Zhou J

References (155)

Title : The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis - Liu_2024_Lipids.Health.Dis_23_44
Author(s) : Liu Y , Dai S , Qin S , Zhou J , Wang Z , Yin G
Ref : Lipids Health Dis , 23 :44 , 2024
Abstract : BACKGROUND AND AIMS: To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations. METHODS: Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software. RESULTS: 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215-Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL. 3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC. CONCLUSIONS: The pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.
ESTHER : Liu_2024_Lipids.Health.Dis_23_44
PubMedSearch : Liu_2024_Lipids.Health.Dis_23_44
PubMedID: 38331899

Title : Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study - Gao_2024_Front.Neurosci_18_1379933
Author(s) : Gao Y , Zhang Y , Chunyu H , Xu Y , Wang Y , Liu S , Chang J , Tang B , Xu C , Lu Y , Zhou J , Kong X , Zhu X , Chen S , Zhou Q , Meng H
Ref : Front Neurosci , 18 :1379933 , 2024
Abstract : OBJECTIVE: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease. METHODS: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes. RESULTS: The average age at diagnosis was 45.93 +/- 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on (18)F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up. CONCLUSION: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.
ESTHER : Gao_2024_Front.Neurosci_18_1379933
PubMedSearch : Gao_2024_Front.Neurosci_18_1379933
PubMedID: 38756408
Gene_locus related to this paper: human-DPP6

Title : Novel polyurethane-degrading cutinase BaCut1 from Blastobotrys sp. G-9 with potential role in plastic bio-recycling - Jiang_2024_J.Hazard.Mater_472_134493
Author(s) : Jiang Z , Chen X , Xue H , Li Z , Lei J , Yu M , Yan X , Cao H , Zhou J , Liu J , Zheng M , Dong W , Li Y , Cui Z
Ref : J Hazard Mater , 472 :134493 , 2024
Abstract : Environmental pollution caused by plastic waste has become global problem that needs to be considered urgently. In the pursuit of a circular plastic economy, biodegradation provides an attractive strategy for managing plastic wastes, whereas effective plastic-degrading microbes and enzymes are required. In this study, we report that Blastobotrys sp. G-9 isolated from discarded plastic in landfills is capable of depolymerizing polyurethanes (PU) and poly (butylene adipate-co-terephthalate) (PBAT). Strain G-9 degrades up to 60% of PU foam after 21 days of incubation at 28 degC by breaking down carbonyl groups via secretory hydrolase as confirmed by structural characterization of plastics and degradation products identification. Within the supernatant of strain G-9, we identify a novel cutinase BaCut1, belonging to the esterase family, that can reproduce the same effect. BaCut1 demonstrates efficient degradation toward commercial polyester plastics PU foam (0.5 mg enzyme/25 mg plastic) and agricultural film PBAT (0.5 mg enzyme/10 mg plastic) with 50% and 18% weight loss at 37 degC for 48 h, respectively. BaCut1 hydrolyzes PU into adipic acid as a major end-product with 42.9% recovery via ester bond cleavage, and visible biodegradation is also identified from PBAT, which is a beneficial feature for future recycling economy. Molecular docking, along with products distribution, elucidates a special substrate-binding modes of BaCut1 with plastic substrate analogue. BaCut1-mediated polyester plastic degradation offers an alternative approach for managing PU plastic wastes through possible bio-recycling.
ESTHER : Jiang_2024_J.Hazard.Mater_472_134493
PubMedSearch : Jiang_2024_J.Hazard.Mater_472_134493
PubMedID: 38696960
Gene_locus related to this paper: 9asco-BaCut1

Title : Depolymerization of the polyester-polyurethane by amidase GatA250 and enhancing the production of 4,4'-methylenedianiline with cutinase LCC - Xin_2024_Biotechnol.J_19_e2300723
Author(s) : Xin K , Lu J , Zeng Q , Zhang T , Liu J , Zhou J , Dong W , Jiang M
Ref : Biotechnol J , 19 :e2300723 , 2024
Abstract : Polyurethane (PU) is a complex polymer synthesized from polyols and isocyanates. It contains urethane bonds that resist hydrolysis, which decreases the efficiency of biodegradation. In this study, we first expressed the amidase GatA250, and then, assessed the enzymatic characterization of GatA250 and its efficiency in degrading the polyester-PU. GatA250 degraded self-synthesized thermoplastic PU film and postconsumption foam with degradation efficiency of 8.17% and 4.29%, respectively. During the degradation, the film released 14.8 microm 4,4'-methylenedianiline (MDA), but 1,4-butanediol (BDO) and adipic acid (AA) were not released. Our findings indicated that GatA250 only cleaved urethane bonds in PU, and the degradation efficiency was extremely low. Hence, we introduced the cutinase LCC, which possesses hydrolytic activity on the ester bonds in PU, and then used both enzymes simultaneously to degrade the polyester-PU. The combined system (LCC-GatA250) had higher degradation efficiency for the degradation of PU film (42.2%) and foam (13.94%). The combined system also showed a 1.80 time increase in the production of the monomer MDA, and a 1.23 and 3.62 times increase in the production of AA and BDO, respectively, compared to their production recorded after treatment with only GatA250 or LCC. This study provides valuable insights into PU pollution control and also proposes applicable solutions to manage PU wastes through bio-recycling.
ESTHER : Xin_2024_Biotechnol.J_19_e2300723
PubMedSearch : Xin_2024_Biotechnol.J_19_e2300723
PubMedID: 38622797
Gene_locus related to this paper: 9bact-g9by57

Title : Identification and characterization of a fungal cutinase-like enzyme CpCut1 from Cladosporium sp. P7 for polyurethane degradation - Liu_2024_Appl.Environ.Microbiol__e0147723
Author(s) : Liu J , Xin K , Zhang T , Wen Y , Li D , Wei R , Zhou J , Cui Z , Dong W , Jiang M
Ref : Applied Environmental Microbiology , :e0147723 , 2024
Abstract : Plastic degradation by biological systems emerges as a prospective avenue for addressing the pressing global concern of plastic waste accumulation. The intricate chemical compositions and diverse structural facets inherent to polyurethanes (PU) substantially increase the complexity associated with PU waste management. Despite the extensive research endeavors spanning over decades, most known enzymes exhibit a propensity for hydrolyzing waterborne PU dispersion (i.e., the commercial Impranil DLN-SD), with only a limited capacity for the degradation of bulky PU materials. Here, we report a novel cutinase (CpCut1) derived from Cladosporium sp. P7, which demonstrates remarkable efficiency in the degrading of various polyester-PU materials. After 12-h incubation at 55 degreesC, CpCut1 was capable of degrading 40.5% and 20.6% of thermoplastic PU film and post-consumer foam, respectively, while achieving complete depolymerization of Impranil DLN-SD. Further analysis of the degradation intermediates suggested that the activity of CpCut1 primarily targeted the ester bonds within the PU soft segments. The versatile performance of CpCut1 against a spectrum of polyester-PU materials positions it as a promising candidate for the bio-recycling of waste plastics.IMPORTANCEPolyurethane (PU) has a complex chemical composition that frequently incorporates a variety of additives, which poses significant obstacles to biodegradability and recyclability. Recent advances have unveiled microbial degradation and enzymatic depolymerization as promising waste PU disposal strategies. In this study, we identified a gene encoding a cutinase from the PU-degrading fungus Cladosporium sp. P7, which allowed the expression, purification, and characterization of the recombinant enzyme CpCut1. Furthermore, this study identified the products derived from the CpCut1 catalyzed PU degradation and proposed its underlying mechanism. These findings highlight the potential of this newly discovered fungal cutinase as a remarkably efficient tool in the degradation of PU materials.
ESTHER : Liu_2024_Appl.Environ.Microbiol__e0147723
PubMedSearch : Liu_2024_Appl.Environ.Microbiol__e0147723
PubMedID: 38445906
Gene_locus related to this paper: 9pezi-CpCut1

Title : Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS\/MS:An application to pharmacokinetic studies - Wang_2024_J.Pharm.Biomed.Anal_246_116199
Author(s) : Wang H , Chen H , Cui X , Zhang Y , Zhou J , Chen X
Ref : J Pharm Biomed Anal , 246 :116199 , 2024
Abstract : Unecritinib (TQ-B3101) is a selective tyrosine kinase receptor inhibitor. In the study, in vitro metabolic experiments revealed that the hydrolysis of TQ-B3101 was mainly catalyzed by carboxylesterase 2 (CES2), followed by CES1. Next, a sensitive and reliable LC-MS/MS method was established for the simultaneous determination of TQ-B3101 and its metabolite crizotinib in rat plasma. To prevent in vitro hydrolysis of TQ-B3101, sodium fluoride, the CESs inhibitor at a concentration of 2 M, was immediately added after whole blood collection. Plasma samples were extracted by acetonitrile-induced protein precipitation method, and chromatographically separated on a Gemini C(18) column (50 mm x 2.0 mm i.d., 5 microm) using gradient elution with a mobile phase of 0.1% formic acid and 5 mmol/L ammonium acetate with 0.1% formic acid. The retention times for TQ-B3101 and crizotinib were 2.61 and 2.38 min, respectively. The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 ? 302.3 for TQ-B3101, m/z 450.3 ? 260.3 for crizotinib, and m/z 494.0 ? 394.3 for imatinib (internal standard). Method validation was conducted in the linear range of 1.00-800 ng/mL for the two analytes. The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib.
ESTHER : Wang_2024_J.Pharm.Biomed.Anal_246_116199
PubMedSearch : Wang_2024_J.Pharm.Biomed.Anal_246_116199
PubMedID: 38744200

Title : Post-Stroke Neuropsychiatric Complications: Types, Pathogenesis, and Therapeutic Intervention - Zhou_2023_Aging.Dis__
Author(s) : Zhou J , Fangma Y , Chen Z , Zheng Y
Ref : Aging Dis , : , 2023
Abstract : Almost all stroke survivors suffer physical disabilities and neuropsychiatric disturbances, which can be briefly divided into post-stroke neurological diseases and post-stroke psychiatric disorders. The former type mainly includes post-stroke pain, post-stroke epilepsy, and post-stroke dementia while the latter one includes post-stroke depression, post-stroke anxiety, post-stroke apathy and post-stroke fatigue. Multiple risk factors are related to these post-stroke neuropsychiatric complications, such as age, gender, lifestyle, stroke type, medication, lesion location, and comorbidities. Recent studies have revealed several critical mechanisms underlying these complications, namely inflammatory response, dysregulation of the hypothalamic pituitary adrenal axis, cholinergic dysfunction, reduced level of 5-hydroxytryptamine, glutamate-mediated excitotoxicity and mitochondrial dysfunction. Moreover, clinical efforts have successfully given birth to many practical pharmaceutic strategies, such as anti-inflammatory medications, acetylcholinesterase inhibitors, and selective serotonin reuptake inhibitors, as well as diverse rehabilitative modalities to help patients physically and mentally. However, the efficacy of these interventions is still under debate. Further investigations into these post-stroke neuropsychiatric complications, from both basic and clinical perspectives, are urgent for the development of effective treatment strategies.
ESTHER : Zhou_2023_Aging.Dis__
PubMedSearch : Zhou_2023_Aging.Dis__
PubMedID: 37199575

Title : Characterization of a novel esterase and construction of a Rhodococcus-Burkholderia consortium capable of catabolism bis (2-hydroxyethyl) terephthalate - Jiang_2023_Environ.Res__117240
Author(s) : Jiang W , Sun J , Dong W , Zhou J , Jiang Y , Zhang W , Xin F , Jiang M
Ref : Environ Research , :117240 , 2023
Abstract : Bis (2-hydroxyethyl) terephthalate (BHET) is one of the main compounds produced by enzymatic hydrolysis or chemical depolymerization of polyethylene terephthalate (PET). However, the lack of understanding on BHET microbial metabolism is a main factor limiting the bio-upcycling of PET. In this study, BHET-degrading strains of Rhodococcus biphenylivorans GA1 and Burkholderia sp. EG1 were isolated and identified, which can grow with BHET as the sole carbon source. Furthermore, a novel esterase gene betH was cloned from strain GA1, which encodes a BHET hydrolyzing esterase with the highest activity at 30 degreesC and pH 7.0. In addition, the co-culture containing strain GA1 and strain EG1 could completely degrade high concentration of BHET, eliminating the inhibition on strain GA1 caused by the accumulation of intermediate metabolite ethylene glycol (EG). This work will provide potential strains and a feasible strategy for PET bio-upcycling.
ESTHER : Jiang_2023_Environ.Res__117240
PubMedSearch : Jiang_2023_Environ.Res__117240
PubMedID: 37783328
Gene_locus related to this paper: 9noca-h0jte1

Title : Enhancing the Hydrolysis and Acyl Transfer Activity of Carboxylesterase DLFae4 by a Combinational Mutagenesis and In-Silico Method - Li_2023_Foods_12_1169
Author(s) : Li L , Ding L , Shao Y , Sun S , Wang M , Xiang J , Zhou J , Wu G , Song Z , Xin Z
Ref : Foods , 12 :1169 , 2023
Abstract : In the present study, a feruloyl esterase DLFae4 identified in our previous research was modified by error-prone PCR and site-directed saturation mutation to enhance the catalytic efficiency and acyltransferase activity further. Five mutants with 6.9-118.9% enhanced catalytic activity toward methyl ferulate (MFA) were characterized under the optimum conditions. Double variant DLFae4-m5 exhibited the highest hydrolytic activity (270.97 U/mg), the Km value decreased by 83.91%, and the Kcat/Km value increased by 6.08-fold toward MFA. Molecular docking indicated that a complex hydrogen bond network in DLFae4-m5 was formed, with four of five bond lengths being shortened compared with DLFae4, which might account for the increase in catalytic activity. Acyl transfer activity assay revealed that the activity of DLFae4 was as high as 1550.796 U/mg and enhanced by 375.49% (5823.172 U/mg) toward 4-nitrophenyl acetate when residue Ala-341 was mutated to glycine (A341G), and the corresponding acyl transfer efficiency was increased by 7.7 times, representing the highest acyltransferase activity to date, and demonstrating that the WGG motif was pivotal for the acyltransferase activity in family VIII carboxylesterases. Further experiments indicated that DLFae4 and variant DLFae4 (A341G) could acylate cyanidin-3-O-glucoside effectively in aqueous solution. Taken together, our study suggested the effectiveness of error-prone PCR and site-directed saturation mutation to increase the specific activity of enzymes and may facilitate the practical application of this critical feruloyl esterase.
ESTHER : Li_2023_Foods_12_1169
PubMedSearch : Li_2023_Foods_12_1169
PubMedID: 36981096

Title : Biochemical characterization of two novel mutations in the human high-affinity choline transporter 1 identified in a patient with congenital myasthenic syndrome - Rizvi_2023_Hum.Mol.Genet__
Author(s) : Rizvi M , Truong TK , Zhou J , Batta M , Moran ES , Pappas J , Chu ML , Caluseriu O , Evrony GD , Leslie EM , Cordat E
Ref : Hum Mol Genet , : , 2023
Abstract : Congenital myasthenic syndrome (CMS) is a heterogeneous condition associated with 34 different genes, including SLC5A7, which encodes the high affinity choline transporter 1 (CHT1). CHT1 is expressed in presynaptic neurons of the neuromuscular junction where it uses the inward sodium gradient to re-uptake choline. Bi-allelic CHT1 mutations often lead to neonatal lethality, and less commonly to non-lethal motor weakness and developmental delays. Here, we report detailed biochemical characterization of two novel mutations in CHT1, p.I294T and p.D349N, that we identified in an 11syear-old patient with a history of neonatal respiratory distress, and subsequent hypotonia and global developmental delay. Heterologous expression of each CHT1 mutant in human embryonic kidney cells showed two different mechanisms of reduced protein function. The p.I294T CHT1 mutant transporter function was detectable, but its abundance and half-life were significantly reduced. In contrast, the p.D349N CHT1 mutant was abundantly expressed at the cell membrane, but transporter function was absent. The residual function of the p.I294T CHT1 mutant may explain the non-lethal form of CMS in this patient, and the divergent mechanisms of reduced CHT1 function that we identified may guide future functional studies of the CHT1 myasthenic syndrome. Based on these in vitro studies that provided a diagnosis, treatment with cholinesterase inhibitor together with physical and occupational therapy significantly improved the patient's strength and quality of life.
ESTHER : Rizvi_2023_Hum.Mol.Genet__
PubMedSearch : Rizvi_2023_Hum.Mol.Genet__
PubMedID: 36611016

Title : Artificial Intelligence Aided Lipase Production and Engineering for Enzymatic Performance Improvement - Ge_2023_J.Agric.Food.Chem__
Author(s) : Ge F , Chen G , Qian M , Xu C , Liu J , Cao J , Li X , Hu D , Xu Y , Xin Y , Wang D , Zhou J , Shi H , Tan Z
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : With the development of artificial intelligence (AI), tailoring methods for enzyme engineering have been widely expanded. Additional protocols based on optimized network models have been used to predict and optimize lipase production as well as properties, namely, catalytic activity, stability, and substrate specificity. Here, different network models and algorithms for the prediction and reforming of lipase, focusing on its modification methods and cases based on AI, are reviewed in terms of both their advantages and disadvantages. Different neural networks coupled with various algorithms are usually applied to predict the maximum yield of lipase by optimizing the external cultivations for lipase production, while one part is used to predict the molecule variations affecting the properties of lipase. However, few studies have directly utilized AI to engineer lipase by affecting the structure of the enzyme, and a set of research gaps needs to be explored. Additionally, future perspectives of AI application in enzymes, including lipase engineering, are deduced to help the redesign of enzymes and the reform of new functional biocatalysts. This review provides a new horizon for developing effective and innovative AI tools for lipase production and engineering and facilitating lipase applications in the food industry and biomass conversion.
ESTHER : Ge_2023_J.Agric.Food.Chem__
PubMedSearch : Ge_2023_J.Agric.Food.Chem__
PubMedID: 37800676

Title : Antibiotic Guanacastane Diterpenoids with Two New Skeletons from Psathyrella candolleana Uncovered by Semisolid and Liquid Media - Zhao_2023_J.Agric.Food.Chem__
Author(s) : Zhao TD , Yang XQ , Zhou J , Yang YB , Ding ZT
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : The culture of Psathyrella candolleana in host Dioscorea opposite medium produced seven new guanacastane diterpenoids, psayamin (1) as an unprecedented 5/7/6/6/6/6/7/5-fused octacyclic spiro scaffold both under liquid and semisolid conditions, psathins A-C (4-6) with a 5/7/6 tricyclic backbone by liquid medium, psathins D-E (7-8) as the same unprecedented skeletons of 5/6/7/6-fused tetracyclic or 6/7/6 tricyclic structures, and psathin F (9) with a 5/7/5/6 tetracyclic backbone by semisolid medium. The structures were elucidated by detailed spectroscopic analyses and those of 1 and 7 were determined by single-crystal X-ray crystallography. The semisolid culture led to four structure types of the guanacastane diterpenoid. Compound 5 showed antifungal activity against phytopathogen Fusarium incarnatum with a minimum inhibitory concentration (MIC) of 8 microg/mL, while compound 4 showed significant antifungal activity against Alternaria sp. with an MIC of 2 microg/mL. Compounds 1 and 8 also showed antifeedant activities against the silkworms with the feeding deterrence indices of 50%, at the concentrations of 50 microg/cm(2). Compound 1 showed significant cytotoxicity with IC(50) at 10.87 +/- 0.24-15.96 +/- 0.30 microM and anti-acetylcholinesterase activity with IC(50) at 37.3 microM. Also, compound 1 remarkably induced apoptosis of HL-60 at 10, 20 microM in a concentration-dependent manner. The spiral ring of 1 was vital in cytotoxicity and anti-acetylcholinesterase activity. The different media fermented by P. candolleana resulted in the chemical diversity of bioactive guanacastane diterpenoids and potential applications in the agricultural and food functions.
ESTHER : Zhao_2023_J.Agric.Food.Chem__
PubMedSearch : Zhao_2023_J.Agric.Food.Chem__
PubMedID: 36656976

Title : MAGL inhibition relieves synovial inflammation and pain via regulating NOX4-Nrf2 redox balance in osteoarthritis - Li_2023_Free.Radic.Biol.Med_208_13
Author(s) : Li X , Tao H , Zhou J , Zhang L , Shi Y , Zhang C , Sun W , Chu M , Chen K , Gu C , Yang X , Geng D , Hao Y
Ref : Free Radic Biol Med , 208 :13 , 2023
Abstract : Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage injury, hyperplasia of bone and inflammatory lesions of synovium. Monoacylglycerol lipase (MAGL), a member of the alpha/beta hydrolase superfamily, is involved in regulation of injury protection and immune-inflammation response. Autoinflammatory response of the synovium and the release of inflammatory mediators play critical roles in occurrence of early-stage OA. Fibroblast-like synoviocytes (FLSs) are resident mesenchymal cells of the synovial tissue. Considering that MAGL inhibition regulates the inflammatory signaling cascade, it is crucial to ascertain the biological effects and specific mechanisms of MAGL in alleviating inflammatory infiltration of OA FLSs. The aim of this study was to investigate the effect of MAGL on biological function in OA FLSs. Results from in vitro experiments showed that MAGL blockade not only effectively inhibited proliferation, invasion and migration of FLSs, but also downregulated expression of inflammatory-associated proteins. Sequencing results indicated that MAGL inhibition significantly suppressed NOX4-mediated oxidative stress, thus promoting Nrf2 nuclear accumulation and inhibiting generation of intracellular reactive oxygen species (ROS). Attenuation of NOX4 further alleviated redox dysplasia and ultimately improved tumor-like phenotypes, such as abnormal proliferation, migration and migration of FLSs. In vivo results corroborated this finding, with MAGL inhibition found to modulate pain and disease progression in an OA rat model. Collectively, these results indicate that MAGL administration is an ideal therapy treating OA.
ESTHER : Li_2023_Free.Radic.Biol.Med_208_13
PubMedSearch : Li_2023_Free.Radic.Biol.Med_208_13
PubMedID: 37516370
Gene_locus related to this paper: human-MGLL

Title : Polyethylene Degradation by a Rhodococcous Strain Isolated from Naturally Weathered Plastic Waste Enrichment - Tao_2023_Environ.Sci.Technol__
Author(s) : Tao X , Ouyang H , Zhou A , Wang D , Matlock H , Morgan JS , Ren AT , Mu D , Pan C , Zhu X , Han A , Zhou J
Ref : Environ Sci Technol , : , 2023
Abstract : Polyethylene (PE) is the most widely produced synthetic polymer and the most abundant plastic waste worldwide due to its recalcitrance to biodegradation and low recycle rate. Microbial degradation of PE has been reported, but the underlying mechanisms are poorly understood. Here, we isolated a Rhodococcus strain A34 from 609 day enriched cultures derived from naturally weathered plastic waste and identified the potential key PE degradation enzymes. After 30 days incubation with A34, 1% weight loss was achieved. Decreased PE molecular weight, appearance of C-O and C=O on PE, palmitic acid in the culture supernatant, and pits on the PE surface were observed. Proteomics analysis identified multiple key PE oxidation and depolymerization enzymes including one multicopper oxidase, one lipase, six esterase, and a few lipid transporters. Network analysis of proteomics data demonstrated the close relationships between PE degradation and metabolisms of phenylacetate, amino acids, secondary metabolites, and tricarboxylic acid cycles. The metabolic roadmap generated here provides critical insights for optimization of plastic degradation condition and assembly of artificial microbial communities for efficient plastic degradation.
ESTHER : Tao_2023_Environ.Sci.Technol__
PubMedSearch : Tao_2023_Environ.Sci.Technol__
PubMedID: 37682848

Title : The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease - Li_2023_Commun.Biol_6_682
Author(s) : Li TZ , Bai CY , Wu B , Zhang CY , Wang WT , Shi TW , Zhou J
Ref : Commun Biol , 6 :682 , 2023
Abstract : Alcoholic liver disease (ALD) and other forms of chronic hepatotoxic injury can lead to transforming growth factor beta1 (TGFbeta1)-induced hepatic fibrosis and compromised liver function, underscoring the need to develop novel treatments for these conditions. Herein, our analyses of liver tissue samples from severe alcoholic hepatitis (SAH) patients and two murine models of ALD reveals that the ALD phenotype was associated with upregulation of the transcription factor ETS domain-containing protein (ELK-3) and ELK-3 signaling activity coupled with downregulation of alpha/beta hydrolase domain containing 10 (ABHD10) and upregulation of deactivating S-palmitoylation of the antioxidant protein Peroxiredoxin 5 (PRDX5). In vitro, we further demonstrate that ELK-3 can directly bind to the ABHD10 promoter to inhibit its transactivation. TGFbeta1 and epidermal growth factor (EGF) signaling induce ABHD10 downregulation and PRDX5 S-palmitoylation via ELK-3. This ELK-3-mediated ABHD10 downregulation drives oxidative stress and disrupts mature hepatocyte function via enhancing S-palmitoylation of PRDX5's Cys100 residue. In vivo, ectopic Abhd10 overexpression ameliorates liver damage in ALD model mice. Overall, these data suggest that the therapeutic targeting of the ABHD10-PRDX5 axis may represent a viable approach to treating ALD and other forms of hepatotoxicity.
ESTHER : Li_2023_Commun.Biol_6_682
PubMedSearch : Li_2023_Commun.Biol_6_682
PubMedID: 37400491
Gene_locus related to this paper: human-ABHD10

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 : Sertoli cell survival and barrier function are regulated by miR-181c\/d-Pafah1b1 axis during mammalian spermatogenesis - Feng_2022_Cell.Mol.Life.Sci_79_498
Author(s) : Feng Y , Chen D , Wang T , Zhou J , Xu W , Xiong H , Bai R , Wu S , Li J , Li F
Ref : Cell Mol Life Sciences , 79 :498 , 2022
Abstract : Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.
ESTHER : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedSearch : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedID: 36008729

Title : APT1-Mediated Depalmitoylation Regulates Hippocampal Synaptic Plasticity - Shen_2022_J.Neurosci_42_2662
Author(s) : Shen ZC , Xia ZX , Liu JM , Zheng JY , Luo YF , Yang H , Li MD , Cao T , Liu HP , Jin GL , Huang HH , Yu CX , Zhou J
Ref : Journal of Neuroscience , 42 :2662 , 2022
Abstract : Palmitoylation may be relevant to the processes of learning and memory, and even disorders, such as post-traumatic stress disorder and aging-related cognitive decline. However, underlying mechanisms of palmitoylation in these processes remain unclear. Herein, we used acyl-biotin exchange, coimmunoprecipitation and biotinylation assays, and behavioral and electrophysiological methods, to explore whether palmitoylation is required for hippocampal synaptic transmission and fear memory formation, and involved in functional modification of synaptic proteins, such as postsynapse density-95 (PSD-95) and glutamate receptors, and detected if depalmitoylation by specific enzymes has influence on glutamatergic synaptic plasticity. Our results showed that global palmitoylation level, palmitoylation of PSD-95 and glutamate receptors, postsynapse density localization of PSD-95, surface expression of AMPARs, and synaptic strength of cultured hippocampal neurons were all enhanced by TTX pretreatment, and these can be reversed by inhibition of palmitoylation with palmitoyl acyl transferases inhibitors, 2-bromopalmitate and N-(tert-butyl) hydroxylamine hydrochloride. Importantly, we also found that acyl-protein thioesterase 1 (APT1)-mediated depalmitoylation is involved in palmitoylation of PSD-95 and glutamatergic synaptic transmission. Knockdown of APT1, not protein palmitoyl thioesterase 1, with shRNA, or selective inhibition, significantly increased AMPAR-mediated synaptic strength, palmitoylation levels, and synaptic or surface expression of PSD-95 and AMPARs. Results from hippocampal tissues and fear-conditioned rats showed that palmitoylation is required for synaptic strengthening and fear memory formation. These results suggest that palmitoylation and APT1-mediated depalmitoylation have critical effects on the regulation of glutamatergic synaptic plasticity, and it may serve as a potential target for learning and memory-associated disorders.SIGNIFICANCE STATEMENT Fear-related anxiety disorders, including post-traumatic stress disorder, are prevalent psychiatric conditions, and fear memory is associated with hyperexcitability in the hippocampal CA1 region. Palmitoylation is involved in learning and memory, but mechanisms coupling palmitoylation with fear memory acquisition remain poorly understood. This study demonstrated that palmitoylation is essential for postsynapse density-95 clustering and hippocampal glutamatergic synaptic transmission, and APT1-mediated depalmitoylation plays critical roles in the regulation of synaptic plasticity. Our study revealed that molecular mechanism about downregulation of APT1 leads to enhancement of AMPAR-mediated synaptic transmission, and that palmitoylation cycling is implicated in fear conditioning-induced synaptic strengthening and fear memory formation.
ESTHER : Shen_2022_J.Neurosci_42_2662
PubMedSearch : Shen_2022_J.Neurosci_42_2662
PubMedID: 35165175
Gene_locus related to this paper: human-LYPLA1

Title : Bisphenol AF induces multiple behavioral and biochemical changes in zebrafish (Danio rerio) at different life stages - Rao_2022_Aquat.Toxicol_253_106345
Author(s) : Rao C , Cao X , Li L , Zhou J , Sun D , Li B , Guo S , Yuan R , Cui H , Chen J
Ref : Aquat Toxicol , 253 :106345 , 2022
Abstract : As common environmental endocrine-disrupting chemicals (EDCs), bisphenol AF (BPAF) raises potential concerns for aquatic organisms due to its widespread presence and continued release in the aquatic environment. This research aimed to use zebrafish embryos and adult fish to explore the effects of environmentally relevant concentrations (5 g/L), 50 g/L and 500 g/L of BPAF on zebrafish embryonic development, behavioral alterations, and the potential mechanisms driving these effects. The results showed that 500 g/L of BPAF severely affected the growth and development of embryos. In behavioral experiments, all concentrations of BPAF significantly inhibited the locomotor activity of larvae, 50 and 500 g/L BPAF significantly altered the anxiety-like and aggressive behavior of adult zebrafish. Furthermore, environmentally relevant concentrations and higher concentrations of BPAF induced varying degrees of oxidative stress in both embryonic and adult fish. The most significant histopathological changes and decreased acetylcholinesterase (AChE) activity were observed in the brain at 50 and 500 g/L of BPAF. We hypothesized that oxidative stress is an important cause of behavioral disturbances in larvae and adult fish. To our best knowledge, the present experiment is a pioneer in studying the effects of BPAF on a variety of complex behaviors (swimming performance, anxiety-like, social behavior, aggression) in zebrafish, which emphasizes the potential health risk of higher concentrations of BPAF in terms of induced neurotoxicity.
ESTHER : Rao_2022_Aquat.Toxicol_253_106345
PubMedSearch : Rao_2022_Aquat.Toxicol_253_106345
PubMedID: 36351319

Title : Neuronal STAT3\/HIF-1alpha\/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A - Jin_2022_Theranostics_12_3196
Author(s) : Jin W , Zhao J , Yang E , Wang Y , Wang Q , Wu Y , Tong F , Tan Y , Zhou J , Kang C
Ref : Theranostics , 12 :3196 , 2022
Abstract : Ischemic stroke is an acute and severe neurological disease with high mortality and disability rates worldwide. Polymerase I and transcript release factor (PTRF) plays a pivotal role in regulating cellular senescence, glucose intolerance, lipid metabolism, and mitochondrial bioenergetics, but its mechanism, characteristics, and functions in neuronal cells following the cerebral ischemia-reperfusion (I/R) injury remain to be determined. Methods: Transcription factor motif analysis, chromatin immunoprecipitation (ChIP), luciferase and co-Immunoprecipitation (co-IP) assays were performed to investigate the mechanisms of PTRF in neuronal cells after I/R injury. Lentiviral-sgRNA against PTRF gene was introduced to HT22 cells, and adeno-associated virus (AAV) encoding a human synapsin (hSyn) promoter-driven construct was transduced a short hairpin RNA (shRNA) against PTRF mRNA in primary neuronal cells and the cortex of the cerebral I/R mice for investigating the role of PTRF in neuronal damage and PLA2G4A change induced by the cerebral I/R injury. Results: Here, we reported that neuronal PTRF was remarkably increased in the cerebral penumbra after I/R injury, and HIF-1alpha and STAT3 regulated the I/R-dependent expression of PTRF via binding to its promoter in neuronal cells. Moreover, overexpression of neuronal PTRF enhanced the activity and stability of PLA2G4A by decreasing its proteasome-mediated degradation pathway. Subsequently, PTRF promoted reprogramming of lipid metabolism and altered mitochondrial bioenergetics, which could lead to oxidative damage, involving autophagy, lipid peroxidation, and ferroptosis via PLA2G4A in neuronal cells. Furthermore, inhibition of neuronal PTRF/PLA2G4A-axis markedly reduced the neurological deficits, cerebral infarct volumes, and mortality rates in the mice following cerebral I/R injury. Conclusion: Our results thus identify that the STAT3/HIF-1alpha/PTRF-axis in neurons, aggravating cerebral I/R injury by regulating the activity and stability of PLA2G4A, might be a novel therapeutic target for ischemic stroke.
ESTHER : Jin_2022_Theranostics_12_3196
PubMedSearch : Jin_2022_Theranostics_12_3196
PubMedID: 35547748

Title : Influence of ligand geometry on cholinesterase enzyme - A comparison of 1-isoindolinone based structural analog with Donepezil - Upadhyay_2022_J.Mol.Struct_1247_
Author(s) : Upadhyay SP , Singh V , Sharma R , Zhou J , Thapa P , Johnson DK , Keightley A , Chen M , Suo W , Sharma M
Ref : J Mol Struct , 1247 : , 2022
Abstract : Donepezil (DNPZ) is one of the few FDA-approved widely used medication in the clinical care of Alzheimer's disease (AD) patients. To investigate the effect of geometry and to find the significance of an enol form if any in DNPZ on acetylcholinesterase (AChE) inhibition, we changed the tetrahedral geometry of DNPZ to planar trigonal pyramidal geometry by replacing the alpha-carbon atom next to ketone functionality with a nitrogen atom. To mimic 1-indanone in DNPZ, we selected 1-isoindolinone framework to synthesize 25 new DNPZ derivatives and characterized using (1)H NMR, (13)C NMR and ESI-MS spectroscopy methods. Drug likeliness profile for each compound was predicted using Molinspiration online software following Lipinski's rule. Commercially available assay kits were used to measure AChE and butyrylcholinesterase (BuChE) inhibitory effects. NIH/3T3 mouse embryonic fibroblast cell line was used to measure cytotoxic and proliferation effects using LDH and MTT assay, respectively. Compound #20 was selected for comparative computational docking, modelling and physicochemical studies. Our results show that DNPZ with tetrahedral geometry has 3-fold higher AChE inhibition as compared to compound #20 with planar trigonal pyramidal geometry. Our approach may be useful as a novel indirect method to study the significance of the enol form in DNPZ (or similar compounds), since constant interconversion between the keto and enol forms does not permit a direct determination of the effect of the enol form of DNPZ in vivo. Overall, we conclude that the tetrahedral is a better fit and any change in geometry significantly drives down the cholinesterase inhibitory effect of DNPZ.
ESTHER : Upadhyay_2022_J.Mol.Struct_1247_
PubMedSearch : Upadhyay_2022_J.Mol.Struct_1247_
PubMedID: 34776532

Title : Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction - Liu_2022_Nat.Commun_13_3490
Author(s) : Liu Z , Yang N , Dong J , Tian W , Chang L , Ma J , Guo J , Tan J , Dong A , He K , Zhou J , Cinar R , Wu J , Salinas AG , Sun L , Kumar M , Sullivan BT , Oldham BB , Pitz V , Makarious MB , Ding J , Kung J , Xie C , Hawes SL , Wang L , Wang T , Chan P , Zhang Z , Le W , Chen S , Lovinger DM , Blauwendraat C , Singleton AB , Cui G , Li Y , Cai H , Tang B
Ref : Nat Commun , 13 :3490 , 2022
Abstract : Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase beta (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism.
ESTHER : Liu_2022_Nat.Commun_13_3490
PubMedSearch : Liu_2022_Nat.Commun_13_3490
PubMedID: 35715418
Gene_locus related to this paper: human-DAGLB , mouse-DGLB

Title : Structurally diverse alkaloids with nine frameworks from Zephyranthes candida and their acetylcholinesterase inhibitory and anti-inflammatory activities - Zhan_2022_Phytochemistry__113564
Author(s) : Zhan G , Gao B , Zhou J , Liu T , Zheng G , Jin Z , Yao G
Ref : Phytochemistry , :113564 , 2022
Abstract : Twenty-six structurally diverse Amaryllidaceae alkaloids, including ten undescribed compounds named zephyranines A-I and 6-O-ethylnerinine, two undescribed natural products zephyranthine-6-one and 3-O-deacetyl-sternbergine, were isolated from whole plants of Zephyranthes candida. Their structures were determined by HRESIMS, 1D and 2D NMR, CD data analysis, NMR and ECD calculations, and single-crystal X-ray diffraction analysis. All structures were classified into nine framework types: 10 b,11-seco-crinine, graciline, crinine, homolycorine, trisphaeridine, lycorine, galasine, tazettine, and belladine. Zephyranine A represents the first naturally occurring 10 b,11-seco-crinine type alkaloid, and zephyranine B is the sixth graciline type alkaloid. 6-O-ethylnerinine is an artifact from the extraction and isolation. All isolates were evaluated for their acetylcholinesterase (AChE) inhibitory and anti-inflammatory activities. Zephyranines A, G, and H exhibited moderate AChE inhibitory activities, with IC(50) values of 8.2, 39.0, and 10.8 microM, respectively. Zephyranine B, haemanthamine, haemanthidine, 11-hydroxyvittatine, and 8-demethoxy-10-O-methylhostasine exhibited potent anti-inflammatory activity on the LPS-induced NO production in RAW264.7 mouse macrophages with IC(50) values of 21.3, 4.6, 12.2, 5.6, and 17.4 microM, respectively. Structure-activity-relationship analysis and docking studies indicated that interactions with the key Trp286 and Tyr337 residues are required for potent AChE inhibitors.
ESTHER : Zhan_2022_Phytochemistry__113564
PubMedSearch : Zhan_2022_Phytochemistry__113564
PubMedID: 36535411

Title : Molecular understanding of acetylcholinesterase adsorption on functionalized carbon nanotubes for enzymatic biosensors - Yang_2022_Phys.Chem.Chem.Phys__
Author(s) : Yang S , Zhao D , Xu Z , Yu H , Zhou J
Ref : Phys Chem Chem Phys , : , 2022
Abstract : The immobilization of acetylcholinesterase on different nanomaterials has been widely used in the field of amperometric organophosphorus pesticide (OP) biosensors. However, the molecular adsorption mechanism of acetylcholinesterase on a nanomaterial's surface is still unclear. In this work, multiscale simulations were utilized to study the adsorption behavior of acetylcholinesterase from Torpedo californica (TcAChE) on amino-functionalized carbon nanotube (CNT) (NH(2)-CNT), carboxyl-functionalized CNT (COOH-CNT) and pristine CNT surfaces. The simulation results show that the active center and enzyme substrate tunnel of TcAChE are both close to and oriented toward the surface when adsorbed on the positively charged NH(2)-CNT, which is beneficial to the direct electron transfer (DET) and accessibility of the substrate molecule. Meanwhile, the NH(2)-CNT can also reduce the tunnel cost of the enzyme substrate of TcAChE, thereby further accelerating the transfer rate of the substrate from the surface or solution to the active center. However, for the cases of TcAChE adsorbed on COOH-CNT and pristine CNT, the active center and substrate tunnel are far away from the surface and face toward the solution, which is disadvantageous for the DET and transportation of enzyme substrate. These results indicate that NH(2)-CNT is more suitable for the immobilization of TcAChE. This work provides a better molecular understanding of the adsorption mechanism of TcAChE on functionalized CNT, and also provides theoretical guidance for the ordered immobilization of TcAChE and the design, development and improvement of TcAChE-OPs biosensors based on functionalized carbon nanomaterials.
ESTHER : Yang_2022_Phys.Chem.Chem.Phys__
PubMedSearch : Yang_2022_Phys.Chem.Chem.Phys__
PubMedID: 35060980

Title : Toxic effects of glyphosate on the intestine, liver, brain of carp and on epithelioma papulosum cyprinid cells: Evidence from in vivo and in vitro research - Cao_2022_Chemosphere__134691
Author(s) : Cao X , Rao C , Cui H , Sun D , Li L , Guo S , Zhou J , Yuan R , Yang S , Chen J
Ref : Chemosphere , :134691 , 2022
Abstract : Glyphosate (GLY) is the most widely used organophosphorus herbicide in agriculture. The present study aimed to analyze the comprehensive toxicological effects of GLY on juvenile common carp and an epithelioma papulosum cyprinid (EPC) cell line. In the in vivo experiments, exposure to GLY (5 and 15 mg/L) for 30 days induced liver inflammation and oxidative damage in common carp and changed the physical barrier of the intestine. Histopathological analysis of the intestine, liver, brain, and changes in oxidative stress biomarkers provided evidence of damage and immune system responses to GLY. Moreover, an inhibitory effect of 15 mg/L GLY on acetylcholinesterase (AChE) activity was found in the brain, which may be an important reason for the significant decrease in both swimming distance and average acceleration of common carp. Cell experiments showed that 0.65 and 3.25 mg/L GLY inhibited the viability of EPCs. Furthermore, oxidative DNA damage, mitochondrial dysfunction, and reactive oxygen species (ROS) production were observed in EPC cells following GLY exposure. Taken together, this study not only highlights the negative effects of GLY on common carp but also enriches the knowledge of the cytotoxicity mechanism to further clarify the comprehensive toxicity of GLY in common carp.
ESTHER : Cao_2022_Chemosphere__134691
PubMedSearch : Cao_2022_Chemosphere__134691
PubMedID: 35489457

Title : Simultaneous CSM-TACE with CalliSpheres() and partial splenic embolization using 8spheres() for hepatocellular carcinoma with hypersplenism: Early prospective multicenter clinical outcome - Zhou_2022_Front.Oncol_12_998500
Author(s) : Zhou J , Feng Z , Liu S , Li X , Liu Y , Gao F , Shen J , Zhang YW , Zhao GS , Zhang M
Ref : Front Oncol , 12 :998500 , 2022
Abstract : BACKGROUND: Primary hepatocellular carcinoma is often complicated with hepatitis and liver cirrhosis. Some patients develop different degrees of splenomegaly, hypersplenism and hypohepatia due to the aggravation of liver cirrhosis, which to some extent interfere with the treatment of tumors and even affect the prognosis of patients. In this study, we prospectively evaluate the efficacy and safety of simultaneous CalliSpheres((a)) microspheres transcatheter arterial chemoembolization (CSM-TACE) and partial splenic embolization (PSE) using 8spheres((a)) for hepatocellular carcinoma (HCC) with hypersplenism. METHODS: Ninety consecutive HCC patients with hypersplenism who underwent CSM-TACE were selected: 32 patients in CSM-TACE+PSE group, and 58 patients in CSM-TACE group. The peripheral blood cell counts (leukocyte, platelet (PLT), liver function and red blood cell (RBC)), CSM-TACE and/or PSE related complications, and the tumor control rate at 1 month after CSM-TACE were compared. The survival time and prognostic factors were also observed. RESULTS: Before CSM-TACE, there were no significant differences in sex, age, Child-Pugh grade, tumor size, and alpha-fetoprotein (AFP) between the two groups. After CSM-TACE, the PLT and white blood cell (WBC) counts in CSM-TACE+PSE group were significantly higher than those in the CSM-TACE group (P<0.05). There were no significant differences in RBC before and after treatment (P > 0.05). In the CSM-TACE group, there were no significant differences in WBC, PLT, and RBC before and after treatment (P > 0.05). There was no significant difference in liver function at 1 month after treatment between the two groups. The cholinesterase (CHE) level in the CSM-TACE+PSE group after CSM-TACE+PSE was obviously higher than that before CSM-TACE+PSE and higher than that in the CSM-TACE group (P<0.05). However, the level of CHE returned to the preoperative level 1 month after CSM-TACE in the CSM-TACE group. The objective response rate (ORR) and median overall survival (OS) in the CSM-TACE+PSE group were higher than those in the CSM-TACE group (P<0.05). The adverse reactions of the two groups were fever, abdominal pain, stomach discomfort, nausea, and vomiting, and no serious complications occurred. The degree of abdominal pain and fever in the experimental group was lower than that in the control group (P > 0.05). CONCLUSIONS: Simultaneous CSM-TACE and PSE using domestic embolization particles for HCC with hypersplenism have good safety and efficacy and has a low incidence of PSE-related adverse events, it is conducive to improving liver function reserve, and can further improve the median OS.
ESTHER : Zhou_2022_Front.Oncol_12_998500
PubMedSearch : Zhou_2022_Front.Oncol_12_998500
PubMedID: 36530976

Title : Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701) - Yu_2022_JHEP.Rep_4_100575
Author(s) : Yu Q , Xu C , Li Q , Ding Z , Lv Y , Liu C , Huang Y , Zhou J , Huang S , Xia C , Meng X , Lu C , Li Y , Tang T , Wang Y , Song Y , Qi X , Ye J , Ju S
Ref : JHEP Rep , 4 :100575 , 2022
Abstract : BACKGROUND & AIMS: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. METHODS: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. RESULTS: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index <=0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (>=1%), and the model had a competitive performance compared with the Baveno VII criteria. CONCLUSIONS: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. LAY SUMMARY: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.
ESTHER : Yu_2022_JHEP.Rep_4_100575
PubMedSearch : Yu_2022_JHEP.Rep_4_100575
PubMedID: 36204707

Title : Future of Structured Lipids: Enzymatic Synthesis and Their New Applications in Food Systems - Zhou_2022_Foods_11_
Author(s) : Zhou J , Lee YY , Mao Y , Wang Y , Zhang Z
Ref : Foods , 11 : , 2022
Abstract : Structured lipids (SLs) refer to a new type of functional lipid obtained by modifying natural triacylglycerol (TAG) through the restructuring of fatty acids, thereby altering the composition, structure, and distribution of fatty acids attached to the glycerol backbones. Due to the unique functional characteristics of SLs (easy to absorb, low in calories, reduced serum TAG, etc.), there is increasing interest in the research and application of SLs. SLs were initially prepared using chemical methods. With the wide application of enzymes in industries and the advantages of enzymatic synthesis (mild reaction conditions, high catalytic efficiency, environmental friendliness, etc.), synthesis of SLs using lipase has aroused great interest. This review summarizes the reaction system of SL production and introduces the enzymatic synthesis and application of some of the latest SLs discussed/developed in recent years, including medium- to long-chain triacylglycerol (MLCT), diacylglycerol (DAG), EPA- and DHA-enriched TAG, human milk fat substitutes, and esterified propoxylated glycerol (EPG). Lastly, several new ways of applying SLs (powdered oil, DAG plastic fat, inert gas spray oil, and emulsion) in the future food industry are also highlighted.
ESTHER : Zhou_2022_Foods_11_
PubMedSearch : Zhou_2022_Foods_11_
PubMedID: 36010399

Title : Predictive value of serum cholinesterase in the mortality of acute pancreatitis: A retrospective cohort study - Wei_2022_Eur.J.Clin.Invest__e13741
Author(s) : Wei M , Xie X , Yu X , Lu Y , Ke L , Ye B , Zhou J , Li G , Li B , Tong Z , Lu G , Li W , Li J
Ref : European Journal of Clinical Investigation , :e13741 , 2022
Abstract : BACKGROUND: Severe acute pancreatitis has a high mortality of 20-40%, but there is lack of optimal prognostic biomarker for the severity of acute pancreatitis (AP) or mortality. This study is designed to investigate the relationship between serum cholinesterase (ChE) level and poor outcomes of AP. METHODS: A total of 1904 AP patients were screened in the study, and we finally got 692 patients eligible for analysis. Patients were divided into 2 groups based on serum ChE. The primary outcome was mortality, and multivariable logistic regression analysis for mortality was completed. Additionally, we used receiver operator characteristic (ROC) curve analysis to clarify the predictive value of serum ChE for mortality and organ failure. RESULTS: 378 patients and 314 patients were included in ChE low and normal group, respectively. Patients in ChE low group were older (46.68+/-12.70 vs 43.56+/-12.13 years old, p=0.001) and had a lower percentage of male (62.4% vs 71.0%, p=0.017) when compared with the ChE normal group. Mortality was significantly different in two groups (10.3% vs 0.0%, p<0.001). Moreover, organ failure also differed significantly in two groups (46.6% vs 8.6%, p<0.001). Decreased ChE level was independently associated with mortality in acute pancreatitis (odds ratio: 0.440; 95% confidence interval, 0.231, 0.838, p=0.013). The area under the curve of serum ChE was 0.875 and 0.803 for mortality and organ failure, respectively. CONCLUSIONS: Lower level of serum ChE was independently associated with the severity and mortality of AP.
ESTHER : Wei_2022_Eur.J.Clin.Invest__e13741
PubMedSearch : Wei_2022_Eur.J.Clin.Invest__e13741
PubMedID: 34981831

Title : GPIHBP1 autoantibody is an independent risk factor for the recurrence of hypertriglyceridemia-induced acute pancreatitis - Zhang_2022_J.Clin.Lipidol__
Author(s) : Zhang G , Yang Q , Mao W , Hu Y , Pu N , Deng H , Yu X , Zhang J , Zhou J , Ye B , Li G , Li B , Ke L , Tong Z , Murakami M , Kimura T , Nakajima K , Cao W , Liu Y , Li W
Ref : J Clin Lipidol , : , 2022
Abstract : BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. OBJECTIVE: We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. METHODS: An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. RESULTS: GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. CONCLUSIONS: The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.
ESTHER : Zhang_2022_J.Clin.Lipidol__
PubMedSearch : Zhang_2022_J.Clin.Lipidol__
PubMedID: 36064883

Title : Application of a novel fluorogenic polyurethane analogue probe in polyester-degrading microorganisms screening by microfluidic droplet - Xu_2022_Microb.Biotechnol__
Author(s) : Xu A , Liu J , Cao S , Xu B , Guo C , Yu Z , Chen X , Zhou J , Dong W , Jiang M
Ref : Microb Biotechnol , : , 2022
Abstract : Application of polyester-degrading microorganisms or enzymes should be considered as an eco-friendly alternative to chemical recycling due to the huge plastic waste disposal nowadays. However, current impranil DLN-based screening of polyester-degrading microorganisms is time-consuming, labour-intensive and unable to distinguish polyesterases from other protease- or amidase-like enzymes. Herein, we present an approach that combined a novel synthetic fluorescent polyurethane analogue probe (FPAP), along with the droplet-based microfluidics to screen polyurethane-degrading microorganisms through fluorescence-activated droplet sorting (FADS) pipeline. The fluorescent probe FPAP exhibited a fluorescence enhancement effect once hydrolysed by polyesterases, along with a strong specificity in discriminating polyesterases from other non-active enzymes. Application of FPAP in a microfluidic droplet system demonstrated that this probe exhibited high sensitivity and efficiency in selecting positive droplets containing leaf-branch compost cutinase (LCC) enzymes. This novel fluorogenic probe, FPAP, combined with the droplet microfluidic system has the potential to be used in the exploitation of novel PUR-biocatalysts for biotechnological and environmental applications.
ESTHER : Xu_2022_Microb.Biotechnol__
PubMedSearch : Xu_2022_Microb.Biotechnol__
PubMedID: 35881631
Gene_locus related to this paper: 9bact-g9by57

Title : Efficiency of donepezil in elderly patients undergoing orthopaedic surgery due to underlying post-operative cognitive dysfunction: study protocol for a multicentre randomised controlled trial - Zhu_2021_Trials_22_688
Author(s) : Zhu H , Cong L , Chen Y , Chen S , Chen L , Huang Z , Zhou J , Xiao J , Huang Y , Su D
Ref : Trials , 22 :688 , 2021
Abstract : BACKGROUND: Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer's disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery. METHODS: A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation. DISCUSSION: This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04423276 . Registered on 14 June 2020.
ESTHER : Zhu_2021_Trials_22_688
PubMedSearch : Zhu_2021_Trials_22_688
PubMedID: 34627332

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 : Biodegradation and up-cycling of polyurethanes: Progress, challenges, and prospects - Liu_2021_Biotechnol.Adv_48_107730
Author(s) : Liu J , He J , Xue R , Xu B , Qian X , Xin F , Blank LM , Zhou J , Wei R , Dong W , Jiang M
Ref : Biotechnol Adv , 48 :107730 , 2021
Abstract : Polyurethanes (PUR) are ranked globally as the 6th most abundant synthetic polymer material. Most PUR materials are specifically designed to ensure long-term durability and high resistance to environmental factors. As the demand for diverse PUR materials is increasing annually in many industrial sectors, a large amount of PUR waste is also being generated, which requires proper disposal. In contrast to other mass-produced plastics such as PE, PP, and PET, PUR is a family of synthetic polymers, which differ considerably in their physical properties due to different building blocks (for example, polyester- or polyether-polyol) used in the synthesis. Despite its xenobiotic properties, PUR has been found to be susceptible to biodegradation by different microorganisms, albeit at very low rate under environmental and laboratory conditions. Discovery and characterization of highly efficient PUR-degrading microbes and enzymes capable of disassembling PUR polymer chains into oligo- and monomeric compounds is of fundamental importance for a circular plastic economy. In this review, the main methods used for screening PUR-degrading microbes and enzymes are summarized and compared in terms of their catalytic mechanisms. Furthermore, recycling and upcycling strategies of waste PUR polymers, including microbial conversion of PUR monomers into value added products, are presented.
ESTHER : Liu_2021_Biotechnol.Adv_48_107730
PubMedSearch : Liu_2021_Biotechnol.Adv_48_107730
PubMedID: 33713745

Title : Oxidase-like Nanozyme-Mediated Altering of the Aspect Ratio of Gold Nanorods for Breaking through H(2)O(2)-Supported Multicolor Colorimetric Assay: Application in the Detection of Acetylcholinesterase Activity and Its Inhibitors - Fu_2021_ACS.Appl.Bio.Mater_4_3539
Author(s) : Fu R , Zhou J , Wang Y , Liu Y , Liu H , Yang Q , Zhao Q , Jiao B , He Y
Ref : ACS Appl Bio Mater , 4 :3539 , 2021
Abstract : A convenient, fast, and colorful colorimetric platform with high resolution for acetylcholinesterase (AChE) activity and its inhibitors detection based on the regulation of oxidase-like nanozyme-mediated etching of gold nanorods (AuNRs) has been proposed in this work. MnO(2) nanosheets are selected as the nanozyme. Their excellent oxidase-like activity enables the etching process to proceed smoothly without the usage of unstable H(2)O(2). When AChE is present, it catalytically hydrolyzes acetylthiocholine (ATCh) to thiocholine (TCh). With high reducing ability, TCh induces the decomposition of MnO(2) nanosheets, causing them to lose their oxidase-like activity. Thus, the etching of AuNRs is hampered. Consequently, with the increasing concentration of AChE, an apparent change in the AuNRs solution color is observed. The proposed platform achieves high-sensitivity detection of AChE (limit of detection = 0.18 mU/mL). Furthermore, the proposed platform also has been demonstrated its applicability for its inhibitors detection. Benefiting from the advantages of convenient and high resolution of visual readout, the proposed platform holds great potential for the detection of AChE and its inhibitors in clinical diagnosis.
ESTHER : Fu_2021_ACS.Appl.Bio.Mater_4_3539
PubMedSearch : Fu_2021_ACS.Appl.Bio.Mater_4_3539
PubMedID: 35014439

Title : Enantioselective determination of phenthoate enantiomers in plant-origin matrices using reversed-phase high performance liquid chromatography-tandem mass spectrometry - Dong_2021_Biomed.Chromatogr__e5229
Author(s) : Dong C , Zhou J , Zuo W , Li Z , Li J , Jiao B
Ref : Biomedical Chromatography , :e5229 , 2021
Abstract : Phenthoate is a chiral organophosphate pesticide with a pair of enantiomers which differ in toxicity, behavior, and insecticidal activity, and its acute toxicity on human health due to the inhibition of acetylcholinesterase highlights the need for enantioselective detection of enantiomers. Therefore, this study is aimed to establish a simple rapid method for separation and detection of phenthoate enantiomers in fruits, vegetables, and grains. The enantiomers were separated using reversed-phase high performance liquid chromatography-tandem mass spectrometry (RP-HPLC-MS/MS) for the first time. Rapid chiral separation (within 9 min) of the target compound was achieved on a chiral OJ-RH column with the mobile phase of methanol/water=85/15(v/v), at a flow rate of 1 mL/min and column temperature of 30 degreesC. Acetonitrile and graphitized carbon black were used as the extractant and sorbent for pretreatment, respectively. This method provides excellent linearity (correlation coefficient no less than 0.9986), high sensitivity (limits of quantification at 5 microg/kg and limits of detection less than 0.25 microg/kg), satisfactory mean recoveries (76.2% to 91.0%) and relative standard deviations (intra-day RSDs ranged from 2.0% to 7.9% and inter-day RSDs ranged from 2.4% to 8.4%). In addition, field trial to explore the stereoselective degradation of phenthoate enantiomers in citrus showed that (-)-phenthoate degraded faster than its antipode, resulting in the relative accumulation of (+)-phenthoate.
ESTHER : Dong_2021_Biomed.Chromatogr__e5229
PubMedSearch : Dong_2021_Biomed.Chromatogr__e5229
PubMedID: 34414593

Title : Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis - Du_2021_Eur.J.Med.Chem_223_113678
Author(s) : Du F , Sun W , Morisseau C , Hammock BD , Bao X , Liu Q , Wang C , Zhang T , Yang H , Zhou J , Xiao W , Liu Z , Chen G
Ref : Eur Journal of Medicinal Chemistry , 223 :113678 , 2021
Abstract : Sepsis, a systemic inflammatory response, caused by pathogenic factors including microorganisms, has high mortality and limited therapeutic approaches. Herein, a new soluble epoxide hydrolase (sEH) inhibitor series comprising a phenyl ring connected to a memantyl moiety via a urea or amide linkage has been designed. A preferential urea pharmacophore that improved the binding properties of the compounds was identified for those series via biochemical assay in vitro and in vivo studies. Molecular docking displayed that 3,5-dimethyl on the adamantyl group in B401 could make van der Waals interactions with residues at a hydrophobic pocket of sEH active site, which might indirectly explain the subnanomolar level activities of memantyl urea derivatives in vitro better than AR-9281. Among them, compound B401 significantly improved the inhibition potency with human and murine sEH IC(50) values as 0.4 nM and 0.5 nM, respectively. Although the median survival time of C57BL/6 mice in LPS-induced sepsis model was slightly increased, the survival rate did not reach significant efficacy. Based on safety profile, metabolic stability, pharmacokinetic and in vivo efficacy, B401 demonstrated the proof of potential for this class of memantyl urea-based sEH inhibitors as therapeutic agents in sepsis.
ESTHER : Du_2021_Eur.J.Med.Chem_223_113678
PubMedSearch : Du_2021_Eur.J.Med.Chem_223_113678
PubMedID: 34218083

Title : Bioremediation of triphenyl phosphate by Pycnoporus sanguineus: Metabolic pathway, proteomic mechanism and biotoxicity assessment - Feng_2021_J.Hazard.Mater_417_125983
Author(s) : Feng M , Zhou J , Yu X , Wang H , Guo Y , Mao W
Ref : J Hazard Mater , 417 :125983 , 2021
Abstract : So far, no information about the biodegradability of TPhP by white rot fungi has previously been made available, herein, Pycnoporus sanguineus was used as the representative to investigate the potential of white rot fungi in TPhP bioremediation. The results suggested that the biodegradation efficiency of 5 mg/L TPhP by P. sanguineus was 62.84% when pH was adjusted to 6 and initial glucose concentration was 5 g/L. Seven biodegradation products were identified, indicating that TPhP was biotransformed through oxidative cleavage, hydroxylation and methylation. The proteomic analysis revealed that cytochrome P450s, aromatic compound dioxygenase, oxidizing species-generating enzymes, methyltransferases and MFS general substrate transporters might occupy important roles in TPhP biotransformation. Carboxylesterase and glutathione S-transferase were induced to resist TPhP stress. The biotreatment by P. sanguineus contributed to a remarkable decrease of TPhP biotoxicity. Bioaugmentation with P. sanguineus could efficiently promote TPhP biodegradation in the water-sediment system due to the cooperation between P. sanguineus and some putative indigenous degraders, including Sphingobium, Burkholderia, Mycobacterium and Methylobacterium. Overall, this study provided the first insights into the degradation pathway, mechanism and security risk assessment of TPhP biodegradation by P. sanguineus and verified the feasibility of utilizing this fungus for TPhP bioremediation applications.
ESTHER : Feng_2021_J.Hazard.Mater_417_125983
PubMedSearch : Feng_2021_J.Hazard.Mater_417_125983
PubMedID: 33975170

Title : Bile salt-dependent lipase promotes the barrier integrity of Caco-2 cells by activating Wnt\/beta-catenin signaling via LRP6 receptor - Qiu_2021_Cell.Tissue.Res_383_1077
Author(s) : Qiu Y , Zhou J , Zhang D , Song H , Qian L
Ref : Cell Tissue Research , 383 :1077 , 2021
Abstract : Bile salt-dependent lipase (BSDL) within intestinal lumen can be endocytosed by enterocytes and support the intestinal barrier function. However, the epithelial-supporting effect of this protein has not been verified in a human cell line and neither the direct signaling pathway nor the function of endocytosis in this process has been clearly identified. We sought to investigate the signaling pathway and the membrane receptor through which BSDL might exert these effects using intestinal epithelial cells. Caco-2 cells were treated with recombinant BSDL, and the barrier function, cell proliferation, and activation of the Wnt signaling pathway were assessed. The effect of Wnt signaling activation induced by BSDL and BSDL endocytosis was investigated in LRP6-silenced and non-silenced cells. Moreover, caveolae- and clathrin-dependent endocytosis inhibitors were also applied respectively to analyze their effects on Wnt signaling activation induced by BSDL. BSDL treatment increased the barrier function but not proliferation of Caco-2 cells. It also induced beta-catenin nuclear translocation and activated Wnt target gene transcription. Moreover, in the Wnt pathway, BSDL increased the levels of non-phosphorylated-beta-catenin (Ser33/37/Thr41) and phosphorylated-beta-catenin (Ser552). Notably, the silencing of LRP6 expression impaired BSDL endocytosis and decreased BSDL-induced beta-catenin nuclear translocation. The inhibition of BSDL endocytosis induced by caveolae-mediated endocytosis inhibitor was stronger than that by clathrin-mediated endocytosis inhibitor, and the Wnt signaling activation associated with its endocytosis was also most likely caveolae-dependent. Our findings suggested that LRP6, a canonical Wnt pathway co-receptor, can mediate BSDL endocytosis and then activate Wnt signaling in Caco-2 cells.
ESTHER : Qiu_2021_Cell.Tissue.Res_383_1077
PubMedSearch : Qiu_2021_Cell.Tissue.Res_383_1077
PubMedID: 33245415

Title : Fusion of Chitin-Binding Domain From Chitinolyticbacter meiyuanensis SYBC-H1 to the Leaf-Branch Compost Cutinase for Enhanced PET Hydrolysis - Xue_2021_Front.Bioeng.Biotechnol_9_762854
Author(s) : Xue R , Chen Y , Rong H , Wei R , Cui Z , Zhou J , Dong W , Jiang M
Ref : Front Bioeng Biotechnol , 9 :762854 , 2021
Abstract : Polyethylene terephthalate (PET) is a mass-produced petroleum-based non-biodegradable plastic that contributes to the global plastic pollution. Recently, biocatalytic degradation has emerged as a viable recycling approach for PET waste, especially with thermophilic polyester hydrolases such as a cutinase (LCC) isolated from a leaf-branch compost metagenome and its variants. To improve the enzymatic PET hydrolysis performance, we fused a chitin-binding domain (ChBD) from Chitinolyticbacter meiyuanensis SYBC-H1 to the C-terminus of the previously reported LCC(ICCG) variant, demonstrating higher adsorption to PET substrates and, as a result, improved degradation performance by up to 19.6% compared to with its precursor enzyme without the binding module. For compare hydrolysis with different binding module, the catalytic activity of LCC(ICCG)-ChBD, LCC(ICCG)-CBM, LCC(ICCG)-PBM and LCC(ICCG)-HFB4 were further investigated with PET substrates of various crystallinity and it showed measurable activity on high crystalline PET with 40% crystallinity. These results indicated that fusing a polymer-binding module to LCC(ICCG) is a promising method stimulating the enzymatic hydrolysis of PET.
ESTHER : Xue_2021_Front.Bioeng.Biotechnol_9_762854
PubMedSearch : Xue_2021_Front.Bioeng.Biotechnol_9_762854
PubMedID: 34976965
Gene_locus related to this paper: 9bact-g9by57

Title : A Polyketide Cyclase That Forms Medium-Ring Lactones - Gao_2021_J.Am.Chem.Soc_143_80
Author(s) : Gao DW , Jamieson CS , Wang G , Yan Y , Zhou J , Houk KN , Tang Y
Ref : Journal of the American Chemical Society , 143 :80 , 2021
Abstract : Medium-ring lactones are synthetically challenging due to unfavorable energetics involved in cyclization. We have discovered a thioesterase enzyme DcsB, from the decarestrictine C1 (1) biosynthetic pathway, that efficiently performs medium-ring lactonizations. DcsB shows broad substrate promiscuity toward linear substrates that vary in lengths and substituents, and is a potential biocatalyst for lactonization. X-ray crystal structure and computational analyses provide insights into the molecular basis of catalysis.
ESTHER : Gao_2021_J.Am.Chem.Soc_143_80
PubMedSearch : Gao_2021_J.Am.Chem.Soc_143_80
PubMedID: 33351624
Gene_locus related to this paper: beab2-j4wat9

Title : Structure-guided engineering of a Thermobifida fusca cutinase for enhanced hydrolysis on natural polyester substrate - Dong_2020_Bioresour.Bioprocess_7_37
Author(s) : Dong Q , Yuan S , Wu L , Su L , Zhao Q , Wu J , Huang W , Zhou J
Ref : Bioresour. Bioprocess , 7 :37 , 2020
Abstract : Cutinases could degrade insoluble polyester, including natural cutin and synthetic plastic. However, their turnover efficiency for polyester remains too low for industrial application. Herein, we report the 1.54-A resolution X-ray crystal structure of a cutinase from Thermobifida fusca and modeling structure in complex with a cutin mimic oligo-polyester C24H42O8. These efforts subsequently guided our design of cutinase variants with less bulky residues in the vicinity of the substrate binding site. The L90A and I213A variants exhibit increased hydrolysis activity (5- and 2.4-fold, respectively) toward cutin and also showed enhanced cotton scouring efficiency compared with the wild-type enzyme.
ESTHER : Dong_2020_Bioresour.Bioprocess_7_37
PubMedSearch : Dong_2020_Bioresour.Bioprocess_7_37
Gene_locus related to this paper: thefu-q6a0i4

Title : Ratiometric sensors with selective fluorescence enhancement effects based on photonic crystals for the determination of acetylcholinesterase and its inhibitor - Liu_2020_J.Mater.Chem.B_8_11001
Author(s) : Liu R , Bao L , Zhang S , Wu Z , Zhou J , Liu C , Yu R
Ref : J Mater Chem B , 8 :11001 , 2020
Abstract : Ratiometric fluorescent sensors are powerful tools for quantitative analyses. However, gold nano-clusters (AuNCs) as typical fluorophores in ratiometric sensors have some disadvantages, such as low luminous efficiency. In this study, a highly sensitive ratiometric fluorescence sensor was fabricated by the combination of AuNCs and fluorescein (FL), and the photonic crystals (PhCs) were used to selectively enhance the fluorescence intensity of AuNCs. This fluorescence sensor was used for the sensitive detection of acetylcholinesterase (AChE) and its inhibitor paraoxon. AChE can catalyze the hydrolysis of acetylthiocholine (ATCh) to form thiocholine (TCh), which can induce the fluorescence quenching of AuNCs while having no obvious influence on the fluorescence intensity of FL. AChE can be determined in the range from 0.1 to 25 mU mL-1 with a limit of detection (LOD) of 0.027 mU mL-1, and paraoxon can be determined in the range of 0.06 to 60 ng mL-1 with a LOD 0.025 ng mL-1. This method, as a new way to selectively improve the fluorescence signal of one of the fluorophores in the ratiometric sensor, would be a promising strategy for the sensitive determination of AChE and its inhibitor.
ESTHER : Liu_2020_J.Mater.Chem.B_8_11001
PubMedSearch : Liu_2020_J.Mater.Chem.B_8_11001
PubMedID: 33225325

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 : Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis - Tu_2020_Nat.Commun_11_971
Author(s) : Tu L , Su P , Zhang Z , Gao L , Wang J , Hu T , Zhou J , Zhang Y , Zhao Y , Liu Y , Song Y , Tong Y , Lu Y , Yang J , Xu C , Jia M , Peters RJ , Huang L , Gao W
Ref : Nat Commun , 11 :971 , 2020
Abstract : Triptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.
ESTHER : Tu_2020_Nat.Commun_11_971
PubMedSearch : Tu_2020_Nat.Commun_11_971
PubMedID: 32080175
Gene_locus related to this paper: triwf-a0a7j7c8l4

Title : Simulated revelation of the adsorption behaviours of acetylcholinesterase on charged self-assembled monolayers - Yang_2020_Nanoscale__
Author(s) : Yang S , Liu J , Zheng H , Zhong J , Zhou J
Ref : Nanoscale , : , 2020
Abstract : An acetylcholinesterase (AChE)-based electrochemical biosensor, as a promising alternative to detect organophosphates (OPs) and carbamate pesticides, has gained considerable attention in recent years, due to the advantages of simplicity, rapidity, reliability and low cost. The bio-activity of AChE immobilized on the surface and the direct electron transfer (DET) rate between an enzyme and an electrode directly determined the analytical performances of the AChE-based biosensor, and experimental studies have shown that the charged surfaces have a strong impact on the detectability of the AChE-based biosensor. Therefore, it is very important to reveal the behaviour of AChE in bulk solution and on charged surfaces at the molecular level. In this work, the adsorption orientation and conformation of AChE from Torpedo californica (TcAChE) on oppositely charged self-assembled monolayers (SAMs), COOH-SAM and NH2-SAM with different surface charge densities, were investigated by parallel tempering Monte Carlo (PTMC) and all-atom molecular dynamics simulations (AAMD). Simulation results show that TcAChE could spontaneously and stably adsorb on two oppositely charged surfaces by the synergy of an electric dipole and charged residue patch, and opposite orientations were observed. The active-site gorge of TcAChE is oriented toward the surface with the "end-on" orientation and the active sites are close to the surface when it is adsorbed on the positively charged surface and the tunnel cost for the substrate is lower than that on the negatively charged surface and in bulk solution, while for TcAChE adsorbed on the negatively charged surface, the active site of TcAChE is far away from the surface and the active-site gorge is oriented toward the solution with a "back-on" orientation. It suggests that the positively charged surface could provide a better microenvironment for the efficient bio-catalytic reaction and quick DET between TcAChE and the electrode surface. Moreover, the RMSD, RMSF, dipole moment, gyration radius, eccentricity and superimposed structures show that only a slight conformational change occurred on the relatively flexible structure of TcAChE during simulations, and the native conformation is well preserved after adsorption. This work helps us better comprehend the adsorption mechanism of TcAChE on charged surfaces and might provide some guidelines for the development of new TcAChE-based amperometric biosensors for the detection of organophosphorus pesticides.
ESTHER : Yang_2020_Nanoscale__
PubMedSearch : Yang_2020_Nanoscale__
PubMedID: 32022070

Title : Identification and functional characterization of a novel heterozygous missense variant in the LPL associated with recurrent hypertriglyceridemia-induced acute pancreatitis in pregnancy - Shi_2020_Mol.Genet.Genomic.Med__e1048
Author(s) : Shi XL , Yang Q , Pu N , Li XY , Chen WW , Zhou J , Li G , Tong ZH , Ferec C , Cooper DN , Chen JM , Li WQ
Ref : Mol Genet Genomic Med , :e1048 , 2020
Abstract : BACKGROUND: Acute pancreatitis in pregnancy (APIP) is a life-threatening disease for both mother and fetus. To date, only three patients with recurrent hypertriglyceridemia-induced APIP (HTG-APIP) have been reported to carry rare variants in the lipoprotein lipase (LPL) gene, which encodes the key enzyme responsible for triglyceride (TG) metabolism. Coincidently, all three patients harbored LPL variants on both alleles and presented with complete or severe LPL deficiency. METHODS: The entire coding regions and splice junctions of LPL and four other TG metabolism genes (APOC2, APOA5, GPIHBP1, and LMF1) were analyzed by Sanger sequencing in a Han Chinese patient who had experienced two episodes of HTG-APIP. The impact of a novel LPL missense variant on LPL protein expression and activity was analyzed by transient expression in HEK293T cells. RESULTS: A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient. This variant did not affect protein synthesis but significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein. CONCLUSION: This report describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG-APIP. Our findings confirm a major genetic contribution to the etiology of individual predisposition to HTG-APIP.
ESTHER : Shi_2020_Mol.Genet.Genomic.Med__e1048
PubMedSearch : Shi_2020_Mol.Genet.Genomic.Med__e1048
PubMedID: 31962008
Gene_locus related to this paper: human-LPL

Title : Electrostatic Effect of Functional Surfaces on the Activity of Adsorbed Enzymes: Simulations and Experiments - Zheng_2020_ACS.Appl.Mater.Interfaces_12_35676
Author(s) : Zheng H , Yang SJ , Zheng YC , Cui Y , Zhang Z , Zhong JY , Zhou J
Ref : ACS Appl Mater Interfaces , 12 :35676 , 2020
Abstract : The efficient immobilization of haloalkane dehalogenase (DhaA) on carriers with retaining of its catalytic activity is essential for its application in environmental remediation. In this work, adsorption orientation and conformation of DhaA on different functional surfaces were investigated by computer simulations; meanwhile, the mechanism of varying the catalytic activity was also probed. The corresponding experiments were then carried out to verify the simulation results. (The simulations of DhaA on SAMs provided parallel insights into DhaA adsorption in carriers. Then, the theory-guided experiments were carried out to screen the best surface functional groups for DhaA immobilization.) The electrostatic interaction was considered as the main impact factor for the regulation of enzyme orientation, conformation, and enzyme bioactivity during DhaA adsorption. The synergy of overall conformation, enzyme substrate tunnel structural parameters, and distance between catalytic active sites and surfaces codetermined the catalytic activity of DhaA. Specifically, it was found that the positively charged surface with suitable surface charge density was helpful for the adsorption of DhaA and retaining its conformation and catalytic activity and was favorable for higher enzymatic catalysis efficiency in haloalkane decomposition and environmental remediation. The neutral, negatively charged surfaces and positively charged surfaces with high surface charge density always caused relatively larger DhaA conformation change and decreased catalytic activity. This study develops a strategy using a combination of simulation and experiment, which can be essential for guiding the rational design of the functionalization of carriers for enzyme adsorption, and provides a practical tool to rationally screen functional groups for the optimization of adsorbed enzyme functions on carriers. More importantly, the strategy is general and can be applied to control behaviors of different enzymes on functional carrier materials.
ESTHER : Zheng_2020_ACS.Appl.Mater.Interfaces_12_35676
PubMedSearch : Zheng_2020_ACS.Appl.Mater.Interfaces_12_35676
PubMedID: 32649833

Title : Rational design and biological evaluation of a new class of thiazolopyridyl tetrahydroacridines as cholinesterase and GSK-3 dual inhibitors for Alzheimer's disease - Jiang_2020_Eur.J.Med.Chem_207_112751
Author(s) : Jiang X , Zhou J , Wang Y , Chen L , Duan Y , Huang J , Liu C , Chen Y , Liu W , Sun H , Feng F , Qu W
Ref : Eur Journal of Medicinal Chemistry , 207 :112751 , 2020
Abstract : A key factor in the success of the MTDLs drug discovery approach is the selection of suitable target proteins. Based on the results of our previous research regarding dual-target inhibitors of AChE/GSK-3beta and analysis of target proteins, in the current study, 28 hybrids were designed and synthesized. Docking studies allowed us to rationalize the binding mode of the synthesized compounds in both targets. In vitro enzyme inhibition studies identified compound GT15 as a lead molecule with preferential AChE/GSK-3beta inhibition (hAChE IC(50) = 1.2 +/- 0.1 nM; hGSK-3beta IC(50) = 22.2 +/- 1.4 nM). In addition, GT15 showed high kinase selectivity for GSK-3, except for DYRK1, with inhibition rate of 83.69% and 67.94% against DYRK1alpha and DYRK1beta at a concentration of 20 muM. The compound also exhibited good permeability across the blood-brain-barrier and ability to inhibit the phosphorylation of tau protein. Upon oral administration, GT15 exhibited promising cognitive improvement in the scopolamine-induced cognitive deficit mice in the Morris water maze model. These results suggest that AChE and GSK-3 based multitargeted approach have therapeutic potential for Alzheimer's disease.
ESTHER : Jiang_2020_Eur.J.Med.Chem_207_112751
PubMedSearch : Jiang_2020_Eur.J.Med.Chem_207_112751
PubMedID: 32950908

Title : Selenoprotein F knockout leads to glucose and lipid metabolism disorders in mice - Zheng_2020_J.Biol.Inorg.Chem_25_1009
Author(s) : Zheng X , Ren B , Li X , Yan H , Xie Q , Liu H , Zhou J , Tian J , Huang K
Ref : J Biol Inorg Chem , 25 :1009 , 2020
Abstract : Selenoprotein F (Selenof), an endoplasmic reticulum (ER)-resident protein, is considered to be involved in glycoprotein folding and quality control in the ER. However, its function has not yet been thoroughly addressed. In this study, proteomics analysis revealed that Selenof deficiency in mice led to the differential expression of hepatic proteins associated with glucose and lipid metabolism. The phenotype analysis revealed that Selenof knockout mice showed glucose intolerance and insulin reduction, even with a normal diet. Additionally, Selenof knockout exacerbated high-fat diet-induced obesity, hyperglycemia, glucose intolerance, and hepatic steatosis. Furthermore, lipoprotein lipase and carboxylesterase 1D, two glycoproteins involved in lipid metabolism, were significantly decreased in the liver of Selenof knockout mice with a normal or high-fat diet. Collectively, these findings suggested that Selenof deficiency might cause the perturbation of glycoprotein quality control and thus contribute to glucose and lipid metabolism disorders, implying a novel biological function of Selenof.
ESTHER : Zheng_2020_J.Biol.Inorg.Chem_25_1009
PubMedSearch : Zheng_2020_J.Biol.Inorg.Chem_25_1009
PubMedID: 32995962

Title : Characterization and Genome Analysis of a Zearalenone-Degrading Bacillus velezensis Strain ANSB01E - Guo_2020_Curr.Microbiol_77_273
Author(s) : Guo Y , Zhou J , Tang Y , Ma Q , Zhang J , Ji C , Zhao L
Ref : Curr Microbiol , 77 :273 , 2020
Abstract : Zearalenone, a nonsteroidal estrogenic mycotoxin mainly produced by Fusarium species, causes reproductive disorders and hyperestrogenic syndromes in animals and humans. The bacterial strain Bacillus velezensis ANSB01E, isolated from chicken cecal content, was capable of effectively degrading zearalenone in both liquid medium and mouldy corn. Moreover, Bacillus velezensis ANSB01E exhibited good antimicrobial activities against animal pathogenic bacteria, including Escherichia coli, Staphylococcus aureus, and Salmonella spp. Genome-based analysis revealed the presence of genes coding peroxiredoxin and alpha/beta hydrolase in Bacillus velezensis ANSB01E, which may be involved in zearalenone degradation. The study on the genome provides insights into the zearalenone degradation mechanisms and advances the potential application of Bacillus velezensis ANSB01E in food and feed industry.
ESTHER : Guo_2020_Curr.Microbiol_77_273
PubMedSearch : Guo_2020_Curr.Microbiol_77_273
PubMedID: 31748861
Gene_locus related to this paper: 9baci-QBK11187

Title : Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6\/JAK2\/STAT3 signaling in glioma - Zhou_2020_Cell.Oncol.(Dordr)_43_461
Author(s) : Zhou J , Jiang Y , Zhao J , Zhang H , Fu J , Luo P , Ma Y , Zou D , Gao H , Hu J , Zhang Y , Jing Z
Ref : Cell Oncol (Dordr) , 43 :461 , 2020
Abstract : PURPOSE: The iron-chelating agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has been found to inhibit cell growth and to induce apoptosis in several human cancers. However, its effects and mechanism of action in glioma are unknown. METHODS: Human glioma cell line LN229 and patient-derived glioma stem cells GSC-42 were applied for both in vitro and in vivo xenograft nude mouse experiments. The anti-tumor effects of Dp44mT were assessed using MTS, EdU, TUNEL, Western blotting, qRT-PCR, luciferase reporter, chromatin immunoprecipitation and immunohistochemical assays. RESULTS: We found that Dp44mT can upregulate the expression of the anti-oncogene N-myc downstream-regulated gene (NDRG)2 by directly binding to and activating the RAR-related orphan receptor (ROR)A. In addition, we found that NDRG2 overexpression suppressed inflammation via activation of interleukin (IL)-6/Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling. CONCLUSIONS: Our data indicate that Dp44mT may serve as an effective drug for the treatment of glioma by targeting RORA and enhancing NDRG2-mediated IL-6/JAK2/STAT3 signaling.
ESTHER : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedSearch : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedID: 32207044
Gene_locus related to this paper: human-NDRG2

Title : Carboxyl ester lipase is highly conserved in utilizing maternal supplied lipids during early development of zebrafish and human - Qiu_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__158663
Author(s) : Qiu Y , Sun S , Yu X , Zhou J , Cai W , Qian L
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :158663 , 2020
Abstract : Carboxyl ester lipase (Cel), is a lipolytic enzyme secreted by the pancreas, which hydrolyzes various species of lipids in the gut. Cel is also secreted by mammary gland during lactation and exists in breast milk. It facilitates dietary fat digestion and absorption, thus contributing to normal infant development. This study aimed to examine whether the Cel in zebrafish embryos has a similar role of maternal lipid utilization as in human infants, and how Cel contributes to the utilization of yolk lipids in zebrafish. The cel1 and cel2 genes were expressed ubiquitously in the blastodisc and yolk syncytial layer before 24 hpf, and in the exocrine pancreas after 72 hpf. The cel1 and cel2 morphants exhibited developmental retardation and yolk sac retention. The total cholesterol, cholesterol ester, free cholesterol, and triglyceride were reduced in the morphants' body while accumulated in the yolk (except triglyceride). The FFA content of whole embryos was much lower in morphants than in standard controls. Moreover, the delayed development in cel (cel1/cel2) double morphants was partially rescued by FFA and cholesterol supplementation. Delayed and weakened cholesterol ester transport to the brain and eyes was observed in cel morphants. Correspondingly, shrunken midbrain tectum, microphthalmia, pigmentation-delayed eyes as well as down-regulated Shh target genes were observed in the CNS of double morphants. Interestingly, cholesterol injections reversed these CNS alterations. Our findings suggested that cel genes participate in the lipid releasing from yolk sac to developing body, thereby contributing to the normal growth rate and CNS development in zebrafish.
ESTHER : Qiu_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__158663
PubMedSearch : Qiu_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__158663
PubMedID: 32061751

Title : Lactobacillus plantarum CQPC02-Fermented Soybean Milk Improves Loperamide-Induced Constipation in Mice - Yi_2019_J.Med.Food_22_1208
Author(s) : Yi R , Peng P , Zhang J , Du M , Lan L , Qian Y , Zhou J , Zhao X
Ref : J Med Food , 22 :1208 , 2019
Abstract : This study determined the ameliorative effects of the novel microorganism, Lactobacillus plantarum CQPC02 (LP-CQPC02), fermented in soybean milk, on loperamide-induced constipation in Kunming mice. High-performance liquid chromatography revealed that LP-CQPC02-fermented soybean milk (LP-CQPC02-FSM) had six types of soybean isoflavones, whereas Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM) only had five types of soybean isoflavones. LP-CQPC02-FSM also contained more total and active soybean isoflavones than LB-FSM and U-FSM. Results from mouse experiments showed that the defecation factors (quantity, fecal weight and water content, gastrointestinal transit ability, and time to first black stool) in the LP-CQPC02-FSM-treated mice were better than those in the LB-FSM- and U-FSM-treated mice. The serum and small intestinal tissue experiments showed that soybean milk increased the motilin, gastrin, endothelin, acetylcholinesterase, substance P, vasoactive intestinal peptide, and glutathione levels and decreased the somatostatin, myeloperoxidase, nitric oxide, and malondialdehyde levels compared with the constipated mice in the control group. The LP-CQPC02-FSM also showed better effects than those of LB-FSM and U-FSM. Further results showed that LP-CQPC02-FSM upregulated cuprozinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), and aquaporin-9 (AQP9) and downregulated the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), inducible nitric oxide synthase (iNOS), and aquaporin-3 (AQP3) in the constipated mice. LP-CQPC02-FSM increased the Bacteroides and Akkermansia abundances and decreased the Firmicutes abundance in the feces of the constipated mice and decreased the Firmicutes/Bacteroides ratio. This study confirmed that LP-CQPC02-FSM partially reversed constipation in mice.
ESTHER : Yi_2019_J.Med.Food_22_1208
PubMedSearch : Yi_2019_J.Med.Food_22_1208
PubMedID: 31621475

Title : Noninvasive Evaluation of Liver Fibrosis Reverse Using Artificial Neural Network Model for Chronic Hepatitis B Patients - Wei_2019_Comput.Math.Methods.Med_2019_7239780
Author(s) : Wei W , Wu X , Zhou J , Sun Y , Kong Y , Yang X
Ref : Comput Math Methods Med , 2019 :7239780 , 2019
Abstract : The diagnostic performance of an artificial neural network model for chronic HBV-induced liver fibrosis reverse is not well established. Our research aims to construct an ANN model for estimating noninvasive predictors of fibrosis reverse in chronic HBV patients after regular antiviral therapy. In our study, 141 consecutive patients requiring liver biopsy at baseline and 1.5 years were enrolled. Several serum biomarkers and liver stiffness were measured during antiviral therapy in both reverse and nonreverse groups. Statistically significant variables between two groups were selected to form an input layer of the ANN model. The ROC (receiver-operating characteristic) curve and AUC (area under the curve) were calculated for comparison of effectiveness of the ANN model and logistic regression model in predicting HBV-induced liver fibrosis reverse. The prevalence of fibrosis reverse of HBV patients was about 39% (55/141) after 78-week antiviral therapy. The Ishak scoring system was used to assess fibrosis reverse. Our study manifested that AST (aspartate aminotransferase; importance coefficient = 0.296), PLT (platelet count; IC = 0.159), WBC (white blood cell; IC = 0.142), CHE (cholinesterase; IC = 0.128), LSM (liver stiffness measurement; IC = 0.125), ALT (alanine aminotransferase; IC = 0.110), and gender (IC = 0.041) were the most crucial predictors of reverse. The AUC of the ANN model and logistic model was 0.809 +/- 0.062 and 0.756 +/- 0.059, respectively. In our study, we concluded that the ANN model with variables consisting of AST, PLT, WBC, CHE, LSM, ALT, and gender may be useful in diagnosing liver fibrosis reverse for chronic HBV-induced liver fibrosis patients.
ESTHER : Wei_2019_Comput.Math.Methods.Med_2019_7239780
PubMedSearch : Wei_2019_Comput.Math.Methods.Med_2019_7239780
PubMedID: 31428186

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

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

Title : Designing of a Cofactor Self-Sufficient Whole-Cell Biocatalyst System for Production of 1,2-Amino Alcohols from Epoxides - Liu_2019_ACS.Synth.Biol_8_734
Author(s) : Liu S , Zhang X , Liu F , Xu M , Yang T , Long M , Zhou J , Osire T , Yang S , Rao Z
Ref : ACS Synth Biol , 8 :734 , 2019
Abstract : Optically pure 1,2-amino alcohols are highly valuable products as intermediates for chiral pharmaceutical products. Here we designed an environmentally friendly non-natural biocatalytic cascade for efficient synthesis of 1,2-amino alcohols from cheaper epoxides. A redesignated omega-transaminase PAKomega-TA was tested and showed good bioactivity at a lower pH than other reported transaminases. The cascade was efficiently constructed as a single one-pot E. coli recombinant, by coupling SpEH (epoxide hydrolase), MnADH (alcohol dehydrogenase), and PAKomega-TA. Furthermore, RBS regulation strategy was used to overcome the rate limiting step by increasing expression of MnADH. For cofactor regeneration and amino donor source, an interesting point was involved as that a cofactor self-sufficient system was designed by expression of GluDH. It established a "bridge" between the cofactor and the cosubstrate, such that the cofactor self-sufficient system could release cofactor (NADP(+)) and cosubstrate (l-Glutamine) regenerated simultaneously. The recombinant E. coli BL21 (SGMP) with cofactor self-sufficient whole-cell cascade biocatalysis showed high ee value (>99%) and high yield, with 99.6% conversion of epoxide ( S)-1a to 1,2-amino alcohol ( S)-1d in 10 h. It further converted ( S)-2a-5a to ( S)-2d-5d with varying conversion rates ranging between 65-96.4%. This study first provides one-step synthesis of optically pure 1,2-amino alcohols from ( S)-epoxides employing a synthetic redox-self-sufficient cascade.
ESTHER : Liu_2019_ACS.Synth.Biol_8_734
PubMedSearch : Liu_2019_ACS.Synth.Biol_8_734
PubMedID: 30840437

Title : Carbon dots co-doped with nitrogen and chlorine for off-on fluorometric determination of the activity of acetylcholinesterase and for quantification of organophosphate pesticides - Yang_2019_Mikrochim.Acta_186_585
Author(s) : Yang M , Liu M , Wu Z , He Y , Ge Y , Song G , Zhou J
Ref : Mikrochim Acta , 186 :585 , 2019
Abstract : Nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) were hydrothermally prepared starting from 4-chloro-1,2-diaminobenzene and dopamine. The N,Cl-CDs exhibit strong orange fluorescence, with excitation/emission maxima at 420/570 nm and a relative high quantum yield (15%). The N,Cl-CDs were employed to detect acetylcholinesterase (AChE) activity and organophosphate pesticides (OPs) which are enzyme inhibitors. Acetylthiocholine is enzymatically split by AChE to produce thiocholine which triggers the decomposition of Ellmans's reagent to form a yellow colored product (2-nitro-5-thiobenzoate anion). The product causes an inner filter effect (IEF) on the fluorescence of the N,Cl-CDs. Fluorescence decreases linearly in the 0.017 to 5.0 Unit.L(-1) AChE activity range, and the detection limit is 2 mUnit.L(-1). If organophosphates are present, the activity of AChE becomes increasingly blocked, and this leads to a less expressed IFE and an increasing recovery of fluorescence. This was used for the quantification of OPs. Response is linear in the 0.3-1000 mug.L(-1) OP concentration range with a 30 ng.L(-1) detection limit. Graphical abstractSchematic representation of the synthesis of nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) and the recognition of organophosphate pesticides by N,Cl-CDs.
ESTHER : Yang_2019_Mikrochim.Acta_186_585
PubMedSearch : Yang_2019_Mikrochim.Acta_186_585
PubMedID: 31363918

Title : Reassembly of native components with donepezil to execute dual-missions in Alzheimer's disease therapy - Zhang_2019_J.Control.Release_296_14
Author(s) : Zhang H , Zhao Y , Yu M , Zhao Z , Liu P , Cheng H , Ji Y , Jin Y , Sun B , Zhou J , Ding Y
Ref : J Control Release , 296 :14 , 2019
Abstract : Alzheimer's disease (AD) is a multifaceted and progressive neurodegenerative disease characterized by accumulation of amyloid-beta (Abeta) and deficits of acetylcholine. Accordingly, the intra-/extra-cerebral level of high density lipoprotein (HDL) is crucial on the pathogenesis of AD; and most of all, various HDL-protein subtypes play a double-edged role in AD pathology, of which apolipoprotein A-I (apoA-I) gives protective outcomes. Inspired from "HDL bionics", we proposed biologically reassembled nanodrugs, donepezil-loaded apolipoprotein A-I-reconstituted HDL (rHDL/Do) that concurrently executed dual-missions of Abeta-targeting clearance and acetylcholinesterase (AChE) inhibition in AD therapy. Once prepared, rHDL/Do nanodrug achieved high drug encapsulation efficiency of 90.47%, and mimicked the configurations and properties of natural lipoproteins aiming to significantly enhance BBB penetration and modulate Abeta-induced neuronal damage both in vitro and in vivo. Surface plasmon resonance (SPR) analysis confirmed that rHDL/Do facilitated microglial-mediated Abeta intake and degradation, demonstrating low KD value with Abeta affinity (2.45x10(-8) of Abeta monomer and 2.78x10(-8) of Abeta oligomer). In AD animal models, daily treatment of rHDL/Do efficiently inhibited AChE activity, ameliorated neurologic variation, promoted Abeta clearance, and rescued memory loss at a safe level. The collective findings indicated that the biological nanodrug was provided with the capacities of BBB penetration, Abeta capture and degradation via microglial cells, and cholinergic dysfunction amelioration after controlled donepezil release. In summary, rHDL/Do nanodrugs could offer a promising strategy to synergize both symptom control and disease modification in AD therapy.
ESTHER : Zhang_2019_J.Control.Release_296_14
PubMedSearch : Zhang_2019_J.Control.Release_296_14
PubMedID: 30639387

Title : Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts - Zhang_2019_Cancer.Lett_465_36
Author(s) : Zhang L , Zhou J , Yan Y , Zhou X , Zhou Q , Du R , Hu S , Ge W , Huang Y , Xu H , Kong Y , Zheng H , Ding Y , Shen Y , Wang W
Ref : Cancer Letters , 465 :36 , 2019
Abstract : Irinotecan (CPT-11) is an anti-tumor drug and formulated as nanomedicines to reduce side effects and improve efficacy. In vivo, CPT-11 must be hydrolyzed by carboxylesterase to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) to exert anti-tumor activity, but the lack of this enzyme in humans causes inefficient generation of SN-38. Thus, direct delivery of SN-38, not relying on carboxylesterase, will potentially achieve higher efficacy. However, it is difficult to effectively formulate SN-38 using current excipients due to its hydrophobicity and tendency to crystallize. Herein, we report the nanodispersion of SN-38 with its amphiphilic prodrug, CPT-11, as an effective treatment for pancreatic cancer (PC). SN-38 and CPT-11 formed stable nanoparticles without any other excipients, and showed potent cytotoxicity against PC cells in vitro, slowed tumor growth in vivo, namely subcutaneously and orthotopically xenografted mice, with minimal adverse effects, and prolonged their overall survival. Even in clinically-relevant patient-derived xenograft (PDX) models, the nanodispersion showed greater anti-tumor efficacy than CPT-11. Importantly, the nanodispersion directly released SN-38, resulting in carboxylesterase-independent anti-tumor activity, in contrast to carboxylesterase-dependent CPT-11. These characteristics may enable the excipient-free nanodispersion to exert potent therapeutic effects in patients.
ESTHER : Zhang_2019_Cancer.Lett_465_36
PubMedSearch : Zhang_2019_Cancer.Lett_465_36
PubMedID: 31479691

Title : Activity-Based Protein Profiling Identifies alpha-Ketoamides as Inhibitors for Phospholipase A2 Group XVI - Zhou_2019_ACS.Chem.Biol_14_164
Author(s) : Zhou J , Mock ED , Martella A , Kantae V , Di X , Burggraaff L , Baggelaar MP , Al-Ayed K , Bakker A , Florea BI , Grimm SH , den Dulk H , Li CT , Mulder L , Overkleeft HS , Hankemeier T , van Westen GJP , van der Stelt M
Ref : ACS Chemical Biology , 14 :164 , 2019
Abstract : Phospholipase A2, group XVI (PLA2G16) is a thiol hydrolase from the HRASLS family that regulates lipolysis in adipose tissue and has been identified as a host factor enabling the cellular entry of picornaviruses. Chemical tools are essential to visualize and control PLA2G16 activity, but they have not been reported to date. Here, we show that MB064, which is a fluorescent lipase probe, also labels recombinant and endogenously expressed PLA2G16. Competitive activity-based protein profiling (ABPP) using MB064 enabled the discovery of alpha-ketoamides as the first selective PLA2G16 inhibitors. LEI110 was identified as a potent PLA2G16 inhibitor ( K(i) = 20 nM) that reduces cellular arachidonic acid levels and oleic acid-induced lipolysis in human HepG2 cells. Gel-based ABPP and chemical proteomics showed that LEI110 is a selective pan-inhibitor of the HRASLS family of thiol hydrolases (i.e., PLA2G16, HRASLS2, RARRES3 and iNAT). Molecular dynamic simulations of LEI110 in the reported crystal structure of PLA2G16 provided insight in the potential ligand-protein interactions to explain its binding mode. In conclusion, we have developed the first selective inhibitor that can be used to study the cellular role of PLA2G16.
ESTHER : Zhou_2019_ACS.Chem.Biol_14_164
PubMedSearch : Zhou_2019_ACS.Chem.Biol_14_164
PubMedID: 30620559

Title : Bioaccumulation and toxicity of methoxychlor on Chinese mitten crab (Eriocheir sinensis) - Cheng_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_221_89
Author(s) : Cheng L , Song W , Rao Q , Zhou J , Zhao Z
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , 221 :89 , 2019
Abstract : Chinese mitten crab, a featured macrobenthos, has been one of the most important economical aquatic species in China. This study assessed the accumulation of an organochlorine pesticide methoxychlor (MXC) in Chinese mitten crab during exposure to 1mg/L of MXC. The results showed the residual concentration of MXC in the ovary and hepatopancreas reached 55.07+/-2.64ng/g and 34.51+/-2.35ng/g, respectively. After exposure, tubular vacuolization of epithelial tissues, condensed egg cells and obvious intervals between egg cell wall and stroma were observed in the hepatopancreas and ovary, respectively. Significant changes of three key metabolic enzymes in hepatopancreas were observed upon exposure to MXC. Compared to the control, acetylcholinesterase level was significantly higher at day 7 (0.15+/-0.01 vs. 0.06+/-0.00U/mgprot); glutathione S-transferase level was elevated at both day 4 (12.01+/-0.48 vs. 3.20+/-0.44U/mgprot) and day 7 (12.84+/-1.01 vs. 8.22+/-0.81U/mgprot); superoxide dismutase was sharply increased at day 4 (21.20+/-0.24 vs. 3.66+/-0.60U/mgprot) but decreased at day 7 (3.74+/-0.12 vs. 9.44+/-0.85U/mgprot). Overall, dissolved MXC accumulated in lipid-rich tissues could cause damages on epithelial cells and egg cells and change metabolic activities of enzymes involved in antioxidative stress and detoxification processes.
ESTHER : Cheng_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_221_89
PubMedSearch : Cheng_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_221_89
PubMedID: 30954688

Title : Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis and Epithelial-Mesenchymal Transition -
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 24 :2795 , 2018
PubMedID: 30184511
Gene_locus related to this paper: human-ABHD5

Title : Mapping in vivo target interaction profiles of covalent inhibitors using chemical proteomics with label-free quantification - van Rooden_2018_Nat.Protoc_13_752
Author(s) : van Rooden EJ , Florea BI , Deng H , Baggelaar MP , van Esbroeck ACM , Zhou J , Overkleeft HS , van der Stelt M
Ref : Nat Protoc , 13 :752 , 2018
Abstract : Activity-based protein profiling (ABPP) has emerged as a valuable chemical proteomics method to guide the therapeutic development of covalent drugs by assessing their on-target engagement and off-target activity. We recently used ABPP to determine the serine hydrolase interaction landscape of the experimental drug BIA 10-2474, thereby providing a potential explanation for the adverse side effects observed with this compound. ABPP allows mapping of protein interaction landscapes of inhibitors in cells, tissues and animal models. Whereas our previous protocol described quantification of proteasome activity using stable-isotope labeling, this protocol describes the procedures for identifying the in vivo selectivity profile of covalent inhibitors with label-free quantitative proteomics. The optimization of our protocol for label-free quantification methods results in high proteome coverage and allows the comparison of multiple biological samples. We demonstrate our protocol by assessing the protein interaction landscape of the diacylglycerol lipase inhibitor DH376 in mouse brain, liver, kidney and testes. The stages of the protocol include tissue lysis, probe incubation, target enrichment, sample preparation, liquid chromatography-mass spectrometry (LC-MS) measurement, data processing and analysis. This approach can be used to study target engagement in a native proteome and to identify potential off targets for the inhibitor under investigation. The entire protocol takes at least 4 d, depending on the number of samples.
ESTHER : van Rooden_2018_Nat.Protoc_13_752
PubMedSearch : van Rooden_2018_Nat.Protoc_13_752
PubMedID: 29565900

Title : Design, synthesis and cholinesterase inhibitory activity of alpha-mangostin derivatives - Chi_2018_Nat.Prod.Res__1
Author(s) : Chi XQ , Hou B , Yang L , Zi CT , Lv YF , Li JY , Ren FC , Yuan MY , Hu JM , Zhou J
Ref : Nat Prod Res , :1 , 2018
Abstract : alpha-mangostin, a polyphenol xanthone derivative, was mainly isolated from pericarps of the mangosteen fruit (Garcinia mangostana L.). In present investigation, a series of derivatives were designed, synthesised and evaluated in vitro for their inhibitory activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among the synthesised xanthones, compounds 1, 9, 13 and 16 showed AChE selective inhibitory activity, 15 was a BuChE selective inhibitor while 2, 3, 5, 6, 7, 12 and 14 were dual inhibitors. The most potent inhibitor of AChE was 16 while 5 was the most potent inhibitor of BuChE with IC50 values of 5.26 muM and 7.55 muM respectively.
ESTHER : Chi_2018_Nat.Prod.Res__1
PubMedSearch : Chi_2018_Nat.Prod.Res__1
PubMedID: 30456989

Title : Identification and Field Evaluation of the Sex Pheromone of Orthaga achatina (Lepidoptera: Pyralidae) - Yan_2018_J.Chem.Ecol_44_886
Author(s) : Yan Q , Li HD , Chen Y , Ye ZF , You XY , Zhou J , Mu LF , Liu SJ , Kong XB , Khuhro SA , Dong SL
Ref : J Chem Ecol , 44 :886 , 2018
Abstract : Orthaga achatina (Lepidoptera: Pyralidae) is the most serious pest in south China of camphor trees, Cinnamomum camphora (L.) Presl, an important urban tree species. Gas chromatography-electroantennographic detection (GC-EAD) of the sex pheromone of O. achatina showed three EAD-active components. Coupled gas chromatography/mass spectrometry analyses identified these as (Z)-11-hexadecenol (Z11-16:OH), (Z)-11-hexadecenyl acetate (Z11-16:OAc), and (3Z,6Z,9Z,12Z,15Z)-tricosapentaene (Z3,Z6,Z9,Z12,Z15-23:H). In field tests using different combinations of the three compounds, male moths were attracted to a mixture of Z11-16:OAc and Z3,Z6,Z9,Z12,Z15-23:H, but less attracted to other blends. Further field tests with different ratios of the two compounds determined the optimal ratio of the binary blend as 500:250. The addition of Z11-16:OH to Z11-16:OAc, or to the binary mixture of Z11-16: OAc and the pentaene did not yield higher catches. This shows that O. achatina uses a mixture of Type I and Type II sex pheromone components. Orthaga achatina is the third Pyraloidea species found to utilize Z3,Z6,Z9,Z12,Z15-23:H as a sex pheromone component.
ESTHER : Yan_2018_J.Chem.Ecol_44_886
PubMedSearch : Yan_2018_J.Chem.Ecol_44_886
PubMedID: 30094705

Title : Regioselectivity Engineering of Epoxide Hydrolase: Near-Perfect Enantioconvergence through a Single Site Mutation - Li_2018_ACS.Catal_8_8314
Author(s) : Li FL , Kong XD , Chen Q , Zheng YC , Xu Q , Chen FF , Fan LQ , Lin GQ , Zhou J , Yu HL , Xu JH
Ref : ACS Catal , 8 :8314 , 2018
Abstract : An epoxide hydrolase from Vigna radiata (VrEH2) affords partial enantioconvergence (84% ee) in the enzymatic hydrolysis of racemic p-nitrostyrene oxide (pNSO), mainly due to insufficient regioselectivity for the (S)-enantiomer (rS = alphaS/betaS = 7.3). To improve the (S)-pNSO regioselectivity, a small but smart library of VrEH2 mutants was constructed by substituting each of four key residues lining the substrate binding site with a simplified amino acid alphabet of Val, Asn, Phe, and Trp. Among the mutants, M263N attacked almost exclusively at Calpha in the (S)-epoxide ring with satisfactory regioselectivity (rS = 99.0), without compromising the original high regioselectivity for the (R)-epoxide (rR = 99.0), resulting in near-perfect enantioconvergence (>99% analytical yield, 98% ee). Structural and conformational analysis showed that the introduced Asn263 formed additional hydrogen bonds with the nitro group in substrate, causing a shift in the substrate binding pose. This shift increased the difference in attacking distances between Calpha and Cbeta, leading to an improved regiopreference toward (S)-pNSO and affording near-perfect enantioconvergence.
ESTHER : Li_2018_ACS.Catal_8_8314
PubMedSearch : Li_2018_ACS.Catal_8_8314
Gene_locus related to this paper: vigra-Vreh3

Title : Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans - Yang_2018_Arch.Toxicol_92_2779
Author(s) : Yang S , Zhang H , Zhang J , Li Y , Jin Y , Zhang S , De Saeger S , Zhou J , Sun F , De Boevre M
Ref : Archives of Toxicology , 92 :2779 , 2018
Abstract : Zearalenone-14-glucoside (ZEN-14G), the modified mycotoxin of zearalenone (ZEN), has attracted considerable attention due to its high potential to be hydrolyzed into ZEN, which would exert toxicity. It has been confirmed that the microflora could metabolize ZEN-14G to ZEN. However, the metabolic profile of ZEN-14G and whether it could be deglucosidated in the liver are unknown. To thoroughly investigate the metabolism of ZEN-14G, in vitro metabolism including phase I and phase II metabolism was studied using liquid chromatography coupled to high-resolution mass spectrometry. Additionally, in vivo metabolism of ZEN-14G was conducted in model animals, rats, by oral administration. As a result, 29 phase I metabolites and 6 phase II metabolites were identified and significant inter-species metabolic differences were observed as well. What is more, ZEN-14G could be considerably deglucosidated into its free form of ZEN after the incubation with animals and human liver microsomes in the absence of NADPH, which was mainly metabolized by human carboxylesterase CES-I and II. Furthermore, results showed that the major metabolic pathways of ZEN-14G were deglucosylation, hydroxylation, hydrogenation and glucuronidation. Although interspecies differences in the biotransformation of ZEN-14G were observed, ZEN, alpha-ZEL-14G, beta-ZEL-14G, alpha-ZEL, ZEN-14G-16GlcA and ZEN-14GlcA were the major metabolites of ZEN-14G. Additionally, a larger yield of 6-OH-ZEN-14G and 8-OH-ZEN-14G was also observed in human liver microsomes. The obtained data would be of great importance for the safety assessment of modified mycotoxin, ZEN-14G, and provide another perspective for risk assessment of mycotoxin.
ESTHER : Yang_2018_Arch.Toxicol_92_2779
PubMedSearch : Yang_2018_Arch.Toxicol_92_2779
PubMedID: 30019167

Title : Z-Ligustilide Exerted Hormetic Effect on Growth and Detoxification Enzymes of Spodoptera litura Larvae - Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
Author(s) : Yi Y , Dou G , Yu Z , He H , Wang C , Li L , Zhou J , Liu D , Shi J , Li G , Pang L , Yang N , Huang Q , Qi H
Ref : Evid Based Complement Alternat Med , 2018 :7104513 , 2018
Abstract : Plants have evolved a variety of phytochemicals to defense insect feeding, whereas insects have also evolved diverse detoxification enzymes, which are adaptively induced as a prosurvival mechanism. Herein, Z-ligustilide in Ligusticum chuanxiong Hort. was found to exhibit a similar trend in the accumulation from December to May as the occurrence of Spodoptera litura (Fabricius) larvae. Importantly, S. litura larvae feeding enhanced Z-ligustilide level in the stem and leaf (p < 0.01). Moreover, Z-ligustilide ranging from 1 to 5 mg.g(-1) exhibited remarkable larvicidal activity, antifeedant activity, and growth inhibition against S. litura larvae. The LC50 values of larvicidal activity for phthalides in L. chuanxiong were compared as follows: Z-ligustilide > levistilide A > senkyunolide A > 3-butylidenephthalide > senkyunolide I, implicating the critical role of conjugated structure. Notably, there was a biphasic dose response for glutathione S-transferase (GST), cytochrome P450 (CYP) 450, Acetylcholinesterase (AChE), and Carboxylesterase (CarE) activities and GSTs1, cytochrome P450 (CYP) 4S9, and CYP4M14 mRNA expression. Particularly, low dose (0.1 mg.g(-1)) of Z-ligustilide conferred the resistance of S. litura larvae against chlorpyrifos (p < 0.05). Together, our data suggest that Z-ligustilide may function in a hormetic way in the chemical defense of L. chuanxiong against S. litura larvae.
ESTHER : Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
PubMedSearch : Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
PubMedID: 30057645

Title : Cellular Uptake of A Taurine-Modified, Ester Bond-Decorated D-Peptide Derivative via Dynamin-Based Endocytosis and Macropinocytosis - Zhou_2018_Mol.Ther_26_648
Author(s) : Zhou J , Du X , Berciu C , Del Signore SJ , Chen X , Yamagata N , Rodal AA , Nicastro D , Xu B
Ref : Mol Ther , 26 :648 , 2018
Abstract : Most of the peptides used for promoting cellular uptake bear positive charges. In our previous study, we reported an example of taurine (bearing negative charges in physiological conditions) promoting cellular uptake of D-peptides. Taurine, conjugated to a small D-peptide via an ester bond, promotes the cellular uptake of this D-peptide. Particularly, intracellular carboxylesterase (CES) instructs the D-peptide to self-assemble and to form nanofibers, which largely disfavors efflux and further enhances the intracellular accumulation of the D-peptide, as supported by that the addition of CES inhibitors partially impaired cellular uptake of this molecule in mammalian cell lines. Using dynamin 1, 2, and 3 triple knockout (TKO) mouse fibroblasts, we demonstrated that cells took up this molecule via macropinocytosis and dynamin-dependent endocytosis. Imaging of Drosophila larval blood cells derived from endocytic mutants confirmed the involvement of multiple endocytosis pathways. Electron microscopy (EM) indicated that the precursors can form aggregates on the cell surface to facilitate the cellular uptake via macropinocytosis. EM also revealed significantly increased numbers of vesicles in the cytosol. This work provides new insights into the cellular uptake of taurine derivative for intracellular delivery and self-assembly of D-peptides.
ESTHER : Zhou_2018_Mol.Ther_26_648
PubMedSearch : Zhou_2018_Mol.Ther_26_648
PubMedID: 29396265

Title : Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis - Dompreh_2018_Antimicrob.Agents.Chemother_62_
Author(s) : Dompreh A , Tang X , Zhou J , Yang H , Topletz A , Adu Ahwireng E , Antwi S , Enimil A , Langaee T , Peloquin CA , Court MH , Kwara A
Ref : Antimicrobial Agents & Chemotherapy , 62 : , 2018
Abstract : Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 (NAT2) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1) and carboxylesterase 2 (CES2) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2, SLCO1B1, and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.
ESTHER : Dompreh_2018_Antimicrob.Agents.Chemother_62_
PubMedSearch : Dompreh_2018_Antimicrob.Agents.Chemother_62_
PubMedID: 29263072

Title : Highly Efficient Enzymatic Acylation of Dihydromyricetin by the Immobilized Lipase with Deep Eutectic Solvents as Cosolvent - Cao_2017_J.Agric.Food.Chem_65_2084
Author(s) : Cao SL , Deng X , Xu P , Huang ZX , Zhou J , Li XH , Zong MH , Lou WY
Ref : Journal of Agricultural and Food Chemistry , 65 :2084 , 2017
Abstract : A novel deep eutectic solvent (DES)-DMSO cosolvent system has been, for the first time, successfully used as the reaction medium for the enzymatic acylation of dihydromyricetin (DMY) catalyzed by the immobilized lipase from Aspergillus niger (ANL). The cosolvent mixture, ChCl:Glycerol-DMSO (1:3, v/v) proved to be the optimal medium. With the newly developed cosolvent, the initial reaction rate of enzymatic acylation of DMY achieved 11.1 mM/h and the conversion of DMY was 91.6%. ANL@PD-MNPs is stable and recyclable in this cosolvent, offering 90% conversion rate after repeated use of 5 times. The lipid-solubility of DMY-16-acetate was 10 times higher than that of its raw materials DMY. The results showed that the DMY-16-acetate product exhibits good antioxidative activity. The present research illustrated that the use of DES-DMSO cosolvent may become a feasible alternative for the synthesis of DMY ester.
ESTHER : Cao_2017_J.Agric.Food.Chem_65_2084
PubMedSearch : Cao_2017_J.Agric.Food.Chem_65_2084
PubMedID: 28244316

Title : Acetylcholinesterase Inhibitory Alkaloids from the Whole Plants of Zephyranthes carinata - Zhan_2017_J.Nat.Prod_80_2462
Author(s) : Zhan G , Zhou J , Liu J , Huang J , Zhang H , Liu R , Yao G
Ref : Journal of Natural Products , 80 :2462 , 2017
Abstract : Eleven new alkaloids (1-11), classified as the 12-acetylplicamine (1), N-deformyl-seco-plicamine (2), plicamine (3-6), 4a-epi-plicamine (7), seco-plicamine (8), and lycorine (9-11) framework types, along with 15 known alkaloids (12-26) were isolated from the whole plants of Zephyranthes carinata. The structures of the new alkaloids 1-11 were established by extensive spectroscopic data interpretation. The absolute configurations of 9 and 10 were defined by single-crystal X-ray diffraction analysis. Zephycarinatines A (1), B (2), and G (7) represent the first examples of 12-acetylplicamine, N-deformyl-seco-plicamine, and 4a-epi-plicamine alkaloids, respectively. Alkaloids 6, 11, 17, and 20-23 exhibited AChE inhibitory activities with IC50 values ranging from 1.21 to 184.05 muM, and a preliminary structure-activity relationship is discussed.
ESTHER : Zhan_2017_J.Nat.Prod_80_2462
PubMedSearch : Zhan_2017_J.Nat.Prod_80_2462
PubMedID: 28898076

Title : The asparagus genome sheds light on the origin and evolution of a young Y chromosome - Harkess_2017_Nat.Commun_8_1279
Author(s) : Harkess A , Zhou J , Xu C , Bowers JE , Van der Hulst R , Ayyampalayam S , Mercati F , Riccardi P , McKain MR , Kakrana A , Tang H , Ray J , Groenendijk J , Arikit S , Mathioni SM , Nakano M , Shan H , Telgmann-Rauber A , Kanno A , Yue Z , Chen H , Li W , Chen Y , Xu X , Zhang Y , Luo S , Gao J , Mao Z , Pires JC , Luo M , Kudrna D , Wing RA , Meyers BC , Yi K , Kong H , Lavrijsen P , Sunseri F , Falavigna A , Ye Y , Leebens-Mack JH , Chen G
Ref : Nat Commun , 8 :1279 , 2017
Abstract : Sex chromosomes evolved from autosomes many times across the eukaryote phylogeny. Several models have been proposed to explain this transition, some involving male and female sterility mutations linked in a region of suppressed recombination between X and Y (or Z/W, U/V) chromosomes. Comparative and experimental analysis of a reference genome assembly for a double haploid YY male garden asparagus (Asparagus officinalis L.) individual implicates separate but linked genes as responsible for sex determination. Dioecy has evolved recently within Asparagus and sex chromosomes are cytogenetically identical with the Y, harboring a megabase segment that is missing from the X. We show that deletion of this entire region results in a male-to-female conversion, whereas loss of a single suppressor of female development drives male-to-hermaphrodite conversion. A single copy anther-specific gene with a male sterile Arabidopsis knockout phenotype is also in the Y-specific region, supporting a two-gene model for sex chromosome evolution.
ESTHER : Harkess_2017_Nat.Commun_8_1279
PubMedSearch : Harkess_2017_Nat.Commun_8_1279
PubMedID: 29093472
Gene_locus related to this paper: aspof-a0a5p1ew48

Title : Discovery of triazole-based uracil derivatives bearing amide moieties as novel dipeptidyl peptidase-IV inhibitors - Deng_2017_Bioorg.Chem_75_357
Author(s) : Deng X , Han L , Zhou J , Zhang H , Li Q
Ref : Bioorg Chem , 75 :357 , 2017
Abstract : Dipeptidyl peptidase-IV (DPP-4) is a validated target for T2DM treatment. We previously reported a novel series of triazole-based uracil derivatives bearing aliphatic carboxylic acids with potent DPP-4 inhibitory activities in vitro, but these compounds showed poor hypoglycemic effects in vivo. Herein we further optimized the triazole moiety by amidation of the carboxylic acid to improve in vivo activities. Two series of compounds 3a-f and 4a-g were designed and synthesized. By screening in DPP-4, compound 4c was identified as a potent DPP-4 inhibitor with the IC(50) value of 28.62 nM. Docking study revealed compound 4c has a favorable binding mode and interpreted the SAR of these analogs. DPP-8 and DPP-9 tests indicated compound 4c had excellent selectivity over DPP-8 and DPP-9. Further in vivo evaluations revealed that compound 4c showed more potent hypoglycemic activity than its corresponding carboxylic acid in ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6 mice. The overall results have shown that compound 4c could be a promising lead for further development of novel DPP-4 agents treating T2DM.
ESTHER : Deng_2017_Bioorg.Chem_75_357
PubMedSearch : Deng_2017_Bioorg.Chem_75_357
PubMedID: 29096096

Title : Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus - Zhou_2017_Sci.Adv_3_eaao4966
Author(s) : Zhou J , Li C , Zhao G , Chu H , Wang D , Yan HH , Poon VK , Wen L , Wong BH , Zhao X , Chiu MC , Yang D , Wang Y , Au-Yeung RKH , Chan IH , Sun S , Chan JF , To KK , Memish ZA , Corman VM , Drosten C , Hung IF , Zhou Y , Leung SY , Yuen KY
Ref : Sci Adv , 3 :eaao4966 , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.
ESTHER : Zhou_2017_Sci.Adv_3_eaao4966
PubMedSearch : Zhou_2017_Sci.Adv_3_eaao4966
PubMedID: 29152574

Title : Amaryllidaceae alkaloids with new framework types from Zephyranthes candida as potent acetylcholinesterase inhibitors - Zhan_2017_Eur.J.Med.Chem_127_771
Author(s) : Zhan G , Liu J , Zhou J , Sun B , Aisa HA , Yao G
Ref : Eur Journal of Medicinal Chemistry , 127 :771 , 2017
Abstract : Three new Amaryllidaceae alkaloids, named zephycandidines I-III (1-3), were isolated from Zephyranthes candida. The structures of 1-3 were elucidated by spectroscopic analyses including HRESIMS, 1H NMR, 13C NMR, DEPT, HSQC, 1H-1H COSY, HMBC, ROESY, and electronic circular dichroism (ECD), as well as ECD calculation. The absolute configuration of 1 was finally established by single crystal X-ray diffraction using Cu Kalpha radiation. Zephycandidines I (1) and III (3) with new framework types represent the first example of 7-phenyl-hexahydroindole and 5,2'-dimethyl-biphenyl-2-ylamine alkaloids, respectively, and their plausible biosynthetic pathway are proposed. Zephycandidine II (2) is the first C3a-phenyl-hexahydroindole type alkaloid isolated from the genus of Zephyranthes. These new alkaloids 1-3 were evaluated for their acetylcholinesterase (AChE) inhibitory activities, and 3 showed potent AChE inhibitory activity with an IC50 value of 8.82 muM, suggesting that the framework of 5,2'-dimethyl-biphenyl-2-ylamine in 3 may be a potential group for the AChE inhibitory activity. The docking studies of 1-3 and galanthamine with AChE revealed that interactions with W286 and Y337 are necessary for the AChE inhibitory activity.
ESTHER : Zhan_2017_Eur.J.Med.Chem_127_771
PubMedSearch : Zhan_2017_Eur.J.Med.Chem_127_771
PubMedID: 27823880

Title : Lactate Promotes Synthetic Phenotype in Vascular Smooth Muscle Cells - Yang_2017_Circ.Res_121_1251
Author(s) : Yang L , Gao L , Nickel T , Yang J , Zhou J , Gilbertsen A , Geng Z , Johnson C , Young B , Henke C , Gourley GR , Zhang J
Ref : Circulation Research , 121 :1251 , 2017
Abstract : RATIONALE: The phenotypes of vascular smooth muscle cells (vSMCs) comprise a continuum bounded by predominantly contractile and synthetic cells. Some evidence suggests that contractile vSMCs can assume a more synthetic phenotype in response to ischemic injury, but the mechanisms that activate this phenotypic switch are poorly understood. OBJECTIVE: To determine whether lactate, which increases in response to regional ischemia, may promote the synthetic phenotype in vSMCs. METHODS AND RESULTS: Experiments were performed with vSMCs that had been differentiated from human induced pluripotent stem cells and then cultured in glucose-free, lactate-enriched (L(+)) medium or in standard (L(-)) medium. Compared with the L(-) medium, the L(+) medium was associated with significant increases in synthetic vSMC marker expression, proliferation, and migration and with significant declines in contractile and apoptotic activity. Furthermore, these changes were accompanied by increases in the expression of monocarboxylic acid transporters and were generally attenuated both by the blockade of monocarboxylic acid transporter activity and by transfection with iRNA for NDRG (N-myc downstream regulated gene). Proteomics, biomarker, and pathway analyses suggested that the L(+) medium tended to upregulate the expression of synthetic vSMC markers, the production of extracellular proteins that participate in tissue construction or repair, and the activity of pathways that regulate cell proliferation and migration. Observations in hypoxia-cultured vSMCs were similar to those in L(+)-cultured vSMCs, and assessments in a swine myocardial infarction model suggested that measurements of lactate levels, lactate-dehydrogenase levels, vSMC proliferation, and monocarboxylic acid transporter and NDRG expression were greater in the ischemic zone than in nonischemic tissues. CONCLUSIONS: These results demonstrate for the first time that vSMCs assume a more synthetic phenotype in a microenvironment that is rich in lactate. Thus, mechanisms that link glucose metabolism to vSMC phenotypic switching could play a role in the pathogenesis and treatment of cardiovascular disease.
ESTHER : Yang_2017_Circ.Res_121_1251
PubMedSearch : Yang_2017_Circ.Res_121_1251
PubMedID: 29021296

Title : Lateral Gene Transfer in a Heavy Metal-Contaminated-Groundwater Microbial Community - Hemme_2016_MBio_7_e02234
Author(s) : Hemme CL , Green SJ , Rishishwar L , Prakash O , Pettenato A , Chakraborty R , Deutschbauer AM , Van Nostrand JD , Wu L , He Z , Jordan IK , Hazen TC , Arkin AP , Kostka JE , Zhou J
Ref : MBio , 7 :e02234 , 2016
Abstract : UNLABELLED: Unraveling the drivers controlling the response and adaptation of biological communities to environmental change, especially anthropogenic activities, is a central but poorly understood issue in ecology and evolution. Comparative genomics studies suggest that lateral gene transfer (LGT) is a major force driving microbial genome evolution, but its role in the evolution of microbial communities remains elusive. To delineate the importance of LGT in mediating the response of a groundwater microbial community to heavy metal contamination, representative Rhodanobacter reference genomes were sequenced and compared to shotgun metagenome sequences. 16S rRNA gene-based amplicon sequence analysis indicated that Rhodanobacter populations were highly abundant in contaminated wells with low pHs and high levels of nitrate and heavy metals but remained rare in the uncontaminated wells. Sequence comparisons revealed that multiple geochemically important genes, including genes encoding Fe(2+)/Pb(2+) permeases, most denitrification enzymes, and cytochrome c553, were native to Rhodanobacter and not subjected to LGT. In contrast, the Rhodanobacter pangenome contained a recombinational hot spot in which numerous metal resistance genes were subjected to LGT and/or duplication. In particular, Co(2+)/Zn(2+)/Cd(2+) efflux and mercuric resistance operon genes appeared to be highly mobile within Rhodanobacter populations. Evidence of multiple duplications of a mercuric resistance operon common to most Rhodanobacter strains was also observed. Collectively, our analyses indicated the importance of LGT during the evolution of groundwater microbial communities in response to heavy metal contamination, and a conceptual model was developed to display such adaptive evolutionary processes for explaining the extreme dominance of Rhodanobacter populations in the contaminated groundwater microbiome. IMPORTANCE: Lateral gene transfer (LGT), along with positive selection and gene duplication, are the three main mechanisms that drive adaptive evolution of microbial genomes and communities, but their relative importance is unclear. Some recent studies suggested that LGT is a major adaptive mechanism for microbial populations in response to changing environments, and hence, it could also be critical in shaping microbial community structure. However, direct evidence of LGT and its rates in extant natural microbial communities in response to changing environments is still lacking. Our results presented in this study provide explicit evidence that LGT played a crucial role in driving the evolution of a groundwater microbial community in response to extreme heavy metal contamination. It appears that acquisition of genes critical for survival, growth, and reproduction via LGT is the most rapid and effective way to enable microorganisms and associated microbial communities to quickly adapt to abrupt harsh environmental stresses.
ESTHER : Hemme_2016_MBio_7_e02234
PubMedSearch : Hemme_2016_MBio_7_e02234
PubMedID: 27048805
Gene_locus related to this paper: 9gamm-a0a154r3c0

Title : Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities - Zhan_2016_Sci.Rep_6_33990
Author(s) : Zhan G , Qu X , Liu J , Tong Q , Zhou J , Sun B , Yao G
Ref : Sci Rep , 6 :33990 , 2016
Abstract : Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 muM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.
ESTHER : Zhan_2016_Sci.Rep_6_33990
PubMedSearch : Zhan_2016_Sci.Rep_6_33990
PubMedID: 27658482

Title : Characterization of a Desiccation Stress Induced Lipase Gene from Brassica napus L. - Zhang_2016_J.Agr.Sci.Tech_18_1129
Author(s) : Zhang H , Zhou J , Zheng X , Zhang Z , Wang Z , Tan X
Ref : J Agr Sci Tech , 18 :1129 , 2016
Abstract : Lipases are known to have important functions in many physiological processes in plants. Here, we cloned a lipase gene via Rapid Amplification of cDNA Ends (RACE) technique from Brassica napus L., designated as BnDIL1 (B. napus Desiccation-Induced Lipase 1). The lipase enzyme activity was confirmed by estimating the lipase activity and reduced lipids content in Saccharomyces cerevisiae (pep4) transformant. Two B. napus lines with different oil contents were employed to examine the transcription profiles of BnDIL1 during the processes of seed morphogenesis, maturation, dormancy, pregermination and germination. The transcription level of lipid degradation pathway was enhanced during the processes of seed maturation, dormancy, pregermination and germination, and was higher in seeds of low oil-contents line than that of high oil-contents line. However, BnDIL1 was significantly activated when seed desiccation started. Both slow desiccation and -fast desiccation- treatments on seedlings dramatically activated the transcription of BnDIL1, while only -slow desiccation- stress, which would induce the cell apoptosis, significantly activated the transcription of lipid degradation gene. This result demonstrated that BnDIL1 in B. napus was desiccation stress dependent gene rather than fatty acids degradation gene.
ESTHER : Zhang_2016_J.Agr.Sci.Tech_18_1129
PubMedSearch : Zhang_2016_J.Agr.Sci.Tech_18_1129

Title : Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition - Ogasawara_2016_Proc.Natl.Acad.Sci.U.S.A_113_26
Author(s) : Ogasawara D , Deng H , Viader A , Baggelaar MP , Breman A , den Dulk H , van den Nieuwendijk AM , Soethoudt M , van der Wel T , Zhou J , Overkleeft HS , Sanchez-Alavez M , Mori S , Nguyen W , Conti B , Liu X , Chen Y , Liu QS , Cravatt BF , van der Stelt M
Ref : Proc Natl Acad Sci U S A , 113 :26 , 2016
Abstract : Diacylglycerol lipases (DAGLalpha and DAGLbeta) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLalpha is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.
ESTHER : Ogasawara_2016_Proc.Natl.Acad.Sci.U.S.A_113_26
PubMedSearch : Ogasawara_2016_Proc.Natl.Acad.Sci.U.S.A_113_26
PubMedID: 26668358
Gene_locus related to this paper: human-DAGLA , human-DAGLB

Title : Clinical, biochemical and molecular analysis of two infants with familial chylomicronemia syndrome - Zhang_2016_Lipids.Health.Dis_15_88
Author(s) : Zhang Y , Zhou J , Zheng W , Lan Z , Huang Z , Yang Q , Liu C , Gao R
Ref : Lipids Health Dis , 15 :88 , 2016
Abstract : Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disease due mainly to inherited deficiencies in the proteins or enzymes involved in the clearance of triglycerides from circulation. It usually happens in late childhood and adolescence, which can have serious consequences if misdiagnosed or untreated. In the present study, we investigated two Chinese male babies (A and B), 30d and 48d in age, respectively, who have milky plasma. Clinical, biochemical, and radiological assessments were performed, while samples from the patients were referred for molecular diagnosis, including genetic testing and subsequent analysis of related genes. The fasting serum lipids of the two patients showed extreme lipid abnormalities. Through a low-lipid formula diet including skimmed milk and dietary advice, their plasma lipid levels were significantly lower and more stable at the time of hospital discharge. The genetic testing revealed compound heterozygote mutations in the lipoprotein lipase (LPL) gene for patient A and two known compound heterozygote LPL gene mutations for the patient B. FCS is the most dramatic example of severe hypertriglyceridemia. Early diagnosis and timely dietary intervention is very important for affected children.
ESTHER : Zhang_2016_Lipids.Health.Dis_15_88
PubMedSearch : Zhang_2016_Lipids.Health.Dis_15_88
PubMedID: 27153815
Gene_locus related to this paper: human-LPL

Title : Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways - Chu_2016_J.Infect.Dis_213_904
Author(s) : Chu H , Zhou J , Wong BH , Li C , Chan JF , Cheng ZS , Yang D , Wang D , Lee AC , Yeung ML , Cai JP , Chan IH , Ho WK , To KK , Zheng BJ , Yao Y , Qin C , Yuen KY
Ref : J Infect Dis , 213 :904 , 2016
Abstract : Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.
ESTHER : Chu_2016_J.Infect.Dis_213_904
PubMedSearch : Chu_2016_J.Infect.Dis_213_904
PubMedID: 26203058

Title : Synthesis and biological evaluation of triazole based uracil derivatives as novel DPP-4 inhibitors - Li_2016_Org.Biomol.Chem_14_9598
Author(s) : Li Q , Han L , Zhang B , Zhou J , Zhang H
Ref : Org Biomol Chem , 14 :9598 , 2016
Abstract : A series of triazole based uracil derivatives were designed and synthesized as novel DPP-4 inhibitors. Compound A01 was identified as a lead compound for SAR studies focused on the structural modification at the S(2') subsite of DPP-4. The novel analogues A02-A25 were obtained by modifying the substituents at the phenyl group, and B01-B09, by introducing the carbonyl group. On screening in DPP-4, compounds B03, B04 and B08 showed a significant improvement in DPP-4 inhibitory activities compared to compound A01 and showed comparable activities to the marketed DPP-4 inhibitor, alogliptin. Docking studies revealed new favorable binding modes of designed compounds in the S(2') subsite and proved that structural modifications in the S(2') subsite were an effective option to increase the inhibition of DPP-4. In vitro DPP-8 and DPP-9 tests indicated that all compounds showed excellent selectivity against DPP-8 and DPP-9. Further in vivo evaluation showed that compound B04 could significantly improve oral glucose tolerance in ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6 mice. These data suggest that compound B04 could be a promising DPP-4 inhibitor for future treatment of T2DM.
ESTHER : Li_2016_Org.Biomol.Chem_14_9598
PubMedSearch : Li_2016_Org.Biomol.Chem_14_9598
PubMedID: 27714283

Title : Nascent Genomic Evolution and Allopatric Speciation of Myroides profundi D25 in Its Transition from Land to Ocean - Zhang_2016_MBio_7_e01946
Author(s) : Zhang YZ , Li Y , Xie BB , Chen XL , Yao QQ , Zhang XY , Kempher ML , Zhou J , Oren A , Qin QL
Ref : MBio , 7 :e01946 , 2016
Abstract : UNLABELLED: A large amount of bacterial biomass is transferred from land to ocean annually. Most transferred bacteria should not survive, but undoubtedly some do. It is unclear what mechanisms these bacteria use in order to survive and even thrive in a new marine environment. Myroides profundi D25(T), a member of the Bacteroidetes phylum, was isolated from deep-sea sediment of the southern Okinawa Trough near the China mainland and had high genomic sequence identity to and synteny with the human opportunistic pathogen Myroides odoratimimus. Phylogenetic and physiological analyses suggested that M. profundi recently transitioned from land to the ocean. This provided an opportunity to explore how a bacterial genome evolved to survive in a novel environment. Changes in the transcriptome were evaluated when both species were cultured under low-salinity conditions and then transferred to high-salinity conditions. Comparative genomic and transcriptomic analyses showed that M. profundi altered transcription regulation in the early stages of survival. In these stages, vertically inherited genes played a key role in the survival of M. profundi. The contribution of M. profundi unique genes, some possibly acquired by horizontal gene transfer (HGT), appeared relatively small, and expression levels of unique genes were diminished under the high-salinity conditions. We postulate that HGT genes might play an important role in longer-term adaptation. These results suggested that some human pathogens might have the ability to survive in and adapt to the marine environment, which may have important implications for public health control in coastal regions. IMPORTANCE: Horizontal gene transfer (HGT) is considered to be important for bacteria to adapt to a different microhabitat. However, our results showed that vertically inherited genes might play more important roles than HGT genes in the nascent adaptation to the marine environment in the bacterium Myroides profundi, which has recently been transferred from land to ocean. M. profundi unique genes had low expression levels and were less regulated under high-salinity conditions, indicating that the contribution of HGT genes to survival of this bacterium under marine high-salinity conditions was limited. In the early adaptation stages, M. profundi apparently survived and adapted mainly by regulating the expression of inherited core genes. These results may explain in part why human pathogens can easily be detected in marine environments.
ESTHER : Zhang_2016_MBio_7_e01946
PubMedSearch : Zhang_2016_MBio_7_e01946
PubMedID: 26758181
Gene_locus related to this paper: 9flao-a0a0b5rs63 , 9flao-a0a0b5rv48

Title : Complete Genome Sequence of Alkaliphilus metalliredigens Strain QYMF, an Alkaliphilic and Metal-Reducing Bacterium Isolated from Borax-Contaminated Leachate Ponds - Hwang_2016_Genome.Announc_4_e01226
Author(s) : Hwang C , Copeland A , Lucas S , Lapidus A , Barry K , Detter JC , Glavina Del Rio T , Hammon N , Israni S , Dalin E , Tice H , Pitluck S , Chertkov O , Brettin T , Bruce D , Han C , Schmutz J , Larimer F , Land ML , Hauser L , Kyrpides N , Mikhailova N , Ye Q , Zhou J , Richardson P , Fields MW
Ref : Genome Announc , 4 : , 2016
Abstract : Alkaliphilus metalliredigens strain QYMF is an anaerobic, alkaliphilic, and metal-reducing bacterium associated with phylum Firmicutes QYMF was isolated from alkaline borax leachate ponds. The genome sequence will help elucidate the role of metal-reducing microorganisms under alkaline environments, a capability that is not commonly observed in metal respiring-microorganisms.
ESTHER : Hwang_2016_Genome.Announc_4_e01226
PubMedSearch : Hwang_2016_Genome.Announc_4_e01226
PubMedID: 27811105
Gene_locus related to this paper: alkmq-a6tu78

Title : Galanthamine, Plicamine, and Secoplicamine Alkaloids from Zephyranthes candida and Their Anti-acetylcholinesterase and Anti-inflammatory Activities - Zhan_2016_J.Nat.Prod_79_760
Author(s) : Zhan G , Zhou J , Liu R , Liu T , Guo G , Wang J , Xiang M , Xue Y , Luo Z , Zhang Y , Yao G
Ref : Journal of Natural Products , 79 :760 , 2016
Abstract : Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 muM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 muM.
ESTHER : Zhan_2016_J.Nat.Prod_79_760
PubMedSearch : Zhan_2016_J.Nat.Prod_79_760
PubMedID: 26913788

Title : A new TLC bioautographic assay for qualitative and quantitative estimation of lipase inhibitors - Tang_2016_Phytochem.Anal_27_5
Author(s) : Tang J , Zhou J , Tang Q , Wu T , Cheng Z
Ref : Phytochem Anal , 27 :5 , 2016
Abstract : INTRODUCTION: Lipase inhibitory assays based on TLC bioautography have made recent progress; however, an assay with greater substrate specificity and quantitative capabilities would advance the efficacy of this particular bioassay. OBJECTIVE: To address these limitations, a new TLC bioautographic assay for detecting lipase inhibitors was developed and validated in this study. METHODS: The new TLC bioautographic assay was based on reaction of lipase with beta-naphthyl myristate and the subsequent formation of the purple dye between beta-naphthol and Fast Blue B salt (FBB). The relative lipase inhibitory capacity (RLIC) was determined by a TLC densitometry with fluorescence detection, expressed as orlistat equivalents in millimoles on a per sample weight basis. Six pure compounds and three natural extracts were evaluated for their potential lipase inhibitory activities by this TLC bioautographic assay. RESULTS: The beta-naphthyl myristate as the substrate improved the detection sensitivity and specificity significantly. The limit of detection (LOD) of this assay was 0.01 ng for orlistat, the current treatment for obesity. This assay has acceptable accuracy (92.07-105.39%), intra-day and inter-day precisions [relative standard deviation (RSD), 2.64-4.40%], as well as intra-plate and inter-plate precisions (RSD, 1.8-4.9%). CONCLUSION: The developed method is rapid, simple, stable, and specific for screening and estimation of the potential lipase inhibitors.
ESTHER : Tang_2016_Phytochem.Anal_27_5
PubMedSearch : Tang_2016_Phytochem.Anal_27_5
PubMedID: 26219532

Title : ST09, a Novel Thioester Derivative of Tacrine, Alleviates Cognitive Deficits and Enhances Glucose Metabolism in Vascular Dementia Rats - Liu_2016_CNS.Neurosci.Ther_22_220
Author(s) : Liu JM , Wu PF , Rao J , Zhou J , Shen ZC , Luo H , Huang JG , Liang X , Long LH , Xie QG , Jiang FC , Wang F , Chen JG
Ref : CNS Neurosci Ther , 22 :220 , 2016
Abstract : AIMS: Chemical entities containing mercapto group have been increasingly attractive in the therapy of central nerve system (CNS) diseases. In the recent study, we screened a series of mercapto-tacrine derivatives with synergistic neuropharmacological profiles in vitro.
METHODS: We investigated the effect and mechanism of ST09, a thioester derivative of tacrine containing a potential mercapto group, on the vascular dementia (VaD) model of rat induced by bilateral common carotid arteries occlusion (2-VO).
RESULTS: ST09 and its active metabolite ST10 retained excellent inhibition on acetylcholinesterase (AChE) activity. ST09 significantly attenuated the 2-VO-induced impairment in spatial acquisition performance and inhibited the 2-VO-induced rise of AChE activity. In the VaD model, ST09 attenuated the oxidative stress and decreased the apoptosis in the cortex and hippocampus. Compared with donepezil, ST09 exhibited a better effect on the regeneration of free thiols in 2-VO rats. Interestingly, ST09, not donepezil, greatly improved glucose metabolism in various brain regions of 2-VO rats using functional imaging of (18) F-labeled fluoro-deoxyglucose (FDG) positron emission tomography (PET).
CONCLUSIONS: ST09 may serve as a more promising agent for the therapy of VaD than tacrine owing to the introduction of a potential mercapto group into the parent skeleton.
ESTHER : Liu_2016_CNS.Neurosci.Ther_22_220
PubMedSearch : Liu_2016_CNS.Neurosci.Ther_22_220
PubMedID: 26813743

Title : Properties of a newly identified esterase from Bacillus sp. K91 and its novel function in diisobutyl phthalate degradation - Ding_2015_PLoS.One_10_e0119216
Author(s) : Ding J , Wang C , Xie Z , Li J , Yang Y , Mu Y , Tang X , Xu B , Zhou J , Huang Z
Ref : PLoS ONE , 10 :e0119216 , 2015
Abstract : The widely used plasticizer phthalate esters (PAEs) have become a public concern because of their effects on environmental contamination and toxicity on mammals. However, the biodegradation of PAEs, especially diisobutyl phthalate (DiBP), remains poorly understood. In particular, genes involved in the hydrolysis of these compounds were not conclusively identified. In this study, the CarEW gene, which encodes an enzyme that is capable of hydrolyzing ro-nitrophenyl esters of fatty acids, was cloned from a thermophilic bacterium Bacillus sp. K91 and heterologously expressed in Escherichia coli BL21 using the pEASY-E2 expression system. The enzyme showed a monomeric structure with a molecular mass of approximately 53.76 kDa and pI of 4.88. The enzyme exhibited maximal activity at pH 7.5 and 45 degreesC, with ro-NP butyrate as the best substrate. The enzyme was fairly stable within the pH range from 7.0 to 8.5. High-pressure liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS) were employed to detect the catabolic pathway of DiBP. Two intermediate products were identified, and a potential biodegradation pathway was proposed. Altogether, our findings present a novel DiBP degradation enzyme and indicate that the purified enzyme may be a promising candidate for DiBP detoxification and for environmental protection.
ESTHER : Ding_2015_PLoS.One_10_e0119216
PubMedSearch : Ding_2015_PLoS.One_10_e0119216
PubMedID: 25746227
Gene_locus related to this paper: bacsu-pnbae

Title : Enzyme-Instructed Intracellular Molecular Self-Assembly to Boost Activity of Cisplatin against Drug-Resistant Ovarian Cancer Cells - Li_2015_Angew.Chem.Int.Ed.Engl_54_13307
Author(s) : Li J , Kuang Y , Shi J , Zhou J , Medina JE , Zhou R , Yuan D , Yang C , Wang H , Yang Z , Liu J , Dinulescu DM , Xu B
Ref : Angew Chem Int Ed Engl , 54 :13307 , 2015
Abstract : Anticancer drug resistance demands innovative approaches that boost the activity of drugs against drug-resistant cancers without increasing the systemic toxicity. Here we show the use of enzyme-instructed self-assembly (EISA) to generate intracellular supramolecular assemblies that drastically boost the activity of cisplatin against drug-resistant ovarian cancer cells. We design and synthesize small peptide precursors as the substrates of carboxylesterase (CES). CES cleaves the ester bond pre-installed on the precursors to form the peptides that self-assemble in water to form nanofibers. At the optimal concentrations, the precursors themselves are innocuous to cells, but they double or triple the activity of cisplatin against the drug-resistant ovarian cancer cells. This work illustrates a simple, yet fundamental, new way to introduce non-cytotoxic components into combination therapies with cisplatin without increasing the systemic burden or side effects.
ESTHER : Li_2015_Angew.Chem.Int.Ed.Engl_54_13307
PubMedSearch : Li_2015_Angew.Chem.Int.Ed.Engl_54_13307
PubMedID: 26365295

Title : Substrate channel evolution of an esterase for the synthesis of cilastatin - Luan_2015_Catal.Sci.Technol_5_2622
Author(s) : Luan ZJ , Li FL , Dou S , Chen Q , Kong XD , Zhou J , Yu HL , Xu JH
Ref : Catal Sci Technol , 5 :2622 , 2015
Abstract : The esterase RhEst1 from Rhodococcus sp. ECU1013 has been reported for the enantioselective hydrolysis of ethyl (S)-(+)-2,2-dimethylcyclopropane carboxylate, producing the building block of cilastatin. In this work, error-prone PCR and site-directed saturation mutagenesis were applied to RhEst1 for activity improvement, with the pH-indicator assay as a high-throughput screening method. As a result, RhEst1A147I/V148F/G254A, with mutations surrounding the substrate access channel, showed a 5-fold increase in its specific activity compared with the native enzyme, as well as a 4-fold increase in protein solubility. Combined with the determination of protein structures and computational analysis, this work shows that the amino acids around the substrate channel play a more important role in the activity evolution of RhEst1 than those in the active site.
ESTHER : Luan_2015_Catal.Sci.Technol_5_2622
PubMedSearch : Luan_2015_Catal.Sci.Technol_5_2622
Gene_locus related to this paper: rhosp-AHY95170

Title : Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury - Zhang_2015_Sci.Rep_5_15503
Author(s) : Zhang J , Yong Y , Li X , Hu Y , Wang J , Wang YQ , Song W , Chen WT , Xie J , Chen XM , Lv X , Hou LL , Wang K , Zhou J , Wang XR , Song JG
Ref : Sci Rep , 5 :15503 , 2015
Abstract : Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a alpha7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.
ESTHER : Zhang_2015_Sci.Rep_5_15503
PubMedSearch : Zhang_2015_Sci.Rep_5_15503
PubMedID: 26499847

Title : Complete genome sequences of one human respiratory syncytial antigenic group a virus from china and its four mouse-adapted isolates - Zhang_2015_Genome.Announc_3_0
Author(s) : Zhang K , He J , Li C , Bose ME , Henrickson KJ , Zhou J , Zheng BJ
Ref : Genome Announc , 3 : , 2015
Abstract : In this study, one human respiratory syncytial antigenic group A virus (HRSV-A-GZ08-0) and its four BALB/c mouse-adapted isolates were sequenced and elucidated. Nineteen nucleotides were mutated between HRSV-A-GZ08-0 and the four mouse-adapted isolates.
ESTHER : Zhang_2015_Genome.Announc_3_0
PubMedSearch : Zhang_2015_Genome.Announc_3_0
PubMedID: 25744999
Gene_locus related to this paper: 9noca-a0a0d5aa12 , 9noca-a0a0d5abi2

Title : [Gene therapy and Alzheimer's disease] - Li_2015_Zhong.Nan.Da.Xue.Xue.Bao.Yi.Xue.Ban_40_428
Author(s) : Li J , Li W , Zhou J
Ref : Zhong Nan Da Xue Xue Bao Yi Xue Ban , 40 :428 , 2015
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the presence of extracellular beta-amyloid in the senile plaques, intracellular aggregates of abnormal phosphorylation of tau protein in the neurofibrillary tangles, neuronal loss and cerebrovascular amyloidosis. The manifestations of clinical symptoms include memory impairment, cognitive decline, altered behavior and language deficit. Currently available drugs in AD therapy consist of acetylcholinesterase inhibitors, NMDA receptor antagonists, non-steroidal anti-inflammatory drugs, etc. Th ese drugs can only alleviate the symptoms of AD. Gene therapy is achieved by vectormediated gene transfer technology, which can delivery DNA or RNA into target cells to promote the expression of a protective or therapeutic protein and silence certain virulence genes.
ESTHER : Li_2015_Zhong.Nan.Da.Xue.Xue.Bao.Yi.Xue.Ban_40_428
PubMedSearch : Li_2015_Zhong.Nan.Da.Xue.Xue.Bao.Yi.Xue.Ban_40_428
PubMedID: 25931222

Title : Lipase adsorption on different nanomaterials: a multi-scale simulation study - Zhao_2015_Phys.Chem.Chem.Phys_17_840
Author(s) : Zhao D , Peng C , Zhou J
Ref : Phys Chem Chem Phys , 17 :840 , 2015
Abstract : Candida antarctica lipase B (CalB) is an efficient biocatalyst for hydrolysis and esterification, which plays an important role in the production of biodiesel in the bioenergy industries. The ordered immobilisation of lipases on different supports would be significant for its enzymatic catalysis in some biodiesel production processes; however, the underlying mechanisms and the preferred lipase orientation are not well understood yet. In this work, a fundamental understanding of the orientation and adsorption mechanism of lipase on four different nanomaterial surfaces with different surface chemistry are explored in detail by a combination of parallel tempering Monte Carlo (PTMC) and molecular dynamics (MD) simulations. Simulation results show that lipase is strongly adsorbed onto the hydrophobic graphite surface, as reflected by the large contact area and interaction energy; while the adsorption onto the hydrophilic TiO2 surface is weak due to two strongly adhered water layers; meanwhile lipase undergoes desorption and reorientation processes. For CalB adsorption on positively and negatively charged surfaces (NH2-SAM and COOH-SAM), the orientation distributions of lipase are narrow, and opposite orientations are obtained. CalB adsorbed on NH2-SAM has its catalytic centre oriented towards the surface, which is not conducive to the substrate binding; while the catalytic centre faces toward the solution when it is adsorbed on the COOH-SAM. Besides, the native structures of CalB adsorbed on different surfaces are preserved, which indicates lipase as a robust enzyme. The simulation results will promote our understanding on how surface properties of nanomaterials, such as charge or hydrophobicity, will affect lipase immobilisation, and help us in the rational design and development of immobilised lipase carriers.
ESTHER : Zhao_2015_Phys.Chem.Chem.Phys_17_840
PubMedSearch : Zhao_2015_Phys.Chem.Chem.Phys_17_840
PubMedID: 25412148

Title : [Effect of PON1 overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning] - Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
Author(s) : Wu B , Wang F , Zhou J , Hou Y , Hong G , Zhao G , Ge Y , Liu Y , Qiu Q , Lu Z
Ref : Zhonghua Yi Xue Za Zhi , 95 :2955 , 2015
Abstract : OBJECTIVE: To investigate the effect of paraoxonase1 (PON1) overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning.
METHODS: Mouse diaphragmatic muscle cells were cultured routinely and infected with overexpression lentivirus. Cells were divided into normal control group, DDVP group, LV-GFP + DDVP group, LV-PON1 + DDVP group. Cell viability was determined by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. The mRNA and protein expression of PON1 and Nrf2 in mouse diaphragmatic muscle cells was measured by RT-PCR and Western blot. Enzyme-linked immunosorbent assay was used to determine levels of acetyl cholinesterase (AchE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) in mouse diaphragmatic muscle cells. The activity of superoxide dismutase (SOD) and catalase (CAT) as well as malondialdehyde (MDA) content in cells was measured by chemical colorimetry.
RESULTS: After induced by 0, 80, 160, 320, 640 micromol/L DDVP for 24 hours, the viability of mouse diaphragmatic muscle cells was (100 +/- 3.82)%, (82.13 +/- 2.60)%, (53.57 +/- 5.05)%, (30.77 +/- 3.30)%, (14.20 +/- 2.19)% respectively, changing in a concentration-dependent manner (P < 0.05). After induced by 160 micromol/L DDVP for 0, 6, 12, 24 hours, the viability of mouse diaphragmatic muscle cells was (100.17 +/- 2.74)%, (76.13 +/- 6.01)%, (66.53 +/- 3.55)%, (53.57 +/- 5.05)%, changing in a time-dependent manner (P < 0.05). The PON1 protein level in LV-PON1 group was higher than that of blank control group (0.370 +/- 0.015 vs 0.232 +/- 0.004, 0.197 +/- 0.015 vs 0.037 +/- 0.003, P < 0.05). The cell viability of LV-PON1 group is higher than that of DDVP group at different time point after induction of DDVP (P < 0.05). After induced by DDVP for 24 hours, the cell apoptosis rate and MDA content in LV-PON1 group were lower than those of DDVP group (P < 0.05). While levels of AchE, PON1 and Nrf2 protein expression, SOD and CAT, HO-1 and NQO-1 were higher than those of DDVP group (P < 0.05).
CONCLUSIONS: The overexpression of PON1 could effectively alleviate AchE inhibition by DDVP and induce Nrf2 expression to exert antioxidant effect, thus protected the mouse diaphragmatic muscle cells.
ESTHER : Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
PubMedSearch : Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
PubMedID: 26814074

Title : Molecular Simulation Study of Feruloyl Esterase Adsorption on Charged Surfaces: Effects of Surface Charge Density and Ionic Strength - Liu_2015_Langmuir_31_10751
Author(s) : Liu J , Peng C , Yu G , Zhou J
Ref : Langmuir , 31 :10751 , 2015
Abstract : The surrounding conditions, such as surface charge density and ionic strength, play an important role in enzyme adsorption. The adsorption of a nonmodular type-A feruloyl esterase from Aspergillus niger (AnFaeA) on charged surfaces was investigated by parallel tempering Monte Carlo (PTMC) and all-atom molecular dynamics (AAMD) simulations at different surface charge densities (+/-0.05 and +/-0.16 C.m(-2)) and ionic strengths (0.007 and 0.154 M). The adsorption energy, orientation, and conformational changes were analyzed. Simulation results show that whether AnFaeA can adsorb onto a charged surface is mainly controlled by electrostatic interactions between AnFaeA and the charged surface. The electrostatic interactions between AnFaeA and charged surfaces are weakened when the ionic strength increases. The positively charged surface at low surface charge density and high ionic strength conditions can maximize the utilization of the immobilized AnFaeA. The counterion layer plays a key role in the adsorption of AnFaeA on the negatively charged COOH-SAM. The native conformation of AnFaeA is well preserved under all of these conditions. The results of this work can be used for the controlled immobilization of AnFaeA.
ESTHER : Liu_2015_Langmuir_31_10751
PubMedSearch : Liu_2015_Langmuir_31_10751
PubMedID: 26379082

Title : Molecular Basis of the General Base Catalysis of an alpha\/beta-Hydrolase Catalytic Triad - Sun_2014_J.Biol.Chem_289_15867
Author(s) : Sun Y , Yin S , Feng Y , Li J , Zhou J , Liu C , Zhu G , Guo Z
Ref : Journal of Biological Chemistry , 289 :15867 , 2014
Abstract : The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to being a specific general base by an open-closed conformational change in the catalysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical alpha/beta-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of half of the alpha-helical cap domain, which causes extensive structural changes in the alpha/beta-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche conformation to form the functional triad. NMR analysis shows that the inactive open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couples formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the nucleophilicity of the triad, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis.
ESTHER : Sun_2014_J.Biol.Chem_289_15867
PubMedSearch : Sun_2014_J.Biol.Chem_289_15867
PubMedID: 24737327
Gene_locus related to this paper: ecoli-YFBB

Title : Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates - Kong_2014_Proc.Natl.Acad.Sci.U.S.A_111_15717
Author(s) : Kong XD , Yuan S , Li L , Chen S , Xu JH , Zhou J
Ref : Proc Natl Acad Sci U S A , 111 :15717 , 2014
Abstract : Optically pure epoxides are essential chiral precursors for the production of (S)-propranolol, (S)-alprenolol, and other beta-adrenergic receptor blocking drugs. Although the enzymatic production of these bulky epoxides has proven difficult, here we report a method to effectively improve the activity of BmEH, an epoxide hydrolase from Bacillus megaterium ECU1001 toward alpha-naphthyl glycidyl ether, the precursor of (S)-propranolol, by eliminating the steric hindrance near the potential product-release site. Using X-ray crystallography, mass spectrum, and molecular dynamics calculations, we have identified an active tunnel for substrate access and product release of this enzyme. The crystal structures revealed that there is an independent product-release site in BmEH that was not included in other reported epoxide hydrolase structures. By alanine scanning, two mutants, F128A and M145A, targeted to expand the potential product-release site displayed 42 and 25 times higher activities toward alpha-naphthyl glycidyl ether than the wild-type enzyme, respectively. These results show great promise for structure-based rational design in improving the catalytic efficiency of industrial enzymes for bulky substrates.
ESTHER : Kong_2014_Proc.Natl.Acad.Sci.U.S.A_111_15717
PubMedSearch : Kong_2014_Proc.Natl.Acad.Sci.U.S.A_111_15717
PubMedID: 25331869
Gene_locus related to this paper: bacme-g9bex6

Title : A Smart Library of Epoxide Hydrolase Variants and the Top Hits for Synthesis of (S)-beta-Blocker Precursors - Kong_2014_Angew.Chem.Int.Ed.Engl_53_6641
Author(s) : Kong XD , Ma Q , Zhou J , Zeng BB , Xu JH
Ref : Angew Chem Int Ed Engl , 53 :6641 , 2014
Abstract : Microtuning of the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical beta-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward bulky substrates.
ESTHER : Kong_2014_Angew.Chem.Int.Ed.Engl_53_6641
PubMedSearch : Kong_2014_Angew.Chem.Int.Ed.Engl_53_6641
PubMedID: 24841567

Title : Molecular traces of alternative social organization in a termite genome - Terrapon_2014_Nat.Commun_5_3636
Author(s) : Terrapon N , Li C , Robertson HM , Ji L , Meng X , Booth W , Chen Z , Childers CP , Glastad KM , Gokhale K , Gowin J , Gronenberg W , Hermansen RA , Hu H , Hunt BG , Huylmans AK , Khalil SM , Mitchell RD , Munoz-Torres MC , Mustard JA , Pan H , Reese JT , Scharf ME , Sun F , Vogel H , Xiao J , Yang W , Yang Z , Zhou J , Zhu J , Brent CS , Elsik CG , Goodisman MA , Liberles DA , Roe RM , Vargo EL , Vilcinskas A , Wang J , Bornberg-Bauer E , Korb J , Zhang G , Liebig J
Ref : Nat Commun , 5 :3636 , 2014
Abstract : Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation.
ESTHER : Terrapon_2014_Nat.Commun_5_3636
PubMedSearch : Terrapon_2014_Nat.Commun_5_3636
PubMedID: 24845553
Gene_locus related to this paper: zoone-a0a067r283 , zoone-a0a067qst6 , zoone-a0a067rbc7 , zoone-a0a067qz43 , zoone-a0a067qn94 , zoone-a0a067rbw9 , zoone-a0a067qx93 , zoone-a0a067rcf4 , zoone-a0a067r8q8 , zoone-a0a067rh81 , zoone-a0a067r506 , zoone-a0a067qxd4 , zoone-a0a067qy86 , zoone-a0a067qsw2 , zoone-a0a067qfp9 , zoone-a0a067ru91 , zoone-a0a067rwu7 , zoone-a0a067rmu8 , zoone-a0a067r773 , zoone-a0a067qlt8 , zoone-a0a067qhm6 , zoone-a0a067qjz2 , zoone-a0a067qs20 , zoone-a0a067rmu4 , zoone-a0a067qty7 , zoone-a0a067rk35 , zoone-a0a067rk64 , zoone-a0a067rj74 , zoone-a0a067rp97 , zoone-a0a067rjm1

Title : Marsupellins A-F, ent-longipinane-type sesquiterpenoids from the Chinese liverwort Marsupella alpine with acetylcholinesterase inhibitory activity - Zhang_2014_J.Nat.Prod_77_1031
Author(s) : Zhang J , Fan P , Zhu R , Li R , Lin Z , Sun B , Zhang C , Zhou J , Lou H
Ref : Journal of Natural Products , 77 :1031 , 2014
Abstract : Acetylcholinesterase (AChE) inhibitory activity-guided fractionation of the Chinese liverwort Marsupella alpine afforded six new [marsupellins A-F (1-6)] and three known (7-9) ent-longipinane-type sesquiterpenoids. The structures were determined from MS and NMR spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-9 exhibited moderate to weak AChE inhibitory activity.
ESTHER : Zhang_2014_J.Nat.Prod_77_1031
PubMedSearch : Zhang_2014_J.Nat.Prod_77_1031
PubMedID: 24673187

Title : Physostigmine reverses disturbances of the intestinal microcirculation during experimental endotoxemia - Zhou_2014_Clin.Hemorheol.Microcirc_56_273
Author(s) : Zhou J , Pavlovic D , Rub J , Masur S , Spassov A , Whynot S , Hung O , Kern H , Saleh Abdo I , Shukla R , Cerny V , Lehmann C
Ref : Clinical Hemorheology Microcirculation , 56 :273 , 2014
Abstract : Intestinal microcirculatory disturbances play an important role in the pathophysiology of sepsis. A neural anti-inflammatory pathway has been suggested as a potential target for therapy that may dampen systemic inflammation. The aim of this study is to investigate the effects of physostigmine, a cholinesterase inhibitor, on the intestinal microcirculation and vascular contractility in experimental endotoxemia. Endotoxemia was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with either physostigmine or saline (control) following LPS challenge. The intestinal microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and non-perfused capillary density (NCD), was examined by intravital microscopy (IVM) 2 hours after LPS administration. The impact of physostigmine on vascular contractility of rat aortic rings was examined by in vitro myography. Physostigmine significantly reduced the number of adhering leukocytes in intestinal submucosal venules (V1 venules: -61%, V3 venules: -36%) of LPS animals. FCD was significantly increased by physostigmine treatment (circular muscle layer: +180%, longitudinal muscle layer: +162%, mucosa: +149%). Low concentrations of physostigmine produced significant contraction of aortic ring preparations, whereas high concentrations produced relaxation. In conclusion, physostigmine treatment significantly improved the intestinal microcirculation in experimental endotoxemia by reducing leukocyte adhesion and increasing FCD.
ESTHER : Zhou_2014_Clin.Hemorheol.Microcirc_56_273
PubMedSearch : Zhou_2014_Clin.Hemorheol.Microcirc_56_273
PubMedID: 23736080

Title : Purification of an amide hydrolase DamH from Delftia sp. T3-6 and its gene cloning, expression, and biochemical characterization - Wang_2014_Appl.Microbiol.Biotechnol_98_7491
Author(s) : Wang F , Hou Y , Zhou J , Li Z , Huang Y , Cui Z
Ref : Applied Microbiology & Biotechnology , 98 :7491 , 2014
Abstract : A highly active amide hydrolase (DamH) was purified from Delftia sp. T3-6 using ammonium sulfate precipitation, diethylaminoethyl anion exchange, hydrophobic interaction chromatography, and Sephadex G-200 gel filtration. The molecular mass of the purified enzyme was estimated to be 32 kDa by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The sequence of the N-terminal 15 amino acid residues was determined to be Gly-Thr-Ser-Pro-Gln-Ser-Asp-Phe-Leu-Arg-Ala-Leu-Phe-Gln-Ser. Based on the N-terminal sequence and results of peptide mass fingerprints, the gene (damH) was cloned by PCR amplification and expressed in Escherichia coli BL21(DE3). DamH was a bifunctional hydrolase showing activity to amide and ester bonds. The specific activities of recombinant DamH were 5,036 U/mg for 2'-methyl-6'-ethyl-2- chloroacetanilide (CMEPA) (amide hydrolase function) and 612 U/mg for 4-nitrophenyl acetate (esterase function). The optimum substrate of DamH was CMEPA, with K m and k cat values of 0.197 mM and 2,804.32 s(-1), respectively. DamH could also hydrolyze esters such as 4-nitrophenyl acetate, glycerol tributyrate, and caprolactone. The optimal pH and temperature for recombinant DamH were 6.5 and 35 degrees C, respectively; the enzyme was activated by Mn(2+) and inhibited by Cu(2+), Zn(2+), Ni(2+), and Fe(2+). DamH was inhibited strongly by phenylmethylsulfonyl and SDS and weakly by ethylenediaminetetraacetic acid and dimethyl sulfoxide.
ESTHER : Wang_2014_Appl.Microbiol.Biotechnol_98_7491
PubMedSearch : Wang_2014_Appl.Microbiol.Biotechnol_98_7491
PubMedID: 24723294

Title : Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition - Ou_2014_Cell.Rep_9_1798
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 9 :1798 , 2014
Abstract : How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of alpha/beta-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in Apc(Min/+) mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKalpha-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressing Abhd5-mediated intracellular lipolysis.
ESTHER : Ou_2014_Cell.Rep_9_1798
PubMedSearch : Ou_2014_Cell.Rep_9_1798
PubMedID: 25482557
Gene_locus related to this paper: human-ABHD5

Title : Crystal structures of Pseudomonas putida esterase reveal the functional role of residues 187 and 287 in substrate binding and chiral recognition - Dou_2014_Biochem.Biophys.Res.Commun_446_1145
Author(s) : Dou S , Kong XD , Ma BD , Chen Q , Zhang J , Zhou J , Xu JH
Ref : Biochemical & Biophysical Research Communications , 446 :1145 , 2014
Abstract : A recombinant carboxylesterase (rPPE) from Pseudomonas putida ECU1011 was previously cloned and engineered to give a potential application for resolving chiral alpha-hydroxy acids including mandelic acids and derivatives. Two variants rPPEW187H and rPPED287A showed a approximately 100-fold increase in activity towards rac-2-acetoxy-2-(2'-chlorophenyl) acetate (rac-AcO-CPA), but rPPED287A had a significant decrease in enantioselectivity (E=8.7) compared to rPPEW187H and the wild-type rPPE (rPPEWT) (E>200). Here we report the crystal structures of rPPEWT and rPPEW187H, both by themselves and in complex with the substrate, to elucidate the structural basis of this phenomenon. An inactive mutation of nucleophile residue S159A was introduced to obtain the structure of rPPES159A/W187H complexed with (S)-AcO-CPA. The structural analysis reveals that the side chain of residue Asp287 in rPPEWT would have a potential steric conflict with (S)-AcO-CPA when the substrate binds at the active site of the enzyme. However, the mutation W187H could facilitate the relocation of Asp287, while D287A directly eliminates the hindrance of Asp287, both of which offer sufficient space for the binding and hydrolysis of substrate. Moreover, Asp287 generates one site of the "three-point attachment model" as a hydrogen-bond donor that determines the excellent enantioselectivity of rPPE in chiral recognition, and D287A would obviously destroy the hydrogen bond and result in the low enantioselectivity of rPPED287A.
ESTHER : Dou_2014_Biochem.Biophys.Res.Commun_446_1145
PubMedSearch : Dou_2014_Biochem.Biophys.Res.Commun_446_1145
PubMedID: 24680822
Gene_locus related to this paper: 9psed-l7pyq2

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

Title : Draft genome sequences of two super-extensively drug-resistant isolates of Mycobacterium tuberculosis from China - Lin_2013_FEMS.Microbiol.Lett_347_93
Author(s) : Lin N , Liu Z , Zhou J , Wang S , Fleming J
Ref : FEMS Microbiology Letters , 347 :93 , 2013
Abstract : The prevalence of drug-resistance in Mycobacterium tuberculosis is already having a negative impact on the control of tuberculosis. We report the draft genome sequences of two super-extensively drug-resistant M. tuberculosis isolates from China, FJ05194 (lineage 2) and GuangZ0019 (lineage 4), and compare them with the H37Rv reference strain to identify possible sources of genetic variation associated with their extensive drug resistance. Our results suggest that their extensive drug resistance probably results from the stepwise accumulation of resistances to individual drugs.
ESTHER : Lin_2013_FEMS.Microbiol.Lett_347_93
PubMedSearch : Lin_2013_FEMS.Microbiol.Lett_347_93
PubMedID: 23965132
Gene_locus related to this paper: mycmm-b2ht49 , myctu-cut3 , myctu-Rv1069c , myctu-RV1215C , myctu-Rv2045c

Title : Complete genome analysis of three Acinetobacter baumannii clinical isolates in China for insight into the diversification of drug resistance elements - Zhu_2013_PLoS.One_8_e66584
Author(s) : Zhu L , Yan Z , Zhang Z , Zhou Q , Zhou J , Wakeland EK , Fang X , Xuan Z , Shen D , Li QZ
Ref : PLoS ONE , 8 :e66584 , 2013
Abstract : BACKGROUND: The emergence and rapid spreading of multidrug-resistant Acinetobacter baumannii strains has become a major health threat worldwide. To better understand the genetic recombination related with the acquisition of drug-resistant elements during bacterial infection, we performed complete genome analysis on three newly isolated multidrug-resistant A. baumannii strains from Beijing using next-generation sequencing technology. METHODOLOGIES/PRINCIPAL FINDINGS: Whole genome comparison revealed that all 3 strains share some common drug resistant elements including carbapenem-resistant bla OXA-23 and tetracycline (tet) resistance islands, but the genome structures are diversified among strains. Various genomic islands intersperse on the genome with transposons and insertions, reflecting the recombination flexibility during the acquisition of the resistant elements. The blood-isolated BJAB07104 and ascites-isolated BJAB0868 exhibit high similarity on their genome structure with most of the global clone II strains, suggesting these two strains belong to the dominant outbreak strains prevalent worldwide. A large resistance island (RI) of about 121-kb, carrying a cluster of resistance-related genes, was inserted into the ATPase gene on BJAB07104 and BJAB0868 genomes. A 78-kb insertion element carrying tra-locus and bla OXA-23 island, can be either inserted into one of the tniB gene in the 121-kb RI on the chromosome, or transformed to conjugative plasmid in the two BJAB strains. The third strains of this study, BJAB0715, which was isolated from spinal fluid, exhibit much more divergence compared with above two strains. It harbors multiple drug-resistance elements including a truncated AbaR-22-like RI on its genome. One of the unique features of this strain is that it carries both bla OXA-23 and bla OXA-58 genes on its genome. Besides, an Acinetobacter lwoffii adeABC efflux element was found inserted into the ATPase position in BJAB0715.
CONCLUSIONS: Our comparative analysis on currently completed Acinetobacter baumannii genomes revealed extensive and dynamic genome organizations, which may facilitate the bacteria to acquire drug-resistance elements into their genomes.
ESTHER : Zhu_2013_PLoS.One_8_e66584
PubMedSearch : Zhu_2013_PLoS.One_8_e66584
PubMedID: 23826102
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : Draft Genome Sequence of Shewanella decolorationis S12, a Dye-Degrading Bacterium Isolated from a Wastewater Treatment Plant - Xu_2013_Genome.Announc_1_e00993
Author(s) : Xu M , Fang Y , Liu J , Chen X , Sun G , Guo J , Hua Z , Tu Q , Wu L , Zhou J , Liu X
Ref : Genome Announc , 1 : , 2013
Abstract : Shewanella decolorationis is a valuable microorganism for degrading diverse synthetic textile dyes. Here, we present an annotated draft genome sequence of S. decolorationis S12, which contains 4,219 protein-coding genes and 86 structural RNAs. This information regarding the genetic basis of this bacterium can greatly advance our understanding of the physiology of this species.
ESTHER : Xu_2013_Genome.Announc_1_e00993
PubMedSearch : Xu_2013_Genome.Announc_1_e00993
PubMedID: 24309738
Gene_locus related to this paper: 9gamm-v1dg58 , 9gamm-v1daq6

Title : Enhanced enantioselectivity of a carboxyl esterase from Rhodobacter sphaeroides by directed evolution - Ma_2013_Appl.Microbiol.Biotechnol_97_4897
Author(s) : Ma J , Wu L , Guo F , Gu J , Tang X , Jiang L , Liu J , Zhou J , Yu H
Ref : Applied Microbiology & Biotechnology , 97 :4897 , 2013
Abstract : The present work created an esterase variant from Rhodobacter sphaeroides (RspE) with enhanced selectivity in hydrolytic kinetic resolutions by directed evolution. A "model" substrate, methyl mandelate, was introduced in the high-throughput screening procedure. E values of a variant CH (Asn62Cys/Leu145His) for six different esters were 10-83, which were a relative improvement compared to 2-20 for the wild type. Our subsequent crystal structure interpretation and molecular dynamics simulations helped shed light on the source of enantioselectivity modified by directed evolution. Though mutations displayed no "direct" interaction with the substrate, they were hypothesized to strengthen the intramolecular interaction in the catalytic cavity of variant. Conformation analysis revealed that the enhanced enantioselectivity of variant CH for the seven substrates applied in this study was derived from the decrease in size of the substrate binding pocket.
ESTHER : Ma_2013_Appl.Microbiol.Biotechnol_97_4897
PubMedSearch : Ma_2013_Appl.Microbiol.Biotechnol_97_4897
PubMedID: 22987200
Gene_locus related to this paper: rhos4-q3j2v1

Title : The clinical study of precise hemihepatectomy guided by middle hepatic vein - Qiu_2012_World.J.Surg_36_2428
Author(s) : Qiu Y , Zhu X , Zhu R , Zhou J , Zhou T , Wang Y , Ding Y
Ref : World J Surg , 36 :2428 , 2012
Abstract : OBJECTIVE This study was designed to analyze the feasibility of classification for hepatic veins preoperatively and to evaluate the safety and therapeutic efficacy of precise hemihepatectomy guided by middle hepatic vein METHODS Thirty patients who underwent precise hemihepatectomy PH group were subjected to multi-slice helical CT hepatic venography preoperatively to achieve Nakamura's and Kawasaki's classification of hepatic veins The hemihepatectomy was performed precisely by the guidance of middle hepatic vein which was revealed by the hepatic venography and confirmed with intraoperative ultrasound The clinical data of these patients were compared with other 38 traditional hemihepatectomy patients control group The amount of intraoperative bleeding and blood transfusion liver function recovery postoperative complications and 1-year follow-up data were compared between two groups RESULTS The ratios of Nakamura's classification type I II and III of hepatic veins were 56.7 17/30 26.7 8/30 and 16.7 5/30 respectively The percentages of Kawasaki's classification type I and II of hepatic veins were 36.7 11/30 and 63.3 19/30 respectively The total 30 cases of precise hemihepatectomies were performed successfully including 13 cases of right hemihepatectomy without MHV 15 cases of left hemihepatectomy without MHV 1 case of right hemihepatectomy with MHV and 1 case of left hemihepatectomy with MHV There was no significant difference in operation-related mortality the amount of intraoperative bleeding and blood transfusion as well as serum alanine aminotransferase total bilirubin and cholinesterase of the third postoperative day between the two groups However negative resection margin and albumin level were more favorable in precise hemihepatectomy group than control group In addition the incidence of postoperative pleural effusion and seroperitoneum was decreased significantly in precise hemihepatectomy group The 1-year tumor-free survival rate was 79 15/19 In PH group which is 48 in control group CONCLUSIONS Preoperative evaluation of hepatic veins is of great value for individual operative program via determination of anatomical type of hepatic veins Precise hemihepatectomy could preserve functional liver tissue with complete venous return to a great extent resulting in fewer incidences of postoperative pleural effusion and seroperitoneum Precise hemihepatectomy also has the potential to achieve more adequate tumor-free resection margin which may result in higher tumor-free survival rate.
ESTHER : Qiu_2012_World.J.Surg_36_2428
PubMedSearch : Qiu_2012_World.J.Surg_36_2428
PubMedID: 22714574

Title : Complete genome sequence of Salmonella enterica serovar pullorum RKS5078 - Feng_2012_J.Bacteriol_194_744
Author(s) : Feng Y , Xu HF , Li QH , Zhang SY , Wang CX , Zhu DL , Cao FL , Li YG , Johnston RN , Zhou J , Liu GR , Liu SL
Ref : Journal of Bacteriology , 194 :744 , 2012
Abstract : Salmonella enterica serovar Pullorum is a chicken-adapted pathogen, causing pullorum disease. Its strict host adaptation has been suspected to result in gene decay. To validate this hypothesis and identify the decayed genes, we sequenced the complete genome of S. Pullorum RKS5078. We found 263 pseudogenes in this strain and conducted functional analyses of the decayed genes.
ESTHER : Feng_2012_J.Bacteriol_194_744
PubMedSearch : Feng_2012_J.Bacteriol_194_744
PubMedID: 22247537
Gene_locus related to this paper: salty-STY1441 , salty-YFBB

Title : Complete genome sequence of the metabolically versatile halophilic archaeon Haloferax mediterranei, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) producer - Han_2012_J.Bacteriol_194_4463
Author(s) : Han J , Zhang F , Hou J , Liu X , Li M , Liu H , Cai L , Zhang B , Chen Y , Zhou J , Hu S , Xiang H
Ref : Journal of Bacteriology , 194 :4463 , 2012
Abstract : Haloferax mediterranei, an extremely halophilic archaeon, has shown promise for production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) from unrelated cheap carbon sources. Here we report the complete genome (3,904,707 bp) of H. mediterranei CGMCC 1.2087, consisting of one chromosome and three megaplasmids.
ESTHER : Han_2012_J.Bacteriol_194_4463
PubMedSearch : Han_2012_J.Bacteriol_194_4463
PubMedID: 22843593

Title : Structural basis of agrin-LRP4-MuSK signaling - Zong_2012_Genes.Dev_26_247
Author(s) : Zong Y , Zhang B , Gu S , Lee K , Zhou J , Yao G , Figueiredo D , Perry K , Mei L , Jin R
Ref : Genes Dev , 26 :247 , 2012
Abstract : Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). However, little is known of how signals are transduced from agrin to MuSK. Here, we present the first crystal structure of an agrin-LRP4 complex, consisting of two agrin-LRP4 heterodimers. Formation of the initial binary complex requires the z8 loop that is specifically present in neuronal, but not muscle, agrin and that promotes the synergistic formation of the tetramer through two additional interfaces. We show that the tetrameric complex is essential for neuronal agrin-induced acetylcholine receptor (AChR) clustering. Collectively, these results provide new insight into the agrin-LRP4-MuSK signaling cascade and NMJ formation and represent a novel mechanism for activation of receptor tyrosine kinases.
ESTHER : Zong_2012_Genes.Dev_26_247
PubMedSearch : Zong_2012_Genes.Dev_26_247
PubMedID: 22302937

Title : Complete genome sequence of Haloarcula hispanica, a Model Haloarchaeon for studying genetics, metabolism, and virus-host interaction - Liu_2011_J.Bacteriol_193_6086
Author(s) : Liu H , Wu Z , Li M , Zhang F , Zheng H , Han J , Liu J , Zhou J , Wang S , Xiang H
Ref : Journal of Bacteriology , 193 :6086 , 2011
Abstract : Haloarcula hispanica is an extremely halophilic archaeon that has an unusually low restriction barrier and is therefore significant for studying archaeal genetics, metabolism, and virus-host interactions. Here we report the complete genome sequence (3,890,005 bp) of H. hispanica strain CGMCC 1.2049, consisting of two chromosomes and one megaplasmid.
ESTHER : Liu_2011_J.Bacteriol_193_6086
PubMedSearch : Liu_2011_J.Bacteriol_193_6086
PubMedID: 21994921
Gene_locus related to this paper: halma-q5uym0

Title : Complete genome sequence of Staphylococcus aureus T0131, an ST239-MRSA-SCCmec type III clone isolated in China - Li_2011_J.Bacteriol_193_3411
Author(s) : Li Y , Cao B , Zhang Y , Zhou J , Yang B , Wang L
Ref : Journal of Bacteriology , 193 :3411 , 2011
Abstract : We report here the complete genome sequence of Staphylococcus aureus T0131, which is a multiresistant clinical isolate recovered in China and the first sequenced epidemic ST239-MRSA-SCCmec type III strain obtained in Asia. Comparison with two published genomes of ST239 reveals the polymorphism among strains of this type from different continents.
ESTHER : Li_2011_J.Bacteriol_193_3411
PubMedSearch : Li_2011_J.Bacteriol_193_3411
PubMedID: 21551295
Gene_locus related to this paper: staau-SA0897

Title : Sesquiterpenoids and lignans from the roots of Valeriana officinalis L - Wang_2011_Chem.Biodivers_8_1908
Author(s) : Wang PC , Ran XH , Chen R , Luo HR , Ma QY , Liu YQ , Hu JM , Huang SZ , Jiang HZ , Chen ZQ , Zhou J , Zhao YX
Ref : Chem Biodivers , 8 :1908 , 2011
Abstract : Two new guaiane-type sesquiterpenoids, valerol A (1) and kessyl 3-acetate (2), together with nine known compounds, valeracetate (3), anismol A (4), orientalol C (5), spatulenol (6), 4alpha,10alpha-epoxyaromadendrane (7), (+)-8-hydroxypinoresinol (8), pinorespiol (9), pinoresinol 4-O-beta-D-glucopyranoside (10), and 8-hydroxypinoresinol 4'-O-beta-D-glucopyranoside (11) were isolated from the roots of Valeriana officinalis. The structures and relative configurations of 1 and 2 were elucidated on the basis of spectroscopic methods (1D- and 2D-NMR, MS, UV, and IR). These compounds were evaluated for inhibitory activity on acetylcholinesterase (AChE) and enhancing activity on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells.
ESTHER : Wang_2011_Chem.Biodivers_8_1908
PubMedSearch : Wang_2011_Chem.Biodivers_8_1908
PubMedID: 22006719

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

Title : The genome of the leaf-cutting ant Acromyrmex echinatior suggests key adaptations to advanced social life and fungus farming - Nygaard_2011_Genome.Res_21_1339
Author(s) : Nygaard S , Zhang G , Schiott M , Li C , Wurm Y , Hu H , Zhou J , Ji L , Qiu F , Rasmussen M , Pan H , Hauser F , Krogh A , Grimmelikhuijzen CJ , Wang J , Boomsma JJ
Ref : Genome Res , 21 :1339 , 2011
Abstract : We present a high-quality (>100x depth) Illumina genome sequence of the leaf-cutting ant Acromyrmex echinatior, a model species for symbiosis and reproductive conflict studies. We compare this genome with three previously sequenced genomes of ants from different subfamilies and focus our analyses on aspects of the genome likely to be associated with known evolutionary changes. The first is the specialized fungal diet of A. echinatior, where we find gene loss in the ant's arginine synthesis pathway, loss of detoxification genes, and expansion of a group of peptidase proteins. One of these is a unique ant-derived contribution to the fecal fluid, which otherwise consists of "garden manuring" fungal enzymes that are unaffected by ant digestion. The second is multiple mating of queens and ejaculate competition, which may be associated with a greatly expanded nardilysin-like peptidase gene family. The third is sex determination, where we could identify only a single homolog of the feminizer gene. As other ants and the honeybee have duplications of this gene, we hypothesize that this may partly explain the frequent production of diploid male larvae in A. echinatior. The fourth is the evolution of eusociality, where we find a highly conserved ant-specific profile of neuropeptide genes that may be related to caste determination. These first analyses of the A. echinatior genome indicate that considerable genetic changes are likely to have accompanied the transition from hunter-gathering to agricultural food production 50 million years ago, and the transition from single to multiple queen mating 10 million years ago.
ESTHER : Nygaard_2011_Genome.Res_21_1339
PubMedSearch : Nygaard_2011_Genome.Res_21_1339
PubMedID: 21719571
Gene_locus related to this paper: acrec-f4we58 , acrec-f4wfr0 , acrec-f4wwr9 , acrec-f4x396 , acrec-f4wlq1 , acrec-f4wk97 , acrec-f4wdb2 , acrec-f4wdb3 , acrec-f4x1t2

Title : Complete genome sequence of the industrial strain Ketogulonicigenium vulgare WSH-001 - Liu_2011_J.Bacteriol_193_6108
Author(s) : Liu L , Li Y , Zhang J , Zhou Z , Liu J , Li X , Zhou J , Du G , Wang L , Chen J
Ref : Journal of Bacteriology , 193 :6108 , 2011
Abstract : Ketogulonicigenium vulgare is an industrial organism commonly used in the vitamin C industry. Here, we report the finished, annotated, and compared 3.28-Mbp high-quality genome sequence of Ketogulonicigenium vulgare WSH-001, a 2-keto-l-gulonic acid-producing industrial strain stocked in our laboratory.
ESTHER : Liu_2011_J.Bacteriol_193_6108
PubMedSearch : Liu_2011_J.Bacteriol_193_6108
PubMedID: 21994934
Gene_locus related to this paper: ketvy-e3f614 , ketvw-f9yby2

Title : Germacrane-type sesquiterpenoids from the roots of Valeriana officinalis var. latifolia - Wang_2010_J.Nat.Prod_73_1563
Author(s) : Wang PC , Ran XH , Chen R , Luo HR , Liu YQ , Zhou J , Zhao YX
Ref : Journal of Natural Products , 73 :1563 , 2010
Abstract : Eight new germacrane-type sesquiterpenoids, volvalerenals A-E (2-6) and volvalerenic acids A-C (7-9), along with four known compounds, were isolated from a chloroform extract of the roots of Valeriana officinalis var. latifolia. The structures and relative configurations of 2-9 were elucidated on the basis of spectroscopic data interpretation. The effects of all compounds isolated on acetylcholinesterase were evaluated.
ESTHER : Wang_2010_J.Nat.Prod_73_1563
PubMedSearch : Wang_2010_J.Nat.Prod_73_1563
PubMedID: 20812738

Title : Comparison of four phaC genes from Haloferax mediterranei and their function in different PHBV copolymer biosyntheses in Haloarcula hispanica - Han_2010_Saline.Systems_6_9
Author(s) : Han J , Li M , Hou J , Wu L , Zhou J , Xiang H
Ref : Saline Systems , 6 :9 , 2010
Abstract : BACKGROUND: The halophilic archaeon Haloferax mediterranei is able to accumulate large amounts of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with high molar fraction of 3-hydroxyvalerate (3HV) from unrelated carbon sources. A Polyhydroxyalkanoate (PHA) synthase composed of two subunits, PhaCHme and PhaEHme, has been identified in this strain, and shown to account for the PHBV biosynthesis.
RESULTS: With the aid of the genome sequence of Hfx. mediterranei CGMCC 1.2087, three additional phaC genes (designated phaC1, phaC2, and phaC3) were identified, which encoded putative PhaCs. Like PhaCHme (54.8 kDa), PhaC1 (49.7 kDa) and PhaC3 (62.5 kDa) possessed the conserved motifs of type III PHA synthase, which was not observed in PhaC2 (40.4 kDa). Furthermore, the longer C terminus found in the other three PhaCs was also absent in PhaC2. Reverse transcription PCR (RT-PCR) revealed that, among the four genes, only phaCHme was transcribed under PHA-accumulating conditions in the wild-type strain. However, heterologous coexpression of phaEHme with each phaC gene in Haloarcula hispanica PHB-1 showed that all PhaCs, except PhaC2, could lead to PHBV accumulation with various 3HV fractions. The three kinds of copolymers were characterized using gel-permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Their thermal properties changed with the variations in monomer composition as well as the different molecular weights (Mw), thus might meet various application requirements. CONCLUSION: We discover three cryptic phaC genes in Hfx. mediterranei, and demonstrate that genetic engineering of these newly identified phaC genes has biotechnological potential for PHBV production with tailor-made material properties.
ESTHER : Han_2010_Saline.Systems_6_9
PubMedSearch : Han_2010_Saline.Systems_6_9
PubMedID: 20727166

Title : Synthesis and bioactivity evaluation of dipeptidyl peptidase IV resistant glucagon-like peptide-1 analogues - Zhou_2010_Protein.Pept.Lett_17_1290
Author(s) : Zhou J , Ni S , Zhang H , Qian H , Chi Y , Huang W , Yu L , Hu X , Chen W
Ref : Protein Pept Lett , 17 :1290 , 2010
Abstract : Glucagon-like peptide -1 (GLP-1) is an incretin hormone displaying glucose-dependent stimulation of insulin secretion and trophic effects on the pancreatic beta-cells. However, GLP-1 is rapidly degraded to GLP-1(9-36) by dipeptidyl peptidase-IV (DPP-IV), which removes the N-terminal dipeptide His(7)-Ala(8). The rapid inactivation of GLP-1 in the blood circulation limits its clinical application. Hence, we replaced the enzymatic hydrolyzation position Ala(8) with other natural amino acids. The GLP-1 analogues were synthesized rapidly and efficiently under microwave irradiation, using Fmoc/tBu orthogonal protection strategy. Studies on blood-glucose-lowering effect of GLP-1 analogues in vivo were undertaken using 10-week-old male Kunming mice. The metabolic stability was tested by incubation with dipeptidyl peptidase-IV (DPP-IV). Generally, Xaa(8)-GLP-1 analogues exhibit resistance to DPP-IV degradation in vitro and stronger hypoglycemic effect than GLP-1. This may help to understand the structure-activity relationship of GLP-1 analogues.
ESTHER : Zhou_2010_Protein.Pept.Lett_17_1290
PubMedSearch : Zhou_2010_Protein.Pept.Lett_17_1290
PubMedID: 20594158

Title : Effects of low-intensity microwave radiation on Tribolium castaneum physiological and biochemical characteristics and survival - Lu_2010_J.Insect.Physiol_56_1356
Author(s) : Lu H , Zhou J , Xiong S , Zhao S
Ref : J Insect Physiol , 56 :1356 , 2010
Abstract : The red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae) is a widespread pest that lives in, and feeds on, wheat flour. Here, we studied the effects of low-intensity microwave radiation (LIMR;
ESTHER : Lu_2010_J.Insect.Physiol_56_1356
PubMedSearch : Lu_2010_J.Insect.Physiol_56_1356
PubMedID: 20438733

Title : Contribution of mobile genetic elements to Desulfovibrio vulgaris genome plasticity - Walker_2009_Environ.Microbiol_11_2244
Author(s) : Walker CB , Stolyar S , Chivian D , Pinel N , Gabster JA , Dehal PS , He Z , Yang ZK , Yen HC , Zhou J , Wall JD , Hazen TC , Arkin AP , Stahl DA
Ref : Environ Microbiol , 11 :2244 , 2009
Abstract : The genome of Desulfovibrio vulgaris strain DePue, a sulfate-reducing Deltaproteobacterium isolated from heavy metal-impacted lake sediment, was completely sequenced and compared with the type strain D. vulgaris Hildenborough. The two genomes share a high degree of relatedness and synteny, but harbour distinct prophage and signatures of past phage encounters. In addition to a highly variable phage contribution, the genome of strain DePue contains a cluster of open-reading frames not found in strain Hildenborough coding for the production and export of a capsule exopolysaccharide, possibly of relevance to heavy metal resistance. Comparative whole-genome microarray analysis on four additional D. vulgaris strains established greater interstrain variation within regions associated with phage insertion and exopolysaccharide biosynthesis.
ESTHER : Walker_2009_Environ.Microbiol_11_2244
PubMedSearch : Walker_2009_Environ.Microbiol_11_2244
PubMedID: 19737303
Gene_locus related to this paper: desvh-q728i3 , desvv-a1vc62 , desvh-q72b15

Title : Enzyme-substrate interaction and characterization of a 2,3-dihydroxybiphenyl 1,2-dioxygenase from Dyella ginsengisoli LA-4 - Li_2009_FEMS.Microbiol.Lett_292_231
Author(s) : Li A , Qu Y , Zhou J , Ma F
Ref : FEMS Microbiology Letters , 292 :231 , 2009
Abstract : A bphC gene (915 bp) encoding 2,3-dihydroxybiphenyl 1,2-dioxygenase (BphC) was amplified by PCR from Dyella ginsengisoli LA-4, which was heterologously expressed in Escherichia coli. The purified His-Tag BphC was able to catalyze the meta-cleavage reaction of the dihydroxylated aromatic rings. According to the specificity constant (K(cat)/K(m)) of BphC_LA-4, the specificity of BphC_LA-4 was determined in the following order: 2,3-dihydroxybiphenyl>3-methylcatechol>catechol>4-chlorocatechol>4-methylcatechol . The experimental data were consistent with the prediction of enzyme-substrate complexes. The highest specific activity of BphC_LA-4 was 118.3 U mg(-1) for 2,3-dihydroxybiphenyl.
ESTHER : Li_2009_FEMS.Microbiol.Lett_292_231
PubMedSearch : Li_2009_FEMS.Microbiol.Lett_292_231
PubMedID: 19187202

Title : Arabidopsis N-MYC DOWNREGULATED-LIKE1, a positive regulator of auxin transport in a G protein-mediated pathway - Mudgil_2009_Plant.Cell_21_3591
Author(s) : Mudgil Y , Uhrig JF , Zhou J , Temple B , Jiang K , Jones AM
Ref : Plant Cell , 21 :3591 , 2009
Abstract : Root architecture results from coordinated cell division and expansion in spatially distinct cells of the root and is established and maintained by gradients of auxin and nutrients such as sugars. Auxin is transported acropetally through the root within the central stele and then, upon reaching the root apex, auxin is transported basipetally through the outer cortical and epidermal cells. The two Gbetagamma dimers of the Arabidopsis thaliana heterotrimeric G protein complex are differentially localized to the central and cortical tissues of the Arabidopsis roots. A null mutation in either the single beta (AGB1) or the two gamma (AGG1 and AGG2) subunits confers phenotypes that disrupt the proper architecture of Arabidopsis roots and are consistent with altered auxin transport. Here, we describe an evolutionarily conserved interaction between AGB1/AGG dimers and a protein designated N-MYC DOWNREGULATED-LIKE1 (NDL1). The Arabidopsis genome encodes two homologs of NDL1 (NDL2 and NDL3), which also interact with AGB1/AGG1 and AGB1/AGG2 dimers. We show that NDL proteins act in a signaling pathway that modulates root auxin transport and auxin gradients in part by affecting the levels of at least two auxin transport facilitators. Reduction of NDL family gene expression and overexpression of NDL1 alter root architecture, auxin transport, and auxin maxima. AGB1, auxin, and sugars are required for NDL1 protein stability in regions of the root where auxin gradients are established; thus, the signaling mechanism contains feedback loops.
ESTHER : Mudgil_2009_Plant.Cell_21_3591
PubMedSearch : Mudgil_2009_Plant.Cell_21_3591
PubMedID: 19948787
Gene_locus related to this paper: arath-At2g19620 , arath-At5g56750 , arath-At5g11790

Title : Genetic and biochemical characterization of the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthase in Haloferax mediterranei - Lu_2008_J.Bacteriol_190_4173
Author(s) : Lu Q , Han J , Zhou L , Zhou J , Xiang H
Ref : Journal of Bacteriology , 190 :4173 , 2008
Abstract : The haloarchaeon Haloferax mediterranei has shown promise for the economical production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a desirable bioplastic. However, little is known at present about the genes involved in PHBV synthesis in the domain Archaea. In this study, we cloned the gene cluster (phaEC(Hme)) encoding a polyhydroxyalkanoate (PHA) synthase in H. mediterranei CGMCC 1.2087 via thermal asymmetric interlaced PCR. Western blotting revealed that the phaE(Hme) and phaC(Hme) genes were constitutively expressed, and both the PhaE(Hme) and PhaC(Hme) proteins were strongly bound to the PHBV granules. Interestingly, CGMCC 1.2087 could synthesize PHBV in either nutrient-limited medium (supplemented with 1% starch) or nutrient-rich medium, up to 24 or 18% (wt/wt) in shaking flasks. Knockout of the phaEC(Hme) genes in CGMCC 1.2087 led to a complete loss of PHBV synthesis, and only complementation with the phaEC(Hme) genes together (but not either one alone) could restore to this mutant the capability for PHBV accumulation. The known haloarchaeal PhaC subunits are much longer at their C termini than their bacterial counterparts, and the C-terminal extension of PhaC(Hme) was proven to be indispensable for its function in vivo. Moreover, the mixture of purified PhaE(Hme)/PhaC(Hme) (1:1) showed significant activity of PHA synthase in vitro. Taken together, our results indicated that a novel member of the class III PHA synthases, composed of PhaC(Hme) and PhaE(Hme), accounted for the PHBV synthesis in H. mediterranei.
ESTHER : Lu_2008_J.Bacteriol_190_4173
PubMedSearch : Lu_2008_J.Bacteriol_190_4173
PubMedID: 18408025
Gene_locus related to this paper: halme-b3frm5

Title : Epoxy functionalised poly(epsilon-caprolactone): synthesis and application - Zhou_2008_Chem.Commun.(Camb)__5806
Author(s) : Zhou J , Wang W , Villarroya S , Thurecht KJ , Howdle SM
Ref : Chem Commun (Camb) , :5806 , 2008
Abstract : Glycidol is used as an initiator for ring-opening polymerisation of epsilon-caprolactone (epsilon-CL) to synthesise epoxy-functionalised poly(epsilon-caprolactone) (PCL) in a reaction catalysed by lipase, and the epoxy-functionalised PCL was further copolymerised with carbon dioxide or anhydride to produce novel graft or hyperbranched copolymers.
ESTHER : Zhou_2008_Chem.Commun.(Camb)__5806
PubMedSearch : Zhou_2008_Chem.Commun.(Camb)__5806
PubMedID: 19009088

Title : Molecular basis of prodrug activation by human valacyclovirase, an alpha-amino acid ester hydrolase - Lai_2008_J.Biol.Chem_283_9318
Author(s) : Lai L , Xu Z , Zhou J , Lee KD , Amidon GL
Ref : Journal of Biological Chemistry , 283 :9318 , 2008
Abstract : Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of alpha-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F1. Crystal structures of the enzyme, two mechanistic mutants, and a complex with a product analogue, when combined with biochemical analysis, reveal the key determinants for substrate recognition; that is, a flexible and mostly hydrophobic acyl pocket, a localized negative electrostatic potential, a large open leaving group-accommodating groove, and a pivotal acidic residue, Asp-123, after the nucleophile Ser-122. This is the first time that a residue immediately after the nucleophile has been found to have its side chain directed into the substrate binding pocket and play an essential role in substrate discrimination in serine hydrolases. These results as well as a phylogenetic analysis establish that the enzyme functions as a specific alpha-amino acid ester hydrolase. Valacyclovirase is a valuable target for amino acid ester prodrug-based oral drug delivery enhancement strategies.
ESTHER : Lai_2008_J.Biol.Chem_283_9318
PubMedSearch : Lai_2008_J.Biol.Chem_283_9318
PubMedID: 18256025
Gene_locus related to this paper: human-BPHL

Title : [Preliminary research of 3D reconstruction of short-segment common peroneal nerve functional fascicles] - Qi_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1031
Author(s) : Qi J , Liu X , Xiong Z , Zhou J , Li S , Liang Y , Zhang Y
Ref : Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi , 22 :1031 , 2008
Abstract : OBJECTIVE: To investigate the feasibility of building the 3D reconstruction of short segment common peroneal nerve functional fascicles based on serial histological sections and computer technology.
METHODS: Five cm of the common peroneal nerve in the popliteal fossa, donated by an adult, was made into the serial transverse freezing sections (n=200) at an interval of 0.25 mm and 10 microm in thickness per section. Acetylcholinesterase staining was adopted and the nerve fascicles were observed by microscope. 2D panorama images were acquired by high-resolution digital camera under microscope (x 100) and mosaic software. Different functional fascicles were distinguished and marked on each section. The topographic database was matched by image processing software. The 3D microstructure of the fascicular groups of 5 cm common peroneal nerve was reconstructed using Amira 3.1 3D reconstruction software.
RESULTS: Based on microanatomy and the results of acetylcholinesterase staining, this segmented common peroneal nerve functional fascicles was divided into sensory tract, motor tract, mixed tract and motor-predominating mixed tract. The cross merging was not evident in the nerve fascicles between deep peroneal nerve and superficial peroneal nerve, but existed within the functional fascicles of the deep peroneal nerve and the superficial peroneal nerve. The results of 3D reconstruction reflected the 3D structure of peripheral nerve and its interior functional fascicles factually, which displayed solely or in combination at arbitrary angles.
CONCLUSION: Based on serial histological sections and computer technology, the 3D microstructure of short-segment peripheral nerve functional fascicles can be reconstructed satisfactorily, indicating the feasibility of building 3D reconstruction of long-segmental peripheral nerve functional fascicles.
ESTHER : Qi_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1031
PubMedSearch : Qi_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1031
PubMedID: 18822721

Title : Monitoring enzyme reaction and screening of inhibitors of acetylcholinesterase by quantitative matrix-assisted laser desorption\/ionization Fourier transform mass spectrometry - Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
Author(s) : Xu Z , Yao S , Wei Y , Zhou J , Zhang L , Wang C , Guo Y
Ref : J Am Soc Mass Spectrom , 19 :1849 , 2008
Abstract : A matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS)-based assay was developed for kinetic measurements and inhibitor screening of acetylcholinesterase. Here, FTMS coupled to MALDI was applied to quantitative analysis of choline using the ratio of choline/acetylcholine without the use of additional internal standard, which simplified the experiment. The Michaelis constant (K(m)) of acetylcholinesterase (AChE) was determined to be 73.9 micromol L(-1) by this approach. For Huperzine A, the linear mixed inhibition of AChE reflected the presence of competitive and noncompetitive components. The half maximal inhibitory concentration (IC(50)) value of galantamine obtained for AChE was 2.39 micromol L(-1). Inhibitory potentials of Rhizoma Coptidis extracts were identified with the present method. In light of the results the referred extracts as a whole showed inhibitory action against AChE. The use of high-resolution FTMS largely eliminated the interference with the determination of ACh and Ch, produced by the low-mass compounds of chemical libraries for inhibitor screening. The excellent correlation with the reported kinetic parameters confirms that the MS-based assay is both accurate and precise for determining kinetic constants and for identifying enzyme inhibitors. The obvious advantages were demonstrated for quantitative analysis and also high-throughput characterization. This study offers a perspective into the utility of MALDI-FTMS as an alternate quantitative tool for inhibitor screening of AChE.
ESTHER : Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
PubMedSearch : Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
PubMedID: 18789720

Title : Molecular characterization of the phaECHm genes, required for biosynthesis of poly(3-hydroxybutyrate) in the extremely halophilic archaeon Haloarcula marismortui - Han_2007_Appl.Environ.Microbiol_73_6058
Author(s) : Han J , Lu Q , Zhou L , Zhou J , Xiang H
Ref : Applied Environmental Microbiology , 73 :6058 , 2007
Abstract : Although many haloarchaea produce biodegradable polyhydroxyalkanoates (PHAs), the genes involved in PHA synthesis in the domain of Archaea have not yet been experimentally investigated yet. In this study, we revealed that Haloarcula marismortui was able to accumulate poly(3-hydroxybutyrate) (PHB) up to 21% of cellular dry weight when cultured in a minimal medium with excessive glucose and identified the phaE(Hm) and phaC(Hm) genes, probably encoding two subunits of a class III PHA synthase. These two genes were adjacent and directed by a single promoter located 26 bp upstream of the transcriptional start site and were constitutively expressed under both nutrient-rich and -limited conditions. Interestingly, PhaC(Hm) was revealed to be strongly bound with the PHB granules, but PhaE(Hm) seemed not to be. Introduction of either the phaE(Hm) or phaC(Hm) gene into Haloarcula hispanica, which harbors highly homologous phaEC(Hh) genes, could enhance the PHB synthesis in the recombinant strains, while coexpression of the both genes always generated the highest PHB yield. Significantly, knockout of the phaEC(Hh) genes in H. hispanica led to a complete loss of the PHA synthase activity. Complementation with phaEC(Hm) genes, but not a single one, restored the capability of PHB accumulation as well as the PHA synthase activity in this phaEC-deleted haloarchaeon. These results indicated that the phaEC genes are required for biosynthesis of PHB and might encode an active PHA synthase in the Haloarcula species.
ESTHER : Han_2007_Appl.Environ.Microbiol_73_6058
PubMedSearch : Han_2007_Appl.Environ.Microbiol_73_6058
PubMedID: 17675423
Gene_locus related to this paper: halma-q5uym0

Title : Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus - Highlander_2007_BMC.Microbiol_7_99
Author(s) : Highlander SK , Hulten KG , Qin X , Jiang H , Yerrapragada S , Mason EO, Jr. , Shang Y , Williams TM , Fortunov RM , Liu Y , Igboeli O , Petrosino J , Tirumalai M , Uzman A , Fox GE , Cardenas AM , Muzny DM , Hemphill L , Ding Y , Dugan S , Blyth PR , Buhay CJ , Dinh HH , Hawes AC , Holder M , Kovar CL , Lee SL , Liu W , Nazareth LV , Wang Q , Zhou J , Kaplan SL , Weinstock GM
Ref : BMC Microbiol , 7 :99 , 2007
Abstract : BACKGROUND: Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. RESULTS: We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. CONCLUSION: USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.
ESTHER : Highlander_2007_BMC.Microbiol_7_99
PubMedSearch : Highlander_2007_BMC.Microbiol_7_99
PubMedID: 17986343
Gene_locus related to this paper: staa3-q2fkj0 , staau-LIP , staau-lipas , staau-MW0741 , staau-MW2456 , staau-q6gfm6 , staau-SA0011 , staau-SA0569 , staau-SA0572 , staau-SA0897 , staau-SA1143 , staau-SA2240 , staau-SA2306 , staau-SA2367 , staau-SA2422 , staau-SAV0321 , staau-SAV0446 , staau-SAV0457 , staau-SAV0655 , staau-SAV1014 , staau-SAV1765 , staau-SAV1793 , staau-SAV2188 , staau-SAV2350 , staau-SAV2594

Title : The DNA sequence, annotation and analysis of human chromosome 3 - Muzny_2006_Nature_440_1194
Author(s) : Muzny DM , Scherer SE , Kaul R , Wang J , Yu J , Sudbrak R , Buhay CJ , Chen R , Cree A , Ding Y , Dugan-Rocha S , Gill R , Gunaratne P , Harris RA , Hawes AC , Hernandez J , Hodgson AV , Hume J , Jackson A , Khan ZM , Kovar-Smith C , Lewis LR , Lozado RJ , Metzker ML , Milosavljevic A , Miner GR , Morgan MB , Nazareth LV , Scott G , Sodergren E , Song XZ , Steffen D , Wei S , Wheeler DA , Wright MW , Worley KC , Yuan Y , Zhang Z , Adams CQ , Ansari-Lari MA , Ayele M , Brown MJ , Chen G , Chen Z , Clendenning J , Clerc-Blankenburg KP , Davis C , Delgado O , Dinh HH , Dong W , Draper H , Ernst S , Fu G , Gonzalez-Garay ML , Garcia DK , Gillett W , Gu J , Hao B , Haugen E , Havlak P , He X , Hennig S , Hu S , Huang W , Jackson LR , Jacob LS , Kelly SH , Kube M , Levy R , Li Z , Liu B , Liu J , Liu W , Lu J , Maheshwari M , Nguyen BV , Okwuonu GO , Palmeiri A , Pasternak S , Perez LM , Phelps KA , Plopper FJ , Qiang B , Raymond C , Rodriguez R , Saenphimmachak C , Santibanez J , Shen H , Shen Y , Subramanian S , Tabor PE , Verduzco D , Waldron L , Wang Q , Williams GA , Wong GK , Yao Z , Zhang J , Zhang X , Zhao G , Zhou J , Zhou Y , Nelson D , Lehrach H , Reinhardt R , Naylor SL , Yang H , Olson M , Weinstock G , Gibbs RA
Ref : Nature , 440 :1194 , 2006
Abstract : After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.
ESTHER : Muzny_2006_Nature_440_1194
PubMedSearch : Muzny_2006_Nature_440_1194
PubMedID: 16641997
Gene_locus related to this paper: human-AADAC , human-AADACL2 , human-ABHD5 , human-ABHD6 , human-ABHD10 , human-ABHD14A , human-APEH , human-BCHE , human-CIB , human-LIPH , human-MGLL , human-NLGN1 , human-PLA1A

Title : Simultaneous enzymatic ring opening polymerisation and RAFT-mediated polymerisation in supercritical CO2 - Thurecht_2006_Chem.Commun.(Camb)__4383
Author(s) : Thurecht KJ , Gregory AM , Villarroya S , Zhou J , Heise A , Howdle SM
Ref : Chem Commun (Camb) , :4383 , 2006
Abstract : This report presents the first simultaneous, metal-free synthesis of block copolymers through combination of enzymatic ring-opening polymerisation of epsilon-caprolactone with RAFT-mediated controlled radical polymerisation of styrene.
ESTHER : Thurecht_2006_Chem.Commun.(Camb)__4383
PubMedSearch : Thurecht_2006_Chem.Commun.(Camb)__4383
PubMedID: 17057851

Title : The DNA sequence of the human X chromosome - Ross_2005_Nature_434_325
Author(s) : Ross MT , Grafham DV , Coffey AJ , Scherer S , McLay K , Muzny D , Platzer M , Howell GR , Burrows C , Bird CP , Frankish A , Lovell FL , Howe KL , Ashurst JL , Fulton RS , Sudbrak R , Wen G , Jones MC , Hurles ME , Andrews TD , Scott CE , Searle S , Ramser J , Whittaker A , Deadman R , Carter NP , Hunt SE , Chen R , Cree A , Gunaratne P , Havlak P , Hodgson A , Metzker ML , Richards S , Scott G , Steffen D , Sodergren E , Wheeler DA , Worley KC , Ainscough R , Ambrose KD , Ansari-Lari MA , Aradhya S , Ashwell RI , Babbage AK , Bagguley CL , Ballabio A , Banerjee R , Barker GE , Barlow KF , Barrett IP , Bates KN , Beare DM , Beasley H , Beasley O , Beck A , Bethel G , Blechschmidt K , Brady N , Bray-Allen S , Bridgeman AM , Brown AJ , Brown MJ , Bonnin D , Bruford EA , Buhay C , Burch P , Burford D , Burgess J , Burrill W , Burton J , Bye JM , Carder C , Carrel L , Chako J , Chapman JC , Chavez D , Chen E , Chen G , Chen Y , Chen Z , Chinault C , Ciccodicola A , Clark SY , Clarke G , Clee CM , Clegg S , Clerc-Blankenburg K , Clifford K , Cobley V , Cole CG , Conquer JS , Corby N , Connor RE , David R , Davies J , Davis C , Davis J , Delgado O , Deshazo D , Dhami P , Ding Y , Dinh H , Dodsworth S , Draper H , Dugan-Rocha S , Dunham A , Dunn M , Durbin KJ , Dutta I , Eades T , Ellwood M , Emery-Cohen A , Errington H , Evans KL , Faulkner L , Francis F , Frankland J , Fraser AE , Galgoczy P , Gilbert J , Gill R , Glockner G , Gregory SG , Gribble S , Griffiths C , Grocock R , Gu Y , Gwilliam R , Hamilton C , Hart EA , Hawes A , Heath PD , Heitmann K , Hennig S , Hernandez J , Hinzmann B , Ho S , Hoffs M , Howden PJ , Huckle EJ , Hume J , Hunt PJ , Hunt AR , Isherwood J , Jacob L , Johnson D , Jones S , de Jong PJ , Joseph SS , Keenan S , Kelly S , Kershaw JK , Khan Z , Kioschis P , Klages S , Knights AJ , Kosiura A , Kovar-Smith C , Laird GK , Langford C , Lawlor S , Leversha M , Lewis L , Liu W , Lloyd C , Lloyd DM , Loulseged H , Loveland JE , Lovell JD , Lozado R , Lu J , Lyne R , Ma J , Maheshwari M , Matthews LH , McDowall J , Mclaren S , McMurray A , Meidl P , Meitinger T , Milne S , Miner G , Mistry SL , Morgan M , Morris S , Muller I , Mullikin JC , Nguyen N , Nordsiek G , Nyakatura G , O'Dell CN , Okwuonu G , Palmer S , Pandian R , Parker D , Parrish J , Pasternak S , Patel D , Pearce AV , Pearson DM , Pelan SE , Perez L , Porter KM , Ramsey Y , Reichwald K , Rhodes S , Ridler KA , Schlessinger D , Schueler MG , Sehra HK , Shaw-Smith C , Shen H , Sheridan EM , Shownkeen R , Skuce CD , Smith ML , Sotheran EC , Steingruber HE , Steward CA , Storey R , Swann RM , Swarbreck D , Tabor PE , Taudien S , Taylor T , Teague B , Thomas K , Thorpe A , Timms K , Tracey A , Trevanion S , Tromans AC , d'Urso M , Verduzco D , Villasana D , Waldron L , Wall M , Wang Q , Warren J , Warry GL , Wei X , West A , Whitehead SL , Whiteley MN , Wilkinson JE , Willey DL , Williams G , Williams L , Williamson A , Williamson H , Wilming L , Woodmansey RL , Wray PW , Yen J , Zhang J , Zhou J , Zoghbi H , Zorilla S , Buck D , Reinhardt R , Poustka A , Rosenthal A , Lehrach H , Meindl A , Minx PJ , Hillier LW , Willard HF , Wilson RK , Waterston RH , Rice CM , Vaudin M , Coulson A , Nelson DL , Weinstock G , Sulston JE , Durbin R , Hubbard T , Gibbs RA , Beck S , Rogers J , Bentley DR
Ref : Nature , 434 :325 , 2005
Abstract : The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
ESTHER : Ross_2005_Nature_434_325
PubMedSearch : Ross_2005_Nature_434_325
PubMedID: 15772651
Gene_locus related to this paper: human-NLGN3 , human-NLGN4X

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : [Huperzine A attenuates cognitive deficits and brain injury after hypoxia-ischemic brain damage in neonatal rats] - Wang_2003_Zhonghua.Er.Ke.Za.Zhi_41_42
Author(s) : Wang LS , Zhou J , Shao XM , Tang XC
Ref : Zhonghua Er Ke Za Zhi , 41 :42 , 2003
Abstract : OBJECTIVE: To investigate the protective effects of Huperzine A, a potent acetylcholinesterase inhibitor, against the hypoxic ischemic brain damage (HIBD) of the cognitive and morphology in the neonatal rats.
METHODS: Postnatal 7 days old rats were given vehicle or Huperzine A (0.05 mg/kg or 0.1 mg/kg, i.p.) following HIBD (unilateral carotid artery ligation followed by hypoxia) or sham operation, and then tested the learning ability and memory in the Morris water maze (MWM) from 36 to 40 postnatal days. The performance in MWM (escape latency, probe time) were recorded to evaluate the learning and memory dysfunction. At the end of MWM trials, the rats were decapitated and their brains were histologically analyzed. The tissue loss in different brain regions including striatum, cortex, and hippocampus were analyzed by image analysis system. The CA(1) subfield neurons numbers were counted to evaluate the brain damage. The acetylcholinesterase histochemistry staining was used to determine the activity of acetylcholinesterase in different brain regions.
RESULTS: Compared with sham-operated group, HIBD rats with the vehicle treatment displayed significant tissue losses in the hippocampus (including CA(1) neurons), cortex, and striatum, as well as severe spatial memory deficits (escape latency: 44 s vs 30 s, P < 0.05, probe time: 14 s vs 40 s, P < 0.01). Huperzine A treatment (0.1 mg/kg) resulted in significant protection against both HI-induced brain tissue losses and spatial memory impairments (mean escape latency: 34 s vs 44 s, P < 0.05, probe time: 35 s vs 14 s,P < 0.01). However, Huperzine A treatment (0.05 mg/kg) did not show any significant improvement of spatial memory impairments (mean escape latency: 45 s vs 44 s, P > 0.05, probe time: 17 s vs 14 s, P > 0.05), but moderate to severe brain tissue losses. There was a pronounced reduction of CA(1) neuron density in ipsilateral hemisphere of vehicle-treated group and 0.05 mg/kg Huperzine A group compared with contralateral hemisphere or ipsilateral hemisphere of sham-operated group and 0.1 mg/kg Huperzine A group (72 vs 232, P < 0.01, 72 vs 229, P < 0.01, respectively). There was a close linear correlation between the CA(1) neurons cell number and the mean escape latency for 5 d acquisition trials (r = 0.777, P < 0.01). CONCLUSION: The unilateral HI brain injury in a neonatal rat model was associated with cognitive deficits, and that Huperzine A treatment may be protective against both brain injury and spatial memory impairment. Huperzine A showed a therapeutic potential for the treatment of hypoxic-ischemic encephalopathy (HIE) caused by the perinatal asphyxia.
ESTHER : Wang_2003_Zhonghua.Er.Ke.Za.Zhi_41_42
PubMedSearch : Wang_2003_Zhonghua.Er.Ke.Za.Zhi_41_42
PubMedID: 14761327

Title : Thermostable esterase from Thermoanaerobacter tengcongensis: high-level expression, purification and characterization - Zhang_2003_Biotechnol.Lett_25_1463
Author(s) : Zhang J , Liu J , Zhou J , Ren Y , Dai X , Xiang H
Ref : Biotechnol Lett , 25 :1463 , 2003
Abstract : The lipA gene encoding a thermostable esterase was cloned from Thermoanaerobacter tengcongensis and over-expressed in Escherichia coli. The recombinant esterase, with a molecular mass of approx. 43 kDa determined by SDS-PAGE, was purified to homogeneity through Sephadex G-100 gel filtration. The purified enzyme actively hydrolyzed tributyrin but not olive oil. Maximum activity was observed on p-nitrophenyl (NP)-propionate (C3) and p-NP-butyrate (C4), with little activity towards p-NP-palmitate (C16). The esterase was optimally active at 70 degrees C (over 15 min) and at pH 9. It is highly thermostable, with a residual activity greater than 80% after incubation at 50 degrees C for more than 10 h. The activity was not inhibited by 5 mM EDTA and PMSF, indicating the esterase is not a metalloenzyme and may contain a specific structure around the catalytic serine residue. In addition, it was stable for 1 h at 37 degrees C in 1% CHAPS and Triton X-100 but not stable in 1% Tween 20 or SDS.
ESTHER : Zhang_2003_Biotechnol.Lett_25_1463
PubMedSearch : Zhang_2003_Biotechnol.Lett_25_1463
PubMedID: 14514051
Gene_locus related to this paper: thete-LIPA

Title : Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells - Wang_2002_Brain.Res.Mol.Brain.Res_107_1
Author(s) : Wang R , Zhou J , Tang XC
Ref : Brain Research Mol Brain Res , 107 :1 , 2002
Abstract : The present studies investigated the effects of tacrine, a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on hydrogen peroxide (H(2)O(2))-induced apoptosis and the expression of apoptosis-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H(2)O(2) (100 microM) triggered typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies showed upregulated p53 and bax mRNA levels with H(2)O(2) treatment. The results were further confirmed at protein levels by immunocytochemistry with specific antibodies. Preincubation with tacrine significantly attenuated H(2)O(2)-induced injury, prevented the cells from apoptosis and attenuated H(2)O(2)-induced overexpression of bax and p53. The present findings suggest that tacrine exert significant protection against H(2)O(2)-induced apoptosis possibly through inhibiting expression of pro-apoptosis genes.
ESTHER : Wang_2002_Brain.Res.Mol.Brain.Res_107_1
PubMedSearch : Wang_2002_Brain.Res.Mol.Brain.Res_107_1
PubMedID: 12414117

Title : Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia - Wang_2002_Brain.Res_949_162
Author(s) : Wang L , Zhou J , Shao X , Tang X
Ref : Brain Research , 949 :162 , 2002
Abstract : The protective effects of huperzine A, a novel acetylcholinesterase inhibitor, on hypoxic-ischemic (HI) brain injury were investigated in neonatal rats. A unilateral HI brain injury was produced by the ligation of left common carotid artery followed by 1 h hypoxia with 7.7% oxygen in 7-day-old rat pups. After 5 weeks, HI brain injury in rat pups resulted in working memory impairments shown by increased escape latency in a water maze and reduced time spent in the target quadrant. The combination of common carotid artery ligation and exposure to a hypoxic environment caused the damage in the striatum, cortex, and hippocampus in the ipsilateral hemisphere, and the neuronal loss in the CA1 region. Huperzine A was administrated daily at the dose of 0.05 or 0.1 mg/kg i.p. for 5 weeks after HI injury. The significant protection against HI injury on behavior and neuropathology was produced by huperzine A at the dose of 0.1 mg/kg. These findings suggest that huperzine A might be beneficial in the treatment of hypoxic-ischemic encephalopathy in neonates.
ESTHER : Wang_2002_Brain.Res_949_162
PubMedSearch : Wang_2002_Brain.Res_949_162
PubMedID: 12213312

Title : Huperzine A attenuates cognitive deficits and hippocampal neuronal damage after transient global ischemia in gerbils - Zhou_2001_Neurosci.Lett_313_137
Author(s) : Zhou J , Zhang HY , Tang XC
Ref : Neuroscience Letters , 313 :137 , 2001
Abstract : The protective effects of huperzine A on transient global ischemia in gerbils were investigated. Five min of global ischemia in gerbils results in working memory impairments shown by increased escape latency in a water maze and reduced time spent in the target quadrant. These signs of dysfunction are accompanied by delayed degeneration of pyramidal hippocampal CA1 neurons and by decrease in acetylcholinesterase activity in the hippocampus. Subchronic oral administration of huperzine A (0.1 mg/kg, twice per day for 14 days) after ischemia significantly reduced the memory impairment, reduced neuronal degeneration in the CA1 region, and partially restored hippocampal choline acetyltransferase activity. The ability of huperzine A to attenuate memory deficits and neuronal damage after ischemia might be beneficial in cerebrovascular type dementia.
ESTHER : Zhou_2001_Neurosci.Lett_313_137
PubMedSearch : Zhou_2001_Neurosci.Lett_313_137
PubMedID: 11682146

Title : Huperzine A and donepezil protect rat pheochromocytoma cells against oxygen-glucose deprivation - Zhou_2001_Neurosci.Lett_306_53
Author(s) : Zhou J , Fu Y , Tang XC
Ref : Neuroscience Letters , 306 :53 , 2001
Abstract : Huperzine A (HupA) and donepezil, two novel selective acetylcholinesterase inhibitors available for Alzheimer's disease, were tested for their ability to alleviate injury from oxygen-glucose deprivation (OGD) in the rat pheochromocytoma line PC12 cells. OGD for 30 min triggered death in more than 50% of cells, along with major changes in morphology and biochemistry including elevated levels of lipid peroxide, superoxide disamutase activity and lactate. Cells pretreated for 2 h with HupA or donepezil showed improved survival and reduced biochemical and morphologic signs of toxicity (statistically significant over the range from 10 microM down to 1.0 and 0.1 microM, respectively). Our results indicated that HupA and donepezil protected PC12 cells against OGD-induced toxicity, most likely by alleviating disturbances of oxidative and energy metabolism.
ESTHER : Zhou_2001_Neurosci.Lett_306_53
PubMedSearch : Zhou_2001_Neurosci.Lett_306_53
PubMedID: 11403956

Title : Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning - Hu_2000_Proc.Natl.Acad.Sci.U.S.A_97_9543
Author(s) : Hu RM , Han ZG , Song HD , Peng YD , Huang QH , Ren SX , Gu YJ , Huang CH , Li YB , Jiang CL , Fu G , Zhang QH , Gu BW , Dai M , Mao YF , Gao GF , Rong R , Ye M , Zhou J , Xu SH , Gu J , Shi JX , Jin WR , Zhang CK , Wu TM , Huang GY , Chen Z , Chen MD , Chen JL
Ref : Proc Natl Acad Sci U S A , 97 :9543 , 2000
Abstract : The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life.
ESTHER : Hu_2000_Proc.Natl.Acad.Sci.U.S.A_97_9543
PubMedSearch : Hu_2000_Proc.Natl.Acad.Sci.U.S.A_97_9543
PubMedID: 10931946
Gene_locus related to this paper: human-ESD

Title : Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem\/progenitor cells - Zhang_2000_Genome.Res_10_1546
Author(s) : Zhang QH , Ye M , Wu XY , Ren SX , Zhao M , Zhao CJ , Fu G , Shen Y , Fan HY , Lu G , Zhong M , Xu XR , Han ZG , Zhang JW , Tao J , Huang QH , Zhou J , Hu GX , Gu J , Chen SJ , Chen Z
Ref : Genome Res , 10 :1546 , 2000
Abstract : Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation.
ESTHER : Zhang_2000_Genome.Res_10_1546
PubMedSearch : Zhang_2000_Genome.Res_10_1546
PubMedID: 11042152
Gene_locus related to this paper: human-LYPLA1

Title : Studies on the comprehensive control of babesiasis in cattle and buffaloes - Zhou_1997_Trop.Anim.Health.Prod_29_66S
Author(s) : Zhou J , Shen J , He G , Wang Q
Ref : Trop Anim Health Prod , 29 :66S , 1997
Abstract : To obtain a highly effective method for controlling babesiosis in cattle and buffalo, an epidemiological survey was carried out at Zuiyun village in Hubai Province. On the grounds of the epidemiological data, control measures which included preventive drugs and killing the vectors were devised. After two years of control no clinical cases of bovine babesiosis were found. The average number of ticks on cattle or buffalo decreased from 9-282 to 0-11.3. Good results were obtained in another epidemic area using this control method. These results indicated that this technique of controlling babesiosis is highly effective.
ESTHER : Zhou_1997_Trop.Anim.Health.Prod_29_66S
PubMedSearch : Zhou_1997_Trop.Anim.Health.Prod_29_66S
PubMedID: 9512748

Title : Speed of Ca2+ channel modulation by neurotransmitters in rat sympathetic neurons - Zhou_1997_J.Neurophysiol_77_2040
Author(s) : Zhou J , Shapiro MS , Hille B
Ref : Journal of Neurophysiology , 77 :2040 , 1997
Abstract : We have measured the onset and recovery speed of inhibition of N-type Ca2+ channels in adult rat superior cervical ganglion neurons by somatostatin (SS), norepinephrine (NE), and oxotremorine-M (oxo-M, a muscarinic agonist), using the whole cell configuration of the patch-clamp method with 5 mM external Ca2+. With a local perfusion pipette system that changed the solution surrounding the cell within 50 ms, we applied agonists at various times before a brief depolarization from -80 mV that elicited I(Ca). At concentrations that produced maximal inhibition, the onset time constants for membrane-delimited inhibition by SS (0.5 microM), NE (10 microM), and oxo-M (20 microM) were 2.1, 0.7, and 1.0 s, respectively. The time constants for NE inhibition depended only weakly on the concentration, ranging from 1.2 to 0.4 s in the concentration range from 0.5 to 100 microM. Inhibition by oxo-M (20 microM) through a different G-protein pathway that uses a diffusible cytoplasmic messenger had a time constant near 9 s. The recovery rate constant from membrane-delimited inhibition was between 0.09 and 0.18 s(-1), significantly higher than the intrinsic GTPase rate of purified G protein Go, suggesting that Ca2+ channels or other proteins in the plasma membrane act as GTPase activating proteins. We also measured the rate of channel reinhibition after relief by strong depolarizing prepulses, which should reflect the kinetics of final steps in the inhibition process. In the presence of different concentrations of NE, reinhibition was four to seven times faster than the onset of inhibition, indicating that the slowest step of inhibition must precede the binding of G protein to the channel. We propose a kinetic model for the membrane-delimited NE inhibition of Ca2+ channels. It postulates two populations of receptors with different affinities for NE, a single population of G proteins, and a single population of Ca2+ channels. This model closely simulated the time courses of onset and recovery of inhibition and reinhibition, as well as the dose-response curve for inhibition of Ca2+ channels by NE.
ESTHER : Zhou_1997_J.Neurophysiol_77_2040
PubMedSearch : Zhou_1997_J.Neurophysiol_77_2040
PubMedID: 9114253

Title : Selective disruption by protein kinases of G-protein-mediated Ca2+ channel modulation - Shapiro_1996_J.Neurophysiol_76_311
Author(s) : Shapiro MS , Zhou J , Hille B
Ref : Journal of Neurophysiology , 76 :311 , 1996
Abstract : 1. We studied the effects of phorbol-12-myristate, 13-acetate (PMA) on G-protein-mediated inhibition of Ca2+ channels by several neurotransmitters in rat superior cervical ganglion (SCG) sympathetic neurons, with the use of the whole cell patch clamp. PMA attenuated membrane-delimited inhibition of calcium currents (ICa) by norepinephrine (NE) and somatostatin by more than half, but did not attenuate inhibition by M1 muscarinic receptors, which use a diffusible cytoplasmic messenger. Inhibition of ICa by NE through pertussis-toxin-sensitive and -insensitive G proteins was equally attenuated by PMA. PMA enhanced ICa in about half the neurons (enhancement of 10 +/- 1%, mean +/- SE) and strongly reduced the holding current in 44 of 61 cells. 2. The M-type K+ current (IM) was not suppressed by PMA, and PMA did not attenuate inhibition of IM by muscarinic agonists, which is also via a diffusible cytoplasmic messenger. 3. Attenuation of NE and somatostatin inhibition by PMA was blocked by 1 microM staurosporine, a broad-spectrum protein kinase inhibitor. Tests with three inhibitors selective for distinct isoforms of protein kinase C (PKC) gave mixed results. PMA's actions were unaffected by 1 microM calphostin C, blocked by 500 nM bisindolylmaleimide, and unaffected by the pseudosubstrate inhibitor PKC19-36. 4. Thus we find that two membrane-delimited signaling pathways that inhibit ion channels in rat SCG neurons are strongly attenuated by PMA, but signaling pathway(s) that use a diffusible cytoplasmic messenger are not. We speculate that a nonstandard PKC isoform, perhaps PKC mu, mediates PMA actions.
ESTHER : Shapiro_1996_J.Neurophysiol_76_311
PubMedSearch : Shapiro_1996_J.Neurophysiol_76_311
PubMedID: 8836227

Title : [Influences of capsaicin and electroacupuncture at point on acetylcholine (ACh) release in the spinal dorsal horn of rats]. [Chinese] - Shi_1995_Chen.Tzu.Yen.Chiu_20_22
Author(s) : Shi J , Zhou J , Ouyang X , Zhong J , Guan X
Ref : Chen Tzu Yen Chiu Acupuncture Research , 20 :22 , 1995
Abstract : The dynamic changes of ACh activity in the spinal dorsal horn of rats were recorded by ACh ion selective microelectrodes. The influence of applying capsaicin to the spinal surface, administering anti-SP surum to the interior of dorsal horn, cutting off dorsal roots and electroacupuncturing at "points" on the ACh activity were studied. The results showed that electroacupuncture at "points" and capsaicin could facilitate ACh release of the spinal dorsal horn, it was fully inhibited by cutting off dorsal roots or obviously inhibited by administering anti-SP surum. The above results indicated that ACh might participate in the primary afferent of painsensation and acupuncture sensation as a neurotransmitter and SP might adjust the release of ACh in spinal dorsal horn.
ESTHER : Shi_1995_Chen.Tzu.Yen.Chiu_20_22
PubMedSearch : Shi_1995_Chen.Tzu.Yen.Chiu_20_22
PubMedID: 8706264