zhong F , Zhong W , Zhu S , Zhao S , Gilbert D , Baumhueter S , Spier G , Carter C , Cravchik A , Woodage T , Ali F , An H , Awe A , Baldwin D , Baden H , Barnstead M , Barrow I , Beeson K , Busam D , Carver A , Center A , Cheng ML , Curry L , Danaher S , Davenport L , Desilets R , Dietz S , Dodson K , Doup L , Ferriera S , Garg N , Gluecksmann A , Hart B , Haynes J , Haynes C , Heiner C , Hladun S , Hostin D , Houck J , Howland T , Ibegwam C , Johnson J , Kalush F , Kline L , Koduru S , Love A , Mann F , May D , McCawley S , McIntosh T , McMullen I , Moy M , Moy L , Murphy B , Nelson K , Pfannkoch C , Pratts E , Puri V , Qureshi H , Reardon M , Rodriguez R , Rogers YH , Romblad D , Ruhfel B , Scott R , Sitter C , Smallwood M , Stewart E , Strong R , Suh E , Thomas R , Tint NN , Tse S , Vech C , Wang G , Wetter J , Williams S , Williams M , Windsor S , Winn-Deen E , Wolfe K , Zaveri J , Zaveri K , Abril JF , Guigo R , Campbell MJ , Sjolander KV , Karlak B , Kejariwal A , Mi H , Lazareva B , Hatton T , Narechania A , Diemer K , Muruganujan A , Guo N , Sato S , Bafna V , Istrail S , Lippert R , Schwartz R , Walenz B , Yooseph S , Allen D , Basu A , Baxendale J , Blick L , Caminha M , Carnes-Stine J , Caulk P , Chiang YH , Coyne M , Dahlke C , Mays A , Dombroski M , Donnelly M , Ely D , Esparham S , Fosler C , Gire H , Glanowski S , Glasser K , Glodek A , Gorokhov M , Graham K , Gropman B , Harris M , Heil J , Henderson S , Hoover J , Jennings D , Jordan C , Jordan J , Kasha J , Kagan L , Kraft C , Levitsky A , Lewis M , Liu X , Lopez J , Ma D , Majoros W , McDaniel J , Murphy S , Newman M , Nguyen T , Nguyen N , Nodell M , Pan S , Peck J , Peterson M , Rowe W , Sanders R , Scott J , Simpson M , Smith T , Sprague A , Stockwell T , Turner R , Venter E , Wang M , Wen M , Wu D , Wu M , Xia A , Zandieh A , Zhu X
Ref : Science , 291 :1304 , 2001
Abstract : A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.
ESTHER : Venter_2001_Science_291_1304
PubMedSearch : Venter_2001_Science_291_1304
PubMedID: 11181995
Gene_locus related to this paper: human-AADAC , human-ABHD1 , human-ABHD10 , human-ABHD11 , human-ACHE , human-BCHE , human-LDAH , human-ABHD18 , human-CMBL , human-ABHD17A , human-KANSL3 , human-LIPA , human-LYPLAL1 , human-NDRG2 , human-NLGN3 , human-NLGN4X , human-NLGN4Y , human-PAFAH2 , human-PREPL , human-RBBP9 , human-SPG21

Title : Complete genomic sequence of Pasteurella multocida, Pm70 - May_2001_Proc.Natl.Acad.Sci.U.S.A_98_3460
Author(s) : May BJ , Zhang Q , Li LL , Paustian ML , Whittam TS , Kapur V
Ref : Proc Natl Acad Sci U S A , 98 :3460 , 2001
Abstract : We present here the complete genome sequence of a common avian clone of Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome 2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6 ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on pairwise comparisons of 1,197 orthologous sequences between P. multocida, Haemophilus influenzae, and Escherichia coli suggest that P. multocida and H. influenzae diverged approximately 270 million years ago and the gamma subdivision of the proteobacteria radiated about 680 million years ago. Two previously undescribed open reading frames, accounting for approximately 1% of the genome, encode large proteins with homology to the virulence-associated filamentous hemagglutinin of Bordetella pertussis. Consistent with the critical role of iron in the survival of many microbial pathogens, in silico and whole-genome microarray analyses identified more than 50 Pm70 genes with a potential role in iron acquisition and metabolism. Overall, the complete genomic sequence and preliminary functional analyses provide a foundation for future research into the mechanisms of pathogenesis and host specificity of this important multispecies pathogen.
ESTHER : May_2001_Proc.Natl.Acad.Sci.U.S.A_98_3460
PubMedSearch : May_2001_Proc.Natl.Acad.Sci.U.S.A_98_3460
PubMedID: 11248100
Gene_locus related to this paper: pasmu-KMT1 , pasmu-metx , pasmu-PLDB , pasmu-PM0055 , pasmu-PM0355 , pasmu-PM1358 , pasmu-q9cjt9 , pasmu-XYNC , pasmu-y825

Title : A whole-genome assembly of Drosophila - Myers_2000_Science_287_2196
Author(s) : Myers EW , Sutton GG , Delcher AL , Dew IM , Fasulo DP , Flanigan MJ , Kravitz SA , Mobarry CM , Reinert KH , Remington KA , Anson EL , Bolanos RA , Chou HH , Jordan CM , Halpern AL , Lonardi S , Beasley EM , Brandon RC , Chen L , Dunn PJ , Lai Z , Liang Y , Nusskern DR , Zhan M , Zhang Q , Zheng X , Rubin GM , Adams MD , Venter JC
Ref : Science , 287 :2196 , 2000
Abstract : We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.
ESTHER : Myers_2000_Science_287_2196
PubMedSearch : Myers_2000_Science_287_2196
PubMedID: 10731133

Title : [Experimental study on effect of bushen yijing recipe in delaying senility of bone and brain of aged male rats] - Zhang_2000_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_20_43
Author(s) : Zhang G , Ma J , Zhang Q
Ref : Zhongguo Zhong Xi Yi Jie He Za Zhi , 20 :43 , 2000
Abstract : OBJECTIVE To evaluate the effect of Bushen Yijing recipe BSYJR in delaying senility of bone and brain of aged male rats and infer its mechanism in delaying systemic senility METHODS Forty male SD rats 24 months old were randomly divided into 4 groups the baseline control group the aged control group 30 months old the BSYJR high dose group and the BSYJR low dose group The latter two groups received BSYJR treatment from 24 months old to 30 months old Bone indexes bone density of the proximal middle and distal segments of left femur and break bending load of right femur and brain indexes binding capacity of M receptor and cholinesterase activity of brain were measured after responding treatment RESULTS In bone BSYJR could not only increase the bone mineral density in various segments of femur but also raise the bending break load of femur dose-effect dependently In brain BSYJR could both up-regulate the binding capacity of M receptor and inhibit the activity of cholinesterase CONCLUSION BSYJR could delay the senility of bone and brain in male rats inferring that it might regulate integrally the abnormality of aging in Kidney Asthenia and Essence Deficiency through mediation of nerve-endocrine-immunity network
ESTHER : Zhang_2000_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_20_43
PubMedSearch : Zhang_2000_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_20_43
PubMedID: 11783337

Title : The genome sequence of Drosophila melanogaster - Adams_2000_Science_287_2185
Author(s) : Adams MD , Celniker SE , Holt RA , Evans CA , Gocayne JD , Amanatides PG , Scherer SE , Li PW , Hoskins RA , Galle RF , George RA , Lewis SE , Richards S , Ashburner M , Henderson SN , Sutton GG , Wortman JR , Yandell MD , Zhang Q , Chen LX , Brandon RC , Rogers YH , Blazej RG , Champe M , Pfeiffer BD , Wan KH , Doyle C , Baxter EG , Helt G , Nelson CR , Gabor GL , Abril JF , Agbayani A , An HJ , Andrews-Pfannkoch C , Baldwin D , Ballew RM , Basu A , Baxendale J , Bayraktaroglu L , Beasley EM , Beeson KY , Benos PV , Berman BP , Bhandari D , Bolshakov S , Borkova D , Botchan MR , Bouck J , Brokstein P , Brottier P , Burtis KC , Busam DA , Butler H , Cadieu E , Center A , Chandra I , Cherry JM , Cawley S , Dahlke C , Davenport LB , Davies P , de Pablos B , Delcher A , Deng Z , Mays AD , Dew I , Dietz SM , Dodson K , Doup LE , Downes M , Dugan-Rocha S , Dunkov BC , Dunn P , Durbin KJ , Evangelista CC , Ferraz C , Ferriera S , Fleischmann W , Fosler C , Gabrielian AE , Garg NS , Gelbart WM , Glasser K , Glodek A , Gong F , Gorrell JH , Gu Z , Guan P , Harris M , Harris NL , Harvey D , Heiman TJ , Hernandez JR , Houck J , Hostin D , Houston KA , Howland TJ , Wei MH , Ibegwam C , Jalali M , Kalush F , Karpen GH , Ke Z , Kennison JA , Ketchum KA , Kimmel BE , Kodira CD , Kraft C , Kravitz S , Kulp D , Lai Z , Lasko P , Lei Y , Levitsky AA , Li J , Li Z , Liang Y , Lin X , Liu X , Mattei B , McIntosh TC , McLeod MP , McPherson D , Merkulov G , Milshina NV , Mobarry C , Morris J , Moshrefi A , Mount SM , Moy M , Murphy B , Murphy L , Muzny DM , Nelson DL , Nelson DR , Nelson KA , Nixon K , Nusskern DR , Pacleb JM , Palazzolo M , Pittman GS , Pan S , Pollard J , Puri V , Reese MG , Reinert K , Remington K , Saunders RD , Scheeler F , Shen H , Shue BC , Siden-Kiamos I , Simpson M , Skupski MP , Smith T , Spier E , Spradling AC , Stapleton M , Strong R , Sun E , Svirskas R , Tector C , Turner R , Venter E , Wang AH , Wang X , Wang ZY , Wassarman DA , Weinstock GM , Weissenbach J , Williams SM , WoodageT , Worley KC , Wu D , Yang S , Yao QA , Ye J , Yeh RF , Zaveri JS , Zhan M , Zhang G , Zhao Q , Zheng L , Zheng XH , Zhong FN , Zhong W , Zhou X , Zhu S , Zhu X , Smith HO , Gibbs RA , Myers EW , Rubin GM , Venter JC
Ref : Science , 287 :2185 , 2000
Abstract : The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.
ESTHER : Adams_2000_Science_287_2185
PubMedSearch : Adams_2000_Science_287_2185
PubMedID: 10731132
Gene_locus related to this paper: drome-1vite , drome-2vite , drome-3vite , drome-a1z6g9 , drome-abhd2 , drome-ACHE , drome-b6idz4 , drome-BEM46 , drome-CG5707 , drome-CG5704 , drome-CG1309 , drome-CG1882 , drome-CG1986 , drome-CG2059 , drome-CG2493 , drome-CG2528 , drome-CG2772 , drome-CG3160 , drome-CG3344 , drome-CG3523 , drome-CG3524 , drome-CG3734 , drome-CG3739 , drome-CG3744 , drome-CG3841 , drome-CG4267 , drome-CG4382 , drome-CG4390 , drome-CG4572 , drome-CG4582 , drome-CG4851 , drome-CG4979 , drome-CG5068 , drome-CG5162 , drome-CG5355 , drome-CG5377 , drome-CG5397 , drome-CG5412 , drome-CG5665 , drome-CG5932 , drome-CG5966 , drome-CG6018 , drome-CG6113 , drome-CG6271 , drome-CG6283 , drome-CG6295 , drome-CG6296 , drome-CG6414 , drome-CG6431 , drome-CG6472 , drome-CG6567 , drome-CG6675 , drome-CG6753 , drome-CG6847 , drome-CG7329 , drome-CG7367 , drome-CG7529 , drome-CG7632 , drome-CG8058 , drome-CG8093 , drome-CG8233 , drome-CG8424 , drome-CG8425 , drome-CG9059 , drome-CG9186 , drome-CG9287 , drome-CG9289 , drome-CG9542 , drome-CG9858 , drome-CG9953 , drome-CG9966 , drome-CG10116 , drome-CG10163 , drome-CG10175 , drome-CG10339 , drome-CG10357 , drome-CG10982 , drome-CG11034 , drome-CG11055 , drome-CG11309 , drome-CG11319 , drome-CG11406 , drome-CG11598 , drome-CG11600 , drome-CG11608 , drome-CG11626 , drome-CG11935 , drome-CG12108 , drome-CG12869 , drome-CG13282 , drome-CG13562 , drome-CG13772 , drome-CG14034 , drome-nlg3 , drome-CG14717 , drome-CG15101 , drome-CG15102 , drome-CG15106 , drome-CG15111 , drome-CG15820 , drome-CG15821 , drome-CG15879 , drome-CG17097 , drome-CG17099 , drome-CG17101 , drome-CG17191 , drome-CG17192 , drome-CG17292 , drome-CG18258 , drome-CG18284 , drome-CG18301 , drome-CG18302 , drome-CG18493 , drome-CG18530 , drome-CG18641 , drome-CG18815 , drome-CG31089 , drome-CG31091 , drome-CG32333 , drome-CG32483 , drome-CG33174 , drome-dnlg1 , drome-este4 , drome-este6 , drome-GH02384 , drome-GH02439 , drome-glita , drome-KRAKEN , drome-lip1 , drome-LIP2 , drome-lip3 , drome-MESK2 , drome-nrtac , drome-OME , drome-q7k274 , drome-Q9VJN0 , drome-Q8IP31 , drome-q9vux3

Title : Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects - Zhang_1998_Mol.Genet.Metab_64_177
Author(s) : Zhang Q , Liu Y , Liu BW , Fan P , Cavanna J , Galton DJ
Ref : Mol Genet Metab , 64 :177 , 1998
Abstract : The large ethnic differences in prevalence of coronary artery disease between China and Europe may relate to both genetic and environmental differences. To assess possible genetic factors we have therefore studied the frequencies of disease-related variants of genes involved in lipid transport in 69 hypertriglyceridemic Chinese subjects and 74 healthy Chinese controls. The loci studied include lipoprotein lipase (Asp9Asn, Asn291Ser, Ser447Ter, and Thr361Thr); apolipoprotein A1 (restriction sites at MspI, XmnI, and PstI); and apolipoprotein (apo) CIII (G3175C). All these variants have been shown in previous literature publications to relate to either dyslipidemia and/or premature coronary heart disease in Caucasians. Two disease-related genetic variants in Europeans (Asp9Asn and Asn291Ser) were not found in the Chinese sample. The apo CIII G3175C variant was found more frequently in the upper tertile distributions for apolipoprotein CIII, apolipoprotein E, and plasma triglyceride/HDL ratios (P < 0.05). The rare allele of the apo AI MspI restriction site polymorphic variant was also found more frequently in the upper tertiles for apo CIII, apo E, and plasma triglyceride/HDL ratios (P < 0.04). Eleven of the most lipaemic Chinese subjects (with fasting plasma triglycerides >700 mg/dl) were analyzed for DNA sequence variation. One novel mutation was observed C1338A (which is a silent mutation at Thr361) and two others that are also found in European subjects (Ala261Thr and Ser447Ter). We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted.
ESTHER : Zhang_1998_Mol.Genet.Metab_64_177
PubMedSearch : Zhang_1998_Mol.Genet.Metab_64_177
PubMedID: 9719626