Zhang T

References (105)

Title : ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2\/STAT3 pathway and interacting with ESM1 - Li_2024_J.Transl.Med_22_46
Author(s) : Li YK , Gao AB , Zeng T , Liu D , Zhang QF , Ran XM , Tang ZZ , Li Y , Liu J , Zhang T , Shi GQ , Zhou WC , Zou WD , Peng J , Zhang J , Li H , Zou J
Ref : J Transl Med , 22 :46 , 2024
Abstract : BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
ESTHER : Li_2024_J.Transl.Med_22_46
PubMedSearch : Li_2024_J.Transl.Med_22_46
PubMedID: 38212795

Title : Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial - Wang_2024_Diabetes.Obes.Metab__
Author(s) : Wang W , Guo X , Zhang C , Ning T , Ma G , Huang Y , Jia R , Zhou D , Cao M , Zhang T , Yao L , Yuan J , Chen L , Wang Y , Jiang C , Dong X , Chen M , Gu Q , Zhang L , Fu Y , Pan T , Bi Y , Song W , Xu J , Lu W , Sun X , Ye Z , Zhang D , Peng L , Lin X , Dai W , Wang Q , Yang W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
ESTHER : Wang_2024_Diabetes.Obes.Metab__
PubMedSearch : Wang_2024_Diabetes.Obes.Metab__
PubMedID: 38221859 || 38618970

Title : Inhibition of RXRA-mediated PLA2G2A improves delirium in COPD mice by regulating endoplasmic reticulum stress pathway and inhibiting cell apoptosis - Zhang_2024_Cell.Mol.Biol.(Noisy-le-grand)_70_226
Author(s) : Zhang T , Wang G
Ref : Cellular & Molecular Biology (Noisy-le-grand) , 70 :226 , 2024
Abstract : Delirium is a common psychiatric complication of chronic obstructive pulmonary disease (COPD). The relief of delirium is considered one of the beneficial ways to treat COPD. However, there are currently no specific drugs that alleviate delirium in COPD patients. Our research aimed to elucidate the specific mechanisms underlying delirium in COPD mice, while also seeking more effective therapeutic targets. In our study, bioinformatics analysis and qRT PCR were used to identify key factors in the development of delirium in COPD animal models. Open field and elevated plus maze tests were used to detect delirium in mice. Tunel staining and HE staining were used to analyze the apoptosis of mouse hippocampus cells. EdU and CCK-8 experiments were used to analyze PC-12 cells vitality and proliferation. JASPAR online database, dual luciferase reporting experiments, ChIP experiments, and IF staining were used to analyze the interaction between RXRA and PLA2G2A. RXRA is highly expressed in the brain tissue of COPD mice with delirium symptoms. The downregulation of RXRA inhibits the delirium state in COPD mice. This is mainly due to the reduction of endoplasmic reticulum stress and cell apoptosis by inhibiting the expression of RXRA. In addition, we also confirmed that RXRA is a transcription factor of PLA2G2A. RXRA has an inhibitory effect on the expression of PLA2G2A. In vitro experiments have confirmed that inhibition of the RXRA/PLA2G2A axis reduces cell apoptosis, thereby alleviating the occurrence and development of delirium in COPD mice. Inhibition of the RXRA/PLA2G2A axis reduces endoplasmic reticulum stress and cell apoptosis. This process alleviates the development of delirium in COPD mice.
ESTHER : Zhang_2024_Cell.Mol.Biol.(Noisy-le-grand)_70_226
PubMedSearch : Zhang_2024_Cell.Mol.Biol.(Noisy-le-grand)_70_226
PubMedID: 38372090

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

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

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

Title : Probing the functional hotspots inside protein hydrophobic pockets by in situ photochemical trifluoromethylation and mass spectrometry - Lai_2024_Chem.Sci_15_2545
Author(s) : Lai C , Tang Z , Liu Z , Luo P , Zhang W , Zhang T , Dong Z , Liu X , Yang X , Wang F
Ref : Chem Sci , 15 :2545 , 2024
Abstract : Due to the complex high-order structures and interactions of proteins within an aqueous solution, a majority of chemical functionalizations happen on the hydrophilic sites of protein external surfaces which are naturally exposed to the solution. However, the hydrophobic pockets inside proteins are crucial for ligand binding and function as catalytic centers and transporting tunnels. Herein, we describe a reagent pre-organization and in situ photochemical trifluoromethylation strategy to profile the functional sites inside the hydrophobic pockets of native proteins. Unbiased mass spectrometry profiling was applied for the characterization of trifluoromethylated sites with high sensitivity. Native proteins including myoglobin, trypsin, haloalkane dehalogenase, and human serum albumin have been engaged in this mild photochemical process and substantial hydrophobic site-specific and structure-selective trifluoromethylation substitutes are obtained without significant interference to their bioactivity and structures. Sodium triflinate is the only reagent required to functionalize the unprotected proteins with wide pH-range tolerance and high biocompatibility. This "in-pocket" activation model provides a general strategy to modify the potential binding pockets and gain essential structural insights into the functional hotspots inside protein hydrophobic pockets.
ESTHER : Lai_2024_Chem.Sci_15_2545
PubMedSearch : Lai_2024_Chem.Sci_15_2545
PubMedID: 38362424

Title : Platinum nanoflowers stabilized with aloe polysaccharides for detection of organophosphorus pesticides in food - Zhao_2023_Int.J.Biol.Macromol__126552
Author(s) : Zhao H , Li R , Zhang T , Zhou L , Wang L , Han Z , Liu S , Zhang J
Ref : Int J Biol Macromol , :126552 , 2023
Abstract : Organophosphorus pesticides can inhibit the activity of acetylcholinesterase and cause neurological diseases. Therefore, it is crucial to establish an efficient and sensitive platform for organophosphorus pesticide detection. In this work, we extracted aloe polysaccharide (AP) from aloe vera with the number average molecular weight of 29,271 Da and investigated its reducing property. We prepared aloe polysaccharide stabilized platinum nanoflowers (AP-Pt(n) NFs), their particle size ranges were 29.4-67.3 nm. Furthermore, AP-Pt(n) NFs exhibited excellent oxidase-like activity and the catalytic kinetics followed the typical Michaelis-Menten equation. They showed strong affinity for 3,3',5,5'-tetramethylbenzidine substrates. More importantly, we developed a simple and effective strategy for the sensitive colorimetric detection of organophosphorus pesticides in food using biocompatible AP-Pt(n) NFs. The detection range was 0.5 microg/L - 140 mg/L, which was wider than many previously reported nanozyme detection systems. This colorimetric biosensor had good selectivity and good promise for bioassay analysis.
ESTHER : Zhao_2023_Int.J.Biol.Macromol__126552
PubMedSearch : Zhao_2023_Int.J.Biol.Macromol__126552
PubMedID: 37660849

Title : Improving pesticide residue detection: Immobilized enzyme microreactor embedded in microfluidic paper-based analytical devices - Zhang_2023_Food.Chem_439_138179
Author(s) : Zhang J , Li Y , Zhang T , Zheng Z , Jing H , Liu C
Ref : Food Chem , 439 :138179 , 2023
Abstract : Orientationally immobilized enzyme microreactors (OIMERs), embedded in microfluidic paper-based analytical devices (microPADs) were developed for improved detection of pesticide residues in food. Acetylcholinesterase (AChE) was orientationally immobilized on the reusable Part I of the microPADs, using the specific affinity binding of concanavalin A (Con A) to a glycosyl group on AChE. Using the disposable Part II, facile colorimetric quantification was performed with a smartphone and software, or qualitative detection by a naked-eye visual test. The AChE immobilized in OIMERs not only had improved activity and stability, but also high sensitivity, with a limit of detection as low as (0.007 +/- 0.003) microg/mL. The method was used to detect pesticides residues in real vegetable samples; the recovery (88.6-102.7%) showed high reliability for pesticide residues detection in foods. A molecular docking study and an enzyme kinetic analysis were conducted to characterize the mechanism of action of the OIMERs.
ESTHER : Zhang_2023_Food.Chem_439_138179
PubMedSearch : Zhang_2023_Food.Chem_439_138179
PubMedID: 38091789

Title : Small molecular fluorescent probes for Alzheimer's disease associated active species - Tang_2023_Chemistry__e202300592
Author(s) : Tang F , Wang K , Liu X , Zhang X , Zhou W , Mu Z , Zhang T , Shu W , Liu Y , Xiao H
Ref : Chemistry , :e202300592 , 2023
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the main cause of dementia worldwide. As the pathogenesis of AD is quite complicated, there is continuous attention to AD-associated active species, such as amyloid-beta plaques, neurofibrillary tangles, metal ions, reactive oxygen/nitrogen/sulphurspecies, cholinesterase, viscosity, formaldehyde and so on. To this end, a series of small molecular fluorescent probes for these active species have been explored for early diagnosis and even remedy of AD. Herein, we systematacially summarize the versatile fluorescent probes mainly in recent three years, including the relationship between the structure and properties as well as the targeted diagnosis and imaging application of all these fluorescent probes. Moreover, the challenges and perspectives of the AD-related fluorescent probes are briefly explicated. We firmly expect this review may provide guidance for constructing new AD-relevant fluorescent probes and promote the clinical study of AD.
ESTHER : Tang_2023_Chemistry__e202300592
PubMedSearch : Tang_2023_Chemistry__e202300592
PubMedID: 37078523

Title : Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase - Wang_2023_Foods_12_
Author(s) : Wang Y , Sun J , Zhang M , Pan K , Liu T , Zhang T , Luo X , Zhao J , Li Z
Ref : Foods , 12 : , 2023
Abstract : Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.
ESTHER : Wang_2023_Foods_12_
PubMedSearch : Wang_2023_Foods_12_
PubMedID: 36673508

Title : The roles of serine hydrolases and serum albumin in alisol B 23-acetate hydrolysis in humans - Zhang_2023_Front.Pharmacol_14_1160665
Author(s) : Zhang T , Zhang F , Zhang Y , Li H , Zhu G , Weng T , Huang C , Wang P , He Y , Hu J , Ge G
Ref : Front Pharmacol , 14 :1160665 , 2023
Abstract : Introduction: Alisol B 23-acetate (AB23A), a major bioactive constituent in the Chinese herb Zexie (Rhizoma Alismatis), has been found with multiple pharmacological activities. AB23A can be readily hydrolyzed to alisol B in mammals, but the hydrolytic pathways of AB23A in humans and the key enzymes responsible for AB23A hydrolysis are still unrevealed. This study aims to reveal the metabolic organs and the crucial enzymes responsible for AB23A hydrolysis in human biological systems, as well as to decipher the impact of AB23A hydrolysis on its biological effects. Methods: The hydrolytic pathways of AB23A in human plasma and tissue preparations were carefully investigated by using Q-Exactive quadrupole-Orbitrap mass spectrometer and LC-UV, while the key enzymes responsible for AB23A hydrolysis were studied via performing a set of assays including reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses. Finally, the agonist effects of both AB23A and its hydrolytic metabolite(s) on FXR were tested at the cellular level. Results: AB23A could be readily hydrolyzed to form alisol B in human plasma, intestinal and hepatic preparations, while human butyrylcholinesterase (hBchE) and human carboxylesterases played key roles in AB23A hydrolysis in human plasma and tissue preparations, respectively. It was also found that human serum albumin (hSA) could catalyze AB23A hydrolysis, while multiple lysine residues of hSA were covalently modified by AB23A, suggesting that hSA catalyzed AB23A hydrolysis via its pseudo-esterase activity. Biological tests revealed that both AB23A and alisol B exhibited similar FXR agonist effects, indicating AB23A hydrolysis did not affect its FXR agonist effect. Discussion: This study deciphers the hydrolytic pathways of AB23A in human biological systems, which is very helpful for deep understanding of the metabolic rates of AB23A in humans, and useful for developing novel prodrugs of alisol B with desirable pharmacokinetic behaviors.
ESTHER : Zhang_2023_Front.Pharmacol_14_1160665
PubMedSearch : Zhang_2023_Front.Pharmacol_14_1160665
PubMedID: 37089921

Title : Rationally Engineered hCES2A Near-Infrared Fluorogenic Substrate for Functional Imaging and High-Throughput Inhibitor Screening - Fan_2023_Anal.Chem_95_15665
Author(s) : Fan Y , Zhang T , Song Y , Sang Z , Zeng H , Liu P , Wang P , Ge G
Ref : Analytical Chemistry , 95 :15665-15672 , 2023
Abstract : Human carboxylesterase 2A (hCES2A) is an important endoplasmic reticulum (ER)-resident enzyme that is responsible for the hydrolytic metabolism or activation of numerous ester-bearing drugs and environmental toxins. The previously reported hCES2A fluorogenic substrates suffer from limited emission wavelength, low specificity, and poor localization accuracy, thereby greatly limiting the in situ functional imaging of hCES2A and drug discovery. Herein, a rational ligand design strategy was adopted to construct a highly specific near-infrared (NIR) substrate for hCES2A. Following scaffold screening and recognition group optimization, HTCF was identified as a desirable NIR fluorophore with excellent photophysical properties and high ER accumulation ability, while several HTCF esters held a high potential to be good hCES2A substrates. Further investigations revealed that TP-HTCF (the tert-pentyl ester of HTCF) was an ideal substrate with ultrahigh sensitivity, excellent specificity, and a substantial signal-to-noise ratio. Upon the addition of hCES2A, TP-HTCF could be rapidly hydrolyzed to release HTCF, a chemically stable product that emitted bright fluorescent signals at around 670 nm. A TP-HTCF-based biochemical assay was then established for the high-throughput screening of potent and cell-active hCES2A inhibitors from an in-house compound library. Furthermore, TP-HTCF displayed high imaging resolution for imaging hCES2A in living cells as well as mouse liver slices and tumor-xenograft mice. Collectively, this study demonstrates a rational strategy for developing highly specific fluorogenic substrates for an ER-resident target enzyme, while TP-HTCF can act as a practical tool for sensing hCES2A in living systems.
ESTHER : Fan_2023_Anal.Chem_95_15665
PubMedSearch : Fan_2023_Anal.Chem_95_15665
PubMedID: 37782032
Gene_locus related to this paper: human-CES2

Title : Green biosynthesis of DHA-phospholipids in tailor-made supersaturated DHA aqueous solution and catalytic mechanism study - Zhang_2023_Food.Chem_431_137164
Author(s) : Zhang T , Wang J , Zhao Y , Wang Z , Hu D , Liu Y , Zhang X , Li H , Zhao B , Li B
Ref : Food Chem , 431 :137164 , 2023
Abstract : Docosahexaenoic acid-phospholipids (DHA-PLs) were prepared via lipase-mediated transesterification of DHA donor and phosphatidylcholine (PC) in a purely aqueous solution. Pre-existing carriers would play the role as "artificial interfaces" to adsorb water-insoluble PC and made them disperse in water. DHA donors were concentrated by a pH-responsive method and presented as supersaturated salt solutions. 153 triacylglycerol lipase structures were analyzed and screened in silico. Transesterification was carried out to further evaluate the six lipase candidates. Lipase B from Candida antarctica (CALB) was the best biocatalyst with 34.8% of DHA incorporation and 80.0% of PLs yields (involving 38.1% PC and 41.9% sn-1 lyso-PC). Toxic organic solvents were avoided. Six possible microunits of our aqueous system consisting of three PLs donors (PC, lyso-PC, sn-glycero-3-PC) and two DHA donors (DHA and DHA salts), were simulated by molecular dynamics (MD) to illustrate the enzymatic mechanism based on diffusional channels, competitive bindings, and enzymatic structures.
ESTHER : Zhang_2023_Food.Chem_431_137164
PubMedSearch : Zhang_2023_Food.Chem_431_137164
PubMedID: 37607420

Title : Green biosynthesis of rare DHA-phospholipids by lipase-catalyzed transesterification with edible algal oil in solvent-free system and catalytic mechanism study - Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
Author(s) : Zhang T , Li B , Wang Z , Hu D , Zhang X , Zhao B , Wang J
Ref : Front Bioeng Biotechnol , 11 :1158348 , 2023
Abstract : Docosahexaenoic acid (DHA)-enriched phosphatidylcholine (PC) has received significant scientific attention due to the health benefits in food and pharmaceutical products. In this work, the edible algal oil rich in DHA-triacylglycerol (DHA-TAG) without pretreatment was first used as the DHA donor for the transesterification of phospholipids (PLs) to prepare three kinds of rare PLs, including DHA-PC, DHA-phosphatidylethanolamine (DHA-PE), and DHA-phosphatidylserine (DHA-PS). Here, 153 protein structures of triacylglycerol lipase (EC 3.1.1.3) were virtually screened and evaluated by transesterification. PLA1 was the best candidate due to a higher DHA incorporation. Results showed that the transesterification of PC with DHA-TAG at 45 degreesC and 0.7% water content (without additional water addition) could produce DHA-PC with 39.1% DHA incorporation at 30 min. The different DHA donors, including forms of fatty acid, methyl ester, and triglycerides, were compared. Molecular dynamics (MD) was used to illustrate the catalytic mechanism at the molecular level containing the diffusions of substrates, the structure-activity relationship of PLA1, and the effect of water content.
ESTHER : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedSearch : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedID: 37064237

Title : Identification and characterization of novel carboxyl ester lipase gene variants in patients with different subtypes of diabetes - Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
Author(s) : Wu H , Shu M , Liu C , Zhao W , Li Q , Song Y , Zhang T , Chen X , Shi Y , Shi P , Fang L , Wang R , Xu C
Ref : BMJ Open Diabetes Res Care , 11 : , 2023
Abstract : INTRODUCTION: Mutations of CEL gene were first reported to cause a new type of maturity-onset diabetes of the young (MODY) denoted as MODY8 and then were also found in patients with type 1 (T1D) and type 2 diabetes (T2D). However, its genotype-phenotype relationship has not been fully determined and how carboxyl ester lipase (CEL) variants result in diabetes remains unclear. The aim of our study was to identify pathogenic variants of CEL in patients with diabetes and confirm their pathogenicity. RESEARCH DESIGN AND METHODS: All five patients enrolled in our study were admitted to Shandong Provincial Hospital and diagnosed with diabetes in the past year. Whole-exome sequencing was performed to identify pathogenic variants in three patients with MODY-like diabetes, one newborn baby with T1D and one patient with atypical T2D, as well as their immediate family members. Then the consequences of the identified variants were predicted by bioinformatic analysis. Furthermore, pathogenic effects of two novel CEL variants were evaluated in HEK293 cells transfected with wild-type and mutant plasmids. Finally, we summarized all CEL gene variants recorded in Human Gene Mutation Database and analyzed the mutation distribution of CEL. RESULTS: Five novel heterozygous variants were identified in CEL gene and they were predicted to be pathogenic by bioinformatic analysis. Moreover, in vitro studies indicated that the expression of CEL(R540C) was remarkably increased, while p.G729_T739del variant did not significantly affect the expression of CEL. Both novel variants obviously abrogated the secretion of CEL. Furthermore, we summarized all reported CEL variants and found that 74.3% of missense mutations were located in exons 1, 3, 4, 10 and 11 and most missense variants clustered near catalytic triad, Arg-83 and Arg-443. CONCLUSION: Our study identified five novel CEL variants in patients with different subtypes of diabetes, expanding the gene mutation spectrum of CEL and confirmed the pathogenicity of several novel variants.
ESTHER : Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
PubMedSearch : Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
PubMedID: 36634979
Gene_locus related to this paper: human-CEL

Title : Discovery of novel deoxyvasicinone derivatives with benzenesulfonamide substituents as multifunctional agents against Alzheimer's disease - Dong_2023_Eur.J.Med.Chem_264_116013
Author(s) : Dong S , Xia J , Wang F , Yang L , Xing S , Du J , Zhang T , Li Z
Ref : Eur Journal of Medicinal Chemistry , 264 :116013 , 2023
Abstract : A series of deoxyvasicinone derivatives with benzenesulfonamide substituents were designed and synthesized to find a multifunctional anti-Alzheimer's disease (AD) drug. The results of the biological activity evaluation indicated that most compounds demonstrated selective inhibition of acetylcholinesterase (AChE). Among them, g17 exhibited the most potent inhibitory effect on AChE (IC(50) = 0.24 +/- 0.04 microM). Additionally, g17 exhibited promising properties as a metal chelator and inhibitor of amyloid beta peptides self-aggregation (68.34 % +/- 1.16 %). Research on oxidative stress has shown that g17 displays neuroprotective effects and effectively suppresses the intracellular accumulation of reactive oxygen species. Besides, g17 demonstrated remarkable anti-neuroinflammatory effects by significantly reducing the production of pro-inflammatory cytokines (such as NO, IL-1beta, and TNF-alpha) and inhibiting the expression of inflammatory mediators iNOS and COX-2. In vivo studies showed that g17 significantly improved AD model mice's cognitive and memory abilities. Histological examination of mouse hippocampal tissue sections using hematoxylin and eosin staining revealed that g17 effectively mitigates neuronal damage. Considering the multifunctional properties of g17, it is regarded as a promising lead compound for treating AD.
ESTHER : Dong_2023_Eur.J.Med.Chem_264_116013
PubMedSearch : Dong_2023_Eur.J.Med.Chem_264_116013
PubMedID: 38052155

Title : Characterization of the metabolism of eupalinolide A and B by carboxylesterase and cytochrome P450 in human liver microsomes - Li_2023_Front.Pharmacol_14_1093696
Author(s) : Li Y , Liu X , Li L , Zhang T , Gao Y , Zeng K , Wang Q
Ref : Front Pharmacol , 14 :1093696 , 2023
Abstract : Eupalinolide A (EA; Z-configuration) and eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role.
ESTHER : Li_2023_Front.Pharmacol_14_1093696
PubMedSearch : Li_2023_Front.Pharmacol_14_1093696
PubMedID: 36762117

Title : Physiologically-based pharmacokinetic modeling to predict methylphenidate exposure affected by interplay among carboxylesterase 1 pharmacogenetics, drug-drug interactions, and sex - Xiao_2022_J.Pharm.Sci__
Author(s) : Xiao J , Shi J , Thompson BR , Smith DE , Zhang T , Zhu HJ
Ref : J Pharm Sci , : , 2022
Abstract : BACKGROUND AND OBJECTIVE: The pharmacokinetics (PK) of methylphenidate (MPH) differ significantly among individuals. Carboxylesterase 1 (CES1) is the primary enzyme metabolizing MPH, and its function is affected by genetic variants, drug-drug interaction (DDI), and sex. The object of this study is to evaluate CES1 pharmacogenetics as related to MPH metabolism using human liver samples and develop a physiologically-based pharmacokinetic (PBPK) modeling approach to investigate the influence of CES1 genotypes and other factors on MPH PK. METHODS: The effect of the CES1 variant G143E (rs71647871) on MPH metabolism was studied utilizing 102 individual human liver S9 (HLS9) fraction samples. PBPK models were developed using the population-based PBPK software PK-Sim(a) by incorporating the HLS9 incubation data. The established models were applied to simulate MPH PK profiles under various clinical scenarios, including different genotypes, drug-alcohol interactions, and the difference between males and females. RESULTSL: The HLS9 incubation study showed that subjects heterozygous for the CES1 variant G143E metabolized MPH at a rate of approximately 50% of that in non-carriers. The developed PBPK models successfully predicted the exposure alteration of MPH from the G143E genetic variant, ethanol-MPH DDI, and sex. Importantly, the study suggests that male G143E carriers who are alcohol consumers are at a higher risk of MPH overexposure. CONCLUSION: PBPK modeling provides a means for better understanding the mechanisms underlying interindividual variability in MPH PK and PD and could be utilized to develop a safer and more effective MPH pharmacotherapy regimen.
ESTHER : Xiao_2022_J.Pharm.Sci__
PubMedSearch : Xiao_2022_J.Pharm.Sci__
PubMedID: 35526575

Title : High-Resolution Bioassay Profiling with Complemented Sensitivity and Resolution for Pancreatic Lipase Inhibitor Screening - Jian_2022_Molecules_27_
Author(s) : Jian J , Yuan J , Fan Y , Wang J , Zhang T , Kool J , Jiang Z
Ref : Molecules , 27 : , 2022
Abstract : How to rapidly and accurately screen bioactive components from complex natural products remains a major challenge. In this study, a screening platform for pancreatic lipase (PL) inhibitors was established by combining magnetic beads-based ligand fishing and high-resolution bioassay profiling. This platform was well validated using a mixture of standard compounds, i.e., (-)- epigallocatechin gallate (EGCG), luteolin and schisandrin. The dose-effect relationship of high-resolution bioassay profiling was demonstrated by the standard mixture with different concentrations for each compound. The screening of PL inhibitors from green tea extract at the concentrations of 0.2, 0.5 and 1.0 mg/mL by independent high-resolution bioassay profiling was performed. After sample pre-treatment by ligand fishing, green tea extract at the concentration of 0.2 mg/mL was specifically enriched and simplified, and consequently screened through the high-resolution bioassay profiling. As a result, three PL inhibitors, i.e., EGCG, (-)-Gallocatechin gallate (GCG) and (-)-Epicatechin gallate (ECG), were rapidly identified from the complex matrix. The established platform proved to be capable of enriching affinity binders and eliminating nonbinders in sample pre-treatment by ligand fishing, which overcame the technical challenges of high-resolution bioassay profiling in the aspects of sensitivity and resolution. Meanwhile, the high-resolution bioassay profiling possesses the ability of direct bioactive assessment, parallel structural analysis and identification after separation. The established platform allowed more accurate and rapid screening of PL inhibitors, which greatly facilitated natural product-based drug screening.
ESTHER : Jian_2022_Molecules_27_
PubMedSearch : Jian_2022_Molecules_27_
PubMedID: 36296516

Title : Mitigation of Memory Impairment with Fermented Fucoidan and lambda-Carrageenan Supplementation through Modulating the Gut Microbiota and Their Metagenome Function in Hippocampal Amyloid-beta Infused Rats - Zhang_2022_Cells_11_
Author(s) : Zhang T , Wu X , Yuan H , Huang S , Park S
Ref : Cells , 11 : , 2022
Abstract : Attenuating acetylcholinesterase and insulin/insulin-like growth factor-1 signaling in the hippocampus is associated with Alzheimer's disease (AD) development. Fucoidan and carrageenan are brown and red algae, respectively, with potent antibacterial, anti-inflammatory, antioxidant and antiviral activities. This study examined how low-molecular-weight (MW) and high-MW fucoidan and lambda-carrageenan would improve memory impairment in Alzheimer's disease-induced rats caused by an infusion of toxic amyloid-beta(Abeta). Fucoidan and lambda-carrageenan were dissected into low-MW by Luteolibacter&nbsp;algae and Pseudoalteromonas&nbsp;carrageenovora. Rats receiving an Abeta(25-35) infusion in the CA1 region of the hippocampus were fed dextrin (AD-Con), 1% high-MW fucoidan (AD-F-H), 1% low-MW fucoidan (AD-F-L), 1% high-MW lambda-carrageenan (AD-C-H), and 1% low-MW lambda-carrageenan (AD-C-L) for six weeks. Rats to receive saline infusion (Normal-Con) had an AD-Con diet. The AD-F-L group showed an improved memory function, which manifested as an enhanced Y-maze spontaneous alternation test, water maze, and passive avoidance tests, similar to the Normal-Con group. AD-F-L also potentiated hippocampal insulin signaling and increased the expression of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the hippocampus. AD-C-L improved the memory function mainly by increasing the BDNF content. AD-F-H and AD-C-H did not improve the memory function. Compared to AD-Con, the ascending order of AD-C-H, AD-F-H, AD-C-L, and AD-F-L increased insulin signaling by enhancing the pSTAT3(a)pAkt(a)pGSK-3beta pathway. AD-F-L improved glucose tolerance the most. Compared to AD-CON, the AD-F-L treatment increased the serum acetate concentrations and compensated for the defect of cerebral glucose metabolism. AD-Con increased Clostridium, Terrisporobacter and Sporofaciens compared to Normal-Con, and AD-F-L and AD-C-L increased Akkermentia. In conclusion, AD-F-L and AD-C-L alleviated the memory function in the rats with induced AD symptoms by modulating.
ESTHER : Zhang_2022_Cells_11_
PubMedSearch : Zhang_2022_Cells_11_
PubMedID: 35892598

Title : Long-Term Effect of Porcine Brain Enzyme Hydrolysate Intake on Scopolamine-Induced Memory Impairment in Rats - Zhang_2022_Int.J.Mol.Sci_23_3361
Author(s) : Zhang T , Kim MJ , Wu X , Yang HJ , Yuan H , Huang S , Yoon SM , Kim KN , Park S
Ref : Int J Mol Sci , 23 :3361 , 2022
Abstract : No study has revealed the effect of porcine brain enzyme hydrolysate (PBEH) on memory impairment. We aimed to examine the hypothesis that PBEH intake modulates memory deficits and cognitive behavior in scopolamine (SC)-induced amnesia rats, and its mechanism, including gut microbiota changes, was determined. Sprague-Dawley male rats had intraperitoneal injections of SC (2 mg/kg body weight/day) at 30 min after daily feeding of casein (MD-control), PBEH (7 mg total nitrogen/mL) at 0.053 mL (Low-PBEH), 0.159 mL (Medium-PBEH), 0.478 mL (High-PBEH), or 10 mg donepezil (Positive-control) per kilogram body weight per day through a feeding needle for six weeks. The Normal-control rats had casein feeding without SC injection. PBEH dose-dependently protected against memory deficits determined by passive avoidance test, Y-maze, water-maze, and novel object recognition test in SC-induced rats compared to the MD-control. The High-PBEH group had a similar memory function to the Positive-control group. Systemic insulin resistance determined by HOMA-IR was lower in the PBEH groups than in the Normal-control but not the Positive-control. In parallel with systemic insulin resistance, decreased cholesterol and increased glycogen contents in the hippocampus in the Medium-PBEH and High-PBEH represented reduced brain insulin resistance. PBEH intake prevented the increment of serum TNF-alpha and IL-1beta concentrations in the SC-injected rats. Hippocampal lipid peroxide and TNF-alpha contents and mRNA TNF-alpha and IL-1beta expression were dose-dependently reduced in PBEH and Positive-control. PBEH decreased the hippocampal acetylcholinesterase activity compared to the MD-control, but not as much as the Positive-control. PBEH intake increased the alpha-diversity of the gut microbiota compared to the MD-control, and the gut microbiota community was separated from MD-control. In metagenome function analysis, PBEH increased the energy metabolism-related pathways of the gut microbiota, including citric acid cycle, oxidative phosphorylation, glycolysis, and amino acid metabolism, which were lower in the MD-control than the Normal-control. In conclusion, alleviated memory deficit by PBEH was associated potentially with not only reducing acetylcholinesterase activity but also improving brain insulin resistance and neuroinflammation potentially through modulating gut microbiota. PBEH intake (1.5-4.5 mL of 7 mg total nitrogen/mL for human equivalent) can be a potential therapeutic agent for improving memory impairment.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_3361
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_3361
PubMedID: 35328781

Title : Simultaneous Inhibitory Effects of All-Trans Astaxanthin on Acetylcholinesterase and Oxidative Stress - Wang_2022_Mar.Drugs_20_
Author(s) : Wang X , Zhang T , Chen X , Xu Y , Li Z , Yang Y , Du X , Jiang Z , Ni H
Ref : Mar Drugs , 20 : , 2022
Abstract : Alzheimers disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was evaluated by a chemical-based method in vitro and cell assay model. The results show that all-trans astaxanthin was a reversible competitive inhibitor and exhibited a strong inhibition effect with half inhibitory concentration (IC(50) value) of 8.64 micromol/L. Furthermore, all-trans astaxanthin inhibited oxidative stress through reducing malondialdehyde content and increasing the activity of superoxide dismutase as well as catalase. All-trans astaxanthin could induce the changes of the secondary structure to reduce acetylcholinesterase activity. Molecular-docking analysis reveals that all-trans astaxanthin prevented substrate from binding to acetylcholinesterase by occupying the space of the active pocket to cause the inhibition. Our finding suggests that all-trans astaxanthin might be a nutraceutical supplement for Alzheimers disease prevention.
ESTHER : Wang_2022_Mar.Drugs_20_
PubMedSearch : Wang_2022_Mar.Drugs_20_
PubMedID: 35447920

Title : Recovery of dopaminergic system after cocaine exposure and impact of a long-acting cocaine hydrolase - Deng_2022_Addict.Biol_27_e13179
Author(s) : Deng J , Zhang T , Zheng X , Shang L , Zhan CG , Zheng F
Ref : Addict Biol , 27 :e13179 , 2022
Abstract : Dysregulation of dopamine transporters (DAT) within the dopaminergic system is an important biomarker of cocaine exposure. Depending on cocaine amount in-taken, one-time exposure in rats could lead to most (>95% of total) of DAT translocating to plasma membrane of the dopaminergic neurons compared to normal DAT distribution (~5.7% on the plasma membrane). Without further cocaine exposure, the time course of striatal DAT distribution, in terms of intracellular and plasma membrane fractions of DAT, represents a recovery process of the dopaminergic system. In this study, we demonstrated that after an acute cocaine exposure of 20 mg/kg (i.p.), the initial recovery process from days 1 to 15 in rats was relatively faster (from >95% on day 1 to ~35.4% on day 15). However, complete recovery of the striatal DAT distribution may take about 60 days. In another situation, with repeated cocaine exposures for once every other day for a total of 17 doses of 20 mg/kg cocaine (i.p.) from days 0 to 32, the complete recovery of striatal DAT distribution may take an even longer time (about 90 days), which represents a consequence of chronic cocaine use. Further, we demonstrated that a highly efficient Fc-fused cocaine hydrolase, CocH5-Fc(M6), effectively blocked cocaine-induced hyperactivity and DAT trafficking with repeated cocaine exposures by maintaining a plasma CocH5-Fc(M6) concentration <=58.7 +/- 2.9 nM in rats. The cocaine hydrolase protected dopaminergic system and helped the cocaine-altered DAT distribution to recover by preventing the dopaminergic system from further damage by cocaine.
ESTHER : Deng_2022_Addict.Biol_27_e13179
PubMedSearch : Deng_2022_Addict.Biol_27_e13179
PubMedID: 35754103

Title : Effects of alcohol on metabolism and toxicity of cocaine in rats - Shang_2022_Toxicol.Rep_9_1586
Author(s) : Shang L , Zheng X , Zhang T , Deng J , Zhan CG , Zheng F
Ref : Toxicol Rep , 9 :1586 , 2022
Abstract : As most cocaine users drink alcohol, it is interesting to understand how a non-lethal dose of alcohol affects the metabolism and toxicity of cocaine. In this study, we examined the correlation between dose-dependent toxicity and the metabolism/pharmacokinetic (PK) profile of cocaine with or without alcohol (ethanol, 1sg/kg) co-administration in rats. The cocaine toxicity in rats with or without alcohol co-administration is characterized by not only the commonly used LD(50), but also the average times for the appearance of convulsion and death as well as total toxicity level (TTL) in the blood. All these data have consistently demonstrated that co-administration of alcohol increased cocaine toxicity, and that the alcohol-enhanced toxicity of cocaine is mainly attributed to the observed two additional metabolites (cocaethylene and norcocaethylene - products of chemical reactions of cocaine with alcohol catalyzed by metabolic enzymes carboxylesterase-1 and liver microsomal cytochrome P450 3A4) that are more toxic than cocaine itself. So, evaluation of the substance TTL should account for the blood levels of not only cocaine itself, but also its all toxic metabolites. In addition, for rats died of a lethal dose of cocaine (60 or 100smg/kg) combined with 1sg/kg alcohol, we also determined the TTL at the time of death, demonstrating that death would occur once the TTL reached a threshold (~16smicroM).
ESTHER : Shang_2022_Toxicol.Rep_9_1586
PubMedSearch : Shang_2022_Toxicol.Rep_9_1586
PubMedID: 36518391

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

Title : Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial - Xu_2022_Diabetes.Obes.Metab__
Author(s) : Xu J , Ling H , Geng J , Huang Y , Xie Y , Zheng H , Niu H , Zhang T , Yuan J , Xiao X
Ref : Diabetes Obes Metab , : , 2022
Abstract : AIMS: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl-peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with metformin. MATERIALS AND METHODS: In this 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2DM patients with glycated hemoglobin A1c (HbA1c) levels ranging from 7.0-9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108+metformin and placebo+metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS: At week 24, the least-square (LS) mean (standard error [SE]) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than that in the placebo group (-0.07% [0.11%]) (P-value <0.001), with a treatment difference of -0.63% (95% confidence interval [CI]: -0.87, -0.39) on full analysis set. A higher proportion of patients achieved an HbA1c >=6.5% (19.7% vs. 8.5%) and HbA1c >=7.0% (50.0% vs. 21.1%) at week 24 in the DBPR108+metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose (2-h PPG) without causing weight gain. The overall frequency of adverse events (AEs) was similar between the two groups. CONCLUSIONS: DBPR108 as add-on therapy to metformin offered a significant improvement in glycemic control, was superior to metformin monotherapy (placebo), and was safe and well-tolerated in T2DM patients that is inadequately controlled with metformin. This article is protected by copyright. All rights reserved.
ESTHER : Xu_2022_Diabetes.Obes.Metab__
PubMedSearch : Xu_2022_Diabetes.Obes.Metab__
PubMedID: 35791646

Title : On the initiation of jasmonate biosynthesis in wounded leaves - Kimberlin_2022_Plant.Physiol__
Author(s) : Kimberlin AN , Holtsclaw RE , Zhang T , Mulaudzi T , Koo AJ
Ref : Plant Physiol , : , 2022
Abstract : The basal level of the plant defense hormone jasmonate (JA) in unstressed leaves is low, but wounding causes its near instantaneous increase. How JA biosynthesis is initiated is uncertain, but the lipolysis step that generates fatty acid precursors is generally considered to be the first step. Here, we used a series of physiological, pharmacological, genetic, and kinetic analyses of gene expression and hormone profiling to demonstrate that the early spiking of JA upon wounding does not depend on the expression of JA biosynthetic genes in Arabidopsis (Arabidopsis thaliana). Using a transgenic system, we showed how decoupling the responses to wounding and JA prevents the perpetual synthesis of JA in wounded leaves. We then used DEFECTIVE IN ANTHER DEHISCENCE1 (DAD1) as a model wound-responsive lipase to demonstrate that although its transient expression in leaves can elicit JA biosynthesis to a low level, an additional level of activation is triggered by wounding, which causes massive accumulation of JA. This wound-triggered boosting effect of DAD1-mediated JA synthesis can happen directly in damaged leaves or indirectly in undamaged remote leaves by the systemically transmitted wound signal. Finally, protein stability of DAD1 was influenced by wounding, alpha-linolenic acid, and mutation in its catalytic site. Together, the data support mechanisms that are independent of gene transcription and translation to initiate the rapid JA burst in wounded leaves and demonstrate how transient expression of the lipase can be used to reveal changes occurring at the level of activity and stability of the key lipolytic step.
ESTHER : Kimberlin_2022_Plant.Physiol__
PubMedSearch : Kimberlin_2022_Plant.Physiol__
PubMedID: 35404431
Gene_locus related to this paper: arath-PLA11

Title : Valorization of Polyethylene Terephthalate to Muconic Acid by Engineering Pseudomonas Putida - Liu_2022_Int.J.Mol.Sci_23_10997
Author(s) : Liu P , Zheng Y , Yuan Y , Zhang T , Li Q , Liang Q , Su T , Qi Q
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Plastic waste is rapidly accumulating in the environment and becoming a huge global challenge. Many studies have highlighted the role of microbial metabolic engineering for the valorization of polyethylene terephthalate (PET) waste. In this study, we proposed a new conceptual scheme for upcycling of PET. We constructed a multifunctional Pseudomonas putida KT2440 to simultaneously secrete PET hydrolase LCC, a leaf-branch compost cutinase, and synthesize muconic acid (MA) using the PET hydrolysate. The final product MA and extracellular LCC can be separated from the supernatant of the culture by ultrafiltration, and the latter was used for the next round of PET hydrolysis. A total of 0.50 g MA was produced from 1 g PET in each cycle of the whole biological processes, reaching 68% of the theoretical conversion. This new conceptual scheme for the valorization of PET waste should have advantages over existing PET upcycling schemes and provides new ideas for the utilization of other macromolecular resources that are difficult to decompose, such as lignin.
ESTHER : Liu_2022_Int.J.Mol.Sci_23_10997
PubMedSearch : Liu_2022_Int.J.Mol.Sci_23_10997
PubMedID: 36232310

Title : Ratiometric fluorescent hydrogel for point-of-care monitoring of organophosphorus pesticide degradation - Li_2022_J.Hazard.Mater_432_128660
Author(s) : Li H , Zou R , Su C , Zhang N , Wang Q , Zhang Y , Zhang T , Sun C , Yan X
Ref : J Hazard Mater , 432 :128660 , 2022
Abstract : The residues of organophosphorus pesticides have caused the potential risk in environment and human health, arousing worldwidely great concern. Herein, we fabricated a robust gold nanoclusters/MnO(2) composites-based hydrogel portable kit for accurate monitoring of paraoxon residues and degradation in Chinese cabbages. With the immobilization of gold nanoclusters/MnO(2) composites into a hydrogel, a ratiometric fluorescent signal is generated by catalyzing the oxidation of o-phenylenediamine, which possesses a built-in correction with low background interference. Coupling with acetylcholinesterase catalytic reactions and pesticide inhibition effect, the portable kit can sensitively detect paraoxon residues with a detection limit of 5.0 ng mL(-1). For on-site quantification, the fluorescent color variations of portable kit are converted into digital information that exhibits applicative linear range toward pesticide. Notably, the hydrogel portable kit was successfully applied for precisely monitoring the residue and degradation of paraoxon in Chinese cabbage, providing a potential pathway toward practical point-of-care testing in food safety monitoring.
ESTHER : Li_2022_J.Hazard.Mater_432_128660
PubMedSearch : Li_2022_J.Hazard.Mater_432_128660
PubMedID: 35334266

Title : QSSR Modeling of Bacillus Subtilis Lipase A Peptide Collision Cross-Sections in Ion Mobility Spectrometry: Local Descriptor Versus Global Descriptor - Ni_2021_Protein.J__
Author(s) : Ni Z , Wang A , Kang L , Zhang T
Ref : Protein J , : , 2021
Abstract : To investigate the structure-dependent peptide mobility behavior in ion mobility spectrometry (IMS), quantitative structure-spectrum relationship (QSSR) is systematically modeled and predicted for the collision cross section values of totally 162 single-protonated tripeptide fragments extracted from the Bacillus subtilis lipase A. Two different types of structure characterization methods, namely, local and global descriptor as well as three machine learning methods, namely, partial least squares (PLS), support vector machine (SVM) and Gaussian process (GP), are employed to parameterize and correlate the structures and values of these peptide samples. In this procedure, the local descriptor is derived from the principal component analysis (PCA) of 516 physicochemical properties for 20 standard amino acids, which can be used to sequentially characterize the three amino acid residues composing a tripeptide. The global descriptor is calculated using CODESSA method, which can generate > 200 statistically significant variables to characterize the whole molecular structure of a tripeptide. The obtained QSSR models are evaluated rigorously via tenfold cross-validation and Monte Carlo cross-validation (MCCV). A comprehensive comparison is performed on the resulting statistics arising from the systematic combination of different descriptor types and machine learning methods. It is revealed that the local descriptor-based QSSR models have a better fitting ability and predictive power, but worse interpretability, than those based on the global descriptor. In addition, since the QSSR modeling using local descriptor does not consider the three-dimensional conformation of tripeptide samples, the method would be largely efficient as compared to the global descriptor.
ESTHER : Ni_2021_Protein.J__
PubMedSearch : Ni_2021_Protein.J__
PubMedID: 33454893

Title : Characterization of Feruloyl Esterase from Bacillus pumilus SK52.001 and Its Application in Ferulic Acid Production from De-Starched Wheat Bran - Duan_2021_Foods_10_
Author(s) : Duan X , Dai Y , Zhang T
Ref : Foods , 10 : , 2021
Abstract : Feruloyl esterase (FAE; EC 3.1.1.73) catalyzes the hydrolysis of the 4-hydroxy-3-methoxycinnamoyl group in an esterified sugar to assist in waste biomass degradation or to release ferulic acid (FA). An FAE-producing strain was isolated from humus soil samples and identified as Bacillus pumilus SK52.001. The BpFAE gene from B. pumilus SK52.001 was speculated and heterogeneously expressed in Bacillus subtilis WB800 for the first time. The enzyme exists as a monomer with 303 amino acids and a molecular mass of 33.6 kDa. Its specific activity was 377.9 +/- 10.3 U/ (mg protein), using methyl ferulate as a substrate. It displays an optimal alkaline pH of 9.0, an optimal temperature of 50 degreesC, and half-lives of 1434, 327, 235, and 68 min at 50, 55, 60, and 65 degreesC, respectively. Moreover, the purified BpFAE released 4.98% FA of the alkali-acidic extractable FA from de-starched wheat bran (DSWB). When the DSWB was enzymatically degraded by the synergistic effect of the BpFAE and commercial xylanase, the FA amount reached 49.47%. It suggested that the alkaline BpFAE from B. pumilus SK52.001, which was heterologously expressed in B. subtilis WB800, possesses great potential for biomass degradation and achieving high-added value FA production from food by-products.
ESTHER : Duan_2021_Foods_10_
PubMedSearch : Duan_2021_Foods_10_
PubMedID: 34071417
Gene_locus related to this paper: bacpu-QWF08340

Title : The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model - Wang_2021_Am.J.Sports.Med__363546520988680
Author(s) : Wang Z , Chen Y , Xiao H , Li S , Zhang T , Hu J , Lu H , Xie H
Ref : Am J Sports Med , :363546520988680 , 2021
Abstract : BACKGROUND: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury. HYPOTHESIS: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10(-5) M ACh group (received FG containing 10(-5) M ACh), 10(-6) M ACh group (received FG containing 10(-6) M ACh), and PYR group (received FG containing 25 microg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis. RESULTS: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10(-5) M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks (P < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group. CONCLUSION: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair. CLINICAL RELEVANCE: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing.
ESTHER : Wang_2021_Am.J.Sports.Med__363546520988680
PubMedSearch : Wang_2021_Am.J.Sports.Med__363546520988680
PubMedID: 33592162

Title : Toxic effects of subacute exposure to acrylamide on motor endplates of the gastrocnemius in rats - Yanxian_2021_Toxicology__152934
Author(s) : Yanxian B , Gu Z , Zhang T , Luo Y , Zhang C , Luo L , Ma Y , Liu J
Ref : Toxicology , :152934 , 2021
Abstract : Acrylamide (ACR) is a recognized toxin that is known to induce neurotoxicity in humans and experimental animals. This study aimed to investigate the toxic effects of subacute exposure of the motor endplate (MEP) of the gastrocnemius in rats to ACR. All rats were randomly divided into control, 9, 18, and 36 mg/kg ACR groups, and ACR was administered by gastric gavage for 21 days. The behavioral tests were performed weekly. On the 22(nd) day, the wet weight of the gastrocnemius was measured. The changes in muscle fiber structure, nerve endings, and MEP in the gastrocnemius were examined by hematoxylin-eosin (HE) and gold chloride staining. Acetylcholinesterase (AChE) content in the gastrocnemius was detected by AChE staining. The expression of AChE and calcitonin gene-related peptide was detected by immunohistochemistry and western blot. Rats exposed to ACR showed a significant increase in gait scores and hind limb splay distance compared with the control group, and the wet weight of the gastrocnemius was reduced, HE staining showed that the muscle fiber structure of the gastrocnemius became thin and the arrangement was dense with nuclear aggregation, gold chloride staining showed that nerve branches decreased and became thin, nerve fibers became short and light, the number of MEPs was decreased, the staining became light, and the structure was not clear. AChE staining showed that the number of MEPs was significantly reduced after exposure to ACR, the shape became small, and the AChE content decreased in a dose-dependent manner. Immunohistochemistry and western blot analysis results of the expression levels of AchE and CGRP showed a decreasing trend as compared to the control group with increasing ACR exposure dose. The reduction in protein levels may be the mechanism by which ACR has a toxic effect on the MEP in the gastrocnemius of rats.
ESTHER : Yanxian_2021_Toxicology__152934
PubMedSearch : Yanxian_2021_Toxicology__152934
PubMedID: 34509579

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

Title : Immobilized lipase catalytic synthesis of phenolamides and their potential against alpha-glucosidase - Zeng_2021_J.Biotechnol__
Author(s) : Zeng F , Zhang H , Xu M , Huang K , Zhang T , Duan J
Ref : J Biotechnol , : , 2021
Abstract : Although coumaroyltyramine (CT) derivatives are one kind of phenolamides with remarkable biological activities, the low content in plants would inhibit their potential use in food and pharmaceutical industries. Therefore, it is necessary to screen an efficient method to produce CT derivatives. A green and efficient method by using lipase as catalyst to synthesize a series of CT derivatives, was thus proposed. To obtain optimum reaction conditions, the effects of various parameters on conversion rate were firstly evaluated. An in vitro alpha-glucosidase inhibitory assay of synthesized compounds was then carried out, and the structure-activity relationship of these compounds was conducted. Under the optimum conditions (MTBE, Nu/S: 2/1, E/S: 20/1, 50 degreesC and 24 h), the conversion rates of synthesized compounds were above 65%. The bioassay results indicated that N-trans-caffeoyltyramine and N-trans-feruloyltyramine had potent activities against alpha-glucosidase with IC(50) of 30.08 microM and 31.94 microM, respectively. The structure-activity relationship results showed that the presence of -OH or -OCH(3) group at C-3 position could boost the activities of CT derivatives. Meanwhile, the presence of -OH group at C-4 position and double bound on caffeoyl moiety as well as the presence of -OH group at C-4' position was essential for the activities of CT derivatives.
ESTHER : Zeng_2021_J.Biotechnol__
PubMedSearch : Zeng_2021_J.Biotechnol__
PubMedID: 33878390

Title : Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy - Zou_2021_J.Proteomics__104124
Author(s) : Zou S , Dong R , Wang J , Liang B , Zhu T , Zhao S , Zhang Y , Wang T , Zou P , Li N , Wang Y , Chen M , Zhou C , Zhang T , Luo L
Ref : J Proteomics , :104124 , 2021
Abstract : We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SIGNIFICANCE: This preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP.
ESTHER : Zou_2021_J.Proteomics__104124
PubMedSearch : Zou_2021_J.Proteomics__104124
PubMedID: 33545297

Title : Biological detoxification of fumonisin by a novel carboxylesterase from Sphingomonadales bacterium and its biochemical characterization - Li_2021_Int.J.Biol.Macromol_169_18
Author(s) : Li Z , Wang Y , Liu Z , Jin S , Pan K , Liu H , Liu T , Li X , Zhang C , Luo X , Song Y , Zhao J , Zhang T
Ref : Int J Biol Macromol , 169 :18 , 2021
Abstract : Fumonisins have posed hazardous threat to human and animal health worldwide. Enzymatic degradation is a desirable detoxification approach but is severely hindered by serious shortage of detoxification enzymes. After mining enzymes by bioinformatics analysis, a novel carboxylesterase FumDSB from Sphingomonadales bacterium was expressed in Escherichia coli, and confirmed to catalyze fumonisin B1 to produce hydrolyzed fumonisin B1 by liquid chromatography mass spectrometry for the first time. FumDSB showed high sequence novelty, sharing only ~34% sequence identity with three reported fumonisin detoxification carboxylesterases. Besides, FumDSB displayed its high degrading activity at 30-40 degreesC within a broad pH range from 6.0 to 9.0, which is perfectly suitable to be used in animal physiological condition. It also exhibited excellent pH stability and moderate thermostability. This study provides a FB1 detoxification carboxylesterase which could be further used as a potential food and feed additive.
ESTHER : Li_2021_Int.J.Biol.Macromol_169_18
PubMedSearch : Li_2021_Int.J.Biol.Macromol_169_18
PubMedID: 33309671
Gene_locus related to this paper: 9sphn-a0a101vlk1

Title : The Roles of Dipeptidyl Peptidase 4 (DPP4) and DPP4 Inhibitors in Different Lung Diseases: New Evidence - Zhang_2021_Front.Pharmacol_12_731453
Author(s) : Zhang T , Tong X , Zhang S , Wang D , Wang L , Wang Q , Fan H
Ref : Front Pharmacol , 12 :731453 , 2021
Abstract : CD26/Dipeptidyl peptidase 4 (DPP4) is a type II transmembrane glycoprotein that is widely expressed in various organs and cells. It can also exist in body fluids in a soluble form. DPP4 participates in various physiological and pathological processes by regulating energy metabolism, inflammation, and immune function. DPP4 inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus. More evidence has shown the role of DPP4 in the pathogenesis of lung diseases, since it is highly expressed in the lung parenchyma and the surface of the epithelium, vascular endothelium, and fibroblasts of human bronchi. It is a potential biomarker and therapeutic target for various lung diseases. During the coronavirus disease-19 (COVID-19) global pandemic, DPP4 was found to be an important marker that may play a significant role in disease progression. Some clinical trials on DPP4 inhibitors in COVID-19 are ongoing. DPP4 also affects other infectious respiratory diseases such as Middle East respiratory syndrome and non-infectious lung diseases such as pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and asthma. This review aims to summarize the roles of DPP4 and its inhibitors in infectious lung diseases and non-infectious diseases to provide new insights for clinical physicians.
ESTHER : Zhang_2021_Front.Pharmacol_12_731453
PubMedSearch : Zhang_2021_Front.Pharmacol_12_731453
PubMedID: 34955820

Title : Development and validation of genomic and epigenomic signatures associated with tumor immune microenvironment in hepatoblastoma - Zhang_2021_BMC.Cancer_21_1156
Author(s) : Zhang Y , Zhang T , Yin Q , Luo H
Ref : BMC Cancer , 21 :1156 , 2021
Abstract : BACKGROUND: This study aimed to probe and verify aberrantly methylated and expressed genes in hepatoblastoma and to analyze their interactions with tumor immune microenvironment. METHODS: Aberrantly methylated and expressed genes were obtained by comprehensively analyzing gene expression and DNA methylation profiles from GSE81928, GSE75271 and GSE78732 datasets. Their biological functions were predicted by the STRING and Metascape databases. CIBERSORT was utilized for inferring the compositions of tumor-infiltrating immune cells (TIICs) in each sample. Correlation between hub genes and immune cells was then analyzed. Hub genes were validated in hepatoblastoma tissues via western blot or immunohistochemistry. After transfection with sh-NOTUM, migration and invasion of HuH-6 and HepG2 cells were investigated. The nude mouse tumorigenesis model was constructed. RESULTS: Totally, 83 aberrantly methylated and expressed genes were determined in hepatoblastoma, which were mainly involved in metabolic and cancer-related pathways. Moreover, their expression was liver-specific. 13 hub genes were screened, which were closely related to immune cells in hepatoblastoma tissues. Among them, it was confirmed that AXIN2, LAMB1 and NOTUM were up-regulated and SERPINC1 was down-regulated in hepatoblastoma than normal tissues. NOTUM knockdown distinctly weakened migration and invasion of HuH-6 and HepG2 cells and tumor growth in vivo. CONCLUSIONS: This study identified aberrantly methylated and expressed signatures that were in relation to immune microenvironment in hepatoblastoma. Targeting NOTUM hub gene could suppress migration and invasion of hepatoblastoma cells. Thus, these aberrantly methylated and expressed genes might act as therapeutic agents in hepatoblastoma therapy.
ESTHER : Zhang_2021_BMC.Cancer_21_1156
PubMedSearch : Zhang_2021_BMC.Cancer_21_1156
PubMedID: 34711185

Title : Developmental neurotoxicity of antimony (Sb) in the early life stages of zebrafish - Xia_2021_Ecotoxicol.Environ.Saf_218_112308
Author(s) : Xia S , Zhu X , Yan Y , Zhang T , Chen G , Lei D , Wang G
Ref : Ecotoxicology & Environmental Safety , 218 :112308 , 2021
Abstract : Accumulating studies have revealed the toxicity of antimony (Sb) to soil-dwelling and aquatic organisms at the individual level. However, little is known about the neurotoxic effects of antimony and its underlying mechanisms. To assess this issue, we investigated the neurotoxicity of antimony (0, 200, 400, 600 and 800 mg/L) in zebrafish embryos. After exposure, zebrafish embryos showed abnormal phenotypes such as a shortened body length, morphological malformations, and weakened heart function. Behavioral experiments indicated that antimony caused neurotoxicity in zebrafish embryos, manifested in a decreased spontaneous movement frequency, delayed response to touch, and reduced movement distance. We also showed that antimony caused a decrease in acetylcholinesterase (AChE) levels in zebrafish embryos, along with decreased expression of neurofunctional markers such as gfap, nestin, mbp, and shha. Additionally, antimony significantly increased reactive oxygen species levels and significantly reduced glutathione (GSH) and superoxide dismutase (SOD) activity. In summary, our findings indicated that antimony can induce developmental toxicity and neurotoxicity in zebrash embryos by affecting neurotransmitter systems and oxidative stress, thus altering behavior. These outcomes will advance our understanding of antimony-induced neurotoxicity, environmental problems, and health hazards.
ESTHER : Xia_2021_Ecotoxicol.Environ.Saf_218_112308
PubMedSearch : Xia_2021_Ecotoxicol.Environ.Saf_218_112308
PubMedID: 33975224

Title : Tacrine accelerates spatial long-term memory via improving impaired neural oscillations and modulating GAD isomers including neuro-receptors in the hippocampus of APP\/PS1 AD mice - Kumari_2020_Brain.Res.Bull__
Author(s) : Kumari E , Li K , Yang Z , Zhang T
Ref : Brain Research Bulletin , : , 2020
Abstract : Tacrine (Amino tetrahydroacridine hydrochloride hydrate) is a non-competitive and reversible inhibitor of acetylcholine esterase, and butylcholinesterase. Alzheimer's disease (AD) shows multiple types of pathological pathway in which cholinergic neuron deficiency is 95 % popular and the oldest pathological mechanism. However, the effect of tacrine on the hippocampal dependent memory is not yet known. In this study, we did verify that tacrine induced recovery of the specific pattern associated memory along with long-term memory through the improvement in the pattern of neural oscillation from deficits condition in the hippocampus of 6th month old AD mice. Our results showed that tacrine improved the performance of Morris water maze related spatial cognitive functions, and enhanced LTP in AD-TAC mice. Furthermore, our results implied that tacrine strongly improve the patterns of neural oscillations, and hippocampal synaptic plasticity in the 6th month old APP-PS1 double transgenic AD-TAC mice via changing the theta and alpha power spectra including with the improvement in theta, alpha and gamma synchronization. Moreover, tacrine generated the improvement in the theta cross spectra, theta-gamma phase-phase synchronization and theta-gamma phase-amplitude coupling. Besides, the data represented that tacrine accelerated the expression of NR2B, SYP and GAD65 while it caused deceleration on the expression of GAD67 neurotransmitter and Abeta. Thus, our results infer that tacrine works as a strong causative agent for improving the specific pattern-associated spatial long-term memory in the AD mice without showing any side effect.
ESTHER : Kumari_2020_Brain.Res.Bull__
PubMedSearch : Kumari_2020_Brain.Res.Bull__
PubMedID: 32473192

Title : A Bioluminescent Probe for Simultaneously Imaging Esterase and Histone Deacetylase Activity in a Tumor - Wang_2020_Anal.Chem_92_15275
Author(s) : Wang C , Du W , Zhang T , Liang G
Ref : Analytical Chemistry , 92 :15275 , 2020
Abstract : The monitoring of esterase (CES) and histone deacetylase (HDAC) activity in living cells has great potential for rapid diagnosis of malignant tumors. At present, using one bioluminescence (BL) probe to simultaneously detect (or image) these two enzymes' activity in tumors has not been reported. Herein, a bioluminescence "turn-on" probe AcAH-Luc (6-acetamidohexanoic acid-d-luciferin) was rationally designed for simultaneously imaging CES and HDAC activity with excellent sensitivity and selectivity. AcAH-Luc was successfully applied in vitro to selectively detect CES and HDAC6, a subtype of HDAC, at a linear concentration range of 0-100 and 0-120 nM with limits of detection (LODs) of 0.495 and 1.14 nM, respectively. In vivo results indicated that about 1/2 and 1/3 of the "turn-on" BL signal of AcAH-Luc was contributed by CES and HDAC activity in the tumors, respectively. We envision that AcAH-Luc might be applied to simultaneously measure (and image) CES and HDAC activity in the clinic for assisting with the precise diagnosis of malignant tumors in the near future.
ESTHER : Wang_2020_Anal.Chem_92_15275
PubMedSearch : Wang_2020_Anal.Chem_92_15275
PubMedID: 33170646

Title : Catalytic activities of cocaine hydrolases against the most toxic cocaine metabolite norcocaethylene - Zheng_2020_Org.Biomol.Chem__
Author(s) : Zheng X , Chen X , Zhang T , Zhan M , Zhan CG , Zheng F
Ref : Org Biomol Chem , : , 2020
Abstract : A majority of cocaine users also consume alcohol. The concurrent use of cocaine and alcohol produces the pharmacologically active metabolites cocaethylene and norcocaethylene, in addition to norcocaine. Both cocaethylene and norcocaethylene are more toxic than cocaine itself. Hence, a truly valuable cocaine-metabolizing enzyme for cocaine abuse/overdose treatment should be effective for the hydrolysis of not only cocaine, but also its metabolites norcocaine, cocaethylene, and norcocaethylene. However, there has been no report on enzymes capable of hydrolyzing norcocaethylene (the most toxic metabolite of cocaine). The catalytic efficiency parameters (kcat and KM) of human butyrylcholinesterase (BChE) and two mutants (known as cocaine hydrolases E14-3 and E12-7) against norcocaethylene have been characterized in the present study for the first time, and they are compared with those against cocaine. According to the obtained kinetic data, wild-type human BChE showed a similar catalytic efficiency against norcocaethylene (kcat = 9.5 min-1, KM = 11.7 muM, and kcat/KM = 8.12 x 105 M-1 min-1) to that against (-)-cocaine (kcat = 4.1 min-1, KM = 4.5 muM, and kcat/KM = 9.1 x 105 M-1 min-1). E14-3 and E12-7 showed an improved catalytic activity against norcocaethylene compared to wild-type BChE. E12-7 showed a 39-fold improved catalytic efficiency against norcocaethylene (kcat = 210 min-1, KM = 6.6 muM, and kcat/KM = 3.18 x 107 M-1 min-1). It has been demonstrated that E12-7 as an exogenous enzyme can efficiently metabolize norcocaethylene in rats.
ESTHER : Zheng_2020_Org.Biomol.Chem__
PubMedSearch : Zheng_2020_Org.Biomol.Chem__
PubMedID: 32101217

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

Title : High-level expression of Thermomyces dupontii thermo-alkaline lipase in Pichia pastoris under the control of different promoters - Wang_2019_3.Biotech_9_33
Author(s) : Wang J , Zhang T , Li Y , Li L , Wang Y , Yang B
Ref : 3 Biotech , 9 :33 , 2019
Abstract : In this study, 15 methanol-inducible and 9 constitutive promoters were used to drive the expression of Thermomyces dupontii lipase (TDL) in Pichia pastoris. Of the 15 methanol-inducible promoters, formaldehyde dehydrogenase promoter (PFLD1) showed the highest efficiency in driving lipase production, followed by alcohol oxidase 1 (PAOX1) and dihydroxyacetone synthase (PDAS1) promoters. The maximum lipase activity of transformants with PFLD1, PAOX1 and PDAS1 promoters in 5-l bioreactor was 27,076, 24,159 and 22,342 U/ml, respectively. For the nine constitutive promoters, glycosyl phosphatidyl inositol-anchored protein promoter (PGCW14) produced the highest amount of lipases in a medium containing glucose or glycerol as the only carbon source, followed by mitochondrial alcohol dehydrogenase isozyme (P0472) and glyceraldehyde-3-phosphate dehydrogenase (PGAP) promoters. The maximum lipase yields in 5-l bioreactors under the control of PGCW14, P0472 and PGAP promoters were 17,353, 15,046 and 14,276 U/ml, respectively. The result of this study not only identifies a few highly efficient promoters for the heterologous expression of TDL in P. pastoris, but also casts some insight into the optimization of protein production in heterologous systems.
ESTHER : Wang_2019_3.Biotech_9_33
PubMedSearch : Wang_2019_3.Biotech_9_33
PubMedID: 30622871
Gene_locus related to this paper: talth-f6lqk7

Title : A transcriptomics-based analysis of the toxicity mechanisms of gabapentin to zebrafish embryos at realistic environmental concentrations - He_2019_Environ.Pollut_251_746
Author(s) : He Y , Li X , Jia D , Zhang W , Zhang T , Yu Y , Xu Y , Zhang Y
Ref : Environ Pollut , 251 :746 , 2019
Abstract : Gabapentin (GPT) has become an emerging contaminant in aquatic environments due to its wide application in medical treatment all over the world. In this study, embryos of zebrafish were exposed to gabapentin at realistically environmental concentrations, 0.1mug/L and 10mug/L, so as to evaluate the ecotoxicity of this emergent contaminant. The transcriptomics profiling of deep sequencing was employed to illustrate the mechanisms. The zebrafish (Danio rerio) embryo were exposed to GPT from 12 hpf to 96 hpf resulting in 136 and 750 genes differentially expressed, respectively. The results of gene ontology (GO) analysis and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis illustrated that a large amount of differentially expressed genes (DEGs) were involved in the antioxidant system, the immune system and the nervous system. RT-qPCR was applied to validate the results of RNA-seq, which provided direct evidence that the selected genes involved in those systems mentioned above were all down-regulated. Acetylcholinesterase (AChE), lysozyme (LZM) and the content of C-reactive protein (CRP) were decreased at the end of exposure, which is consistent with the transcriptomics results. The overall results of this study demonstrate that GPT simultaneously affects various vital functionalities of zebrafish at early developmental stage, even at environmentally relevant concentrations.
ESTHER : He_2019_Environ.Pollut_251_746
PubMedSearch : He_2019_Environ.Pollut_251_746
PubMedID: 31121539

Title : Seawater acidification increases copper toxicity: A multi-biomarker approach with a key marine invertebrate, the Pacific Oyster Crassostrea gigas - Cao_2019_Aquat.Toxicol_210_167
Author(s) : Cao R , Zhang T , Li X , Zhao Y , Wang Q , Yang D , Qu Y , Liu H , Dong Z , Zhao J
Ref : Aquat Toxicol , 210 :167 , 2019
Abstract : Ocean acidification (OA) has been found to increase the release of free Cu(2+) in seawater. However, only a handful of studies have investigated the influence of OA on Cu accumulation and cellular toxicity in bivalve species. In this study, Pacific oysters, Crassostrea gigas, were exposed to 25 mug/L Cu(2+) at three pH levels (8.1, 7.8 and 7.6) for 14 and 28 days. Physiological and histopathological parameters [(clearance rate (CR), respiration rate (RR), histopathological damage and condition index (CI)), oxidative stress and neurotoxicity biomarkers [superoxide dismutase (SOD) and glutathione transferase (GST) activities, lipid peroxidation (LPO) and acetylcholinesterase (AChE) activity], combined with glycolytic enzyme activities [pyruvate kinase (PK) and hexokinase (HK)] were investigated in C. gigas. The bioconcentration of Cu was increased in soft tissues of Cu-exposed oysters under OA. Our results suggest that both OA and Cu could lead to physiological disturbance, oxidative stress, cellular damage, disturbance in energy metabolism and neurotoxicity in oysters. The inhibited CR, increased glycolytic enzymes activities and decreased CI suggested that the energy metabolism strategy adopted by oysters was not sustainable in the long term. Furthermore, integrated biomarker response (IBR) results found that OA and Cu exposure lead to severe stress to oysters, and co-exposure was the most stressful condition. Results from this study highlight the need to include OA in future environmental assessments of pollutants and hazardous materials to better elucidate the risks of those environmental perturbations.
ESTHER : Cao_2019_Aquat.Toxicol_210_167
PubMedSearch : Cao_2019_Aquat.Toxicol_210_167
PubMedID: 30870663

Title : Design, synthesis and evaluation of novel ferulic acid derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease - Lan_2019_Bioorg.Chem__103413
Author(s) : Lan JS , Zeng RF , Jiang XY , Hou JW , Liu Y , Hu ZH , Li HX , Li Y , Xie SS , Ding Y , Zhang T
Ref : Bioorg Chem , :103413 , 2019
Abstract : A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced beta-amyloid (Abeta) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7nM for hAChE and 0.66muM for hBuChE) and the good Abeta aggregation inhibition (49.2% at 20muM), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Abeta-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation.
ESTHER : Lan_2019_Bioorg.Chem__103413
PubMedSearch : Lan_2019_Bioorg.Chem__103413
PubMedID: 31791679

Title : Design, Synthesis, and Biological Evaluation of Dual-Target Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 9A (PDE9A) for the Treatment of Alzheimer's Disease - Hu_2019_ACS.Chem.Neurosci_10_537
Author(s) : Hu J , Huang YD , Pan T , Zhang T , Su T , Li X , Luo HB , Huang L
Ref : ACS Chem Neurosci , 10 :537 , 2019
Abstract : A series of dual-target AChE/PDE9A inhibitor compounds were designed, synthesized, and evaluated as anti-Alzheimer's Disease (AD) agents. Among these target compounds, 11a (AChE: IC50 = 0.048 muM; PDE9A: IC50 = 0.530 muM) and 11b (AChE: IC50 = 0.223 muM; PDE9A: IC50 = 0.285 muM) exhibited excellent and balanced dual-target AChE/PDE9A inhibitory activities. Meanwhile, those two compounds possess good blood-brain barrier (BBB) penetrability and low neurotoxicity. Especially, 11a and 11b could ameliorate learning deficits induced by scopolamine (Scop). Moreover, 11a could also improve cognitive and spatial memory in Abeta25-35-induced cognitive deficit mice in the Morris water-maze test. In summary, our research developed a series of potential dual-target AChE/PDE9A inhibitors, and the data indicated that 11a was a promising candidate drug for the treatment of AD.
ESTHER : Hu_2019_ACS.Chem.Neurosci_10_537
PubMedSearch : Hu_2019_ACS.Chem.Neurosci_10_537
PubMedID: 30252439

Title : Design, synthesis, and evaluation of isoflavone analogs as multifunctional agents for the treatment of Alzheimer's disease - Wang_2019_Eur.J.Med.Chem_168_207
Author(s) : Wang D , Hu M , Li X , Zhang D , Chen C , Fu J , Shao S , Shi G , Zhou Y , Wu S , Zhang T
Ref : Eur Journal of Medicinal Chemistry , 168 :207 , 2019
Abstract : A series of novel isoflavone analogs were designed, synthesized, and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease. In vitro evaluations revealed that some ligands had multifunctional profiles, including potent blockage of histamine 3 receptor (H3R), excellent inhibition of acetylcholinesterase (AChE), neuroprotective effects and anti-neuroinflammatory properties. Among these derivatives, compound 9b exhibited the highest ability to block H3R (IC50=0.27muM) and good inhibitory activity against AChE (IC50=0.08muM). Additionally, compound 9b showed obvious neuroprotective effect on SH-SY5Y by preventing copper-induced neuronal damage and potent anti-neuroinflammatory activity by inhibiting the production of inflammatory factors on BV-2cells. A molecular modeling study revealed that 9b acts as a mixed-type inhibitor that interacts simultaneously with H3R and AChE. Moreover, in vivo data revealed that compound 9b did not cause acute toxicity in mice at doses up to 1000mg/kg, and had desirable pharmacokinetic properties, as well as a good blood-brain barrier (BBB) permeability (log BB=1.24+/-0.07). Further studies demonstrated that chronic oral treatment with 9b significantly improved cognitive dysfunction in scopolamine-induced AD mice in the step-down passive avoidance test. Taken together, the present study showed that compound 9b is a promising multifunctional drug candidate for the treatment of Alzheimer's disease.
ESTHER : Wang_2019_Eur.J.Med.Chem_168_207
PubMedSearch : Wang_2019_Eur.J.Med.Chem_168_207
PubMedID: 30822710

Title : Electroacupuncture prevents cognitive impairment induced by lipopolysaccharide via inhibition of oxidative stress and neuroinflammation - Han_2018_Neurosci.Lett_683_190
Author(s) : Han YG , Qin X , Zhang T , Lei M , Sun FY , Sun JJ , Yuan WF
Ref : Neuroscience Letters , 683 :190 , 2018
Abstract : Oxidative stress and neuroinflammation play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced cognitive impairment. This study aims to observe the effect of electroacupuncture (EA) on the cognitive function in LPS-induced mice, and its regulation on hippocampal alpha7 nicotinic acetylcholine receptors (alpha7nAChR), oxidative and proinflammatory factors. Adult male C57BL/6 nice were used to establish animal model of LPS-induced cognitive impairment, and were randomly divided into three groups (n=16): control group, model group (LPS: 5mg/kg), and EA group. The cognitive function was measured by Morris water-maze test, and protein expression of alpha7nAChR in hippocampus was detected by immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to measure hippocampal proinflammatory cytokines. The results showed that LPS significantly impaired working and spatial memory of mice, which could be attenuated by EA treatment. EA prevented LPS-induced decrease of alpha7nAChR protein, acetylcholine (ACh) content and choline acetyltransferase (ChAT) activity, and prevented LPS-induced increase of acetylcholinesterase (AChE) activity (P<0.05). EA significantly decreased malondialdehyde (MDA) and hydrogen peroxide (H2O2), and increased the contents of catalase (CAT) and glutathione (GSH) in hippocampus of LPS-treated Mice (P<0.05). EA also prevented LPS-induced increase of proinflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in hippocampus (P<0.05). In conclusion, electroacupuncture can improve the learning and memory in LPS-treated mice, and its mechanism may be related to enhanced expression of alpha7-nAChR and cholinergic factors, and suppression of oxidative stress and neuroinflammation in hippocampus.
ESTHER : Han_2018_Neurosci.Lett_683_190
PubMedSearch : Han_2018_Neurosci.Lett_683_190
PubMedID: 29885447

Title : The Impairment of Trans Fatty Acids on Learning, Memory and Brain Amino Acid Neurotransmitters in Mice - Zhang_2018_J.Nutr.Sci.Vitaminol.(Tokyo)_64_63
Author(s) : Zhang T , Liu P , Sun Y , Ren N , Nie S
Ref : J Nutr Sci Vitaminol (Tokyo) , 64 :63 , 2018
Abstract : The aim of the study was to demonstrate the impairment of trans fatty acids (TFAs) in neurological disorders in mice. Forty-eight male Kunming mice were randomly divided into four groups with twelve in each group, namely a control group (corn oil group), and TFA groups with low, middle and high dosages. The tested chemicals were given by gavage, once a day, for 12 wk in total, with the volume of the intragastric liquid as 0.1 mL/10 g of body weight. The mice in the control group were given corn oil only. The mice in the TFA groups were given TFA solution (doses were 25, 50 and 100 mg/kg of body weight, respectively). The Morris circle water maze was used to test learning and memory of mice. The activity of acetylcholinesterase (AChE), nitric oxide synthase (NOS) and the level of brain amino acid neurotransmitters were tested. In the Morris water maze task, and compared to the control group, TFAs showed no obvious effect on learning or memory. TFA intake led to a significant decrease of AChE in all TFA groups, and the increase in levels of NOS in the high-dose group. Meanwhile, intake of TFAs increased the levels of Asp, Glu, Gly, and Tau in all TFA groups. The results suggest that long-term intake of TFAs probably impairs learning, memory and brain neurotransmitters in mice.
ESTHER : Zhang_2018_J.Nutr.Sci.Vitaminol.(Tokyo)_64_63
PubMedSearch : Zhang_2018_J.Nutr.Sci.Vitaminol.(Tokyo)_64_63
PubMedID: 29491274

Title : Organic matter modifies biochemical but not most behavioral responses of the clam Ruditapes philippinarum to nanosilver exposure - Zhang_2018_Mar.Environ.Res_133_105
Author(s) : Zhang T , Pan JF , Hunt DE , Chen M , Wang B
Ref : Mar Environ Research , 133 :105 , 2018
Abstract : Adsorption of dissolved organic matter (DOM) can alter the environmental fate, bioavailability and toxicity of silver nanoparticles (Ag NPs). However, a number of questions remain about DOM's ability to modify nanotoxicity. Here, we examine the impact of humic acid (HA, as a model DOM) on the toxicity of Ag NPs (10 mug L(-1)) in the marine clam Ruditapes philippinarum. Results showed that DOM additions to Ag NP treatments reduce clam silver tissue burdens and the oxidative stress response. However, HA does not significantly affect the impact of Ag NPs on clam acetylcholinesterase activity and feeding behavior (measured as filtration rate). Overall, the integrated biological response index supports the conclusion that humic acid reduces the toxicity of Ag NPs, clearly indicating the importance of considering environmental factors when assessing potential risks posed by nanomaterials in natural settings.
ESTHER : Zhang_2018_Mar.Environ.Res_133_105
PubMedSearch : Zhang_2018_Mar.Environ.Res_133_105
PubMedID: 29254654

Title : Online screening of acetylcholinesterase inhibitors in natural products using monolith-based immobilized capillary enzyme reactors combined with liquid chromatography-mass spectrometry - Wang_2018_J.Chromatogr.A_1563_135
Author(s) : Wang L , Zhao Y , Zhang Y , Zhang T , Kool J , Somsen GW , Wang Q , Jiang Z
Ref : Journal of Chromatography A , 1563 :135 , 2018
Abstract : In order to develop a direct and reliable method for discovering lead compounds from traditional Chinese medicines (TCMs), a comparative online ligand fishing platform was developed using immobilized capillary enzyme reactors (ICERs) in combination with liquid chromatography-mass spectrometry (LC-MS). Methacrylate-based monolithic capillaries (400mum I.D.x10cm) containing epoxy reactive groups were used as support to immobilize the target enzyme acetylcholinesterase (AChE). The activity and kinetic parameters of the AChE-ICER were investigated using micro-LC-UV. Subsequently, ligand fishing and identification from mixtures was carried out using the complete AChE-ICER-LC-MS platform. For efficient distinction of true actives from false positives, highly automated comparative analyses were run alternatingly using AChE-ICERs and negative control-ICERs, both online installed in the system. After washing unbound compounds to the waste, bound ligands were eluted from the AChE-ICER to a trapping loop using a denaturing solution. The trapped ligands were further separated and identified using LC-MS. Non-specific binding to the monolith support or non-functional sites of the immobilized enzyme was investigated by exposing analytes to the negative control-ICER. The specificity of the proposed approach was verified by analyzing a known AChE inhibitor in the presence of an inactive compound. The platform was applied to screen for AChE inhibitors in extracts of Corydalis yanhusuo. Eight compounds (columbamine, jatrorrhizine, coptisine, palmatine, berberine, dehydrocorydaline, tetrahydropalmatine and corydaline) with AChE binding affinity were detected and identified, and their AChE inhibitory activities were further verified by an in vitro enzymatic inhibition assay. Experimental results show that the proposed comparative online ligand fishing platform is suitable for rapid screening and mass-selective detection of AChE inhibitors in complex mixtures.
ESTHER : Wang_2018_J.Chromatogr.A_1563_135
PubMedSearch : Wang_2018_J.Chromatogr.A_1563_135
PubMedID: 29866504

Title : Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease - Wang_2018_Cardiol.Res.Pract_2018_9141320
Author(s) : Wang D , Wu Y , Wang A , Chen Y , Zhang T , Hu N
Ref : Cardiol Res Pract , 2018 :9141320 , 2018
Abstract : Objective: Donepezil, a widely used cholinesterase inhibitor for treating Alzheimer's disease, has been reported to induce bradyarrhythmias and torsade de pointes. In this study, we aimed at determining electrocardiogram changes of donepezil administration in elderly patients with ischemic heart disease, who tend to suffer from cognitive disorders. Methods: Sixty patients with ischemic heart disease and mild cognitive impairment were treated with donepezil (5 mg/day) and followed up for at least four weeks. A twenty-four-hour ambulatory electrocardiogram was performed for the analysis of heart rate variability. The ECG parameters including heart rate (HR), PR and RR intervals, QT interval, and QRS duration were recorded at the baseline and after donepezil administration. Results: Donepezil administration resulted in significant reduction in mean HR and the lowest HR and prolongation of PR and RR intervals, whereas it had no significant effects on QRS duration and QT parameters including QT, corrected QT interval, QT dispersion, and Tpeak-end interval. HRV analysis showed that donepezil administration significantly improved parasympathetic function, indicated by decreased low/high frequency (LF/HF) ratio and high frequency (HF) components and oscillation of RR intervals. Conclusions: These data demonstrated that donepezil administration decreased HR, prolonged PR interval, and increased parasympathetic function without affecting QRS duration and QT intervals, suggesting that it can be used safely in elderly patients with ischemic heart disease.
ESTHER : Wang_2018_Cardiol.Res.Pract_2018_9141320
PubMedSearch : Wang_2018_Cardiol.Res.Pract_2018_9141320
PubMedID: 29850230

Title : E4bp4 regulates carboxylesterase 2 enzymes through repression of the nuclear receptor Rev-erbalpha in mice - Zhao_2018_Biochem.Pharmacol_152_293
Author(s) : Zhao M , Zhang T , Yu F , Guo L , Wu B
Ref : Biochemical Pharmacology , 152 :293 , 2018
Abstract : Carboxylesterases (CES) are a family of phase I enzymes that play an important role in xenobiotic clearance and lipid metabolism. Here, we investigate a potential role of E4 promoter-binding protein 4 (E4bp4) in regulation of Ces and CPT-11 (irinotecan, a first-line drug for treating colorectal cancer) pharmacokinetics in mice. Mouse hepatoma Hepa-1c1c7 cells were transfected with Rev-erbalpha expression plasmid or siRNA targeting E4bp4. The relative mRNA and protein levels of Ces enzymes in the cells or the livers of wild-type and E4bp4-deficient (E4bp4(-/-)) mice were determined by qPCR and Western blotting, respectively. Transcriptional regulation of Ces by E4bp4/Rev-erbalpha were investigated using luciferase reporter, mobility shift, and co-immunoprecipitation (Co-IP) assays. Pharmacokinetic studies were performed with wild-type and E4bp4(-/-) mice after intraperitoneal injection of CPT-11. E4bp4 ablation down-regulated an array of hepatic Ces genes in mice. E4bp4(-/-) mice also showed reduced Ces-mediated metabolism and elevated systemic exposure of CPT-11, a well-known Ces substrate. Consistently, E4bp4 knockdown reduced the expression of Ces genes (Ces2b, Ces2e and Ces2f) in Hepa-1c1c7 cells. Furthermore, Rev-erbalpha repressed the transcription of Ces2b, whereas E4bp4 antagonized this repressive action. Co-IP experiment confirmed a direct interaction between E4bp4 and Rev-erbalpha. Through a combination of promoter analysis and mobility shift assays, we demonstrated that Rev-erbalpha trans-repressed Ces (Ces2b) through its specific binding to the -767 to-754bp promoter region. In conclusion, E4bp4 regulates Ces enzymes through inhibition of the transrepression activity of Rev-erbalpha, thereby impacting the metabolism and pharmacokinetics of Ces substrates.
ESTHER : Zhao_2018_Biochem.Pharmacol_152_293
PubMedSearch : Zhao_2018_Biochem.Pharmacol_152_293
PubMedID: 29653076

Title : Modification-free carbon dots as turn-on fluorescence probe for detection of organophosphorus pesticides - Lin_2018_Food.Chem_245_1176
Author(s) : Lin B , Yan Y , Guo M , Cao Y , Yu Y , Zhang T , Huang Y , Wu D
Ref : Food Chem , 245 :1176 , 2018
Abstract : It is important to detect pesticides residues due to the concern over food safety. In this work, the burning ash of waste paper was used as carbon source to synthesize carbon dots (C-dots). The fluorescence of obtained C-dots could been turn off by Fe(3+) which was from Fe(2+) oxidized by H2O2, organophosphorus pesticides could effectively inhibit the production of H2O2 by destroying the acetylcholinesterase activity, so the fluorescence of C-dots hold turning on in the presence of organophosphorus pesticides. Based on above principle that the fluorescence intensity of C-dots was proportional to the pesticides concentration, take chlorpyrifos for example, a universal method for pesticides detection was established. The linear range was 0.01-1.0mug/mL with detection limit of 3ng/mL. The method was reliable and sensitive to actual samples. The imaging of chlorpyrifos on cabbages leaves indicated this method could be used for visualization detection of organophosphorus pesticides in vegetables.
ESTHER : Lin_2018_Food.Chem_245_1176
PubMedSearch : Lin_2018_Food.Chem_245_1176
PubMedID: 29287338

Title : Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease - Lan_2017_J.Enzyme.Inhib.Med.Chem_32_776
Author(s) : Lan JS , Hou JW , Liu Y , Ding Y , Zhang Y , Li L , Zhang T
Ref : J Enzyme Inhib Med Chem , 32 :776 , 2017
Abstract : A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Abeta (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC50, 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 muM for eqBuChE and 4.4 muM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Abeta (1-42) aggregation (64.7% at 20 muM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases.
ESTHER : Lan_2017_J.Enzyme.Inhib.Med.Chem_32_776
PubMedSearch : Lan_2017_J.Enzyme.Inhib.Med.Chem_32_776
PubMedID: 28585866

Title : The sea cucumber genome provides insights into morphological evolution and visceral regeneration - Zhang_2017_PLoS.Biol_15_e2003790
Author(s) : Zhang X , Sun L , Yuan J , Sun Y , Gao Y , Zhang L , Li S , Dai H , Hamel JF , Liu C , Yu Y , Liu S , Lin W , Guo K , Jin S , Xu P , Storey KB , Huan P , Zhang T , Zhou Y , Zhang J , Lin C , Li X , Xing L , Huo D , Sun M , Wang L , Mercier A , Li F , Yang H , Xiang J
Ref : PLoS Biol , 15 :e2003790 , 2017
Abstract : Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.
ESTHER : Zhang_2017_PLoS.Biol_15_e2003790
PubMedSearch : Zhang_2017_PLoS.Biol_15_e2003790
PubMedID: 29023486
Gene_locus related to this paper: stija-a0a2g8k9s2 , stija-a0a2g8ka54 , stija-a0a2g8jd52 , stija-a0a2g8l0w8

Title : Design, synthesis and biological evaluation of novel coumarin-N-benzyl pyridinium hybrids as multi-target agents for the treatment of Alzheimer's disease - Lan_2017_Eur.J.Med.Chem_139_48
Author(s) : Lan JS , Ding Y , Liu Y , Kang P , Hou JW , Zhang XY , Xie SS , Zhang T
Ref : Eur Journal of Medicinal Chemistry , 139 :48 , 2017
Abstract : Combining N-benzyl pyridinium moiety and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activities were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for ChE and Abeta (1-42) self-aggregation, and clearly selective inhibition to MAO-B over MAO-A. Of these compounds, compound 7f was the most potent inhibitor for hMAO-B, and it was also a good and balanced inhibitor to ChEs and hMAO-B (0.0373 muM for eeAChE; 2.32 muM for eqBuChE; 1.57 muM for hMAO-B). Molecular modeling and kinetic studies revealed that compound 7f was a mixed-type inhibitor, which bond simultaneously to CAS and PAS of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, compound 7f with no toxicity on PC12 neuroblastoma cells, showed good ability to inhibit Abeta (1-42) self-aggregation and cross the BBB. Collectively, all these results suggested that compound 7f might be a promising multi-target lead candidate worthy of further pursuit.
ESTHER : Lan_2017_Eur.J.Med.Chem_139_48
PubMedSearch : Lan_2017_Eur.J.Med.Chem_139_48
PubMedID: 28797883

Title : The Role of AChE in Swimming Behavior of Daphnia magna: Correlation Analysis of Both Parameters Affected by Deltamethrin and Methomyl Exposure - Ren_2017_J.Toxicol_2017_3265727
Author(s) : Ren Q , Zhao R , Wang C , Li S , Zhang T , Ren Z , Yang M , Pan H , Xu S , Zhu J , Wang X
Ref : J Toxicol , 2017 :3265727 , 2017
Abstract : The unpredictable toxicity of insecticides may cause behavior disorder of biological organisms. In order to assess the role of acetylcholinesterase (AChE) in swimming behavior of Daphnia magna, a correlation analysis of both parameters in 24 h exposure of deltamethrin (DM) and methomyl (MT) was investigated. The behavior responses of D. magna in DM (13.36 mug/L and 33.40 mug/L) and MT (19.66 mug/L and 49.15 mug/L) suggested that recovery behavior in the adjustment phase was crucial, and behavior homeostasis provided them with an optimal way to achieve a wider tolerance against environmental stress. During the experiment, positive effects on AChE activity occurred in the beginning of the exposure. Even though the de novo synthesis of AChE in D. magna might help it recover, the AChE inhibition in different treatments could be observed. Some induction effects on AChE activity at the beginning of exposure occurred, and a 50% decrease may cause toxic effects on behavior. In most treatments, the results showed that both behavior strength and AChE activity stayed in the same field within a correlation circle. These results illustrated that the environmental stress caused by both DM and MT could inhibit AChE activity and subsequently induce a stepwise behavior response, though both pesticides affect it as direct and indirect inhibitors, respectively.
ESTHER : Ren_2017_J.Toxicol_2017_3265727
PubMedSearch : Ren_2017_J.Toxicol_2017_3265727
PubMedID: 29201050
Gene_locus related to this paper: dapul-ACHE1

Title : Comammox in drinking water systems - Wang_2017_Water.Res_116_332
Author(s) : Wang Y , Ma L , Mao Y , Jiang X , Xia Y , Yu K , Li B , Zhang T
Ref : Water Res , 116 :332 , 2017
Abstract : The discovery of complete ammonia oxidizer (comammox) has fundamentally upended our perception of the global nitrogen cycle. Here, we reported four metagenome assembled genomes (MAGs) of comammox Nitrospira that were retrieved from metagenome datasets of tap water in Singapore (SG-bin1 and SG-bin2), Hainan province, China (HN-bin3) and Stanford, CA, USA (ST-bin4). Genes of phylogenetically distinct ammonia monooxygenase subunit A (amoA) and hydroxylamine dehydrogenase (hao) were identified in these four MAGs. Phylogenetic analysis based on ribosomal proteins, AmoA, hao and nitrite oxidoreductase (subunits nxrA and nxrB) sequences indicated their close relationships with published comammox Nitrospira. Canonical ammonia-oxidizing microbes (AOM) were also identified in the three tap water samples, ammonia-oxidizing bacteria (AOB) in Singapore's and Stanford's samples and ammonia-oxidizing archaea (AOA) in Hainan's sample. The comammox amoA-like sequences were also detected from some other drinking water systems, and even outnumbered the AOA and AOB amoA-like sequences. The findings of MAGs and the occurrences of AOM in different drinking water systems provided a significant clue that comammox are widely distributed in drinking water systems.
ESTHER : Wang_2017_Water.Res_116_332
PubMedSearch : Wang_2017_Water.Res_116_332
PubMedID: 28390307
Gene_locus related to this paper: 9bact-a0a1w9j1f6 , 9prot-a0a1w9iez0 , 9prot-a0a1w9i2z8 , 9prot-a0a1w9hbq4 , 9prot-a0a1w9jph2

Title : Does time difference of the acetylcholinesterase (AChE) inhibition in different tissues exist? A case study of zebra fish (Danio rerio) exposed to cadmium chloride and deltamethrin - Zhang_2017_Chemosphere_168_908
Author(s) : Zhang T , Yang M , Pan H , Li S , Ren B , Ren Z , Xing N , Qi L , Ren Q , Xu S , Song J , Ma J
Ref : Chemosphere , 168 :908 , 2017
Abstract : In order to illustrate time difference in toxic effects of cadmium chloride (CdCl2) and deltamethrin (DM), AChE activities were measured in different tissues, liver, muscle, brain, and gill, of Zebra fish (Danio rerio) across different concentrations in this research. The average AChE activity decreased comparing to 0.0 TU with DM (82.81% in 0.1 TU, 56.14% in 1.0 TU and 44.68% in 2.0 TU) and with CdCl2 (74.68% in 0.1 TU, 52.05% in 1.0 TU and 50.14% in 2.0 TU) showed an overall decrease with the increase of exposure concentrations. According to Self-Organizing Map (SOM), the AChE activities were characterized in relation with experimental conditions, showing an inverse relationship with exposure time. As the exposure time was longer, the AChE activities were correspondingly lower. The AChE inhibition showed time delay in sublethal treatments (0.1 TU) in different tissues: the AChE was first inhibited in brain by chemicals followed by gill, muscle and liver (brain > gill > muscle > liver). The AChE activity was almost inhibited synchronously in higher environmental stress (1.0 TU and 2.0 TU). As the AChE inhibition can induce abnormal of behavior movement, these results will be helpful to the mechanism of stepwise behavior responses according to the time difference in different tissues rather than the whole body AChE activity.
ESTHER : Zhang_2017_Chemosphere_168_908
PubMedSearch : Zhang_2017_Chemosphere_168_908
PubMedID: 27825714

Title : Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors - Lan_2017_Eur.J.Med.Chem_133_184
Author(s) : Lan JS , Zhang T , Liu Y , Yang J , Xie SS , Liu J , Miao ZY , Ding Y
Ref : Eur Journal of Medicinal Chemistry , 133 :184 , 2017
Abstract : A series of new donepezil derivatives were designed synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced beta-amyloid (Abeta) aggregation, and moderate antioxidant activity. Especially, compound 5b presented the greatest ability to inhibit cholinesterase (IC50, 1.9 nM for eeAChE and 0.8 nM for hAChE), good inhibition of Abeta aggregation (53.7% at 20 muM) and good antioxidant activity (0.54 trolox equivalents). Kinetic and molecular modeling studies indicated that compound 5b was a mixed-type inhibitor, binding simultaneously to the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, compound 5b could reduce PC12 cells death induced by oxidative stress and Abeta (1-42). Moreover, in vivo experiments showed that compound 5b was nontoxic and tolerated at doses up to 2000 mg/kg. These results suggested that compound 5b might be an excellent multifunctional agent for AD treatment.
ESTHER : Lan_2017_Eur.J.Med.Chem_133_184
PubMedSearch : Lan_2017_Eur.J.Med.Chem_133_184
PubMedID: 28388521

Title : Effect of Linker Length and Flexibility on the Clostridium thermocellum Esterase Displayed on Bacillus subtilis Spores - Chen_2017_Appl.Biochem.Biotechnol_182_168
Author(s) : Chen H , Wu B , Zhang T , Jia J , Lu J , Chen Z , Ni Z , Tan T
Ref : Appl Biochem Biotechnol , 182 :168 , 2017
Abstract : In fusion protein design strategies, the flexibility and length of linkers are important parameters affecting the bioactivity of multifunctional proteins. A series of fusion proteins with different linkers were constructed. The effect of temperature, pH, and organic solvents was investigated on the enzymatic activity. Fusion proteins with P1(PTPTPT) and P2((PTPTPT)2) linkers remained highly active with wide temperature range. At pH 9.6, the relative activity of fusion proteins with (PTPTPT)2 and S2(EGKSSGSGSESKST) linkers was 70 and 62 % (1.75 and 1.5 times of that of non-linker ones). Fusion proteins with S3((GGGGS)4) linker retained 55 % activity after 5 h of incubation at 80 degrees C (1.2-fold of that of non-linker fusion proteins and 1.9-fold of GGGGS-linker fusion proteins). Finally, the relative activity of fusion proteins having different linkers was increased with 20 % dimethyl sulfoxide (DMSO) and methanol; relative activity of fusion proteins with EGKSSGSGSESKST linkers was enhanced 1.5- and 2.2-fold, respectively. These results suggest that longer flexible linker can enhance the activity and stability of displayed esterase than shorter flexible linker. Optimizing peptide linkers with length, flexibility, and amino acid composition could improve the thermostability and activity of the displayed enzyme.
ESTHER : Chen_2017_Appl.Biochem.Biotechnol_182_168
PubMedSearch : Chen_2017_Appl.Biochem.Biotechnol_182_168
PubMedID: 27933482

Title : Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors - Si_2016_Bioorg.Med.Chem.Lett_26_2380
Author(s) : Si W , Zhang T , Zhang L , Mei X , Dong M , Zhang K , Ning J
Ref : Bioorganic & Medicinal Chemistry Lett , 26 :2380 , 2016
Abstract : A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44nM and 13.58nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study.
ESTHER : Si_2016_Bioorg.Med.Chem.Lett_26_2380
PubMedSearch : Si_2016_Bioorg.Med.Chem.Lett_26_2380
PubMedID: 27017111

Title : Potential anti-obesity effects of a long-acting cocaine hydrolase - Zheng_2016_Chem.Biol.Interact_259_99
Author(s) : Zheng X , Deng J , Zhang T , Yao J , Zheng F , Zhan CG
Ref : Chemico-Biological Interactions , 259 :99 , 2016
Abstract : A long-acting cocaine hydrolase, known as CocH3-Fc(M3), engineered from human butyrylcholinesterase (BChE) was tested, in this study, for its potential anti-obesity effects. Mice on a high-fat diet gained significantly less body weight when treated weekly with 1 mg/kg CocH3-Fc(M3) compared to control mice, though their food intake was similar. There is no correlation between the average body weight and the average food intake, which is consistent with the previously reported observation in BChE knockout mice. In addition, molecular modeling was carried out to understand how ghrelin binds with CocH3, showing that ghrelin binds with CocH3 in a similar mode as ghrelin binding with wild-type human BChE. The similar binding structure mode explains why CocH3 has a similar catalytic activity against ghrelin.
ESTHER : Zheng_2016_Chem.Biol.Interact_259_99
PubMedSearch : Zheng_2016_Chem.Biol.Interact_259_99
PubMedID: 27163854

Title : Fibroblast growth factor 21 protects mouse brain against d-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation - Yu_2015_Pharmacol.Biochem.Behav_133_122
Author(s) : Yu Y , Bai F , Wang W , Liu Y , Yuan Q , Qu S , Zhang T , Tian G , Li S , Li D , Ren G
Ref : Pharmacol Biochem Behav , 133 :122 , 2015
Abstract : Fibroblast growth factor 21 (FGF21) is a hormone secreted predominantly in the liver, pancreas and adipose tissue. Recently, it has been reported that FGF21-Transgenic mice can extend their lifespan compared with wild type counterparts. Thus, we hypothesize that FGF21 may play some roles in aging of organisms. In this study d-galactose (d-gal)-induced aging mice were used to study the mechanism that FGF21 protects mice from aging. The three-month-old Kunming mice were subcutaneously injected with d-gal (180mg.kg(-1).d(-1)) for 8weeks and administered simultaneously with FGF21 (1, 2 or 5mg.kg(-1).d(-1)). Our results showed that administration of FGF21 significantly improved behavioral performance of d-gal-treated mice in water maze task and step-down test, reduced brain cell damage in the hippocampus, and attenuated the d-gal-induced production of MDA, ROS and advanced glycation end products (AGEs). At the same time, FGF21 also markedly renewed the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total anti-oxidation capability (T-AOC), and decreased the enhanced total cholinesterase (TChE) activity in the brain of d-gal-treated mice. The expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and member-anchored receptor for AGEs (RAGE) declined significantly after FGF21 treatment. Furthermore, FGF21 suppressed inflamm-aging by inhibiting IkappaBalpha degradation and NF-kappaB p65 nuclear translocation. The expression levels of pro-inflammatory cytokines, such as TNF-alpha and IL-6, decreased significantly. In conclusion, these results suggest that FGF21 protects the aging mice brain from d-gal-induced injury by attenuating oxidative stress damage and decreasing AGE formation.
ESTHER : Yu_2015_Pharmacol.Biochem.Behav_133_122
PubMedSearch : Yu_2015_Pharmacol.Biochem.Behav_133_122
PubMedID: 25871519

Title : Lipoprotein lipase deficiency leads to alpha-synuclein aggregation and ubiquitin C-terminal hydrolase L1 reduction - Yang_2015_Neurosci_290_1
Author(s) : Yang H , Zhou T , Wang H , Liu T , Ueda K , Zhan R , Zhao L , Tong Y , Tian X , Zhang T , Jin Y , Han X , Li Z , Zhao Y , Guo X , Xiao W , Fan D , Liu G , Chui D
Ref : Neuroscience , 290 :1 , 2015
Abstract : We have previously reported that presynaptic dysfunction and cognitive decline have been found in lipoprotein lipase (LPL) deficient mice, but the mechanism remains to be elucidated. Accumulating evidence supported that alpha-synuclein (alpha-syn) and ubiquitin C-terminal hydrolase L1 (UCHL1) are required for normal synaptic and cognitive function. In this study, we found that alpha-syn aggregated and the expression of UCHL1 decreased in the brain of LPL deficient mice. Reduction of UCHL1 was resulted from nuclear retention of DNA cytosine-5-methyltransferase 1 in LPL knockout mice. Reverse changes were found in cultured cells overexpressing LPL. Furthermore, deficiency of LPL increased ubiquitination of alpha-syn. These results indicated that aggregation of alpha-syn and reduction of UCHL1 expression in LPL-deficient mice may affect synaptic function.
ESTHER : Yang_2015_Neurosci_290_1
PubMedSearch : Yang_2015_Neurosci_290_1
PubMedID: 25595992

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

Title : Silibinin inhibits acetylcholinesterase activity and amyloid beta peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease - Duan_2015_Neurobiol.Aging_36_1792
Author(s) : Duan S , Guan X , Lin R , Liu X , Yan Y , Zhang T , Chen X , Huang J , Sun X , Li Q , Fang S , Xu J , Yao Z , Gu H
Ref : Neurobiology of Aging , 36 :1792 , 2015
Abstract : Alzheimer's disease (AD) is characterized by amyloid beta (Abeta) peptide aggregation and cholinergic neurodegeneration. Therefore, in this paper, we examined silibinin, a flavonoid extracted from Silybum marianum, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Abeta peptide aggregation for AD treatment. To achieve this, we used molecular docking and molecular dynamics simulations to examine the affinity of silibinin with Abeta and AChE in silico. Next, we used circular dichroism and transmission electron microscopy to study the anti-Abeta aggregation capability of silibinin in vitro. Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay, immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun experiment were performed on silibinin-treated APP/PS1 transgenic mice. In molecular dynamics simulations, silibinin interacted with Abeta and AChE to form different stable complexes. After the administration of silibinin, AChE activity and Abeta aggregations were down-regulated, and the quantity of AChE also decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater scores in the Morris Water Maze. Moreover, silibinin could increase the number of newly generated microglia, astrocytes, neurons, and neuronal precursor cells. Taken together, these data suggest that silibinin could act as a dual inhibitor of AChE and Abeta peptide aggregation, therefore suggesting a therapeutic strategy for AD treatment.
ESTHER : Duan_2015_Neurobiol.Aging_36_1792
PubMedSearch : Duan_2015_Neurobiol.Aging_36_1792
PubMedID: 25771396

Title : Expression and Characterization of a New Thermostable Esterase from Clostridium thermocellum - Zhang_2015_Appl.Biochem.Biotechnol_177_1437
Author(s) : Zhang T , Chen H , Ni Z , Tian R , Jia J , Chen Z , Yang S
Ref : Appl Biochem Biotechnol , 177 :1437 , 2015
Abstract : The thermostable esterase from the thermophilic bacterium Clostridium thermocellum DSM 1313 was expressed in Escherichia coli and purified by Ni(2+) affinity chromatography. Its molecular weight was approximately 35 kDa according to 12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The enzyme exhibited the highest specific activity with p-nitrophenyl butyrate (285 s(-1) mM(-1)). The activity of the esterase was greatest at 65 degrees C, and the esterase maintained residual activity levels of 70 and 50 % after 3 h incubation at 65 and 70 degrees C, respectively. Its activity was optimal at pH 7.0, was enhanced in the presence of Ca(2+) and Mg(2+), and was inhibited by Ni(2+) and Cu(2+). The addition of surfactants, such as Tween-20, Tween-80, Triton X-100, and SDS, at concentrations of 5 % (v/v) significantly inhibited the lipolytic action of the esterase. Enzyme activity was relatively stable in 10 % methanol, and 50 % residual activity was seen in 10 % DMSO, demonstrating its potential in biodiesel production and industrial applications.
ESTHER : Zhang_2015_Appl.Biochem.Biotechnol_177_1437
PubMedSearch : Zhang_2015_Appl.Biochem.Biotechnol_177_1437
PubMedID: 26373940
Gene_locus related to this paper: clotm-q4cf59

Title : Expression and display of a novel thermostable esterase from Clostridium thermocellum on the surface of Bacillus subtilis using the CotB anchor protein - Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439
Author(s) : Chen H , Zhang T , Jia J , Vastermark A , Tian R , Ni Z , Chen Z , Chen K , Yang S
Ref : J Ind Microbiol Biotechnol , 42 :1439 , 2015
Abstract : Esterases expressed in microbial hosts are commercially valuable, but their applications are limited due to high costs of production and harsh industrial processes involved. In this study, the esterase-DSM (from Clostridium thermocellum) was expressed and successfully displayed on the spore surface, and the spore-associated esterase was confirmed by western blot analysis and activity measurements. The optimal temperature and pH of spore surface-displayed DSM was 60 and 8.5 degrees C, respectively. It also demonstrates a broad temperature and pH optimum in the range of 50-70, 7-9.5 degrees C. The spore surface-displayed esterase-DSM retained 78, 68 % of its original activity after 5 h incubation at 60 and 70 degrees C, respectively, which was twofold greater activity than that of the purified DSM. The recombinant spores has high activity and stability in DMSO, which was 49 % higher than the retained activity of the purified DSM in DMSO (20 % v/v), and retained 65.2 % of activity after 7 h of incubation in DMSO (20 % v/v). However, the recombinant spores could retain 77 % activity after 3 rounds of recycling. These results suggest that enzyme displayed on the surface of the Bacillus subtilis spore could serve as an effective approach for enzyme immobilization.
ESTHER : Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439
PubMedSearch : Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439
PubMedID: 26318029

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

Title : The Toxicity and Detoxifying Mechanism of Cycloxaprid and Buprofezin in Controlling Sogatella furcifera (Homoptera: Delphacidae) - Chang_2015_J.Insect.Sci_15_
Author(s) : Chang X , Yuan Y , Zhang T , Wang D , Du X , Wu X , Chen H , Chen Y , Jiao Y , Teng H
Ref : J Insect Sci , 15 : , 2015
Abstract : The effects of cycloxaprid (a modified neonicotinoid insecticide) and buprofezin (a thiadiazine insecticide) on mortality of the white-backed planthopper (WBPH), Sogatella furcifera, were determined in laboratory assays. Cycloxaprid killed WBPH nymphs and adults but buprofezin killed only nymphs, and cycloxaprid acted faster than buprofezin. One day after infestation, mortality of third-instar nymphs was >65% with cycloxaprid at 125 mg liter(-1) but was <38% with buprofezin at 148 mg liter(-1). By the 4th day after infestation, however, control of nymphs by the two insecticides was similar, and cycloxaprid at 125 mg liter(-1) caused >/=80% mortality of adults but buprofezin at 148 mg liter(-1) (the highest rate tested) caused almost no adult mortality. LC50 values for cycloxaprid were lowest with nymphs, intermediate with adult males, and highest with adult females. Although buprofezin was slower acting than cycloxaprid, its LC50 for nymphs 5 d after infestation was 3.79-fold lower than that of cycloxaprid. Mean carboxylesterase (CarE) specific activity of nymphal WBPH treated with cycloxaprid and buprofezin was higher than that of control, but there was no significant difference between cycloxaprid and control (no insecticide), and it was significantly higher for buprofezin than those of cycloxaprid and control. For glutathione S-transferase and mixed function oxygenase, the specific activity of nymphal WBPH treated with buprofezin was significantly higher than those of cycloxaprid and control, too.
ESTHER : Chang_2015_J.Insect.Sci_15_
PubMedSearch : Chang_2015_J.Insect.Sci_15_
PubMedID: 26175461

Title : Conotoxin alphaD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors - Xu_2015_Sci.Rep_5_14261
Author(s) : Xu S , Zhang T , Kompella SN , Yan M , Lu A , Wang Y , Shao X , Chi C , Adams DJ , Ding J , Wang C
Ref : Sci Rep , 5 :14261 , 2015
Abstract : Nicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system. From the venom of Conus generalis, we identified a novel dimeric nAChR-inhibiting alphaD-conotoxin GeXXA. By solving the crystal structure and performing structure-guided dissection of this toxin, we demonstrated that the monomeric C-terminal domain of alphaD-GeXXA, GeXXA-CTD, retains inhibitory activity against the alpha9alpha10 nAChR subtype. Furthermore, we identified that His7 of the rat alpha10 nAChR subunit determines the species preference of alphaD-GeXXA, and is probably part of the binding site of this toxin. These results together suggest that alphaD-GeXXA cooperatively binds to two inter-subunit interfaces on the top surface of nAChR, thus allosterically disturbing the opening of the receptor. The novel antagonistic mechanism of alphaD-GeXXA via a new binding site on nAChRs provides a valuable basis for the rational design of new nAChR-targeting compounds.
ESTHER : Xu_2015_Sci.Rep_5_14261
PubMedSearch : Xu_2015_Sci.Rep_5_14261
PubMedID: 26395518

Title : Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1 - Wang_2014_Genome.Announc_2_e00171
Author(s) : Wang X , Wang Q , Zhang W , Wang Y , Li L , Wen T , Zhang T , Zhang Y , Xu J , Hu J , Li S , Liu L , Liu J , Jiang W , Tian J , Li Y , Schuler D , Wang L , Li J
Ref : Genome Announc , 2 : , 2014
Abstract : We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and "domestication" by accelerated evolution of the strain upon repeated passaging.
ESTHER : Wang_2014_Genome.Announc_2_e00171
PubMedSearch : Wang_2014_Genome.Announc_2_e00171
PubMedID: 24625872
Gene_locus related to this paper: maggm-v6ezc0

Title : CD26\/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection - Cai_2014_PLoS.One_9_e112060
Author(s) : Cai Y , Yu SQ , Postnikova EN , Mazur S , Bernbaum JG , Burk R , Zhang T , Radoshitzky SR , Muller MA , Jordan I , Bollinger L , Hensley LE , Jahrling PB , Kuhn JH
Ref : PLoS ONE , 9 :e112060 , 2014
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
ESTHER : Cai_2014_PLoS.One_9_e112060
PubMedSearch : Cai_2014_PLoS.One_9_e112060
PubMedID: 25409519

Title : Genome characteristics reveal the impact of lichenization on lichen-forming fungus Endocarpon pusillum Hedwig (Verrucariales, Ascomycota) - Wang_2014_BMC.Genomics_15_34
Author(s) : Wang YY , Liu B , Zhang XY , Zhou QM , Zhang T , Li H , Yu YF , Zhang XL , Hao XY , Wang M , Wang L , Wei JC
Ref : BMC Genomics , 15 :34 , 2014
Abstract : BACKGROUND: Lichen is a classic mutualistic organism and the lichenization is one of the fungal symbioses. The lichen-forming fungus Endocarpon pusillum is living in symbiosis with the green alga Diplosphaera chodatii Bialsuknia as a lichen in the arid regions.
RESULTS: 454 and Illumina technologies were used to sequence the genome of E. pusillum. A total of 9,285 genes were annotated in the 37.5 Mb genome of E. pusillum. Analyses of the genes provided direct molecular evidence for certain natural characteristics, such as homothallic reproduction and drought-tolerance. Comparative genomics analysis indicated that the expansion and contraction of some protein families in the E. pusillum genome reflect the specific relationship with its photosynthetic partner (D. chodatii). Co-culture experiments using the lichen-forming fungus E. pusillum and its algal partner allowed the functional identification of genes involved in the nitrogen and carbon transfer between both symbionts, and three lectins without signal peptide domains were found to be essential for the symbiotic recognition in the lichen; interestingly, the ratio of the biomass of both lichen-forming fungus and its photosynthetic partner and their contact time were found to be important for the interaction between these two symbionts.
CONCLUSIONS: The present study lays a genomic analysis of the lichen-forming fungus E. pusillum for demonstrating its general biological features and the traits of the interaction between this fungus and its photosynthetic partner D. chodatii, and will provide research basis for investigating the nature of its drought resistance and symbiosis.
ESTHER : Wang_2014_BMC.Genomics_15_34
PubMedSearch : Wang_2014_BMC.Genomics_15_34
PubMedID: 24438332
Gene_locus related to this paper: endpu-u1ggx3 , endpu-u1hiw6 , endpu-u1gx33 , endpu-u1hli9 , endpu-u1hmu1 , endpu-u1htc7 , endpu-u1gu60

Title : Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects - Yore_2014_Cell_159_318
Author(s) : Yore MM , Syed I , Moraes-Vieira PM , Zhang T , Herman MA , Homan EA , Patel RT , Lee J , Chen S , Peroni OD , Dhaneshwar AS , Hammarstedt A , Smith U , McGraw TE , Saghatelian A , Kahn BB
Ref : Cell , 159 :318 , 2014
Abstract : Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high-fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.
ESTHER : Yore_2014_Cell_159_318
PubMedSearch : Yore_2014_Cell_159_318
PubMedID: 25303528

Title : Genome Sequence of a Promising Hydrogen-Producing Facultative Anaerobic Bacterium, Brevundimonas naejangsanensis Strain B1 - Su_2014_Genome.Announc_2_e00542
Author(s) : Su H , Zhang T , Bao M , Jiang Y , Wang Y , Tan T
Ref : Genome Announc , 2 : , 2014
Abstract : Brevundimonas naejangsanensis strain B1 is a newly isolated, facultative anaerobic bacterium capable of producing hydrogen with high efficiency. Here, we present a 2.94-Mb assembly of the genome sequence of strain B1, which may provide further insights into the molecular mechanism of hydrogen production from bioresource.
ESTHER : Su_2014_Genome.Announc_2_e00542
PubMedSearch : Su_2014_Genome.Announc_2_e00542
PubMedID: 24903872
Gene_locus related to this paper: 9caul-a0a172y535 , 9caul-a0a172y4n5

Title : Poster: Novel strategy of blocking nAChR revealed by dissecting a dimeric conotoxin alphaD-GeXXA -
Author(s) : Kompella SN , Xu S , Zhang T , Yan M , Shao X , Chi C , Ding J , Wang C , Adams DJ
Ref : Biochemical Pharmacology , 86 :1229 , 2013
PubMedID:

Title : Design, synthesis and biological evaluation of organophosphorous-homodimers as dual binding site acetylcholinesterase inhibitors - Xie_2013_Bioorg.Med.Chem_21_278
Author(s) : Xie R , Zhao Q , Zhang T , Fang J , Mei X , Ning J , Tang Y
Ref : Bioorganic & Medicinal Chemistry , 21 :278 , 2013
Abstract : The cluster effect is an effective strategy to explore new lead compounds, and has been successfully applied in rational drug design and screening. A series of novel organophosphorous-homodimers were designed and synthesized based on the dual-site structure characteristics of acetylcholinesterase (AChE). The compounds were evaluated in vitro for their inhibitory activity to AChE extracted from Drosophila melanogaster and Musca domestic. Compound 4H showed an excellent inhibitor activity to both Drosophila melanogaster and Musca domestic with the corresponding IC(50) values of 23 and 168nM, respectively. Meanwhile, its activities against Drosophila melanogaster and Musca domestic AChE were more than 10,00,000 and 100,000-fold higher compared with the parent compound (MH), and was up to 245 and 107-fold higher than those of the positive control omethoate. The molecular docking study revealed that 4H possessed an optimal spacer length and can perfectly fit into the central pocket, active gorge, and peripheral site of DmAChE, and consequently exhibited highly improved inhibitor potency to DmAChE. The bioassay tests showed that 4 series compounds showed prominent insecticidal activities against both Lipaphser erysimi and Tetranychus cinnbarinus at a concentration of 200mg/L. The insecticide activity of compound 4H was particularly significant that can cause 96% mortality to Tetranychus cinnbarinus after 24h of treatment.
ESTHER : Xie_2013_Bioorg.Med.Chem_21_278
PubMedSearch : Xie_2013_Bioorg.Med.Chem_21_278
PubMedID: 23200223

Title : Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity - Dai_2013_Mol.Cell.Endocrinol_377_123
Author(s) : Dai Z , Qi W , Li C , Lu J , Mao Y , Yao Y , Li L , Zhang T , Hong H , Li S , Zhou T , Yang Z , Yang X , Gao G , Cai W
Ref : Mol Cell Endocrinol , 377 :123 , 2013
Abstract : Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL.
ESTHER : Dai_2013_Mol.Cell.Endocrinol_377_123
PubMedSearch : Dai_2013_Mol.Cell.Endocrinol_377_123
PubMedID: 23850519

Title : Genome of Cupriavidus sp. HMR-1, a Heavy Metal-Resistant Bacterium - Li_2013_Genome.Announc_1_e00202
Author(s) : Li LG , Cai L , Zhang T
Ref : Genome Announc , 1 :e00202 , 2013
Abstract : Cupriavidus sp. HMR-1 was isolated from a heavy metal-enriched culture of activated sludge from a wastewater treatment plant in Hong Kong. Here, we release the HMR-1 genome to provide basic genetic characteristics for a better understanding of its multiple heavy metal resistance properties.
ESTHER : Li_2013_Genome.Announc_1_e00202
PubMedSearch : Li_2013_Genome.Announc_1_e00202
PubMedID: 23409271
Gene_locus related to this paper: ralme-q1lsa6 , ralme-q1le88 , ralme-q1ldn9 , ralme-q1lg42 , 9burk-l2e892

Title : Genome sequence of the date palm Phoenix dactylifera L - Al-Mssallem_2013_Nat.Commun_4_2274
Author(s) : Al-Mssallem IS , Hu S , Zhang X , Lin Q , Liu W , Tan J , Yu X , Liu J , Pan L , Zhang T , Yin Y , Xin C , Wu H , Zhang G , Ba Abdullah MM , Huang D , Fang Y , Alnakhli YO , Jia S , Yin A , Alhuzimi EM , Alsaihati BA , Al-Owayyed SA , Zhao D , Zhang S , Al-Otaibi NA , Sun G , Majrashi MA , Li F , Tala , Wang J , Yun Q , Alnassar NA , Wang L , Yang M , Al-Jelaify RF , Liu K , Gao S , Chen K , Alkhaldi SR , Liu G , Zhang M , Guo H , Yu J
Ref : Nat Commun , 4 :2274 , 2013
Abstract : Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm's unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants.
ESTHER : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedSearch : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedID: 23917264
Gene_locus related to this paper: phodc-a0a2h3y3d5 , phodc-a0a2h3z529 , phodc-a0a2h3y147 , phodc-a0a2h3xrz4 , phodc-a0a3q0ic37 , phodc-a0a2h3yxf0 , phodc-a0a2h3zh01 , phodc-a0a3q0hs32

Title : Melamine induced spatial cognitive deficits associated with impairments of hippocampal long-term depression and cholinergic system in Wistar rats - An_2012_Neurobiol.Learn.Mem_100C_18
Author(s) : An L , Yang Z , Zhang T
Ref : Neurobiol Learn Mem , 100C :18 , 2012
Abstract : Our previous studies reported that hippocampus was one of the target sites of melamine, by which the spatial cognition and hippocampal long-term potentiation (LTP) could be impaired. The aim of present study was to investigate whether cognitive behavior impairment induced by melamine was associated with the alteration of hippocampal long-term depression (LTD), and try to interpret the potential underlying mechanism. Wistar rats were used to establish an animal model and melamine administered at a dose of 300mg/kg/day for 4weeks. Water maze behavior and long-term depression (LTD) in hippocampal CA3-CA1 pathway were measured, followed by enzyme linked immunosorbent assay (ELISA), by which acetylcholine (ACh) level and acetylcholinesterase (AChE) activity were determined. Results showed that learning and reversal learning abilities were significantly impaired by melamine. The field excitatory postsynaptic potential (fEPSP) slopes were significantly higher in melamine group compared to that in control group. Furthermore, the function of cholinergic system was damaged associated with decreased Ach level and enhanced AChE activity in melamine-treated rats. It suggested that melamine induced abnormal inhibitory effect on synaptic plasticity of hippocampus, which partly resulted in reduced LTD and further damaged cognitive flexibility. Melamine could also induce dysfunctional cholinergic system, which was associated with the poor performance of animals in MWM (Morris water maze) tests.
ESTHER : An_2012_Neurobiol.Learn.Mem_100C_18
PubMedSearch : An_2012_Neurobiol.Learn.Mem_100C_18
PubMedID: 23231966

Title : Genome of Bacillus macauensis ZFHKF-1, a long-chain-forming bacterium - Cai_2012_J.Bacteriol_194_4780
Author(s) : Cai L , Zhang T
Ref : Journal of Bacteriology , 194 :4780 , 2012
Abstract : Here, we report the draft genome sequence of Bacillus macauensis ZFHKF-1, a novel long-chain bacterium previously isolated and identified by us (Zhang T, Fan XJ, Hanada S, Kamagata Y, Fang HHP, J. Syst. Evol. Microbiol. 56:349-353, 2006). The genome provides basic genetic information to understand this particular species and explore the potential mechanism of long-chain formation. The type strain is ZFHKF-1 (= JCM 13285 = DSM 17262).
ESTHER : Cai_2012_J.Bacteriol_194_4780
PubMedSearch : Cai_2012_J.Bacteriol_194_4780
PubMedID: 22887677
Gene_locus related to this paper: 9baci-i8amx7 , 9baci-i8ujr5

Title : Species variation in small molecule components of animal vitreous - Mains_2012_Invest.Ophthalmol.Vis.Sci_53_4778
Author(s) : Mains J , Tan LE , Zhang T , Young L , Shi R , Wilson C
Ref : Invest Ophthalmol Vis Sci , 53 :4778 , 2012
Abstract : PURPOSE: We characterized differences in biochemical composition of the vitreous of different animal species with respect to small molecule constituents. METHODS: Vitreous samples were extracted from sheep, pig, Dutch Belted rabbits, and New Zealand white rabbits. The vitreous samples were investigated for acetylcholinesterase (AChE) activity and, in addition, were subjected to metabolomics determination using mass spectrometry. RESULTS: AChE activity varied across the species investigated with greater activity noted in larger animals. Principal component analysis demonstrated species differentiation in relation to metabolomic profile. Key peaks identified the importance of animal diet on small molecule composition of the vitreous. CONCLUSIONS: Our results highlighted principal and consistent differences in small molecule composition and enzymatic activity of the vitreous depending on species. Interesting differences were demonstrated, showing that diet potentially can impact on components of and metabolites contained within the vitreous. Material will be exchanged between vascular and retinal tissue with the vitreous compartment and as a nonvascular, slowly equilibrating "sink" might reflect changes in transporter activity. As a first step, understanding the differences in the metabolic profile of vitreous from different species may impact interpretation of such activity across different species.
ESTHER : Mains_2012_Invest.Ophthalmol.Vis.Sci_53_4778
PubMedSearch : Mains_2012_Invest.Ophthalmol.Vis.Sci_53_4778
PubMedID: 22669713

Title : Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres - Paterson_2012_Nature_492_423
Author(s) : Paterson AH , Wendel JF , Gundlach H , Guo H , Jenkins J , Jin D , Llewellyn D , Showmaker KC , Shu S , Udall J , Yoo MJ , Byers R , Chen W , Doron-Faigenboim A , Duke MV , Gong L , Grimwood J , Grover C , Grupp K , Hu G , Lee TH , Li J , Lin L , Liu T , Marler BS , Page JT , Roberts AW , Romanel E , Sanders WS , Szadkowski E , Tan X , Tang H , Xu C , Wang J , Wang Z , Zhang D , Zhang L , Ashrafi H , Bedon F , Bowers JE , Brubaker CL , Chee PW , Das S , Gingle AR , Haigler CH , Harker D , Hoffmann LV , Hovav R , Jones DC , Lemke C , Mansoor S , ur Rahman M , Rainville LN , Rambani A , Reddy UK , Rong JK , Saranga Y , Scheffler BE , Scheffler JA , Stelly DM , Triplett BA , Van Deynze A , Vaslin MF , Waghmare VN , Walford SA , Wright RJ , Zaki EA , Zhang T , Dennis ES , Mayer KF , Peterson DG , Rokhsar DS , Wang X , Schmutz J
Ref : Nature , 492 :423 , 2012
Abstract : Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups.
ESTHER : Paterson_2012_Nature_492_423
PubMedSearch : Paterson_2012_Nature_492_423
PubMedID: 23257886
Gene_locus related to this paper: gosra-a0a0d2qg22 , gosra-a0a0d2w3z1 , gosra-a0a0d2uuz7 , gosra-a0a0d2rxs2 , gosra-a0a0d2sdk0 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , gosra-a0a0d2vdc5 , gosra-a0a0d2vj24 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8kis4 , gosra-a0a0d2pul0 , gosra-a0a0d2p3f2 , gosra-a0a0d2ril5 , gosra-a0a0d2s7d5 , gosra-a0a0d2t9b3 , gosra-a0a0d2tw88 , gosra-a0a0d2umz5 , gosra-a0a0d2pzd7 , gosra-a0a0d2scu7 , gosra-a0a0d2vcx6

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 : [A noninvasive diagnostic model of liver fibrosis using serum markers in primary biliary cirrhosis] - Ma_2012_Zhonghua.Nei.Ke.Za.Zhi_51_618
Author(s) : Ma JL , Wang R , Zhang FK , Jia JD , Ou XJ , Zhang T , Wang Y , Duan WJ , Zhao XY , You H , Ma H
Ref : Zhonghua Nei Ke Za Zhi , 51 :618 , 2012
Abstract : OBJECTIVE To verify and assess diagnostic value of noninvasive diagnostic model of liver fibrosis in primary biliary cirrhosis PBC based on conventional laboratory markers METHODS Seventy-three patients with PBC diagnosed by liver biopsy between January 2003 and June 2011 in Beijing Friendship Hospital Capital Medical University were recruited in this study Correlation analysis and logistic regression analysis between the conventional laboratory markers and histology stages were assessed A liver fibrosis diagnostic model was established based upon aforementioned biomarkers and verified by its sensitivity and specificity for predicting the liver fibrosis RESULTS The predictive model H index consisting of five conventional laboratory markers i.e platelet count serum cholinesterase albumin HDL-C and prothrombin time activity could predict advanced fibrosis stages III-IV with an AUC(ROC of 0.861 The sensitivity of predicting the absence of advanced fibrosis using H index 2.20 was 96.6 and the specificity of predicting the presence of advanced fibrosis using H index 0.41 was 93.2 CONCLUSION The established noninvasive diagnostic model consisting of five laboratory markers could accurately distinguish pathological changes of early stage PBC stages I-II from advanced stage PBC stages III-IV).
ESTHER : Ma_2012_Zhonghua.Nei.Ke.Za.Zhi_51_618
PubMedSearch : Ma_2012_Zhonghua.Nei.Ke.Za.Zhi_51_618
PubMedID: 23158860

Title : Homo- and hetero-dimers of inactive organophosphorous group binding at dual sites of AChE - Zhao_2011_Bioorg.Med.Chem.Lett_21_6404
Author(s) : Zhao Q , Xie R , Zhang T , Fang J , Mei X , Ning J , Tang Y
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :6404 , 2011
Abstract : Homo- and hetero-dimers of inactive organophosphorous group(s) dramatically enhanced the acetylcholinesterase (AChE; EC 3.1.1.7) inhibiting potency, with the highest potency observed at a tether length of 6 methylene groups (6d) for the homodimers, and 7 methylene groups (8e) for the heterodimers. The docking model of Drosophila melanogaster AChE suggested that 6d and 8e bound at the catalytic and peripheral sites of AChE, in which two organophosphorous groups of 6d individually oriented towards TRP83 of catalytic sites and TRP321 of peripheral sites, and phthalicimide group of 8e was appropriately arranged for a pi-pi interaction with the phenyl ring of TYR330, furthermore, the organophosphorous group introduced hydrophobic interaction with TRP83. The compounds prepared in this work demonstrated high insecticidal activity to Lipaphis erysimi and Tetranychus cinnbarinus at the concentration 300mg/L.
ESTHER : Zhao_2011_Bioorg.Med.Chem.Lett_21_6404
PubMedSearch : Zhao_2011_Bioorg.Med.Chem.Lett_21_6404
PubMedID: 21940169

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

Title : Route of nicotine administration influences in vivo dopamine neuron activity: habituation, needle injection, and cannula infusion - Dong_2010_J.Mol.Neurosci_40_164
Author(s) : Dong Y , Zhang T , Li W , Doyon WM , Dani JA
Ref : Journal of Molecular Neuroscience , 40 :164 , 2010
Abstract : Mesolimbic dopamine (DA) systems play a critical role in tobacco addiction driven by nicotine. Nicotine activates midbrain DA neurons and, consequently, elevates DA concentrations in targets, especially in the nucleus accumbens (NAc) of the ventral striatum. The route of drug administration influences the impact of addictive drugs. Here, we examine whether the nature of the administration alters DA neuron activity and DA concentrations in the NAc. Using unhabituated naive freely moving rats, microdialysis measurements showed that nicotine administered via needle injection caused greater DA release in the NAc than the same dose administered via an implanted chronic cannula. After habituation to the needle injections, however, there was no significant difference in DA signaling between the needle and cannula routes of administration. Consistent with these microdialysis results after habituation, our in vivo tetrode unit recordings showed no significant difference in midbrain DA neuron activity in response to nicotine delivered by needle or cannula as long as predictive cues were avoided
ESTHER : Dong_2010_J.Mol.Neurosci_40_164
PubMedSearch : Dong_2010_J.Mol.Neurosci_40_164
PubMedID: 19714495

Title : A novel degradation pathway of chloroaniline in Diaphorobacter sp. PCA039 entails initial hydroxylation. - Zhang_2010_World.J.Microbiol.Biotechnol_26_665
Author(s) : Zhang T , Ren HF , Liu Y , Zhu BL , Liu ZP , Liu SJ
Ref : World J Microbiol Biotechnol , 26 :665 , 2010
Abstract : A novel degradation pathway of chloroaniline in Diaphorobacter sp. PCA039 entails initial hydroxylation. A novel gene cluster (pca), involved in the degradation of p-chloroaniline, was identified from Diaphorobacter sp. PCA039 capable of utilizing p-chloroaniline as sole carbon, nitrogen and energy source for growth. There were 29 ORFs in the pca cluster, in the order of pcaTRKLMNOPR D C I U R D C U EFGXJHYWZI I QS. Based on sequence analysis, they were putatively identified as encoding a multicomponent phenol-hydroxylating oxygenase (pcaKLMNOP), two extradiol ring-cleavage dioxygenases, transcriptional regulatory proteins, enzymes mediating chlorocatechol degradation, and transportation functions. The genes pcaKLMNOP exhibited significant sequence identity (94%) to those of phenol hydroxylases (PH) from other bacteria, inferring that they might encode a multicomponent PH. This PH activity was also functionally characterized with the recombinant strain E. coli TOP10-S201 showing only PH activity, indicating that the degradation of p-chloroaniline by strain PCA039 was initiated by hydroxylation instead of normal dioxygenation. The other nineteen genes, pcaR D C I U R D C U EFGXJHYWZI I , encode for further degradation of p-chloroaniline to intermediates of the TCA-cycle and transposases. RT-PCR revealed that the hydrolytic (pcaF) and dehydrogenetic pathways (pcaE, pcaH), the two degrading branches, are both necessary for complete degradation of aniline, p-chloroaniline, phenol and also 4-aminophenol; and of the two C23O sets, PcaRDCU and PcaRDCU, PcaC1 is produced in the degradation of above four substrates, while PcaC2 is only expressed in p-chloroaniline degradation, suggesting that both C23O sets are needed for complete degradation of p-chloroaniline.
ESTHER : Zhang_2010_World.J.Microbiol.Biotechnol_26_665
PubMedSearch : Zhang_2010_World.J.Microbiol.Biotechnol_26_665
PubMedID:
Gene_locus related to this paper: 9burk-q58lx7

Title : Gene cloning and characterization of a novel esterase from activated sludge metagenome - Zhang_2009_Microb.Cell.Fact_8_67
Author(s) : Zhang T , Han WJ
Ref : Microb Cell Fact , 8 :67 , 2009
Abstract : A metagenomic library was prepared using pCC2FOS vector containing about 3.0 Gbp of community DNA from the microbial assemblage of activated sludge. Screening of a part of the un-amplified library resulted in the finding of 1 unique lipolytic clone capable of hydrolyzing tributyrin, in which an esterase gene was identified. This esterase/lipase gene consists of 834 bp and encodes a polypeptide (designated EstAS) of 277 amino acid residuals with a molecular mass of 31 kDa. Sequence analysis indicated that it showed 33% and 31% amino acid identity to esterase/lipase from Gemmata obscuriglobus UQM 2246 (ZP_02733109) and Yarrowia lipolytica CLIB122 (XP_504639), respectively; and several conserved regions were identified, including the putative active site, HSMGG, a catalytic triad (Ser92, His125 and Asp216) and a LHYFRG conserved motif. The EstAS was overexpressed, purified and shown to hydrolyse p-nitrophenyl (NP) esters of fatty acids with short chain lengths (< or = C8). This EstAS had optimal temperature and pH at 35 degrees C and 9.0, respectively, by hydrolysis of p-NP hexanoate. It also exhibited the same level of stability over wide temperature and pH ranges and in the presence of metal ions or detergents. The high level of stability of esterase EstAS with its unique substrate specificities make itself highly useful for biotechnological applications.
ESTHER : Zhang_2009_Microb.Cell.Fact_8_67
PubMedSearch : Zhang_2009_Microb.Cell.Fact_8_67
PubMedID: 20028524
Gene_locus related to this paper: 9bact-b6vfq6

Title : Phthalates biodegradation in the environment - Liang_2008_Appl.Microbiol.Biotechnol_80_183
Author(s) : Liang DW , Zhang T , Fang HH , He J
Ref : Applied Microbiology & Biotechnology , 80 :183 , 2008
Abstract : Phthalates are synthesized in massive amounts to produce various plastics and have become widespread in environments following their release as a result of extensive usage and production. This has been of an environmental concern because phthalates are hepatotoxic, teratogenic, and carcinogenic by nature. Numerous studies indicated that phthalates can be degraded by bacteria and fungi under aerobic, anoxic, and anaerobic conditions. This paper gives a review on the biodegradation of phthalates and includes the following aspects: (1) the relationship between the chemical structure of phthalates and their biodegradability, (2) the biodegradation of phthalates by pure/mixed cultures, (3) the biodegradation of phthalates under various environments, and (4) the biodegradation pathways of phthalates.
ESTHER : Liang_2008_Appl.Microbiol.Biotechnol_80_183
PubMedSearch : Liang_2008_Appl.Microbiol.Biotechnol_80_183
PubMedID: 18592233

Title : Prolonged effects of poly(lactic-co-glycolic acid) microsphere-containing huperzine A on mouse memory dysfunction induced by scopolamine - Wang_2007_Basic.Clin.Pharmacol.Toxicol_100_190
Author(s) : Wang C , Zhang T , Ma H , Liu J , Fu F , Liu K
Ref : Basic Clin Pharmacol Toxicol , 100 :190 , 2007
Abstract : Huperzine A is an anticholinesterase and cognitive enhancer, which is able to alleviate the symptoms of memory dysfunction in the mouse. The fast metabolization rate and narrow therapeutic spectrum makes it unfit for clinical use. Poly(lactic-co-glycolic acid) microsphere as delivery system effectively maintains the blood concentration of huperzine A by a slow-release effect over a long time. In the present article, we investigated the prolonged protective effect of microsphere-containing huperzine A on memory dysfunction induced by scopolamine. Spectrophotometric assay was used to determine the activity of acetylcholinesterase (AChE) and passive avoidance tests to evaluate memory performance. The results show that a bolus dose of microsphere-containing huperzine A (at a dose of 300 microg/kg or 600 microg/kg) administered intramuscularly can effectively maintain drug activity and significantly decrease the activity of AChE from day 3 to 14, the strongest effect seen on day 3 and 7. Accompanying the reduction of the activity of AChE, microsphere-containing huperzine A (300 microg/kg or 600 microg/kg) remarkably increased transfer latency time and no transfer response on the second trial through mitigating the memory impairments induced by scopolamine as compared to the scopolamine model group. Microsphere-containing huperzine A showed cognitive enhancing properties and anticholinesterase activity and may thus be a candidate for treatment of memory impairment.
ESTHER : Wang_2007_Basic.Clin.Pharmacol.Toxicol_100_190
PubMedSearch : Wang_2007_Basic.Clin.Pharmacol.Toxicol_100_190
PubMedID: 17309523

Title : [Associations of genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with low birth weight in neonates] - Liang_2005_Beijing.Da.Xue.Xue.Bao_37_85
Author(s) : Liang HY , Chen DF , Zhang T , Yang F , Wang LL , Chen L , Wu BY
Ref : Beijing Da Xue Xue Bao , 37 :85 , 2005
Abstract : OBJECTIVE: To investigate whether genetic polymorphisms in the microsomal epoxide hydrolase gene (EPHX1) and the glutathione S-transferase theta1 gene (GSTT1) are associated with low birth weight in neonates.
METHODS: Using standard questionnaires, 246 singleton live born mother-neonates pairs (73 cases were mother-low birth weight neonate pairs and 173 controls were mother-non low birth weight neonate pairs) were investigated by the trained field workers with case-control study at the hospital in Anqing, Anhui Province, China between 1998 and 1999. A total of 246 neonates were genotyped for genetic polymorphisms in the EPHX1 gene and the GSTT1 gene by a polymerase chain reaction-restriction fragment length polymorphism assay. Multiple linear regression models were used to estimate the association of the genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with neonatal low birth weight, adjusting for maternal age, education, parity, neonatal sex and gestational age.
RESULTS: EPHX1 His139His homozygote was not associated with low birth weight among neonates, compared with EPHX1 His139Arg heterozygote/Arg139Arg homozygote before and after adjustment confounders. GSTT1 absent genotype group also was not associated with low birth weight among neonates, compared with GSTT1 present genotype group before and after adjustment confounders. When both EPHX1 139 polymorphism and GSTT1 polymorphism were considered, a significant reduction in birth weight was found among neonates with EPHX1 His139His homozygote and GSTT1 absent genotype (OR=3.46, P=0.035). CONCLUSION: The combination between genetic polymorphisms in the EPHX1 gene and the GSTT1 gene in neonates is significantly associated with neonatal low birth weight.
ESTHER : Liang_2005_Beijing.Da.Xue.Xue.Bao_37_85
PubMedSearch : Liang_2005_Beijing.Da.Xue.Xue.Bao_37_85
PubMedID: 15719050

Title : Potential applications of nicotinic ligands in the laboratory and clinic - Dani_2004_Bioorg.Med.Chem.Lett_14_1837
Author(s) : Dani JA , De Biasi M , Liang Y , Peterson J , Zhang L , Zhang T , Zhou FM
Ref : Bioorganic & Medicinal Chemistry Lett , 14 :1837 , 2004
Abstract : The nicotinic acetylcholine receptor (nAChR) is a receptor, ion channel complex composed of five polypeptide subunits. There are many different nAChR subtypes constructed from a variety of different subunit combinations. This structural diversity contributes to the varied roles of nAChRs in the peripheral and central nervous system, and this diversity offers an excellent opportunity for chemists who are producing ligands. Subunit specific ligands could have wide and varied effects in the laboratory as experimental tools and in the clinic as therapeutic agents. Because presynaptic nAChRs have been shown to enhance the release of many neurotransmitters, new nicotinic ligands that potentiate nAChR activity would be very useful. Such ligands could enhance the release of various neurotransmitters during degenerative diseases that cause neurotransmitter systems to decrease their output. For example, boosting the release from cholinergic neurons would help patients with Alzheimer's disease, and boosting the release from dopaminergic neurons would help patients with Parkinson's disease.
ESTHER : Dani_2004_Bioorg.Med.Chem.Lett_14_1837
PubMedSearch : Dani_2004_Bioorg.Med.Chem.Lett_14_1837
PubMedID: 15050611

Title : Nicotinic cholinergic synaptic mechanisms in the ventral tegmental area contribute to nicotine addiction - Pidoplichko_2004_Learn.Mem_11_60
Author(s) : Pidoplichko VI , Noguchi J , Areola OO , Liang Y , Peterson J , Zhang T , Dani JA
Ref : Learn Mem , 11 :60 , 2004
Abstract : Tobacco use is a major health problem that is estimated to cause 4 million deaths a year worldwide. Nicotine is the main addictive component of tobacco. It acts as an agonist to activate and desensitize nicotinic acetylcholine receptors (nAChRs). A component of nicotine's addictive power is attributable to actions on the mesolimbic dopaminergic system, which serves a fundamental role in the acquisition of behaviors that are inappropriately reinforced by addictive drugs. Here we show that nicotine, in the same concentration and time ranges as obtained from tobacco, has three main actions that regulate the activity of midbrain dopamine (DA) neurons. Nicotine first activates and then desensitizes nAChRs on the DA neurons. This process directly excites the DA neurons for a short period of time before the nAChRs desensitize. Nicotine also enhances glutamatergic excitation and decreases GABAergic inhibition onto DA neurons. These events increase the probability for synaptic plasticity, such as long-term potentiation. The short-lived direct excitation of the DA neurons coupled with the enhanced glutamatergic afferent activity provides the presynaptic and postsynaptic coincidence necessary to initiate synaptic potentiation. In total, these synaptic events lead to a relatively long-lasting heightened activity of midbrain DA neurons. Consistent with other summarized studies, this work indicates that the synaptic changes normally associated with learning and memory can be influenced and commandeered during the nicotine addiction process.
ESTHER : Pidoplichko_2004_Learn.Mem_11_60
PubMedSearch : Pidoplichko_2004_Learn.Mem_11_60
PubMedID: 14747518

Title : Identification of cytochrome P450 1A2 as enzyme involved in the microsomal metabolism of Huperzine A - Ma_2003_Eur.J.Pharmacol_461_89
Author(s) : Ma X , Wang H , Xin J , Zhang T , Tu Z
Ref : European Journal of Pharmacology , 461 :89 , 2003
Abstract : Huperzine A is a reversible and selective cholinesterase inhibitor approved for the treatment of Alzheimer's disease. To identify which cytochrome P450 (CYP) isoenzymes are involved in the metabolism of Huperzine A, an in vitro study was performed with rat liver microsomes and immunoinhibition and chemical inhibition methods. Huperzine A metabolism was analyzed with high-performance liquid chromatography (HPLC) and expressed as Huperzine A disappearance rate. Result showed that 76.2% of Huperzine A metabolism was inhibited by CYP1A2 antibody and 17.8% by CYP3A1/2 antibody. Inhibitory effects produced by CYP2C11 and 2E1 antibodies were minor. The CYP1A2 substrate phenacetin showed an inhibitory effect of 70.3%. In conclusion, Huperzine A metabolism in rat liver microsomes is mediated primarily by CYP1A2, with a probable secondary contribution of CYP3A1/2. CYP2C11 and 2E1 are likely not involved in Huperzine A metabolism.
ESTHER : Ma_2003_Eur.J.Pharmacol_461_89
PubMedSearch : Ma_2003_Eur.J.Pharmacol_461_89
PubMedID: 12586202

Title : Acute effects of huperzine A and tacrine on rat liver - Ma_2003_Acta.Pharmacol.Sin_24_247
Author(s) : Ma XC , Xin J , Wang HX , Zhang T , Tu ZH
Ref : Acta Pharmacol Sin , 24 :247 , 2003
Abstract : AIM: To observe the acute effects of huperzine A and tacrine on rat liver.
METHODS: Changes of liver coefficient, serum biochemistry, and histopathology were detected after single dose. In vitro cytotoxicity was assessed by determining extracellular and intracellular amount of lactate dehydrogenase in cultured hepatocytes.
RESULTS: Both huperzine A and tacrine raised liver coefficient and increased serum aspartate aminotransferase and alanine aminotransferase. Tacrine induced liver histopathologic changes. The acute effects of huperzine A on liver could be redressed by atropine, while effects of tacrine on liver could not. Concentration-dependent in vitro cytotoxicity occurred with tacrine, but not with huperzine A. CONCLUSION: The acute effects of huperzine A on rat liver are not related to hepatotoxicity. The acute effects of tacrine on rat liver are related to hepatotoxicity.
ESTHER : Ma_2003_Acta.Pharmacol.Sin_24_247
PubMedSearch : Ma_2003_Acta.Pharmacol.Sin_24_247
PubMedID: 12617774