Guo Z

References (61)

Title : Integrated transcriptomics and metabolomics analyses reveal the aerobic biodegradation and molecular mechanisms of 2,3',4,4',5-pentachlorodiphenyl (PCB 118) in Methylorubrum sp. ZY-1 - Wu_2024_Chemosphere__141921
Author(s) : Wu Y , Zhu M , Ouyang X , Qi X , Guo Z , Yuan Y , Dang Z , Yin H
Ref : Chemosphere , :141921 , 2024
Abstract : 2,3',4,4',5-pentachlorodiphenyl (PCB 118), a highly representative PCB congener, has been frequently detected in various environments, garnering much attention across the scientific community. The degradation of highly chlorinated PCBs by aerobic microorganisms is challenging due to their hydrophobicity and persistence. Herein, the biodegradation and adaptation mechanisms of Methylorubrum sp. ZY-1 to PCB 118 were comprehensively investigated using an integrative approach that combined degradation performance, product identification, metabolomic and transcriptomic analyses. The results indicated that the highest degradation efficiency of 0.5 mg L(-1) PCB 118 reached 75.66% after seven days of inoculation when the bacteria dosage was 1.0 g L(-1) at pH 7.0. A total of eleven products were identified during the degradation process, including low chlorinated PCBs, hydroxylated PCBs, and ring-opening products, suggesting that strain ZY-1 degraded PCB 118 through dechlorination, hydroxylation, and ring-opening pathways. Metabolomic analysis demonstrated that the energy supply and redox metabolism of strain ZY-1 was disturbed with exposure to PCB 118. To counteract this environmental stress, strain ZY-1 adjusted both the fatty acid synthesis and purine metabolism. The analysis of transcriptomics disclosed that multiple intracellular and extracellular oxidoreductases (e.g., monooxygenase, alpha/beta hydrolase and cytochrome P450) participated in the degradation of PCB 118. Besides, active efflux of PCB 118 and its degradation intermediates mediated by multiple transporters (e.g., MFS transporter and ABC transporter ATP-binding protein) might enhance bacterial resistance against these substances. These discoveries provided the inaugural insights into the biotransformation of strain ZY-1 to PCB 118 stress, illustrating its potential in the remediation of contaminated environments.
ESTHER : Wu_2024_Chemosphere__141921
PubMedSearch : Wu_2024_Chemosphere__141921
PubMedID: 38588902
Gene_locus related to this paper: meted-c7c8u4 , meted-c7cge7 , meted-c7ci36

Title : Conocarpus lancifolius (Combretaceae): Pharmacological Effects, LC-ESI-MS\/MS Profiling and In Silico Attributes - Khurm_2023_Metabolites_13_
Author(s) : Khurm M , Guo Y , Wu Q , Zhang X , Ghori MU , Rasool MF , Imran I , Saqib F , Wahid M , Guo Z
Ref : Metabolites , 13 : , 2023
Abstract : In folklore medicine, Conocarpus lancifolius is used to treat various illnesses. The main objective of this study was a comprehensive investigation of Conocarpus lancifolius leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 +/- 0.15 microg GAE/mg) and flavonoids (47.54 +/- 0.45 microg QE/mg) with stronger antiradical effects through DPPH (IC(50) = 16.66 +/- 0.42 microg/mL), TAC (77.33 +/- 0.41 microg AAE/mg) and TRP (79.11 +/- 0.67 microg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC(50) = 110.13 +/- 1.71 microg/mL) activity through a modified Ellman's method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest.
ESTHER : Khurm_2023_Metabolites_13_
PubMedSearch : Khurm_2023_Metabolites_13_
PubMedID: 37512501

Title : A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs - Bogojevic_2023_J.Org.Chem__
Author(s) : Bogojevic O , Zhang Y , Wolff CD , Johnsen NK , Arevang C , Guo Z
Ref : J Org Chem , : , 2023
Abstract : Fatty acid esters of hydroxy fatty acids (FAHFAs), a newly discovered class of human endogenous complex lipids showing great promise for treating diabetes and inflammatory diseases, exist naturally in extremely low concentrations. This work reports a chemo-enzymatic approach for the comprehensive synthesis of phospholipids containing FAHFAs via sequential steps: hydratase-catalyzed hydration of unsaturated fatty acids to generate structurally diverse hydroxy fatty acids (HFAs), followed by the selective esterification of these HFAs with fatty acids mediated by secondary alcohol-specific Candida antarctica lipase A (CALA), resulting in the formation of a series of diverse FAHFA analogs. The final synthesis is completed through carbodiimide-based coupling of FAHFAs with glycerophosphatidylcholine. Optimal reaction conditions are identified for each step, and the substrate affinity of CALA, responsible for the catalytic mechanisms during FAHFA production, is evaluated through molecular docking. Compared to multistep lab-tedious chemical synthesis, this route, relying on natural building blocks and natural biocatalysts, is significantly facile, scalable, and highly selective, affording high yields (74-98 mol %) in each step for the construction of higher FAHFA-PC series (10/12/13-FAHFAs). The developed strategy aims to increase the availability of naturally occurring FAHFA species and provide the tools for the construction of versatile and novel analogs of FAHFA conjugates.
ESTHER : Bogojevic_2023_J.Org.Chem__
PubMedSearch : Bogojevic_2023_J.Org.Chem__
PubMedID: 38156819

Title : RNA m(6) A Methylation Suppresses Insect Juvenile Hormone Degradation to Minimize Fitness Costs in Response to A Pathogenic Attack - Guo_2023_Adv.Sci.(Weinh)__e2307650
Author(s) : Guo Z , Bai Y , Zhang X , Guo L , Zhu L , Sun D , Sun K , Xu X , Yang X , Xie W , Wang S , Wu Q , Crickmore N , Zhou X , Zhang Y
Ref : Adv Sci (Weinh) , :e2307650 , 2023
Abstract : Bioinsecticides and transgenic crops based on the bacterial pathogen Bacillus thuringiensis (Bt) can effectively control diverse agricultural insect pests, nevertheless, the evolution of resistance without obvious fitness costs has seriously eroded the sustainable use of these Bt products. Recently, it has been discovered that an increased titer of juvenile hormone (JH) favors an insect host (Plutella xylostella) to enhance fitness whilst resisting the Bt pathogen, however, the underlying regulatory mechanisms of the increased JH titer are obscure. Here, the involvement of N(6) -methyladenosine (m(6) A) RNA modification in modulating the availability of JH in this process is defined. Specifically, it is found that two m(6) A methyltransferase subunit genes, PxMettl3 and PxMettl14, repress the expression of a key JH-degrading enzyme JH esterase (JHE) to induce an increased JH titer, mitigating the fitness costs associated with a robust defense against the Bt pathogen. This study identifies an as-yet uncharacterized m(6) A-mediated epigenetic regulator of insect hormones for maintaining fitness during pathogen defense and unveils an emerging Bt resistance-related m(6) A methylation atlas in insects, which further expands the functional landscape of m(6) A modification and showcases the pivotal role of epigenetic regulation in host-pathogen interactions.
ESTHER : Guo_2023_Adv.Sci.(Weinh)__e2307650
PubMedSearch : Guo_2023_Adv.Sci.(Weinh)__e2307650
PubMedID: 38087901

Title : The impact of ABCB1 and CES1 polymorphisms on the safety of dabigatran in patients with non-valvular atrial fibrillation - Zhu_2022_BMC.Cardiovasc.Disord_22_481
Author(s) : Zhu Z , Qian C , Su C , Tao H , Mao J , Guo Z , Zhu X , Pan J
Ref : BMC Cardiovasc Disord , 22 :481 , 2022
Abstract : BACKGROUND: This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF). METHODS: We conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up. RESULTS: Eighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P = 0.013). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 SNP c.2482-2236G > A (rs4148738) was associated with major bleeding events in the addictive model (P = 0.046, OR = 3.29) and dominant model (P = 0.040, OR = 8.17). Additionally, the ABCB1 SNP c.3435 C > T (rs1045642) was associated with the incidence of major bleeding events in the addictive model (P = 0.043, OR = 3.34) and dominant model (P = 0.046, OR = 7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events. CONCLUSION: Our results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.
ESTHER : Zhu_2022_BMC.Cardiovasc.Disord_22_481
PubMedSearch : Zhu_2022_BMC.Cardiovasc.Disord_22_481
PubMedID: 36368930

Title : Ancestral sequence reconstruction and spatial structure analysis guided alteration of longer-chain substrate catalysis for Thermomicrobium roseum lipase - Ma_2022_Enzyme.Microb.Technol_156_109989
Author(s) : Ma D , Xin Y , Guo Z , Shi Y , Zhang L , Li Y , Gu Z , Ding Z , Shi G
Ref : Enzyme Microb Technol , 156 :109989 , 2022
Abstract : Thermomicrobium roseum DSM 5159 lipase (TrLip) is an enzyme with marked thermostability and excellent solvent resistance. However, TrLip reveals relatively high catalytic efficiency on short-chain substrates but poor activity against mid-long or long-chain fatty acids, which would limit its industrial application. In this study, ancestral sequence reconstruction (ASR), a common engineering tool for the evolutionary history of protein families, was employed to identify the natural evolutionary trends within 5 A around the catalytic center. Two mutation libraries were constructed, one for the catalytic center and the other for the pocket flexibility. A total of 69 mutants were expressed and purified in the Escherichia coli expression system to determine the kinetic parameters, and W219G could significantly enhance the catalytic efficiency against substrates with 12-, 16- and 18-carbon side chains. In addition, the double mutant W219G/F265M could further catalyze the breakdown of the above three substrates up to 6.34-, 4.21- and 4.86-folds compared to the wild-type TrLip, while the initial pH and thermostability were maintained. Through bioinformatics analysis, the significantly enhanced catalytic efficiency against longer-side chain substrates should be associated with the reduction of steric hindrance. With the outstanding stability and the promoted activity, TrLip should be of great potential in chemical and food industry.
ESTHER : Ma_2022_Enzyme.Microb.Technol_156_109989
PubMedSearch : Ma_2022_Enzyme.Microb.Technol_156_109989
PubMedID: 35134708
Gene_locus related to this paper: therp-b9l0x7

Title : Simultaneous measurement of six biomarkers of dichlorvos in blood by ultra performance liquid chromatography-quadrupole\/electrostatic field orbitrap mass spectrometry - Li_2022_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1208_123381
Author(s) : Li P , Zhang C , Guo Z , Wei Z , Yun K , Liu Y
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1208 :123381 , 2022
Abstract : A protocol was developed, via a data-dependent high-resolution tandem mass spectrometry (ddHRMS/MS), to detect six biomarkers of dichlorvos in its metabolites and blood adducts of butyrylcholinesterase and albumin without using standard synthetic peptides. Firstly, the adducts of dimethoxy phosphonate (DMP-BChE) and the aged adducts of methoxy phosphonate (MxP-BChE) were isoloated by immunomagnetic separation (IMS), and then digested to DMP-nonapeptide and MxP-nonapeptide by pepsin. The dichlorvos and its metabolites (Trimethyl phosphate, Dimethyl phosphate) were analyzed in the supernatant of IMS treatment after protein precipitation. The precipitate was digested by pronase to phosphorylated tyrosine (DMP-Tyr), which were quantified by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry (UPLC-MS). The linearity of detector response of all biomarkers was studied in their respective ranges, and the correlation coefficients (R(2)) were all greater than 0.9981. The limits of detection (LOD) and limits of quantification (LOQ) were 0.2-10 ng/mL and 0.5-20 ng/mL, respectively. The recoveries of the six biomarkers were 78.6-110.0 %, matrix effect were 64.1-106.8 %. Inter- and intra-assay precision had coefficients of variation of >=13.2 % and >=9.7 %, respectively. In addition, MxP- BChE, DMP-Tyr, TMP, DMP and DDVP were detected in the blood of three cases who died from DDVP poisoning, but DMP- BChE was not detected in all of them, which may be caused by the instability of DMP- BChE and its easy aging to form MxP-BCHE.
ESTHER : Li_2022_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1208_123381
PubMedSearch : Li_2022_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1208_123381
PubMedID: 35932694

Title : A bi-enzymatic cascade pathway towards optically pure FAHFAs - Zhang_2021_Chembiochem__
Author(s) : Zhang Y , Eser BE , Guo Z
Ref : Chembiochem , : , 2021
Abstract : Recently discovered endogenous mammalian lipids fatty acid esters of hydroxy fatty acids (FAHFAs), proved to have anti-inflammatory and anti-diabetic effects. Due to their extremely low abundancies in vivo , forging a feasible scenario for FAHFA synthesis is critical for their use in uncovering biological mechanism or clinical trials. Here, we showcase a fully enzymatic approach, a novel in vitro bi-enzymatic cascade system, enabling an effective conversion of nature-abundant fatty acids into FAHFAs. Two hydratases from L. acidophilus were used for converting unsaturated fatty acids to various enantiomeric hydroxy fatty acids, followed by esterification with another fatty acid catalyzed by C. antarctica lipase A (CALA). Various FAHFAs were synthesized in a semi-preparative scale using this bi-enzymatic approach in a one-pot two-step operation mode. In all, we demonstrate that hydratase-CALA system offers a promising route for synthesis of optically pure structure-diverse FAHFAs.
ESTHER : Zhang_2021_Chembiochem__
PubMedSearch : Zhang_2021_Chembiochem__
PubMedID: 33792147

Title : 3D-Printed, Portable, Fluorescent-Sensing Platform for Smartphone-Capable Detection of Organophosphorus Residue Using Reaction-Based Aggregation Induced Emission Luminogens - Jiao_2021_ACS.Sens__
Author(s) : Jiao Z , Guo Z , Huang X , Yang J , Huang J , Liu Y , Liu G , Zhang P , Song C , Tang BZ
Ref : ACS Sens , : , 2021
Abstract : Development of an easy-to-use, low-cost, household device can help the consumer quickly identify an organophosphorus (OP) residue concentration level. In this work, we demonstrate a 3D-printed, portable, fluorescent-sensing platform for smartphone-capable detection of OPs in vegetables. For development of the proposed device, we utilize the smartphone for capturing the strong thiol-activated fluorescence, which was produced by hydrolysis of OPs in the presence of alkali. The thiol-responsive AIEgen (maleimide-functionalized tetraphenylethylene) was non-emissive in both solution and the solid state but could be readily lighted up by the click addition of thiol to its MI pendant. An android application "Detection" has been developed on the basis of the gray value to analyze the different concentration levels of OPs in vegetable samples. The gray value was linearly related with the concentration of five kinds of organophosphorus residue, ranging from 0 to 20 microg/mL. It was also applied for determination of OPs residue in the leaves of cowpea, celery, and Chinese cabbage. Different from acetylcholinesterase enzyme-based sensors for poor stability under high temperature, the proposed method was a direct detection method for OPs and can be used for rapid monitoring of OPs residue concentration levels before LC-MS analysis.
ESTHER : Jiao_2021_ACS.Sens__
PubMedSearch : Jiao_2021_ACS.Sens__
PubMedID: 34406746

Title : Monoterpene indole alkaloids with acetylcholinesterase inhibitory activity from the leaves of Rauvolfia vomitoria - Zhan_2020_Bioorg.Chem_102_104136
Author(s) : Zhan G , Miao R , Zhang F , Chang G , Zhang L , Zhang X , Zhang H , Guo Z
Ref : Bioorg Chem , 102 :104136 , 2020
Abstract : Seventeen monoterpene indole alkaloids, including seven new alkaloids (1-7) and ten known analogues (8-17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C(22) yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2-3) and affinisine oxindole (5-6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2-3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1-17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 muM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC(50) value of 16.39 +/- 1.41 muM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were weak inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD.
ESTHER : Zhan_2020_Bioorg.Chem_102_104136
PubMedSearch : Zhan_2020_Bioorg.Chem_102_104136
PubMedID: 32738570

Title : Lipase catalysis of alpha-linolenic acid-rich medium- and long-chain triacylglycerols from perilla oil and medium-chain triacylglycerols with reduced by-products - Huang_2020_J.Sci.Food.Agric_100_4565
Author(s) : Huang Z , Cao Z , Guo Z , Chen L , Wang Z , Sui X , Jiang L
Ref : J Sci Food Agric , 100 :4565 , 2020
Abstract : BACKGROUND: Medium- and long- chain triacylglycerols (MLCTs) are functional structural lipids that can provide the human body with essential fatty acids and a faster energy supply. This study aimed to prepare MLCTs rich in alpha-linolenic by enzymatic interesterification of perilla oil and medium-chain triacylglycerols (MCTs), catalyzed by Lipozyme RM IM, Lipozyme TL IM, Lipozyme 435, and Novozyme 435 respectively. RESULTS: The effects of lipase loading, concentration of MCTs, reaction temperature, and reaction time on the yield of MLCTs were investigated. It was found that the reaction achieved more than a 70% yield of MLCTs in triacylglycerols under the conditions of 400 g kg(-1) MCTs and 60 g kg(-1) lipase loading after equilibrium. A novel two-stage deodorization was also applied to purify the interesterification products. The triacylglycerols reach over 97% purity in the products with significant removal (P < 0.05) of the free fatty acids, and the trans fatty acids were strictly controlled at below 1%. There was more than 40% alpha-linolenic in the purified products, with long-chain fatty acids mostly occupying the desired sn-2 position in acylglycerols, which are more active in hydrolysis. CONCLUSION: A series of novel alpha-linolenic acid-rich medium- and long-chain triacylglycerols was prepared. Under appropriate reaction conditions, the yield of MLCTs in triacylglycerols was above 70%. A novel two-stage deodorization can be used to promote the elimination of free fatty acids and limit the generation of trans fatty acids.
ESTHER : Huang_2020_J.Sci.Food.Agric_100_4565
PubMedSearch : Huang_2020_J.Sci.Food.Agric_100_4565
PubMedID: 32419135

Title : Monoterpene indole alkaloids with diverse skeletons from the stems of Rauvolfia vomitoria and their acetylcholinesterase inhibitory activities - Zhan_2020_Phytochemistry_177_112450
Author(s) : Zhan G , Miao R , Zhang F , Hao X , Zheng X , Zhang H , Zhang X , Guo Z
Ref : Phytochemistry , 177 :112450 , 2020
Abstract : Nine undescribed monoterpene indole alkaloids, rauvomitorine A-I, including an unprecedented C-9-methoxymethylene-sarpagine framework alkaloid, two rare suaveoline framework type alkaloids, and six yohimbine framework type alkaloids, as well as eleven known alkaloids, were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). The structures of the unreported alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis with Cu Kalpha radiation. Rauvomitorine A with an unreported framework type represents the first example of C-9-methoxymethylene-sarpagine alkaloids and its plausible biosynthetic pathway was proposed. All the isolated alkaloids were evaluated their acetylcholinesterase inhibitory (AChE) activities and cytotoxicity against five cancer cell lines and some of them exhibited potential anti-AChE activities with IC50 values ranging from 49.76 to 186.62 muM. Importantly, this is the first report of the AChE inhibitory activities on suaveoline framework type alkaloids, suggesting this type of alkaloids may be valuable sources for the discovery of AChE inhibitory agents. A preliminary structure-activity relationship for AChE inhibitory activities of the isolated alkaloids is also discussed, providing some clues to designing lead compounds for AChE inhibitors.
ESTHER : Zhan_2020_Phytochemistry_177_112450
PubMedSearch : Zhan_2020_Phytochemistry_177_112450
PubMedID: 32580106

Title : Peraksine derivatives with potential anti-inflammatory activities from the stems of Rauvolfia vomitoria - Zhan_2020_Fitoterapia__104704
Author(s) : Zhan G , Miao R , Zhang F , Hao Y , Zhang Y , Khurm M , Zhang X , Guo Z
Ref : Fitoterapia , :104704 , 2020
Abstract : Five new peraksine derivatives rauvomine C-G (1-5) along with four known analogues (6-9) were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). Structural determinations of the new monoterpene indole alkaloids were elucidated via comprehensive spectroscopic analyses and ECD calculations. Rauvomine C (1) with an unprecedented framework type represents the first example of C(18) peraksine-type nor-monoterpene indole alkaloid featuring a chlorine atom at C-16 and its plausible biosynthetic pathway was also proposed. All the isolates were evaluated for their anti-inflammatory, cytotoxic, and acetylcholinesterase inhibitory activities. Among them, the new framework alkaloid rauvomine C (1) showed significant anti-inflammatory activities on NO production in LPS-induced RAW264.7 mouse macrophages with IC(50) value of 10.76 muM. Additionally, peraksine-type alkaloids featuring pyran ring (5, 8, and 9) exhibited potential anti-inflammatory activities with IC(50) values ranging from 17.52 to 20.99 muM.
ESTHER : Zhan_2020_Fitoterapia__104704
PubMedSearch : Zhan_2020_Fitoterapia__104704
PubMedID: 32827693

Title : Rhizomucor miehei lipase-catalysed synthesis of cocoa butter equivalent from palm mid-fraction and stearic acid: Characteristics and feasibility as cocoa butter alternative - Huang_2020_Food.Chem__128407
Author(s) : Huang Z , Guo Z , Xie D , Cao Z , Chen L , Wang H , Jiang L , Shen Q
Ref : Food Chem , :128407 , 2020
Abstract : In this study, cocoa butter equivalents (CBEs) were prepared through enzymatic interesterification of palm mid-fraction (PMF) with stearic acid (SA). The reaction process parameters were experimented and the performance of the product was analysed. PMF and stearic acid (at a mass ratio of 1:2) were catalysed by 80 g kg(-1) enzyme loading of Lipozyme RM IM fromRhizomucor mieheiat 60 degreeC for 120 min. The yield of the CBE product was more than 92%, and the CBE resembled cocoa butter (CB) in terms of its triacylglycerol composition. The hardness of the CBE product was higher than that of CB at different storage temperatures, but this difference was not obvious at 25 degreeC. The polymorphic structures and SFC curve of the CBE were similar to those of the CB. In addition, the CBE could be mixed with CB in any ratio without an obvious eutectic phenomena. Up to 40% CBE could be added to CB without significantly affecting the thermodynamic properties of CB. Thus, replacing CB with the CBE product is feasible.
ESTHER : Huang_2020_Food.Chem__128407
PubMedSearch : Huang_2020_Food.Chem__128407
PubMedID: 33129620

Title : Carboxylesterase 2 and Intestine Transporters Contribute to the Low Bioavailability of Allisartan, a Prodrug of Exp3174 for Hypertension Treatment in Humans - Li_2019_Drug.Metab.Dispos_47_843
Author(s) : Li X , Sun J , Guo Z , Zhong D , Chen X
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 47 :843 , 2019
Abstract : Exp3174 is an active metabolite of losartan for the treatment of hypertension. Allisartan (ALS3) is a marketed ester prodrug of Exp3174 to reduce bioavailability variation of losartan in China. However, ALS3 exhibited a lower oral absorption than losartan in humans. In this study, the enzymes and transporters involved in ALS3 and Exp3174 disposition were investigated to clarify the mechanisms. ALS3 underwent extensive hydrolysis to Exp3174 in S9 of Caco-2 cells, human intestine microsomes (HIM), recombinant carboxylesterase (rCES) 1, and rCES2. ALS3 exhibited similar affinity in HIM and rCES2 with K m values of 6.92 and 6.77 muM, respectively, indicating that ALS3 is mainly hydrolyzed to Exp3174 in human intestine by CES2. Transport assays of ALS3 and Exp3174 suggested that ALS3 and Exp3174 are substrates of P-glycoprotein, breast cancer resistance protein, and multidrug resistance protein 2 with poor permeability. Organic anion-transporting polypeptide 2B1 showed higher affinity and clearance toward ALS3 (K m 0.75 muM and intrinsic clearance 215 mul/min/mg) than those of Exp3174 (K m 7.85 muM and intrinsic clearance 16.1 mul/min/mg), indicating that ALS3 is preferred to be uptaken into intestinal epithelia. Hydrolysis of ALS3 was increased from approximately 30% to 55% in CES2-transfected human embryonic kidney 293-OATP2B1 cells, indicating the possible interplay between OATP2B1 and CES2. The influx and efflux of ALS3 across Caco-2 cells increased the potential of ALS3 hydrolysis to Exp3174, and the produced Exp3174 was rapidly pumped out, which led to undetectable ALS3 and Exp3174 in basolateral (receiver) side in Caco-2 cells. Overall, our study provided supportive evidences that the interplay between CES2 and transporters in intestine contributes to the low bioavailability of ALS3 in humans.
ESTHER : Li_2019_Drug.Metab.Dispos_47_843
PubMedSearch : Li_2019_Drug.Metab.Dispos_47_843
PubMedID: 31076412

Title : Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2 - Yu_2019_Int.J.Mol.Sci_20_
Author(s) : Yu M , Zhang L , Liu Y , Liu D , Guo Z
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets alpha/beta-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2.
ESTHER : Yu_2019_Int.J.Mol.Sci_20_
PubMedSearch : Yu_2019_Int.J.Mol.Sci_20_
PubMedID: 31035455
Gene_locus related to this paper: human-ABHD2

Title : Fabricating an Acetylcholinesterase Modulated UCNPs-Cu(2+) Fluorescence Biosensor for Ultrasensitive Detection of Organophosphorus Pesticides-Diazinon in Food - Wang_2019_J.Agric.Food.Chem_67_4071
Author(s) : Wang P , Li H , Hassan MM , Guo Z , Zhang ZZ , Chen Q
Ref : Journal of Agricultural and Food Chemistry , 67 :4071 , 2019
Abstract : In this study, a highly sensitive upconversion fluorescence (FL) biosensor was developed for the detection of organophosphorus pesticides (OPs) based on an acetylcholinesterase (AChE) modulated FL "off-on-off" strategy. The luminescence of synthesized UCNPs could be quenched strongly by Cu(2+) due to an energy transfer effect. Upon addition of AChE and acetylthiocholine (ATCh), the enzymatic hydrolysate (thiocholine) could seize Cu(2+) from UCNPs-Cu(2+) mixture, resulting in the quenched FL triggered on. OPs could irreversibly impede the activity of AChE, which caused the formation of thiocholine to decrease, thus, reduced the recovery of FL. Under the optimum conditions, a linear detection range from 0.1 to 50 ng/mL was achieved for the representative OPs (diazinon) with LOD of 0.05 ng/mL. Furthermore, the ability of the biosensor to detect OPs was also confirmed in adulterated environmental and agricultural samples. In validation analysis, the proposed sensor showed satisfactory results ( p > 0.05) with GC-MS.
ESTHER : Wang_2019_J.Agric.Food.Chem_67_4071
PubMedSearch : Wang_2019_J.Agric.Food.Chem_67_4071
PubMedID: 30888170

Title : Neuroprotective effects of matrine on scopolamine-induced amnesia via inhibition of AChE\/BuChE and oxidative stress - Sun_2019_Metab.Brain.Dis_34_173
Author(s) : Sun K , Bai Y , Zhao R , Guo Z , Su X , Li P , Yang P
Ref : Metabolic Brain Disease , 34 :173 , 2019
Abstract : The present study was designed to evaluate the effects of matrine (MAT) on scopolamine (SCOP)-induced learning and memory impairment. After successive oral administration of MAT to mice for three days at doses of 0.4, 2, and 10 mg/kg, we assessed improvements in learning and memory and investigated the mechanism of action of SCOP-induced amnesia. Donepezil at a dose of 3 mg/kg was used as a standard memory enhancer. MAT significantly improved SCOP-induced learning and memory impairment in novel object recognition and Y-maze tests at doses of 0.4, 2, and 10 mg/kg. Furthermore, MAT inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and decreased oxidative stress in the brain, as evidenced by increased total antioxidant capacity, total superoxide dismutase levels, and catalase activities as well as decreased malondialdehyde levels. Additionally, there was a significant negative correlation between the percentage of spontaneous alternation in the Y maze and AChE activity in the cortex and hippocampus. MAT ameliorated SCOP-induced amnesia by the inhibition of both AChE/BuChE activities and oxidative stress. This study provides further evidence to encourage the development of MAT as a drug for the prevention or treatment of Alzheimer's disease.
ESTHER : Sun_2019_Metab.Brain.Dis_34_173
PubMedSearch : Sun_2019_Metab.Brain.Dis_34_173
PubMedID: 30406376

Title : Genome-wide association studies reveal genetic loci associated with plasma cholinesterase activity in ducks - Xu_2019_Anim.Genet_50_287
Author(s) : Xu Y , Liu H , Jiang Y , Fan W , Hu J , Zhang Y , Guo Z , Xie M , Huang W , Liu X , Zhou Z , Hou S
Ref : Anim Genet , 50 :287 , 2019
Abstract : Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non-liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck x mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome-wide association studies were conducted. A region of about 1.5 Mb (21.8-23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (-logP = 21.45) and 8 weeks (-logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity.
ESTHER : Xu_2019_Anim.Genet_50_287
PubMedSearch : Xu_2019_Anim.Genet_50_287
PubMedID: 30994195
Gene_locus related to this paper: anapl-BCHE

Title : Inhibiting Abeta toxicity in Alzheimer's disease by a pyridine amine derivative - Zhu_2019_Eur.J.Med.Chem_168_330
Author(s) : Zhu Z , Yang T , Zhang L , Liu L , Yin E , Zhang C , Guo Z , Xu C , Wang X
Ref : Eur Journal of Medicinal Chemistry , 168 :330 , 2019
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder with no radical therapy. Aggregation of amyloid beta-peptide (Abeta) induced by various factors is associated with pathogenesis of AD. A pyridine amine derivative, 3-bis(pyridin-2-ylmethyl)aminomethyl-5-hydroxybenzyltriphenylphosphonium bromide (PAT), is synthesized. The inhibition of self- and metal-induced Abeta aggregation by PAT is confirmed by thioflavine T fluorescence, circular dichroism spectroscopy, and TEM. Western blot, RT-PCR and fluorescence imaging indicate that PAT can alleviate the Abeta-induced paralysis, reduce the production of ROS, and protect the mitochondrial function in transgenic C. elegans. Genetic analyses indicate that heat shock protein is involved in the alleviation of Abeta toxicity. PAT also inhibits the activity of acetylcholinesterase in C. elegans. Morris water maze test shows that the memory and cognitive ability of APP/PS1 AD model mice are significantly improved by PAT. Both in vitro and in vivo studies demonstrate that PAT is effective in counteracting Abeta toxicity and ameliorating cognitive functions in AD mice, and therefore a potential lead compound of anti-AD drugs.
ESTHER : Zhu_2019_Eur.J.Med.Chem_168_330
PubMedSearch : Zhu_2019_Eur.J.Med.Chem_168_330
PubMedID: 30826509

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

Title : Amide Synthesis via Aminolysis of Ester or Acid with an Intracellular Lipase - Zeng_2018_ACS.Catal_8_8856
Author(s) : Zeng S , Liu J , Anankanbil S , Chen M , Guo Z , Adams JP , Snajdrova R , Li Z
Ref : ACS Catal , 8 :8856 , 2018
Abstract : A unique lipase (SpL) from Sphingomonas sp. HXN-200 was discovered as the first intracellular enzyme for the aminolysis of ester or acid to produce amide. Reactions of a series of esters and amines with SpL gave the corresponding amides 3a-g in high yield with high activity. SpL also showed high enantioselectivity and high activity for enantioselective ester aminolysis, producing amides (R)-3h-j in high ee from the corresponding racemic ester or amine. Moreover, SpL was found to be highly active for the aminolysis of carboxylic acid, which was generally considered infeasible with the known aminolysis enzymes. The aminolysis of several carboxylic acids afforded the corresponding amides 3a, 3d, 3k, 3l, and 3n in good yield. The intracellular SpL was expressed in Escherichia coli cells to give an efficient whole-cell biocatalyst for amide synthesis. Remarkably, high catalytic activity was observed in the presence of water at 2-4% (v/v) for free enzyme and 16% (v/v) for whole cells, respectively. Accordingly, E. coli (SpL) wet cells were used as easily available and practical catalysts for the aminolysis of ester or acid, producing a group of useful and valuable amides in high concentration (up to 103 mM) and high yield. The newly discovered intracellular SpL with unique properties is a promising catalyst for green and efficient synthesis of amides.
ESTHER : Zeng_2018_ACS.Catal_8_8856
PubMedSearch : Zeng_2018_ACS.Catal_8_8856
PubMedID:
Gene_locus related to this paper: sphmc-SpL

Title : Genetically engineered cerebral organoids model brain tumor formation - Bian_2018_Nat.Methods_15_631
Author(s) : Bian S , Repic M , Guo Z , Kavirayani A , Burkard T , Bagley JA , Krauditsch C , Knoblich JA
Ref : Nat Methods , 15 :631 , 2018
Abstract : Brain tumors are among the most lethal and devastating cancers. Their study is limited by genetic heterogeneity and the incompleteness of available laboratory models. Three-dimensional organoid culture models offer innovative possibilities for the modeling of human disease. Here we establish a 3D in vitro model called a neoplastic cerebral organoid (neoCOR), in which we recapitulate brain tumorigenesis by introducing oncogenic mutations in cerebral organoids via transposon- and CRISPR-Cas9-mediated mutagenesis. By screening clinically relevant mutations identified in cancer genome projects, we defined mutation combinations that result in glioblastoma-like and central nervous system primitive neuroectodermal tumor (CNS-PNET)-like neoplasms. We demonstrate that neoCORs are suitable for use in investigations of aspects of tumor biology such as invasiveness, and for evaluation of drug effects in the context of specific DNA aberrations. NeoCORs will provide a valuable complement to the current basic and preclinical models used to study brain tumor biology.
ESTHER : Bian_2018_Nat.Methods_15_631
PubMedSearch : Bian_2018_Nat.Methods_15_631
PubMedID: 30038414

Title : Activity-dependent Synaptic Recruitment of Neuroligin 1 in Spinal Dorsal Horn Contributed to Inflammatory Pain - Zhao_2018_Neurosci_388_1
Author(s) : Zhao JY , Duan XL , Yang L , Liu JP , He YT , Guo Z , Hu XD , Suo ZW
Ref : Neuroscience , 388 :1 , 2018
Abstract : Neuroligin 1 (NLGN1), a cell adhesion molecule present at excitatory glutamatergic synapses, has been shown to be critical for synaptic specialization and N-methyl-d-aspartate (NMDA)-subtype glutamate receptor-dependent synaptic plasticity. Whether and how NLGN1 is engaged in nociceptive behavioral sensitization remains largely unknown. In this study, we found an activity-dependent regulation of NLGN1 synaptic expression in pain-related spinal cord dorsal horns of mice. The enhancement of neuronal activity by pharmacological activation of NMDA receptor (NMDAR) or removal of GABAergic inhibition in intact mice significantly increased NLGN1 concentration at synaptosomal membrane fraction. Intraplantar injection of complete Freund's adjuvant (CFA) also increased the NLGN1 expression at synapses. NMDAR might act through Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and Src-family protein tyrosine kinase member Fyn to induce the synaptic redistribution of NLGN1. We also found that one of the important roles of NLGN1 was to facilitate the clustering of NMDAR at synapses. The NLGN1-targeting siRNA suppressed the synaptic expression of GluN2B-containing NMDAR in CFA-injected mice and meanwhile, attenuated the inflammatory mechanical allodynia and thermal hypersensitivity. These data suggested that tissue injury-induced synaptic redistribution of NLGN1 was involved in the development of pain hypersensitivity through facilitating the synaptic incorporation of NMDARs.
ESTHER : Zhao_2018_Neurosci_388_1
PubMedSearch : Zhao_2018_Neurosci_388_1
PubMedID: 30049666

Title : Acetylcholinesterase Is a Potential Biomarker for a Broad Spectrum of Organic Environmental Pollutants - Fu_2018_Environ.Sci.Technol_52_8065
Author(s) : Fu H , Xia Y , Chen Y , Xu T , Xu L , Guo Z , Xu H , Xie HQ , Zhao B
Ref : Environ Sci Technol , 52 :8065 , 2018
Abstract : Acetylcholinesterase (AChE, EC 3.1.1.7) is a classical biomarker for monitoring contamination and intoxication of organophosphate (OP) and carbamate pesticides. In addition to these classical environmental AChE inhibitors, other organic toxic substances have been found to alter AChE activity in various species. These emerging organic AChE disruptors include certain persistent organic pollutants (POPs), polycyclic aromatic hydrocarbons (PAHs), and wildly used chemicals, most of which have received considerable public health concern in recent years. It is necessary to re-evaluate the environmental significances of AChE in terms of these toxic substances. Therefore, the present review is aiming to summarize correlations of AChE activity of certain organisms with the level of the contaminants in particular habitats, disruptions of AChE activity upon treatment with the emerging disruptors in vivo and in vitro, and action mechanisms underlying the effects on AChE. Over 40 chemicals belonging to six main categories were reviewed, including 12 POPs listed in the Stockholm Convention. AChE activity in certain organisms has been found to be well correlated with the contamination level of certain persistent pesticides and PAHs in particular habitats. Moreover, it has been documented that most of the listed toxic chemicals could inhibit AChE activity in diverse species ranging from invertebrates to mammals. Besides directly inactivating AChE, the mechanisms in terms of interference with the biosynthesis have been recognized for some emerging AChE disruptors, particularly for dioxins. The collected evidence suggests that AChE could serve as a potential biomarker for a diverse spectrum of organic environmental pollutants.
ESTHER : Fu_2018_Environ.Sci.Technol_52_8065
PubMedSearch : Fu_2018_Environ.Sci.Technol_52_8065
PubMedID: 29995397

Title : Rationale behind the near-ideal catalysis of Candida antarctica lipase A (CAL-A) for highly concentrating omega-3 polyunsaturated fatty acids into monoacylglycerols - He_2017_Food.Chem_219_230
Author(s) : He Y , Li J , Kodali S , Chen B , Guo Z
Ref : Food Chem , 219 :230 , 2017
Abstract : Dramatic decline in the quality and quantity of omega-3 PUFAs from marine resource demands new environmental-friendly technology to produce high quality omega-3 PUFAs concentrates in a better bioavailable form. Accordingly this work demonstrated an exceptionally highly efficient non-aqueous approach that non-regiospecific and non omega-3 PUFAs preferential Candida antarctica lipase A (CAL-A), functioning as a near-ideal biocatalyst, is capable to directly concentrate omega-3 PUFAs from 20% to 30% in oils to up to >90% in monoacylglycerols form through one step reaction. The rationale behind the experimental observation is justified and the catalytic property and specificity of an ideal enzyme tackling this task are defined. High selectivity and efficiency, excellent reusability of biocatalyst, general applicability for concentrating omega-3 PUFAs from both fish and microalgae oils, simple process for product recovery (e.g. by short path distillation), make this novel approach a highly industrially relevant and with potential application in food and drug industries.
ESTHER : He_2017_Food.Chem_219_230
PubMedSearch : He_2017_Food.Chem_219_230
PubMedID: 27765222
Gene_locus related to this paper: canan-lipasA

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

Title : Chlorogenic Acid Prevents Alcohol-induced Brain Damage in Neonatal Rat - Guo_2017_Transl.Neurosci_8_176
Author(s) : Guo Z , Li J
Ref : Transl Neurosci , 8 :176 , 2017
Abstract : The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells.
ESTHER : Guo_2017_Transl.Neurosci_8_176
PubMedSearch : Guo_2017_Transl.Neurosci_8_176
PubMedID: 29318034

Title : Production of new human milk fat substitutes by enzymatic acidolysis of microalgae oils from Nannochloropsis oculata and Isochrysis galbana - He_2017_Bioresour.Technol_238_129
Author(s) : He Y , Qiu C , Guo Z , Huang J , Wang M , Chen B
Ref : Bioresour Technol , 238 :129 , 2017
Abstract : Human milk fat substitutes (HMFs) with four kinds of n-3 fatty acid for infant formula were firstly synthesized using triacylglycerols (TAGs) from Nannochloropsis oculata rich in PA at the sn-2 position and free fatty acids (FFAs) from Isochrysis galbana rich in n-3 polyunsaturated fatty acids (n-3 PUFAs-ALA/SDA/DHA) via solvent-free acidolysis with Novozym 435, Lipozyme 435, TL-IM and RM-IM as biocatalysts. The results show that the resulting HMFs contain total n-3 PUFA of 13.92-17.12% and PA of 59.38-68.13% at the sn-2 position under the optimal conditions (mole ratio FFAs/TAG 3:1, 60 degC (Novozym 435 and Lipozyme TL-IM) and 50 degC (Lipozyme 435 and RM-IM), lipase loading 10%, reaction time 24h). Moreover, among the tested enzymes, Lipozyme 435, TL-IM, and RM-IM display the fatty acid selectivity towards SDA, LA and ALA, and OA, respectively. Overall, the examined lipases are promising biocatalysts for producing high-value microalgal HMFs in a cost-effective manner.
ESTHER : He_2017_Bioresour.Technol_238_129
PubMedSearch : He_2017_Bioresour.Technol_238_129
PubMedID: 28433900

Title : The near-ideal catalytic property of Candida antarctica lipase A to highly concentrate n-3 polyunsaturated fatty acids in monoacylglycerols via one-step ethanolysis of triacylglycerols - He_2016_Bioresour.Technol_219_466
Author(s) : He Y , Li J , Kodali S , Chen B , Guo Z
Ref : Bioresour Technol , 219 :466 , 2016
Abstract : Declining quantity/quality of available n-3 polyunsaturated fatty acids (n-3 PUFAs) resources demand innovative technology to concentrate n-3 PUFAs from low quality oils into value-added products/health-beneficial ingredients rich in n-3 PUFAs. This work proposed the catalytic property and specificity of an ideal enzyme required to tackle this task and identified Candida antarctica lipase A (CAL-A) is such a near-ideal enzyme in practice, which concentrates n-3 PUFAs from 25% to 27% in oils to a theoretically closer value 90% in monoacylglycerols (MAGs) via one-step enzymatic ethanolysis. Non-regiospecificity and high non-n-3 PUFAs preference of CAL-A are the catalytic feature to selectively cleave non-n-3 PUFAs in all 3 positions of triacylglycerols (TAGs); while high ethanol/TAGs ratio, low operation temperature and high tolerance to polar ethanol are essential conditions beyond biocatalyst itself. C-13 Nuclear magnetic resonance ((13)C NMR) analysis and competitive factor estimation verified the hypothesis and confirmed the plausible suggestion of catalytic mechanism of CAL-A.
ESTHER : He_2016_Bioresour.Technol_219_466
PubMedSearch : He_2016_Bioresour.Technol_219_466
PubMedID: 27521783

Title : NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway - Ai_2016_Cancer.Biol.Ther_17_943
Author(s) : Ai R , Sun Y , Guo Z , Wei W , Zhou L , Liu F , Hendricks DT , Xu Y , Zhao X
Ref : Cancer Biol Ther , 17 :943 , 2016
Abstract : N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however beta-catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and beta-catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and beta-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression.
ESTHER : Ai_2016_Cancer.Biol.Ther_17_943
PubMedSearch : Ai_2016_Cancer.Biol.Ther_17_943
PubMedID: 27414086

Title : Accumulation and effects of Cr(VI) in Japanese medaka (Oryzias latipes) during chronic dissolved and dietary exposures - Chen_2016_Aquat.Toxicol_176_208
Author(s) : Chen H , Mu L , Cao J , Mu J , Klerks PL , Luo Y , Guo Z , Xie L
Ref : Aquat Toxicol , 176 :208 , 2016
Abstract : Chromium (Cr) is an essential metal and a nutritional supplement for both human and agricultural uses. It is also a pollutant from a variety of industrial uses. These uses can lead to elevated Cr levels in aquatic environments, where it can enter and affect aquatic organisms. Its accumulation and subsequent effects in fish have received relatively little attention, especially for chronic exposure. In the present study, Japanese medaka were chronically exposed to dissolved or dietary Cr(VI) for 3 months. Cr accumulation in liver, gills, intestine, and brain was evaluated. Effects on the antioxidant system, nervous system (acetylcholinesterase, AChE), digestive system (alpha-glucosidase, alpha-Glu), and tissue histology (liver and gills) were also assessed. Cr accumulation was observed in the intestine and liver of fish exposed to Cr-contaminated brine shrimp. However, chronic dissolved Cr exposure led to significant Cr accumulation in all organs tested. Analysis of the subcellular distribution of Cr in medaka livers revealed that 37% of the Cr was present in the heat stable protein fraction. The dissolved Cr exposure had pronounced effects on the antioxidant system in the liver, with an elevated ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) and decreases in GSH and glutathione S-transferase (GST). The alpha-Glu activity in the intestine was significantly inhibited. In addition, Cr exposure caused histopathological alterations in the gills and liver. In general, the effects of dietary Cr were relatively minor, possible due to the much lower accumulation in the fish. Our results imply that Japanese medaka accumulate Cr mainly via uptake of dissolved Cr(VI).
ESTHER : Chen_2016_Aquat.Toxicol_176_208
PubMedSearch : Chen_2016_Aquat.Toxicol_176_208
PubMedID: 27162070

Title : Production and concentration of monoacylglycerols rich in omega-3 polyunsaturated fatty acids by enzymatic glycerolysis and molecular distillation - Solaesa_2016_Food.Chem_190_960
Author(s) : Solaesa A G , Sanz MT , Falkeborg M , Beltran S , Guo Z
Ref : Food Chem , 190 :960 , 2016
Abstract : Production of monoacylglycerols (MAGs) rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) was conducted through short path distillation (SPD) of an acylglycerol mixture (containing 67% MAGs) produced by enzymatic glycerolysis of sardine oil with glycerol. A stepwise SPD process in a UIC KDL 5 system (vacuum 10(-3)mbar, feeding flow 1.0 mL/min) was proceeded: the first distillation performed at evaporator temperature (TE) of 110 degreeC to remove glycerol completely and most of FFAs; and the second distillation at optimized TE 155 degreeC; resulting in a stream distillate with 91% purity and 94% overall recovery of MAGs. This work also demonstrated that SPD is able to concentrate n-3 PUFAs in MAG form by distilling at proper TE e.g. 125 degreeC, where n-3 PUFAs are concentrated in the residues. Moreover, this work mapped out a complete processing diagram for scalable production of n-3 PUFAs enriched MAGs as potential food emulsifier and ingredient.
ESTHER : Solaesa_2016_Food.Chem_190_960
PubMedSearch : Solaesa_2016_Food.Chem_190_960
PubMedID: 26213062

Title : An Atypical alpha\/beta-Hydrolase Fold Revealed in the Crystal Structure of Pimeloyl-Acyl Carrier Protein Methyl Esterase BioG from Haemophilus influenzae - Shi_2016_Biochemistry_55_6705
Author(s) : Shi J , Cao X , Chen Y , Cronan JE , Guo Z
Ref : Biochemistry , 55 :6705 , 2016
Abstract : Pimeloyl-acyl carrier protein (ACP) methyl esterase is an alpha/beta-hydrolase that catalyzes the last biosynthetic step of pimeloyl-ACP, a key intermediate in biotin biosynthesis. Intriguingly, multiple nonhomologous isofunctional forms of this enzyme that lack significant sequence identity are present in diverse bacteria. One such esterase, Escherichia coli BioH, has been shown to be a typical alpha/beta-hydrolase fold enzyme. To gain further insights into the role of this step in biotin biosynthesis, we have determined the crystal structure of another widely distributed pimeloyl-ACP methyl esterase, Haemophilus influenzae BioG, at 1.26 A. The BioG structure is similar to the BioH structure and is composed of an alpha-helical lid domain and a core domain that contains a central seven-stranded beta-pleated sheet. However, four of the six alpha-helices that flank both sides of the BioH core beta-sheet are replaced with long loops in BioG, thus forming an unusual alpha/beta-hydrolase fold. This structural variation results in a significantly decreased thermal stability of the enzyme. Nevertheless, the lid domain and the residues at the lid-core interface are well conserved between BioH and BioG, in which an analogous hydrophobic pocket for pimelate binding as well as similar ionic interactions with the ACP moiety are retained. Biochemical characterization of site-directed mutants of the residues hypothesized to interact with the ACP moiety supports a similar substrate interaction mode for the two enzymes. Consequently, these enzymes package the identical catalytic function under a considerably different protein surface.
ESTHER : Shi_2016_Biochemistry_55_6705
PubMedSearch : Shi_2016_Biochemistry_55_6705
PubMedID: 27933801
Gene_locus related to this paper: haein-y1552

Title : Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer's Rodent Models - Wu_2015_Sci.Rep_5_15032
Author(s) : Wu Y , Luo X , Liu X , Liu D , Wang X , Guo Z , Zhu L , Tian Q , Yang X , Wang JZ
Ref : Sci Rep , 5 :15032 , 2015
Abstract : Although Alzheimer's disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated beta-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models.
ESTHER : Wu_2015_Sci.Rep_5_15032
PubMedSearch : Wu_2015_Sci.Rep_5_15032
PubMedID: 26463268

Title : Dodecenyl succinylated alginate as a novel material for encapsulation and hyperactivation of lipases - Falkeborg_2015_Carbohydr.Polym_133_194
Author(s) : Falkeborg M , Paitaid P , Shu AN , Perez B , Guo Z
Ref : Carbohydr Polym , 133 :194 , 2015
Abstract : Alginate was modified with dodecenyl succinic anhydride (SAC12) in an aqueous reaction medium at neutral pH. The highest degree of succinylation (33.9+/-3.5%) was obtained after 4h at 30 degrees C, using four mole SAC12 per mol alginate monomer. Alginate was modified with succinic anhydride (SAC0) for comparison, and the structures and thermal properties of alg-SAC0 and alg-SAC12 were evaluated using FTIR, (1)H NMR, and DSC. Calcium-hydrogel beads were formed from native and modified alginates, in which lipases were encapsulated with a load of averagely 76mug lipase per mg alginate, irrespective of the type of alginate. Lipases with a "lid", which usually are dependent on interfacial activation, showed a 3-fold increase in specific activity toward water-soluble substrates when encapsulated in alg-SAC12, compared to the free lipase. Such hyperactivation was not observed for lipases independent of interfacial activation, or for lipases encapsulated in native alginate or alg-SAC0 hydrogels.
ESTHER : Falkeborg_2015_Carbohydr.Polym_133_194
PubMedSearch : Falkeborg_2015_Carbohydr.Polym_133_194
PubMedID: 26344272

Title : Characterization and mechanism insight of accelerated catalytic promiscuity of Sulfolobus tokodaii (ST0779) peptidase for aldol addition reaction - Li_2015_Appl.Microbiol.Biotechnol_99_9625
Author(s) : Li R , Perez B , Jian H , Jensen MM , Gao R , Dong M , Glasius M , Guo Z
Ref : Applied Microbiology & Biotechnology , 99 :9625 , 2015
Abstract : A novel peptidase from thermophilic archaea Sulfolobus tokodaii (ST0779) is examined for its catalytic promiscuity of aldol addition, which shows comparable activity as porcine pancreatic lipase (PPL, one of the best enzymes identified for biocatalytic aldol addition) at 30 degrees C but much accelerated activity at elevated temperature. The molecular catalytic efficiency kcat/Km (M(-1) s(-1)) of this thermostable enzyme at 55 degrees C adds up to 140 times higher than that of PPL at its optimum temperature 37 degrees C. The fluorescence quenching analysis depicts that the binding constants of PPL are significantly higher than those of ST0779, and their numbers of binding sites show opposite temperature dependency. Thermodynamic parameters estimated by fluorescence quenching analysis unveil distinctly different substrate-binding modes between PPL and ST0779: the governing binding interaction between PPL and substrates is hydrophobic force, while the dominating substrate-binding forces for ST0779 are van der Waals and H-bonds interactions. A reasonable mechanism for ST0779-catalyzed aldol reaction is proposed based on kinetic study, spectroscopic analysis, and molecular stereostructure simulation. This work represents a successful example to identify a new enzyme for catalytic promiscuity, which demonstrates a huge potential to discover and exploit novel biocatalyst from thermophile microorganism sources.
ESTHER : Li_2015_Appl.Microbiol.Biotechnol_99_9625
PubMedSearch : Li_2015_Appl.Microbiol.Biotechnol_99_9625
PubMedID: 26169629
Gene_locus related to this paper: sulto-ST0779

Title : Preparation and characterization of a novel thermostable lipase from Thermomicrobium roseum - Fang_2021_Catal.Sci.Technol_11_7386
Author(s) : Fang Y , Zhou Y , Xin Y , Shi Y , Guo Z , Li Y , Gu Z , Ding Z , Shi G , Zhang L
Ref : Catal Sci Technol , 11 :7386 , 2015
Abstract : In this study, a hypothetical lipase gene from Thermomicrobium roseum DSM 5159 (GenBank: ACM04789.1) was recombinantly expressed and characterized. The TrLIP gene was inserted into two different plasmids (pTIG and pMA5 constructed by our laboratory) and further expressed in E. coli BL21 and B. subtilis W600 (TrLIPB/E), respectively. After purification, TrLipE/B showed a single band at approx. 38 kDa on 10% reducing SDS-PAGE gels. The successful expression of TrLipE/B was further confirmed by peptide map fingerprinting (PMF) analysis. For both expression systems, the target enzyme revealed marked stability over a wide temperature and pH range. In E. coli BL21, the optimal temperature and pH were 85 C and 8.5, while these were 90 C and 9 in B. subtilis W600. Additionally, the studied TrLipE/B was found to show remarkable tolerance in mixed systems constituted by water and organic solvents. Depending on the different expression systems, TrLipB has better enzymatic properties, in particular, thermostability and organic solvent tolerance. Based on the circular dichroism (CD) analysis, the corresponding helix, beta-sheet, beta-turn and random coil compositions were slightly different between TrLipE (34.8%, 11.2%, 23.4% and 30.6%) and TrLipB (35.9%, 11.1%, 23.3% and 29.7%). The thermostability of TrLipE/B was further verified with nano-DSC analysis. The melting temperature (Tm) and denaturation enthalpy (deltaH) of TrLipE were 97.51 C and 1637 KJ mol-1, 98.53 C and 1463 kJ mol-1 for TrLipB. The substrate specificity and enzymatic kinetics were analyzed as well. The studied TrLipE/B's capability to catalyze p-nitrophenol esters with different carbon chain lengths was verified. Enzymatic transesterification of immobilized TrLipB was confirmed, with a molar conversion rate of 23.32%. This research therefore provides a candidate that could be applied for biocleanser production and organic synthesis, especially under environments requiring high temperature.
ESTHER : Fang_2021_Catal.Sci.Technol_11_7386
PubMedSearch : Fang_2021_Catal.Sci.Technol_11_7386
PubMedID:

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 : Memory-Enhancing Effects of the Crude Extract of Polygala tenuifolia on Aged Mice - Li_2014_Evid.Based.Complement.Alternat.Med_2014_392324
Author(s) : Li Z , Liu Y , Wang L , Liu X , Chang Q , Guo Z , Liao Y , Pan R , Fan TP
Ref : Evid Based Complement Alternat Med , 2014 :392324 , 2014
Abstract : Learning and memory disorders arise from distinct age-associated processes, and aging animals are often used as a model of memory impairment. The root of Polygala tenuifolia has been commonly used in some Asian countries as memory enhancer and its memory improvement has been reported in various animal models. However, there is less research to verify its effect on memory functions in aged animals. Herein, the memory-enhancing effects of the crude extract of Polygala tenuifolia (EPT) on normal aged mice were assessed by Morris water maze (MWM) and step-down passive avoidance tests. In MWM tests, the impaired spatial memory of the aged mice was partly reversed by EPT (100 and 200 mg/kg; P < 0.05) as compared with the aged control mice. In step-down tests, the nonspatial memory of the aged mice was improved by EPT (100 and 200 mg/kg; P < 0.05). Additionally, EPT could increase superoxide dismutase (SOD) and catalase (CAT) activities, inhibit monoamine oxidase (MAO) and acetyl cholinesterase (AChE) activities, and decrease the levels of malondialdehyde (MDA) in the brain tissue of the aged mice. The results showed that EPT improved memory functions of the aged mice probably via its antioxidant properties and via decreasing the activities of MAO and AChE.
ESTHER : Li_2014_Evid.Based.Complement.Alternat.Med_2014_392324
PubMedSearch : Li_2014_Evid.Based.Complement.Alternat.Med_2014_392324
PubMedID: 24744810

Title : Crystal Structures of E. coli Native MenH and Two Active Site Mutants. - Johnston_2013_Plos.One_8_e61325
Author(s) : Johnston JM , Jiang M , Guo Z , Baker EN
Ref : PLoS ONE , 8 :e61325 , 2013
Abstract : Recent revision of the biosynthetic pathway for menaquinone has led to the discovery of a previously unrecognized enzyme 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase, also known as MenH. This enzyme has an alpha/beta hydrolase fold with a catalytic triad comprising Ser86, His232, and Asp210. Mutational studies identified a number of conserved residues of importance to activity, and modeling further implicated the side chains of Tyr85 and Trp147 in formation of a non-standard oxyanion hole. We have solved the structure of E. coli MenH (EcMenH) at 2.75 A resolution, together with the structures of the active site mutant proteins Tyr85Phe and Arg124Ala, both at 2.5 A resolution. EcMenH has the predicted alpha/beta hydrolase fold with its core alpha/beta domain capped by a helical lid. The active site, a long groove beneath the cap, contains a number of conserved basic residues and is found to bind exogeneous anions, modeled as sulfate and chloride, in all three crystal structures. Docking studies with the MenH substrate and a transition state model indicate that the bound anions mark the binding sites for anionic groups on the substrate. The docking studies, and careful consideration of the active site geometry, further suggest that the oxyanion hole is of a conventional nature, involving peptide NH groups, rather than the proposed site involving Tyr85 and Trp147. This is in accord with conclusions from the structure of S. aureus MenH. Comparisons with the latter do, however, indicate differences in the periphery of the active site that could be of relevance to selective inhibition of MenH enzymes.
ESTHER : Johnston_2013_Plos.One_8_e61325
PubMedSearch : Johnston_2013_Plos.One_8_e61325
PubMedID: 23637813
Gene_locus related to this paper: ecoli-YFBB

Title : Genome Sequence of Mycoplasma columbinum Strain SF7 - Guo_2013_Genome.Announc_1_e0015713
Author(s) : Guo Z , Xu X , Zheng Q , Li T , Kuang S , Zhang Z , Chen Y , Lu X , Zhou R , Bi D , Jin H
Ref : Genome Announc , 1 :e0015713 , 2013
Abstract : Mycoplasma columbinum is a member of nonglycolytic Mycoplasma species which can hydrolyze arginine. Increasingly research has revealed that M. columbinum is associated with respiratory disease of pigeons and that the respiratory disease symptoms could be eliminated via the use of mycoplasma treatment medicine. Here we report the genome sequence of M. columbinum strain SF7, which is the first genome report for M. columbinum.
ESTHER : Guo_2013_Genome.Announc_1_e0015713
PubMedSearch : Guo_2013_Genome.Announc_1_e0015713
PubMedID: 23599295

Title : Enhanced catalytic activity of lipase encapsulated in PCL nanofibers - Song_2012_Langmuir_28_6157
Author(s) : Song J , Kahveci D , Chen M , Guo Z , Xie E , Xu X , Besenbacher F , Dong M
Ref : Langmuir , 28 :6157 , 2012
Abstract : Use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Enzyme immobilization as an effective strategy for improving the enzyme activity has emerged from developments especially in nanoscience and nanotechnology. Here, lipase from Burkholderia cepacia (LBC), as an example of the luxuriant enzymes, was successfully encapsulated in polycaprolactone (PCL) nanofibers, proven by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Evaluated in both organic and aqueous medium, the activation factor of the encapsulated enzymes in the hydrolysis reaction was generally higher than that in the transesterification reaction. Enhanced catalytic activities were found when 5-20 w/w % of LBC was loaded. The effect of different solvents pretreatment on the activity of immobilized LBC was also investigated. The highest activation factor was found up to 14 for the sample containing acetone-treated LBC/PCL (10 w/w %). The encapsulated lipase reserved 50% of its original activity after the 10th run in the transesterification reaction in hexane medium. The mechanism of activation of lipase catalytic ability based on active PCL nanofiberous matrix is proposed.
ESTHER : Song_2012_Langmuir_28_6157
PubMedSearch : Song_2012_Langmuir_28_6157
PubMedID: 22397625

Title : Genome sequence of Mycoplasma iowae strain 695, an unusual pathogen causing deaths in turkeys - Wei_2012_J.Bacteriol_194_547
Author(s) : Wei S , Guo Z , Li T , Zhang T , Li X , Zhou Z , Li Z , Liu M , Luo R , Bi D , Chen H , Zhou R , Jin H
Ref : Journal of Bacteriology , 194 :547 , 2012
Abstract : Mycoplasma iowae is associated mainly with reduced hatchability in turkeys and is well known for the unusual ability of phenotypic variation in the Mycoplasma surface components as well as a relative resistance to heat, bile salts, and many antimicrobials. A subset of unique genes and a gene cluster responsible for these characteristics could be identified from the genome. Here, we report the first genome sequence of this species.
ESTHER : Wei_2012_J.Bacteriol_194_547
PubMedSearch : Wei_2012_J.Bacteriol_194_547
PubMedID: 22207750

Title : Microarray analysis of gene regulations and potential association with acephate-resistance and fitness cost in Lygus lineolaris - Zhu_2012_PLoS.One_7_e37586
Author(s) : Zhu YC , Guo Z , He Y , Luttrell R
Ref : PLoS ONE , 7 :e37586 , 2012
Abstract : The tarnished plant bug has become increasingly resistant to organophosphates in recent years. To better understand acephate resistance mechanisms, biological, biochemical, and molecular experiments were systematically conducted with susceptible (LLS) and acephate-selected (LLR) strains. Selection of a field population with acephate significantly increased resistance ratio to 5.9-fold, coupled with a significant increase of esterase activities by 2-fold. Microarray analysis of 6,688 genes revealed 329 up- and 333 down-regulated (>/=2-fold) genes in LLR. Six esterase, three P450, and one glutathione S-transferase genes were significantly up-regulated, and no such genes were down-regulated in LLR. All vitellogenin and eggshell protein genes were significantly down-regulated in LLR. Thirteen protease genes were significantly down-regulated and only 3 were up-regulated in LLR. More than twice the number of catalysis genes and more than 3.6-fold of metabolic genes were up-regulated, respectively, as compared to those down-regulated with the same molecular and biological functions. The large portion of metabolic or catalysis genes with significant up-regulations indicated a substantial increase of metabolic detoxification in LLR. Significant increase of acephate resistance, increases of esterase activities and gene expressions, and variable esterase sequences between LLS and LLR consistently demonstrated a major esterase-mediated resistance in LLR, which was functionally provable by abolishing the resistance with esterase inhibitors. In addition, significant elevation of P450 gene expression and reduced susceptibility to imidacloprid in LLR indicated a concurrent resistance risk that may impact other classes of insecticides. This study demonstrated the first association of down-regulation of reproductive- and digestive-related genes with resistance to conventional insecticides, suggesting potential fitness costs associated with resistance development. This study shed new light on the understanding of the molecular basis of insecticide resistance, and the information is highly valuable for development of chemical control guidelines and tactics to minimize resistance and cross-resistance risks.
ESTHER : Zhu_2012_PLoS.One_7_e37586
PubMedSearch : Zhu_2012_PLoS.One_7_e37586
PubMedID: 22655059
Gene_locus related to this paper: lygli-i3wnt1 , lygli-q5sex5

Title : Major putative pesticide receptors, detoxification enzymes, and transcriptional profile of the midgut of the tobacco budworm, Heliothis virescens (Lepidoptera: Noctuidae) - Zhu_2011_J.Invertebr.Pathol_106_296
Author(s) : Zhu YC , Guo Z , Chen MS , Zhu KY , Liu XF , Scheffler B
Ref : J Invertebr Pathol , 106 :296 , 2011
Abstract : Insecticide resistance mechanisms, including those for Cry proteins (Bt), in Heliothis virescens are not well understood. Sequencing of midgut transcriptomes may facilitate the discovery of the genes responsible for resistance development. In this study, a total of 5856 Sanger sequences were obtained and assembled to 1687 contigs (464) and singletons (1233) with average length of 507 bp. Blast similarity search showed that 1372 cDNAs from this study matched different genes or cDNAs in the GenBank and other sequence databases. Blast2go annotation identified 611 highly similar proteins with metabolic and cellular processes as major biological functions and catalytic activity and binding as major molecular functions. At least 143 contigs and singletons were associated with pesticide activation, detoxification, and resistance development. These cDNAs, with average length of 601 bp, matched nine groups of pesticide resistance related genes. At least 80 cDNAs coded for Bt resistance related enzymes and potential receptors, including 58 proteinases, 4 cadherins, 13 aminopeptidase, and 5 alkaline phosphatases. Other putative detoxification enzymes included 20 cytochrome P450 oxidases, 11 glutathione S-transferases, 9 esterases, 8 sodium channels, and 15 cytochrome oxidases. Of the 143 contigs and singletons, 111 cDNA sequences seemed to be new resistance candidate gene transcripts in GenBank because they either priorly matched resistance candidate cDNAs of other species, or had low sequence identity with those previously sequenced from H. virescens. This study provides a foundation for future research to develop a gut-specific DNA microarray for analysis of the global changes of gene expression in response to biological and chemical pesticides. Future development resistance management strategies could benefit from this study and help continue research to identify key genes targetable by classic and novel approaches.
ESTHER : Zhu_2011_J.Invertebr.Pathol_106_296
PubMedSearch : Zhu_2011_J.Invertebr.Pathol_106_296
PubMedID: 21056043

Title : Genome sequence of duck pathogen Mycoplasma anatis strain 1340 - Guo_2011_J.Bacteriol_193_5883
Author(s) : Guo Z , Chen P , Ren P , Kuang S , Zhou Z , Li Z , Liu M , Shi D , Xiao Y , Wang X , Zhou R , Jin H , Bi D
Ref : Journal of Bacteriology , 193 :5883 , 2011
Abstract : Mycoplasma anatis, a member of the class Mollicutes, is the causative agent of a contagious infectious disease of domestic ducklings, wild birds, and eggs. Increasing reports show that coinfection of M. anatis with Escherichia coli results in substantial economic impacts on the duck farms in China. Here, we announce the first genome sequence of M. anatis.
ESTHER : Guo_2011_J.Bacteriol_193_5883
PubMedSearch : Guo_2011_J.Bacteriol_193_5883
PubMedID: 21952548

Title : Genome sequence of poultry pathogen Riemerella anatipestifer strain RA-YM - Zhou_2011_J.Bacteriol_193_1284
Author(s) : Zhou Z , Peng X , Xiao Y , Wang X , Guo Z , Zhu L , Liu M , Jin H , Bi D , Li Z , Sun M
Ref : Journal of Bacteriology , 193 :1284 , 2011
Abstract : Riemerella anatipestifer is a Gram-negative, rod-shaped bacterium associated with epizootic infections in poultry. R. anatipestifer strain RA-YM, belonging to the serotype 1 prevalent in China, is a clinically isolated strain with high-level virulence. Here, we report the first genome sequence of this species.
ESTHER : Zhou_2011_J.Bacteriol_193_1284
PubMedSearch : Zhou_2011_J.Bacteriol_193_1284
PubMedID: 21183670
Gene_locus related to this paper: riean-e6jgw6 , riean-e6jh69 , riean-e6jim0

Title : Structural and functional analysis of Rv0554 from Mycobacterium tuberculosis: testing a putative role in menaquinone biosynthesis - Johnston_2010_Acta.Crystallogr.D.Biol.Crystallogr_66_909
Author(s) : Johnston JM , Jiang M , Guo Z , Baker EN
Ref : Acta Crystallographica D Biol Crystallogr , 66 :909 , 2010
Abstract : Mycobacterium tuberculosis, the cause of tuberculosis, is a devastating human pathogen against which new drugs are urgently needed. Enzymes from the biosynthetic pathway for menaquinone are considered to be valid drug targets. The protein encoded by the open reading frame Rv0554 has been expressed, purified and subjected to structural and functional analysis to test for a putative role in menaquinone biosynthesis. The crystal structure of Rv0554 has been solved and refined in two different space groups at 2.35 and 1.9 A resolution. The protein is dimeric, with an alpha/beta-hydrolase monomer fold. In each monomer, a large cavity adjacent to the catalytic triad is enclosed by a helical lid. Dimerization is mediated by the lid regions. Small-molecule additives used in crystallization bind in the active site, but no binding of ligands related to menaquinone biosynthesis could be detected and functional assays failed to support possible roles in menaquinone biosynthesis.
ESTHER : Johnston_2010_Acta.Crystallogr.D.Biol.Crystallogr_66_909
PubMedSearch : Johnston_2010_Acta.Crystallogr.D.Biol.Crystallogr_66_909
PubMedID: 20693690
Gene_locus related to this paper: myctu-bpoC

Title : Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor - Tian_2010_Endocrinology_151_3049
Author(s) : Tian L , Gao J , Hao J , Zhang Y , Yi H , O'Brien TD , Sorenson R , Luo J , Guo Z
Ref : Endocrinology , 151 :3049 , 2010
Abstract : Inhibition of dipeptidyl peptidase IV (DPP-IV) activity by NVP-DPP728, a DPP-IV inhibitor, improves the therapeutic efficacy of glucagon-like peptide-1 (GLP-1). CD26 is a membrane-associated glycoprotein with DPP-IV activity and is expressed on lymphocytes. We investigated the effect of NVP-DPP728 on reversing new-onset diabetes in nonobese diabetic (NOD) mice and modulating the inflammatory response and stimulating beta-cell regeneration. New-onset diabetic NOD mice were treated with NVP-DPP728 for 2, 4, and 6 wk. Blood glucose level was monitored. Regulatory T cells in thymus and secondary lymph nodes, TGF-beta1 and GLP-1 in plasma, and the insulin content in the pancreas were measured. Immunostaining for insulin and bromodeoxyuridine (BrdU) were performed. The correlation of beta-cell replication with inflammation was determined. In NVP-DPP728-treated NOD mice, diabetes could be reversed in 57, 74, and 73% of mice after 2, 4, and 6 wk treatment, respectively. Insulitis was reduced and the percentage of CD4(+)CD25(+)FoxP3(+) regulatory T cells was increased in treated NOD mice with remission. Plasma TGF-beta1 and GLP-1, the insulin content, and both insulin(+) and BrdU(+) beta-cells in pancreas were also significantly increased. No significant correlations were found between numbers of both insulin(+) and BrdU(+) beta-cells in islets and beta-cell area or islets with different insulitis score in NOD mice with remission of diabetes. In conclusion, NVP-DPP728 treatment can reverse new-onset diabetes in NOD mice by reducing insulitis, increasing CD4(+)CD25(+)FoxP3(+) regulatory T cells, and stimulating beta-cell replication. beta-Cell replication is not associated with the degree of inflammation in NVP-DPP728-treated NOD mice.
ESTHER : Tian_2010_Endocrinology_151_3049
PubMedSearch : Tian_2010_Endocrinology_151_3049
PubMedID: 20444936

Title : Draft genome sequences of Yersinia pestis isolates from natural foci of endemic plague in China - Eppinger_2009_J.Bacteriol_191_7628
Author(s) : Eppinger M , Guo Z , Sebastian Y , Song Y , Lindler LE , Yang R , Ravel J
Ref : Journal of Bacteriology , 191 :7628 , 2009
Abstract : To gain insights into the evolutionary origin, emergence, and pathogenicity of the etiologic agent of plague, we have sequenced the genomes of four Yersinia pestis strains isolated from the zoonotic rodent reservoir in foci of endemic plague in China. These resources enable in-depth studies of Y. pestis sequence variations and detailed whole-genome comparisons of very closely related genomes from the supposed site of the origin and the emergence of global pandemics of plague.
ESTHER : Eppinger_2009_J.Bacteriol_191_7628
PubMedSearch : Eppinger_2009_J.Bacteriol_191_7628
PubMedID: 19820101
Gene_locus related to this paper: yerpe-BIOH , yerpe-dlhh , yerpe-PIP , yerpe-PLDB , yerpe-PTRB , yerpe-Y0507 , yerpe-y3224 , yerpe-YPLA , yerpe-YPO0180 , yerpe-YPO0667 , yerpe-YPO0773 , yerpe-YPO0986 , yerpe-YPO1501 , yerpe-YPO1997 , yerpe-YPO2526 , yerpe-YPO2814

Title : Catalytic mechanism of SHCHC synthase in the menaquinone biosynthesis of Escherichia coli: identification and mutational analysis of the active site residues - Jiang_2009_Biochemistry_48_6921
Author(s) : Jiang M , Chen X , Wu XH , Chen M , Wu YD , Guo Z
Ref : Biochemistry , 48 :6921 , 2009
Abstract : (1R,6R)-2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) synthase (MenH) is an alpha/beta fold enzyme containing a catalytically essential serine-histidine-aspartate triad typical of serine proteases but catalyzes a pyruvate elimination reaction initiated by alpha-proton abstraction in the menaquinone biosynthetic pathway of Escherichia coli. In this study, we identify the active site residues in the synthase through sequence analysis and structural modeling and study their mechanistic roles in MenH catalysis. Steady-state kinetic characterization of site-directed mutants of the active site residues shows that three conserved arginine residues (Arg-90, Arg-124, and Arg-168) likely form ionic salt bridges with three carboxylate groups of the substrate in the Michaelis complex and that the side-chain polar groups of the conserved tyrosine (Tyr-85) and tryptophan (Trp-147) residues likely donate hydrogen bonds to form an "oxyanion hole". In addition, the pH dependence of the MenH kinetic properties reveals a catalytic base with a pK(a) highly dependent on the hydroxyl group of the triad serine residue in the enzymatic reaction. Moreover, proton inventory experiments demonstrate that the SHCHC synthase adopts one-proton catalysis like many serine proteases. These results allow the proposal of a mechanism in which the histidine residue of the MenH triad serves as a general base catalyst to deprotonate the triad seryl hydroxyl group in the alpha-proton abstraction from the substrate. As such, the MenH triad performs a simple and fundamental proton transfer reaction occurring repeatedly in the reactions catalyzed by serine proteases and alpha/beta fold hydrolases, suggesting a common evolutionary origin for all serine-histidine-aspartate triads serving different catalytic functions.
ESTHER : Jiang_2009_Biochemistry_48_6921
PubMedSearch : Jiang_2009_Biochemistry_48_6921
PubMedID: 19545176
Gene_locus related to this paper: ecoli-YFBB

Title : Identification and characterization of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase in the menaquinone biosynthesis of Escherichia coli - Jiang_2008_Biochemistry_47_3426
Author(s) : Jiang M , Chen X , Guo ZF , Cao Y , Chen M , Guo Z
Ref : Biochemistry , 47 :3426 , 2008
Abstract : Menaquinone is a lipid-soluble molecule that plays an essential role as an electron carrier in the respiratory chain of many bacteria. We have previously shown that its biosynthesis in Escherichia coli involves a new intermediate, 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC), and requires an additional enzyme to convert this intermediate into (1 R,6 R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC). Here, we report the identification and characterization of MenH (or YfbB), an enzyme previously proposed to catalyze a late step in menaquinone biosynthesis, as the SHCHC synthase. The synthase catalyzes a proton abstraction reaction that results in 2,5-elimination of pyruvate from SEPHCHC and the formation of SHCHC. It is an efficient enzyme ( k cat/ K M = 2.0 x 10 (7) M (-1) s (-1)) that provides a smaller transition-state stabilization than other enzymes catalyzing proton abstraction from carbon acids. Despite its lack of the proposed thioesterase activity, the SHCHC synthase is homologous to the well-characterized C-C bond hydrolase MhpC. The crystallographic structure of the Vibrio cholerae MenH protein closely resembles that of MhpC and contains a Ser-His-Asp triad typical of serine proteases. Interestingly, this triad is conserved in all MenH proteins and is essential for the SHCHC synthase activity. Mutational analysis found that the catalytic efficiency of the E. coli protein is reduced by 1.4 x 10 (3), 2.1 x 10 (5), and 9.3 x 10 (3) folds when alanine replaces serine, histidine, and aspartate of the triad, respectively. These results show that the SHCHC synthase is closely related to alpha/beta hydrolases but catalyzes a reaction mechanistically distinct from all known hydrolase reactions.
ESTHER : Jiang_2008_Biochemistry_47_3426
PubMedSearch : Jiang_2008_Biochemistry_47_3426
PubMedID: 18284213
Gene_locus related to this paper: ecoli-YFBB

Title : Characterization of lipase in reversed micelles formulated with cibacron blue F-3GA modified span 85 - Zhang_2007_Biotechnol.Prog_23_108
Author(s) : Zhang DH , Guo Z , Dong XY , Sun Y
Ref : Biotechnol Prog , 23 :108 , 2007
Abstract : Sorbitan trioleate (Span 85) modified by Cibacron Blue F-3GA (CB) was prepared and used as an affinity surfactant to formulate a reversed micellar system for Candida rugosa lipase (CRL) solubilization. The system was characterized and evaluated by employing CRL-catalyzed hydrolysis of olive oil as a model reaction. The micellar hydrodynamic radius results reflected, to some extent, the redistribution of surfactant and water after enzyme addition, and the correlation between surfactant formulation, water content (W0), micellar size, and enzyme activity. An adequate modification density of CB was found to be important for the reversed micelles to retain enough hydration capacity and achieve high enzyme activity. Compared with the results in AOT-based reversed micelles, CRL in this micellar system exhibited a different activity behavior versus W0. The optimal pH and temperature of the encapsulated lipase remained unchanged, but the apparent activity was significantly higher than that of the native enzyme in bulk solution. Kinetic studies indicated that the encapsulated lipase in the reversed micelles of CB-formulated Span 85 followed the Michaelis-Menten equation. The Michaelis constant was found to decrease with increasing surfactant concentration, suggesting an increase of the enzyme affinity for the substrate. Stability of the lipase in the reversed micelles was negatively correlated to W0.
ESTHER : Zhang_2007_Biotechnol.Prog_23_108
PubMedSearch : Zhang_2007_Biotechnol.Prog_23_108
PubMedID: 17269677

Title : A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates - Chen_2007_PLoS.One_2_e315
Author(s) : Chen C , Tang J , Dong W , Wang C , Feng Y , Wang J , Zheng F , Pan X , Liu D , Li M , Song Y , Zhu X , Sun H , Feng T , Guo Z , Ju A , Ge J , Dong Y , Sun W , Jiang Y , Yan J , Yang H , Wang X , Gao GF , Yang R , Yu J
Ref : PLoS ONE , 2 :e315 , 2007
Abstract : BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.
ESTHER : Chen_2007_PLoS.One_2_e315
PubMedSearch : Chen_2007_PLoS.One_2_e315
PubMedID: 17375201
Gene_locus related to this paper: strsu-a4vws4 , strsu-q302y4 , strsy-a4vus4 , strsy-a4vwf6

Title : Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH - Kazantseva_2006_Science_314_982
Author(s) : Kazantseva A , Goltsov A , Zinchenko R , Grigorenko AP , Abrukova AV , Moliaka YK , Kirillov AG , Guo Z , Lyle S , Ginter EK , Rogaev EI
Ref : Science , 314 :982 , 2006
Abstract : The molecular mechanisms controlling human hair growth and scalp hair loss are poorly understood. By screening about 350,000 individuals in two populations from the Volga-Ural region of Russia, we identified a gene mutation in families who show an inherited form of hair loss and a hair growth defect. Affected individuals were homozygous for a deletion in the LIPH gene on chromosome 3q27, caused by short interspersed nuclear element-retrotransposon-mediated recombination. The LIPH gene is expressed in hair follicles and encodes a phospholipase called lipase H (alternatively known as membrane-associated phosphatidic acid-selective phospholipase A1alpha), an enzyme that regulates the production of bioactive lipids. These results suggest that lipase H participates in hair growth and development.
ESTHER : Kazantseva_2006_Science_314_982
PubMedSearch : Kazantseva_2006_Science_314_982
PubMedID: 17095700
Gene_locus related to this paper: human-LIPH

Title : Muscle type-dependent responses to insulin in intramyocellular triglyceride turnover in obese rats - Guo_2005_Obes.Res_13_2081
Author(s) : Guo Z , Zhou L
Ref : Obes Res , 13 :2081 , 2005
Abstract : OBJECTIVE: To understand the role of hyperinsulinemia in intramyocellular (imc) triglyceride (TG) accumulation and in regulating imcTG turnover. RESEARCH METHODS AND PROCEDURES: imcTG was first prelabeled by continuous infusion of [U-(14)C]glycerol (pulse), and then the rate of label loss from the prelabeled imcTG pool (turnover) in gastrocnemius, tibialis anterior, and soleus muscle of awake, high-fat-fed obese rats during the subsequent hyperinsulinemic-euglycemic clamp experiments (chase) was determined.
RESULTS: Post-absorptive basal fractional imcTG turnover rate in soleus was 0.010 +/- 0.001/min, significantly lower than that in gastrocnemius (0.026 +/- 0.002/min, p < 0.001) or tibialis anterior (0.030 +/- 0.002/min, p < 0.0001), a pattern reciprocal to their imcTG pool size. Insulin infusion at 25 pmol/kg per minute resulted in pathophysiological hyperinsulinemia (5-fold increase over the baseline value). This caused an increase in imcTG turnover by 3-fold in soleus (0.029 +/- 0.006/min, p = 0.002) but a decrease in gastrocnemius (0.012 +/- 0.003/min, p = 0.001) and in tibialis anterior (0.0064 +/- 0.001/min, p < 0.0001). Pathophysiological hyperinsulinemia suppressed hormone-sensitive lipase activity in heart (p = 0.01) and mesenteric fat (p = 0.05) but not in skeletal muscle (p > 0.05). The pool size of imcTG was not affected by hyperinsulinemia. DISCUSSION: The results demonstrated muscle-type dependence in the response of imcTG turnover to hyperinsulinemia in the obesity model. The reciprocal insulin effects on imcTG turnover in oxidative vs. oxidative-glycolytic muscle indicated a possibility that oxidative muscle contributes more to insulin resistance under hyperinsulinemia if imcTG-fatty acid oxidation is a function of turnover. imcTG turnover does not seem to regulate imcTG pool size acutely.
ESTHER : Guo_2005_Obes.Res_13_2081
PubMedSearch : Guo_2005_Obes.Res_13_2081
PubMedID: 16421341

Title : Characteristics of immobilized lipase on hydrophobic superparamagnetic microspheres to catalyze esterification - Guo_2004_Biotechnol.Prog_20_500
Author(s) : Guo Z , Sun Y
Ref : Biotechnol Prog , 20 :500 , 2004
Abstract : A novel immobilized lipase (from Candida rugosa) on hydrophobic and superparamagnetic microspheres was prepared and used as a biocatalyst to catalyze esterification reactions in diverse solvents and reaction systems. The results showed that the immobilized lipase had over 2-fold higher activities in higher log P value solvents. An exponential increase of lipase activity against log P of two miscible solvent mixtures was observed for the first time. Both free and immobilized lipase achieved its maximum activity at the range of water activity (a(w)) 0.5-0.8 or higher. At a(w) 0.6, the immobilized lipase exhibited markedly higher activities in heptane and a solvent-free system than did the native lipase. In multicompetitive reactions, the alcohol specificity of the lipase showed a strong chain-length dependency, and the immobilized enzyme exhibited more preference for a longer-chain alcohol, which is different from previous reports. The immobilized lipase showed higher specificities for butyric acid and the medium-chain-length fatty acids (C(8)-C(12)). Then, the immobilized lipase was extended to solvent-free synthesis of glycerides from glycerol and fatty acids. Recovered by magnetic separation, the immobilized lipase exhibited good reusability in repeated batch reaction, indicating its promising feature for biotechnology application.
ESTHER : Guo_2004_Biotechnol.Prog_20_500
PubMedSearch : Guo_2004_Biotechnol.Prog_20_500
PubMedID: 15058995

Title : Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans - Song_2004_DNA.Res_11_179
Author(s) : Song Y , Tong Z , Wang J , Wang L , Guo Z , Han Y , Zhang J , Pei D , Zhou D , Qin H , Pang X , Zhai J , Li M , Cui B , Qi Z , Jin L , Dai R , Chen F , Li S , Ye C , Du Z , Lin W , Yu J , Yang H , Huang P , Yang R
Ref : DNA Research , 11 :179 , 2004
Abstract : Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity.
ESTHER : Song_2004_DNA.Res_11_179
PubMedSearch : Song_2004_DNA.Res_11_179
PubMedID: 15368893
Gene_locus related to this paper: yerpe-BIOH , yerpe-IRP1 , yerpe-PIP , yerpe-PLDB , yerpe-PTRB , yerpe-q8zey9 , yerpe-Y0644 , yerpe-y1616 , yerpe-y3224 , yerpe-YPLA , yerpe-YPO0180 , yerpe-YPO0667 , yerpe-YPO0773 , yerpe-YPO0776 , yerpe-YPO0986 , yerpe-YPO1501 , yerpe-YPO1997 , yerpe-YPO2002 , yerpe-YPO2336 , yerpe-YPO2526 , yerpe-YPO2638 , yerpe-YPO2814

Title : Genetics of metabolic variations between Yersinia pestis biovars and the proposal of a new biovar, microtus - Zhou_2004_J.Bacteriol_186_5147
Author(s) : Zhou D , Tong Z , Song Y , Han Y , Pei D , Pang X , Zhai J , Li M , Cui B , Qi Z , Jin L , Dai R , Du Z , Wang J , Guo Z , Huang P , Yang R
Ref : Journal of Bacteriology , 186 :5147 , 2004
Abstract : Yersinia pestis has been historically divided into three biovars: antiqua, mediaevalis, and orientalis. On the basis of this study, strains from Microtus-related plague foci are proposed to constitute a new biovar, microtus. Based on the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis strains can be assigned to one of four biovars: antiqua (glycerol positive, arabinose positive, and nitrate positive), mediaevalis (glycerol positive, arabinose positive, and nitrate negative), orientalis (glycerol negative, arabinose positive, and nitrate positive), and microtus (glycerol positive, arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene results in the glycerol-negative characteristic of biovar orientalis strains. Two kinds of point mutations in the napA gene may cause the nitrate reduction-negative characteristic in biovars mediaevalis and microtus, respectively. A 122-bp frameshift deletion in the araC gene may lead to the arabinose-negative phenotype of biovar microtus strains. Biovar microtus strains have a unique genomic profile of gene loss and pseudogene distribution, which most likely accounts for the human attenuation of this new biovar. Focused, hypothesis-based investigations on these specific genes will help delineate the determinants that enable this deadly pathogen to be virulent to humans and give insight into the evolution of Y. pestis and plague pathogenesis. Moreover, there may be the implications for development of biovar microtus strains as a potential vaccine.
ESTHER : Zhou_2004_J.Bacteriol_186_5147
PubMedSearch : Zhou_2004_J.Bacteriol_186_5147
PubMedID: 15262951
Gene_locus related to this paper: yerpe-YPLA

Title : A clinical analysis of 104 cases of acute pure and mixed organophosphate poisoning - Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
Author(s) : Zhang J , Zhao J , Sun S , Ma H , Zhao C , Guo Z , Wang F
Ref : Zhonghua Nei Ke Za Zhi , 41 :544 , 2002
Abstract : OBJECTIVE To study the difference of the clinical manifestations between single and mixed acute organophosphate (OP) poisoning. METHODS: The clinical signs and symptoms, the activity of cholinesterase (ChE) in erythrocytes, plasma and whole blood, and the level of AST, CK, LDH and ALT were compared between a single OP poisoning group (Group S) and a mixed OP poisoning group (Group C). RESULTS: Group S and Group C compare with: (1) Symptoms and signs on arrival at hospital: Group C was found to have more cases showing, nausea and vomiting than group S with obvious difference (P < 0.05). (2) The rates of other symptoms and signs were of no significant difference between the 2 groups. The activity of cholinesterase of the 2 groups on arrival at hospital: Whole blood ChE < 0.30: 16 cases and 14 cases; > 0.30 approximately : 24 cases and 19 cases; 0.50 approximately 0.70: 14 cases and 17 cases; erythrocyte ChE < 0.30: 18 cases and 14 cases; > 0.30 approximately : 22 cases and 21 cases; 0.50 approximately 0.70: 14 cases and 15 cases; plasma ChE < 0.30: 28 cases and 25 cases; > 0.30 approximately : 10 cases and 12 cases; 0.50 approximately 0.70: 16 cases and 13 cases; chi(2) = 0.852, 1.444, 0.509. There was no obvious difference (P > 0.05). (3) Positive rates of serum biochemical parameters between the 2 groups within 72 hours after arrival at hospital: Group S AST 24 cases, ALT 18 cases, CK 42 cases, LDH 22 cases, Tbil 21 cases; Group C AST 20 cases, ALT 11 cases, CK 32 cases, LDH 18 cases, Tbil 17 cases. There was also no obvious difference (P > 0.05). (4) Positive rate of ECG: between the 2 group on arrival at hospital Group S 24 cases, Group C 19 cases. No obvious difference was shown (P > 0.05). (5) Fatality rates between the 2 groups: Group S 7.41% (4/54), Group C 6.00% (3/50), chi(2) = 0.082, P > 0.05. CONCLUSION: Acute mixed OP poisoning and single OP poisoning show no significant difference in clinical manifestations. The treatment measures for single OP poisoning also has good effect fo mixed OP poisoning.
ESTHER : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
PubMedSearch : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_544
PubMedID: 12421504