Wang P

References (108)

Title : Alteration of the intestinal microbiota and serum metabolites in a mouse model of Pon1 gene ablation - Li_2024_Faseb.j_38_e23611
Author(s) : Li J , Yan K , Wang S , Wang P , Jiao J , Dong Y
Ref : Faseb j , 38 :e23611 , 2024
Abstract : Mutations in the Paraoxonase 1 (Pon1) gene underlie aging, cardiovascular disease, and impairments of the nervous and gastrointestinal systems and are linked to the intestinal microbiome. The potential role of Pon1 in modulating the intestinal microbiota and serum metabolites is poorly understood. The present study demonstrated that mice with genomic excision of Pon1 by a multiplexed guide RNA CRISPR/Cas9 approach exhibited disrupted gut microbiota, such as significantly depressed alpha-diversity and distinctly separated beta diversity, accompanied by varied profiles of circulating metabolites. Furthermore, genomic knock in of Pon1 exerted a distinct effect on the intestinal microbiome and serum metabolome, including dramatically enriched Aerococcus, linoleic acid and depleted Bacillus, indolelactic acid. Specifically, a strong correlation was established between bacterial alterations and metabolites in Pon1 knockout mice. In addition, we identified metabolites related to gut bacteria in response to Pon1 knock in. Thus, the deletion of Pon1 affects the gut microbiome and functionally modifies serum metabolism, which can lead to dysbiosis, metabolic dysfunction, and infection risk. Together, these findings put forth a role for Pon1 in microbial alterations that contribute to metabolism variations. The function of Pon1 in diseases might at least partially depend on the microbiome.
ESTHER : Li_2024_Faseb.j_38_e23611
PubMedSearch : Li_2024_Faseb.j_38_e23611
PubMedID: 38597925

Title : Phytochemical Profiling and Biological Activities of Pericarps and Seeds Reveal the Controversy on Enucleation or Nucleus-Retaining of Cornus officinalis Fruits - Zhang_2024_Molecules_29_
Author(s) : Zhang J , Niu P , Li M , Wang Y , Ma Y , Wang P
Ref : Molecules , 29 : , 2024
Abstract : The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, alpha-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better alpha-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.
ESTHER : Zhang_2024_Molecules_29_
PubMedSearch : Zhang_2024_Molecules_29_
PubMedID: 38611753

Title : Neuroprotective effects of Shenghui decoction via inhibition of the JNK\/p38 MAPK signaling pathway in an AlCl(3)-induced zebrafish (Danio rerio) model of Alzheimer's disease - Lu_2024_J.Ethnopharmacol__117993
Author(s) : Lu H , Ran S , Zhang Y , Chen Y , Tan A , Wang P
Ref : J Ethnopharmacol , :117993 , 2024
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a multi-factorial degenerative disease, and multi-targeted therapies targeting multiple pathogenic mechanisms should be explored. Shenghui decoction (SHD) is an ancient traditional Chinese medicine (TCM) formula used clinically to alleviate AD. However, the precise mechanism of action of SHD as a therapeutic agent for AD remains unclear. AIM OF THE STUDY: This study investigated the neuroprotective properties and potential mechanisms of action of SHD in mitigating AD-like symptoms induced by AlCl(3) in a zebrafish model. MATERIALS AND METHODS: Active components of SHD were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Zebrafish were exposed to AlCl(3) (200 microg/L) for 30 days to establish an AD zebrafish model. AlCl(3)-exposed zebrafish were treated with SHD or donepezil. Behavioral tests were used to assess learning and memory, locomotor activity, and AD-related anxiety and aggression in AlCl(3)-exposed zebrafish. Nissl staining and transmission electron microscopy were used to evaluate histological alterations in brain neurons. The concentrations of pro-inflammatory cytokines (tumor necrosis factor-alpha, TNF-alpha; interleukin-1beta, IL-1beta) were quantified using Enzyme-linked immunosorbent assay (ELISA). Markers of oxidative stress and cholinergic activity (acetylcholinesterase, AChE) were detected using biochemical assays. Western blotting and immunofluorescence were used to detect the protein expression levels of Abeta, p-tau, PSD-95, synaptophysin, TLR4, phosphorylation of NF-kappaB p65, p38, and JNK. RESULTS: Fifteen SHD compounds were identified by UPLC-MS/MS analysis. SHD improved AlCl(3)-induced dyskinesia, learning and memory impairment, anxiety-like behavior, and aggressive behavior in zebrafish. AlCl(3)-exposed zebrafish showed AD-like pathology, overexpression of Abeta, hyperphosphorylated tau protein, marked neuronal damage, decreased expression of synaptic proteins, synaptophysin, and PSD-95, and impairment of synaptic structural plasticity. These effects were reversed by the SHD treatment. We also observed that SHD ameliorated oxidative stress and decreased AChE activity and inflammatory cytokine levels. These effects are similar to those observed for donepezil. Meanwhile, SHD could decrease the protein expression of TLR4 and inhibit phosphorylation of NF-kappaB, JNK, and p38 MAPK. These results demonstrate that SHD has the potential to exert neuroprotective effects, which may be partly mediated via inhibition of the JNK/p38 MAPK signaling pathway. CONCLUSIONS: Our findings revealed the therapeutic mechanism of SHD in mitigating AD progression and suggested that SHD is a potent neuroprotectant that contributes to the future development of TCM modernization and broader clinical applications.
ESTHER : Lu_2024_J.Ethnopharmacol__117993
PubMedSearch : Lu_2024_J.Ethnopharmacol__117993
PubMedID: 38423408

Title : Efficacy and Safety of Plasma Exchange Combined with Hemoperfusion in the Treatment of Organophosphorus Poisoning: A Meta-Analysis - Yao_2023_Blood.Purif__1
Author(s) : Yao Z , Wang P , Fu Q , Song Q , Wang W , Liu A , Zhang P
Ref : Blood Purif , :1 , 2023
Abstract : INTRODUCTION: The aim of the study was to systematically evaluate the efficacy and safety of plasma exchange combined with hemoperfusion in the treatment of organophosphorus poisoning. METHODS: PubMed, Embase, the Cochrane Library, China National Knowledge Internet, Wanfang database, and Weipu database were searched for articles about this subject. Literature screening and selection were conducted in strict accordance with the inclusion and exclusion criteria. RESULTS: 14 randomized controlled trials with 1,034 participants were included in this meta-analysis study, including 518 cases in plasma exchange combined with hemoperfusion group (the combination treatment group) and 516 cases in hemoperfusion group (the control group). Compared with the control group, the combination treatment group was associated with a higher effective rate (relative risk [RR] = 1.20, 95% confidence interval [CI] [1.11, 1.30], p < 0.00001) and lower fatality rate (RR = 0.28, 95% CI [0.15, 0.52], p< 0.0001); reduced TNF-alpha (standardized mean difference [SMD] = -1.95, 95% CI [-2.42, -1.48], p < 0.00001), IL-6 (SMD = -1.94, 95% CI [-3.08, -0.80], p = 0.0009), and C-reactive protein (CRP) (SMD = -1.94, 95% CI [-2.86, -1.03], p < 0.0001); shorten coma time (SMD = -1.99, 95% CI [-2.75, -1.24], p < 0.00001), recovery time of cholinesterase activity (SMD = -1.71, 95% CI [-1.90, -1.53], p < 0.00001), and hospital stay (SMD = -1.29, 95% CI [-1.59, -0.98], p < 0.00001). The incidence of complications in the combination treatment group such as liver and kidney damage (RR = 0.30, 95% CI [0.18, 0.50], p < 0.00001), pulmonary infection (RR = 0.29, 95% CI [0.18, 0.47], p < 0.00001), and intermediate syndrome (RR = 0.32, 95% CI [0.21, 0.49], p < 0.00001) was lower than that in the control group. CONCLUSIONS: The current evidence suggests that the combination of plasma exchange with hemoperfusion therapy can reduce the mortality of patients with organophosphorus poisoning, shorten the recovery time of cholinesterase activity and the time of coma, reduce the average length of hospital stay, and reduce the levels of IL-6, TNF-alpha, and CRP, but high-quality randomized double-blind controlled trials are still required to confirm the current findings in the future.
ESTHER : Yao_2023_Blood.Purif__1
PubMedSearch : Yao_2023_Blood.Purif__1
PubMedID: 37302392

Title : Role of cholinergic innervation in biliary remnants of patients with biliary atresia - Yang_2023_Front.Pediatr_11_1278978
Author(s) : Yang J , Chen X , Wang W , Su Y , Liu K , Abudusalamu A , Li D , He Y , Wang P , Xiong X , Feng J
Ref : Front Pediatr , 11 :1278978 , 2023
Abstract : OBJECTIVE: Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery. METHODS: Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed. RESULTS: In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R(2 )= 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063). CONCLUSIONS: Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.
ESTHER : Yang_2023_Front.Pediatr_11_1278978
PubMedSearch : Yang_2023_Front.Pediatr_11_1278978
PubMedID: 38259596

Title : Functional Imaging and Inhibitor Screening of Human Pancreatic Lipase by a Resorufin-Based Fluorescent Probe - Hou_2023_Biosensors.(Basel)_13_
Author(s) : Hou FB , Zhang N , Zhu GH , Fan YF , Sun MR , Nie LL , Ge GB , Zheng YJ , Wang P
Ref : Biosensors (Basel) , 13 : , 2023
Abstract : Human pancreatic lipase (hPL) is a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, and inhibition of hPL is effective in reducing triglyceride intake, thereby preventing and treating obesity. In this study, a series of fatty acids with different carbon chain lengths were constructed to the fluorophore resorufin based on the substrate preference of hPL. Among them, RLE was found to have the best combination of stability, specificity, sensitivity and reactivity towards hPL. Under physiological conditions, RLE can be rapidly hydrolyzed by hPL and released to resorufin, which triggered approximately 100-fold fluorescence enhancement at 590 nm. RLE was successfully applied for sensing and imaging of endogenous PL in living systems with low cytotoxicity and high imaging resolution. Moreover, a visual high-throughput screening platform was established using RLE, and the inhibitory effects of hundreds of drugs and natural products toward hPL were evaluated. Collectively, this study reports a novel and highly specific enzyme-activatable fluorogenic substrate for hPL that could serve as a powerful tool for monitoring hPL activity in complex biological systems and showcases the potential to explore physiological functions and rapid screening of inhibitors.
ESTHER : Hou_2023_Biosensors.(Basel)_13_
PubMedSearch : Hou_2023_Biosensors.(Basel)_13_
PubMedID: 36832049

Title : Discovery of quinazolin-4(3H)-one derivatives as novel AChE inhibitors with anti-inflammatory activities - Lv_2023_Eur.J.Med.Chem_254_115346
Author(s) : Lv L , Maimaitiming M , Huang Y , Yang J , Chen S , Sun Y , Zhang X , Li X , Xue C , Wang P , Wang CY , Liu Z
Ref : Eur Journal of Medicinal Chemistry , 254 :115346 , 2023
Abstract : A series of quinazolin-4(3H)-one derivatives was designed through scaffold-hopping strategy and synthesized as novel multifunctional anti-AD agents demonstrating both cholinesterase inhibition and anti-inflammatory activities. Their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were evaluated, and the enzyme kinetics study as well as detailed binding mode via molecular docking were performed for selected compounds. MR2938 (B12) displayed promising AChE inhibitory activity with an IC(50) value of 5.04 microM and suppressed NO production obviously (IC(50) = 3.29 microM). Besides, it was able to decrease the mRNA levels of pro-inflammatory cytokines IL-1beta, TNF-alpha, IL-6 and CCL2 at 1.25 microM. Further mechanism study suggested that MR2938 suppressed the neuroinflammation through blocking MAPK/JNK and NF-kappaB signaling pathways. All these results indicate that MR2938 is a good starting point to develop multifunctional anti-AD lead compounds.
ESTHER : Lv_2023_Eur.J.Med.Chem_254_115346
PubMedSearch : Lv_2023_Eur.J.Med.Chem_254_115346
PubMedID: 37043994

Title : Computational design of highly efficient thermostable MHET hydrolases and dual enzyme system for PET recycling - Zhang_2023_Commun.Biol_6_1135
Author(s) : Zhang J , Wang H , Luo Z , Yang Z , Zhang Z , Wang P , Li M , Zhang Y , Feng Y , Lu D , Zhu Y
Ref : Commun Biol , 6 :1135 , 2023
Abstract : Recently developed enzymes for the depolymerization of polyethylene terephthalate (PET) such as FAST-PETase and LCC-ICCG are inhibited by the intermediate PET product mono(2-hydroxyethyl) terephthalate (MHET). Consequently, the conversion of PET enzymatically into its constituent monomers terephthalic acid (TPA) and ethylene glycol (EG) is inefficient. In this study, a protein scaffold (1TQH) corresponding to a thermophilic carboxylesterase (Est30) was selected from the structural database and redesigned in silico. Among designs, a double variant KL-MHETase (I171K/G130L) with a similar protein melting temperature (67.58 degreesC) to that of the PET hydrolase FAST-PETase (67.80 degreesC) exhibited a 67-fold higher activity for MHET hydrolysis than FAST-PETase. A fused dual enzyme system comprising KL-MHETase and FAST-PETase exhibited a 2.6-fold faster PET depolymerization rate than FAST-PETase alone. Synergy increased the yield of TPA by 1.64 fold, and its purity in the released aromatic products reached 99.5%. In large reaction systems with 100 g/L substrate concentrations, the dual enzyme system KL36F achieved over 90% PET depolymerization into monomers, demonstrating its potential applicability in the industrial recycling of PET plastics. Therefore, a dual enzyme system can greatly reduce the reaction and separation cost for sustainable enzymatic PET recycling.
ESTHER : Zhang_2023_Commun.Biol_6_1135
PubMedSearch : Zhang_2023_Commun.Biol_6_1135
PubMedID: 37945666
Gene_locus related to this paper: geost-est30

Title : Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma ameliorate scopolamine-induced cognitive impairment by regulating the cholinergic and synaptic associated proteins - Xie_2023_J.Ethnopharmacol_311_116400
Author(s) : Xie Y , Liu L , Zheng J , Shi K , Ai W , Zhang X , Wang P , Lan Z , Chen L
Ref : J Ethnopharmacol , 311 :116400 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Polygoni Multiflori Radix Praeparata (PMRP) and Acori Tatarinowii Rhizoma (ATR) is often used in traditional Chinese medicine to prevent and treat Alzheimer's disease (AD). However, it is not clear whether the effects and mechanisms of the decoction prepared by traditional decocting method (PA) is different from that prepared by modern decocting method (P + A). AIM OF THE STUDY: The present study aimed to investigate the differences in the protective effects of PA and P + A on scopolamine induced cognitive impairment, and to explore its potential mechanism. MATERIALS AND METHODS: To assess the protective effect of PA and P + A on cognitive dysfunction, the mice were orally administrated with PA (1.56, 6.24 g kg(-1)day(-1)) and P + A (1.56, 6.24 g kg(-1)day(-1)) for 26 days before co-treatment with scopolamine (4 mg kg(-1)day(-1), i.p.). The learning and memory abilities of mice were examined by Morris water maze test, and the expressions of proteins related to cholinergic system and synaptic function were detected by the methods of ELISA, real-time PCR and Western blotting. Then, molecular docking technique was used to verify the effect of active compounds in plasma after PA administration on Acetylcholinesterase (AChE) protein. Finally, the Ellman method was used to evaluate the effects of different concentrations of PA, P + A (1 microg/mL-100 mg/mL) and the compounds (1-100 microM) on AChE activity in vitro. RESULTS: On one hand, in the scopolamine-induced cognitive impairment mouse model, both of PA and P + A could improve the cognitive impairment, while the effect of PA on cognitive amelioration was better than that of P + A. Moreover, PA regulated the cholinergic and synaptic functions by enhancing the concentration of acetylcholine (ACh), the mRNA levels of CHT1, Syn, GAP-43 and PSD-95, and the related proteins (CHT1, VACHT, Syn, GAP-43 and PSD-95), and significantly inhibiting the expression of AChE protein. Meanwhile, P + A only up-regulated the mRNA levels of GAP-43 and PSD-95, increased the expressions of CHT1, VACHT, Syn, GAP-43 and PSD-95 proteins, and inhibited the expression of AChE protein. On the other hand, the in vitro study showed that some compounds including emodin-8-o-beta-d-Glucopyranoside, THSG and alpha-Asarone inhibited AChE protein activity with the IC(50) values 3.65 microM, 5.42 microM and 9.43 microM, respectively. CONCLUSIONS: These findings demonstrate that both of PA and P + A can ameliorate the cognitive deficits by enhancing cholinergic and synaptic related proteins, while PA has the stronger improvement effect on the cholinergic function, which may be attributed to the compounds including THSG, emodin, emodin-8-O-beta-D-glucopyranoside and alpha-asarone. The present study indicated that PA has more therapeutic potential in the treatment of neurodegenerative diseases such as AD. The results provide the experimental basis for the clinical use of PA.
ESTHER : Xie_2023_J.Ethnopharmacol_311_116400
PubMedSearch : Xie_2023_J.Ethnopharmacol_311_116400
PubMedID: 37003402

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 : A rationally engineered specific near-infrared fluorogenic substrate of human pancreatic lipase for functional imaging and inhibitor screening - Hou_2023_Analyst__
Author(s) : Hou FB , Zhang N , Hou XD , Liu W , Fan YF , Zhu GH , Wu Y , Sun MR , Zhao B , Ge GB , Wang P
Ref : Analyst , : , 2023
Abstract : Obesity, now widespread all over the world, is frequently associated with several chronic diseases. Human pancreatic lipase (hPL) is a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, and the inhibition of hPL is effective in reducing triglyceride intake and thus preventing and treating obesity. In this work, a practical sequential screening strategy was developed to construct a highly selective near-infrared fluorogenic substrate 7-STCFC for hPL. Under physiological conditions, 7-STCFC can be rapidly hydrolyzed by hPL to form 7-HTCFC, which triggers 254-fold NIR signal enhancement at 670 nm. 7-STCFC was successfully applied for the sensing and imaging of endogenous PL in living systems (including living cells, tissues and organs) with low cytotoxicity and high imaging resolution. Moreover, a high-throughput screening platform was established using 7-STCFC, and the inhibitory effects of 94 kinds of herbs toward hPL were evaluated. Among them, Pu-erh tea stood out with outstanding hPL inhibitory effects, and the inhibitory ingredients and involved inhibitory mechanism were further revealed, which strongly facilitates the discovery of novel anti-obesity agents targeting hPL. Collectively, these findings suggested that our strategy was practical to develop an isoform-specific fluorogenic substrate for a target enzyme, and 7-STCFC was a powerful tool for monitoring PL activity in complex biological systems with value for exploring physiological functions and rapid screening of inhibitors.
ESTHER : Hou_2023_Analyst__
PubMedSearch : Hou_2023_Analyst__
PubMedID: 37092796

Title : De Novo Computational Design of a Lipase with Hydrolysis Activity towards Middle-Chained Fatty Acid Esters - Huang_2023_Int.J.Mol.Sci_24_8581
Author(s) : Huang J , Xie X , Zheng Z , Ye L , Wang P , Xu L , Wu Y , Yan J , Yang M , Yan Y
Ref : Int J Mol Sci , 24 :8581 , 2023
Abstract : Innovations in biocatalysts provide great prospects for intolerant environments or novel reactions. Due to the limited catalytic capacity and the long-term and labor-intensive characteristics of mining enzymes with the desired functions, de novo enzyme design was developed to obtain industrial application candidates in a rapid and convenient way. Here, based on the catalytic mechanisms and the known structures of proteins, we proposed a computational protein design strategy combining de novo enzyme design and laboratory-directed evolution. Starting with the theozyme constructed using a quantum-mechanical approach, the theoretical enzyme-skeleton combinations were assembled and optimized via the Rosetta "inside-out" protocol. A small number of designed sequences were experimentally screened using SDS-PAGE, mass spectrometry and a qualitative activity assay in which the designed enzyme 1a8uD(1) exhibited a measurable hydrolysis activity of 24.25 +/- 0.57 U/g towards p-nitrophenyl octanoate. To improve the activity of the designed enzyme, molecular dynamics simulations and the RosettaDesign application were utilized to further optimize the substrate binding mode and amino acid sequence, thus keeping the residues of theozyme intact. The redesigned lipase 1a8uD(1)-M8 displayed enhanced hydrolysis activity towards p-nitrophenyl octanoate-3.34 times higher than that of 1a8uD(1). Meanwhile, the natural skeleton protein (PDB entry 1a8u) did not display any hydrolysis activity, confirming that the hydrolysis abilities of the designed 1a8uD(1) and the redesigned 1a8uD(1)-M8 were devised from scratch. More importantly, the designed 1a8uD(1)-M8 was also able to hydrolyze the natural middle-chained substrate (glycerol trioctanoate), for which the activity was 27.67 +/- 0.69 U/g. This study indicates that the strategy employed here has great potential to generate novel enzymes exhibiting the desired reactions.
ESTHER : Huang_2023_Int.J.Mol.Sci_24_8581
PubMedSearch : Huang_2023_Int.J.Mol.Sci_24_8581
PubMedID: 37239928
Gene_locus related to this paper: 9zzzz-1a8uD1

Title : Bioaccumulation, metabolism and toxicological effects of chiral insecticide malathion and its metabolites in zebrafish (Danio rerio) - Cui_2023_Chemosphere_318_137898
Author(s) : Cui J , Wei Y , Jiang J , Xiao S , Liu X , Zhou Z , Liu D , Wang P
Ref : Chemosphere , 318 :137898 , 2023
Abstract : The bioaccumulation, metabolism, tissue-specific distribution and toxicity of the widely used organophosphorous pesticide malathion to zebrafish were investigated on an enantiomeric level for evaluating the environmental risks. The metabolites were also monitored and evaluated. Malathion was metabolized by zebrafish very fast with the half-life of 0.12 d and showed a middle accumulation capacity in zebrafish with bioaccumulation factor (BCF) of 12.9 after a 15-d exposure. Brain could enrich higher concentration of malathion than other tissues. The metabolites malaoxon, malathion/malaoxon monocarboxylic acid (DMA), malathion/malaoxon dicarboxylic acid (DCA), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP) were found, in which DMTP and DCA were in higher level, indicating the metabolism was mainly induced by carboxylesterase degradation. The accumulation of malathion and malaoxon was stereoselective in zebrafish tissues, exhibiting S-enantiomer preferentially enriched. The acute toxicity test showed rac-malathion was low toxic to zebrafish, which was 1.2 and 1.6 folds more toxic than S-malathion and R-malathion respectively. Malaoxon was highly toxic to zebrafish and approximately 32 times more toxic than malathion. The toxicity of other metabolites was lower than malathion. Malathion could cause an apparent developmental toxicity to zebrafish embryo, including bradycardia, hatchability reduction and deformity, and abnormal movement patterns in zebrafish larva. Chronic toxicity indicated that malathion and malaoxon induced oxidative damage and neurotoxicity in the liver, brain and gill of zebrafish, and malaoxon exhibited a relatively high injury to the zebrafish brain. The results can provide information for the comprehensive assessment of the potential risk of malathion to aquatic organisms and highlight the necessity of consideration of stereoselectivity and metabolites when systemically evaluating pesticides.
ESTHER : Cui_2023_Chemosphere_318_137898
PubMedSearch : Cui_2023_Chemosphere_318_137898
PubMedID: 36702415

Title : Computational Modeling Study of the Binding of Aging and Non-Aging Inhibitors with Neuropathy Target Esterase - Wu_2023_Molecules_28_
Author(s) : Wu W , Huang J , Han P , Zhang J , Wang Y , Jin F , Zhou Y , Wang P
Ref : Molecules , 28 : , 2023
Abstract : Neuropathy target esterase (NTE) is a serine hydrolase with phospholipase B activity, which is involved in maintaining the homeostasis of phospholipids. It can be inhibited by aging inhibitors such as some organophosphorus (OP) compounds, which leads to delayed neurotoxicity with distal degeneration of axons. However, the detailed binding conformation of aging and non-aging inhibitors with NTE is not known. In this study, new computational models were constructed by using MODELLER 10.3 and AlphaFold2 to further investigate the inhibition mechanism of aging and non-aging compounds using molecular docking. The results show that the non-aging compounds bind the hydrophobic pocket much deeper than aging compounds and form the hydrophobic interaction with Phe1066. Therefore, the unique binding conformation of non-aging compounds may prevent the aging reaction. These important differences of the binding conformations of aging and non-aging inhibitors with NTE may help explain their different inhibition mechanism and the protection of non-aging NTE inhibitors against delayed neuropathy.
ESTHER : Wu_2023_Molecules_28_
PubMedSearch : Wu_2023_Molecules_28_
PubMedID: 38005352 || 38067477

Title : Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones - Yi_2023_Plant.Physiol__
Author(s) : Yi F , An G , Song A , Cheng K , Liu J , Wang C , Wu S , Wang P , Zhu J , Liang Z , Chang Y , Chu Z , Cai C , Zhang X , Chen A , Xu J , Burritt DJ , Herrera-Estrella L , Tran LP , Li W , Cai Y
Ref : Plant Physiol , : , 2023
Abstract : Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation.
ESTHER : Yi_2023_Plant.Physiol__
PubMedSearch : Yi_2023_Plant.Physiol__
PubMedID: 36718522

Title : Molecular mechanisms by which targeted muscle reinnervation improves the microenvironment of spinal cord motor neurons and target muscles - Lu_2022_Neurosci.Lett_789_136879
Author(s) : Lu W , Jiang Z , Tang C , Wang P , Yang L
Ref : Neuroscience Letters , 789 :136879 , 2022
Abstract : Targeted muscle reinnervation is a clinically valuable nerve transfers technology used to reconstruct the information sources reconstruct the motor nerve information sources lost because of nerve injury. This study aimed to investigate the effects and underlying molecular mechanisms of hind limb TMR on motor neurons and target muscles in rats after tibial nerve transection (TNT). Immunohistochemistry was performed to detect acetylcholinesterase expression in the target muscles and myelin basic protein, neuregulin-1 (NRG1), and ErbB2 expression in the tibial nerve of rats. Masson's trichrome staining was performed to observe fibrillar collagen expression in the target muscles. Western blot analysis was used to detect the protein expression of NRG1 and its receptor, ErbB2, in the target muscles. TMR significantly enhanced NRG1, ErbB2, and myelin basic protein expression in nerve fibers compared with those in the TNT group and exerted a protective effect on the maintenance of a large number of nerve fibers and myelin sheath thickness. The above results indicated that TMR can regulate NRG1 and ErbB2 expression in residual nerve fibers and protect the integrity of the myelin sheath, thus improving the functional status of the target muscles, which is beneficial for restoring hind limb motor function after TNT.
ESTHER : Lu_2022_Neurosci.Lett_789_136879
PubMedSearch : Lu_2022_Neurosci.Lett_789_136879
PubMedID: 36152746

Title : Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues - Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
Author(s) : Zhang X , Xu W , Xu R , Wang Z , Wang P , Peng K , Li M , Li J , Tan Y , Wang X , Pei H
Ref : Oxid Med Cell Longev , 2022 :4594956 , 2022
Abstract : Cytoplasmic lipid droplets (LDs) can store neutral lipids as an energy source when needed and also regulate the key metabolic processes of intracellular lipid accumulation, which is associated with several metabolic diseases. The perilipins (Plins) are a family of proteins that associate with the surface of LDs. As a member of Plins superfamily, perilipin 5 (Plin5) coats LDs in cardiomyocytes, which is significantly related to reactive oxygen species (ROS) production originated from mitochondria in the heart, consequently determining the progression of diabetic cardiomyopathy. Plin5 may play a bidirectional function in lipid metabolism which is in a state of dynamic balance. In the basic state, Plin5 inhibited the binding of comparative gene identification-58 (CGI-58) to adipose triglyceride lipase (ATGL) by binding CGI-58, thus inhibiting lipolysis. However, when the body is under stress (such as cold, fasting, exercise, and other stimuli), protein kinase A (PKA) phosphorylates and activates Plin5, which then causes Plin5 to release the binding site of CGI-58 and ATGL, prompting CGI-58 to bind to ATGL and activate ATGL activity, thus accelerating the lipolysis process, revealing the indispensable role of Plin5 in lipid turnover. Here, the purpose of this review is to summarize the present understanding of the bidirectional regulation role of Plin5 in oxidative tissues and to reveal its potential role in diabetic cardiomyopathy protection.
ESTHER : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedSearch : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedID: 35401929

Title : The Detoxification Enzymatic Responses of Plutella xylostella (Lepidoptera: Plutellidae) to Cantharidin - Sun_2022_J.Econ.Entomol__
Author(s) : Sun H , Wang P , Wei C , Li Y , Zhang Y
Ref : J Econ Entomol , : , 2022
Abstract : Plutella xylostella (L.) (Lepidoptera: Plutellidae) is one of the most destructive pests of Brassicaceae vegetables. Cantharidin is an insect-derived defensive toxin, which has been reported to have toxicity to a variety of pests and especially lepidopteran pests. Although the toxicity of cantharidin on P. xylostella has been demonstrated, there is little information available on the specific detoxification response of P. xylostella against cantharidin. This study investigates the enzymatic response (including serine/threonine phosphatases [PSPs], carboxylesterases [CarEs], glutathione-S-transferases [GSTs], and cytochrome P450 monooxygenases [P450]) in P. xylostella to the sublethal and low lethal concentrations of cantharidin (LC10 and LC25). Results showed that the inhibitory activity of PSPs was increased and then decreased in vivo, while PSPs activity could be almost completely inhibited in vitro. Interestingly, the activities of detoxification enzymes (GST, CarE, and P450) in P. xylostella displayed a trend of decreasing and then increasing after exposure to the two concentrations of cantharidin. Notably, the increase in P450 enzyme activity was the most significant. The increasing trend of detoxification enzyme activity was congruent with the recovery trend of PSPs activity. This study contributes to our understanding of the detoxification mechanism of cantharidin in P. xylostella and helps in the further development of biogenic agents.
ESTHER : Sun_2022_J.Econ.Entomol__
PubMedSearch : Sun_2022_J.Econ.Entomol__
PubMedID: 36073195

Title : Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes - Yu_2022_PLoS.Pathog_18_e1010552
Author(s) : Yu X , Tong L , Zhang L , Yang Y , Xiao X , Zhu Y , Wang P , Cheng G
Ref : PLoS Pathog , 18 :e1010552 , 2022
Abstract : Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases.
ESTHER : Yu_2022_PLoS.Pathog_18_e1010552
PubMedSearch : Yu_2022_PLoS.Pathog_18_e1010552
PubMedID: 35679229

Title : Nuclear access of DNlg3 c-terminal fragment and its function in regulating innate immune response genes - Xie_2022_Biochem.Biophys.Res.Commun_641_93
Author(s) : Xie H , Liu S , Fu Y , Cheng Q , Wang P , Bi CL , Wang R , Chen MM , Fang M
Ref : Biochemical & Biophysical Research Communications , 641 :93 , 2022
Abstract : Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism.
ESTHER : Xie_2022_Biochem.Biophys.Res.Commun_641_93
PubMedSearch : Xie_2022_Biochem.Biophys.Res.Commun_641_93
PubMedID: 36525929

Title : Ferulic acid- and gallic ester-acylated pectin: Preparation and characterization - Chen_2022_J.Food.Sci__
Author(s) : Chen P , Wang P , Hong P
Ref : J Food Sci , : , 2022
Abstract : In this study, pectin was modified with ferulic acid (Fa), trans-ferulic acid (trans-Fa), methyl gallate (MG), and ethyl gallate (EG) via the enzymatic method using aqueous/organic phases to enhance its physiochemical and bio-active properties. Results revealed that lipase might catalyze the hydrolysis of the ester bond within pectin in aqueous phase and prompt the transesterification between the hydroxyl group in the para position in Fa/trans-Fa or the 2'-OH group of MG/EG and the carboxylic group of pectin in the organic phase. The graft ratio was 21.00%, 21.67%, 13.24%, and 11.93% for the Fa-, trans-Fa-, MG-, and EG-modified pectin, respectively. In addition, compared with native pectin, the modified pectin exhibited improved apparent viscosity and emulsion activity. Moreover, the clearance of 1,1-diphenyl-2-picryl hydrazine (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) was effectively enhanced for the modified pectin. Furthermore, the modified pectin exhibited strong antibacterial activity against Escherichia coli and Staphylococcus aureus while no cytotoxic effects based on the results of cell culture experiments. Our results provide a theoretical basis for the expansion of pectin applications in the food and pharmaceutical industries.
ESTHER : Chen_2022_J.Food.Sci__
PubMedSearch : Chen_2022_J.Food.Sci__
PubMedID: 35708190

Title : Chain-locked precursor ion scanning based HPLC-MS\/MS for in-depth molecular analysis of lipase-catalyzed transesterification of structured phospholipids containing w-3 fatty acyl chains - Zhang_2022_Food.Chem_399_133982
Author(s) : Zhang M , Wang P , Jin D , Jian S , Wu J , Huang M , Xie H , Zhao Q , Yang H , Luo P , Yuan H , Xue J , Shen Q
Ref : Food Chem , 399 :133982 , 2022
Abstract : Lipase-catalyzed transesterification of structured phospholipids (sPLs) is a hot topic, but the structural variation of the fatty acyl chains in intact phospholipids at the molecular level remains unclear to date. The present study explored the detailed characteristics of synthesized phospholipids through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in precursor ion scan mode. The optimal conditions were in-depth inspected and determined for the reaction system, including phospholipase A1 as catalyst, 15% lipase loading, and 1% water content. The sPLs enriched with EPA/DHA were structurally and quantitatively characterized by focusing on the fragments of m/z 301.6 (eicosapentaenoic acid, EPA) and m/z 327.6 (docosahexaenoic acid, DHA), and the results were statistically analyzed using partial least squares discriminant analysis and clustered heatmap hierarchical clustering analysis. PC 38:6 (18:1/20:5), PC 38:7 (18:2/20:5), PC o-40:6 (o-18:0/22:6), and PE 40:8 (18:2/22:6) etc. were revealed as the main variables that were active in the reaction.
ESTHER : Zhang_2022_Food.Chem_399_133982
PubMedSearch : Zhang_2022_Food.Chem_399_133982
PubMedID: 36027811

Title : Galantamine attenuates autoinflammation in a mouse model of familial mediterranean fever - Mughrabi_2022_Mol.Med_28_148
Author(s) : Mughrabi IT , Ochani M , Tanovic M , Wang P , Diamond B , Sherry B , Pavlov VA , Ozen S , Kastner DL , Chae JJ , Al-Abed Y
Ref : Mol Med , 28 :148 , 2022
Abstract : BACKGROUND: Autoinflammatory diseases, a diverse group of inherited conditionsscharacterized by excessive innate immune activation, have limited therapeutic options. Neuroimmune circuits of the inflammatory reflex control innate immune overactivation and can be stimulated to treat disease using the acetylcholinesterase inhibitor galantamine. METHODS: We tested the efficacy of galantamine in a rodent model of the prototypical autoinflammatory disease familial Mediterranean fever (FMF). Multiple chronic disease markers were evaluated in animals that received long-term galantamine treatment compared to vehicle. RESULTS: Long-term treatment with galantamine attenuated the associated splenomegaly and anemia which are characteristic features of this disease. Further, treatment reduced inflammatory cell infiltration into affected organs and a subcutaneous air pouch. CONCLUSIONS: These findings suggest that galantamine attenuates chronic inflammation in this mouse model of FMF. Further research is warranted to explore the therapeutic potential of galantamine in FMF and other autoinflammatory diseases.
ESTHER : Mughrabi_2022_Mol.Med_28_148
PubMedSearch : Mughrabi_2022_Mol.Med_28_148
PubMedID: 36494621

Title : A stable biosensor based on chitosan-modified graphene for detecting organophosphorus pesticides - Zhang_2021_Biotechnol.Appl.Biochem__
Author(s) : Zhang J , Hu H , Wang P , Zhang C , Wuma J , Yang L
Ref : Biotechnol Appl Biochem , : , 2021
Abstract : An acetylcholinesterase (AChE) biosensor was successfully fabricated with a stable structure and high detection accuracy. Graphene (Gra) nano-fragments modified with chitosan and acetylcholinesterase were successively drip-coated on the surface of a glassy carbon electrode via a layer-by-layer assembly method. The concentration range of the sensor to detect dichlorvos was 0.1 nM to 100000 nM, and the limit of detection was 54 pM. Chitosan (CS) was used to modify graphene for the first time, which enhanced the mechanical flexibility of these graphene nanostructures, significantly improving the stability and detection accuracy of this sensor. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2021_Biotechnol.Appl.Biochem__
PubMedSearch : Zhang_2021_Biotechnol.Appl.Biochem__
PubMedID: 33660328

Title : The disassembly of lipid droplets in Chlamydomonas - Li-Beisson_2021_New.Phytol__
Author(s) : Li-Beisson Y , Kong F , Wang P , Lee Y , Kang BH
Ref : New Phytol , : , 2021
Abstract : Lipid droplets (LDs) are ubiquitous and specialized organelle in eukaryotic cells. Consisting of a triacylglycerol core surrounded by a monolayer of membrane lipids, LDs are decorated with proteins and have myriad functions, from carbon/energy storage to membrane lipid remodeling and signal transduction. The biogenesis and turnover of LDs are therefore tightly coordinated with cellular metabolic needs in a fluctuating environment. LD turnover requires remodeling of the protein coat, lipolysis, autophagy and fatty acid beta-oxidation. Several key components of these processes have been identified in Chlamydomonas (Chlamydomonas reinhardtii), including the major lipid droplet protein, a CXC-domain containing regulatory protein, the phosphatidylethanolamine-binding DTH1 (DELAYED IN TAG HYDROLYSIS1), two lipases, and two enzymes involved in fatty acid beta-oxidation. Here, we review LD turnover and discuss its physiological significance in Chlamydomonas, a major model green microalga in research on algal oil.
ESTHER : Li-Beisson_2021_New.Phytol__
PubMedSearch : Li-Beisson_2021_New.Phytol__
PubMedID: 34028037

Title : Characterization of a carboxylesterase with hyper-thermostability and alkali-stability from Streptomyces lividans TK24 - Chang_2021_Extremophiles__
Author(s) : Chang X , Wu S , Chen J , Xiong S , Wang P , Shi X , Wang A , Wang B
Ref : Extremophiles , : , 2021
Abstract : A gene (estA', 804 bp) from Streptomyces lividans TK24 was artificially synthesized and successfully overexpressed as a 6His-tagged fusion protein in Escherichia coli. It encoded a carboxylesterase (EstA) that composed of 267 amino acids with a predicted molecular weight of 28.56 kDa. Multiple sequence alignment indicated that EstA has typical characteristics of esterases, including a catalytic triad (Ser93-Asp194-His224) and a conserved pentapeptide motif (Gly91-Leu92-Ser93-Met94-Gly95). Simultaneously, phylogenetic analysis indicated that EstA belongs to family VI. Biochemical characterization displayed its optimum enzyme activity was at 55 and pH 8.5. Additionally, EstA exhibited higher activity towards short carbon substrates and showed the outstanding catalytic efficiency for pNPA2 with k(cat)/K(m) of 2296.14 +/- 10.35 s(-1) mM(-1). Notably, EstA has hyper-thermostability and good alkali stability. The activity of EstA did not change obviously when incubated at 50 and 100 for 337 and 1 h, independently. Besides, by incubating at 100 for 6 h, EstA remained about half of its initial activity. Moreover, EstA showed stability at pH ranging from 8.0 to 11.0, and about 90% residual enzyme activity was reserved by being treated at pH 8.0 or 9.0 for 80 h, especially. Such multiple features prepare EstA for a potential candidate in the field of biological catalysis of some industrial applications under harsh conditions.
ESTHER : Chang_2021_Extremophiles__
PubMedSearch : Chang_2021_Extremophiles__
PubMedID: 33515353
Gene_locus related to this paper: strco-SCO2123

Title : Aggregation-induced emission luminogen@manganese dioxide core-shell nanomaterial-based paper analytical device for equipment-free and visual detection of organophosphorus pesticide - Chen_2021_J.Hazard.Mater_413_125306
Author(s) : Chen J , Chen X , Wang P , Liu S , Chi Z
Ref : J Hazard Mater , 413 :125306 , 2021
Abstract : Organophosphorus pesticide (OP) residues have gathered considerable attention because of their significant threat to society development and healthy life. Developing a sensitive and practical OPs sensor is highly urgent, whereas remains a huge challenge. To this end, we fabricated a high-performance fluorescence paper analytical device (PAD) for apparatus-free and visual sensing of OPs based on aggregation-induced emission (AIE) luminogen's bright emission in aggregated state, unique response of MnO(2) to thiol compounds, and difference of MnO(2) and Mn(2+) in quenching fluorescence. AIE nanoparticles PTDNPs-0.10 and MnO(2) respectively acted as core and shell to prepare PTDNPs@MnO(2), which possessed high stability and were dripped on cellulose paper's surface to fabricate AIE-PAD. The sensing mechanism is that OPs-treated acetylcholinesterase (AChE) prevents the formation of thiocholine, thereby minimizing the reduction of MnO(2) into Mn(2+) and changing the output signal. As a result, equipment-free and visual sensing of OPs was acquired with limit of detection of 1.60 ng/mL. This work justifies the feasibility of applying core-shell material to develop high-performance sensor and substituting complex/expensive solution-phase sensor with PAD, providing a new avenue to bring OPs analysis out of the lab and into the world.
ESTHER : Chen_2021_J.Hazard.Mater_413_125306
PubMedSearch : Chen_2021_J.Hazard.Mater_413_125306
PubMedID: 33588332

Title : LIPG: an inflammation and cancer modulator - Hong_2021_Cancer.Gene.Ther_28_27
Author(s) : Hong C , Deng R , Wang P , Lu X , Zhao X , Wang X , Cai R , Lin J
Ref : Cancer Gene Therapy , 28 :27 , 2021
Abstract : Endothelial lipase (LIPG/EL) performs fundamental and vital roles in the human body, including cell composition, cytokine expression, and energy provision. Since LIPG predominantly functions as a phospholipase as well as presents low levels of triglyceride lipase activity, it plays an essential role in lipoprotein metabolism, and involves in the metabolic syndromes such as inflammatory response and atherosclerosis. Cytokines significantly affect LIPG expression in endothelial cells in many diseases. Recently, it is suggested that LIPG contributes to cancer initiation and progression, and LIPG attached increasing importance to its potential for future targeted therapy.
ESTHER : Hong_2021_Cancer.Gene.Ther_28_27
PubMedSearch : Hong_2021_Cancer.Gene.Ther_28_27
PubMedID: 32572177
Gene_locus related to this paper: human-LIPG

Title : Binding Peptide-Guided Immobilization of Lipases with Significantly Improved Catalytic Performance Using Escherichia coli BL21(DE3) Biofilms as a Platform - Dong_2021_ACS.Appl.Mater.Interfaces__
Author(s) : Dong H , Zhang W , Xuan Q , Zhou Y , Zhou S , Huang J , Wang P
Ref : ACS Appl Mater Interfaces , : , 2021
Abstract : Developing novel immobilization methods to maximize the catalytic performance of enzymes has been a permanent pursuit of scientific researchers. Engineered Escherichia coli biofilms have attracted great concern as surface display platforms for enzyme immobilization. However, current biological conjugation methods, such as the SpyTag/SpyCatcher tagging pair, that immobilize enzymes onto E. coli biofilms seriously hamper enzymatic performance. Through phage display screening of lipase-binding peptides (LBPs) and co-expression of CsgB (nucleation protein of curli nanofibers) and LBP2-modified CsgA (CsgALBP2, major structural subunit of curli nanofibers) proteins, we developed E. coli BL21::deltaCsgA-CsgB-CsgALBP2 (LBP2-functionalized) biofilms as surface display platforms to maximize the catalytic performance of lipase (Lip181). After immobilization onto LBP2-functionalized biofilm materials, Lip181 showed increased thermostability, pH, and storage stability. Surprisingly, the relative activity of immobilized Lip181 increased from 8.43 to 11.33 U/mg through this immobilization strategy. Furthermore, the highest loading of lipase on LBP2-functionalized biofilm materials reached up to 27.90 mg/g of wet biofilm materials, equivalent to 210.49 mg/g of dry biofilm materials, revealing their potential as a surface with high enzyme loading capacity. Additionally, immobilized Lip181 was used to hydrolyze phthalic acid esters, and the hydrolysis rate against dibutyl phthalate was up to 100%. Thus, LBP2-mediated immobilization of lipases was demonstrated to be far more advantageous than the traditional SpyTag/SpyCatcher strategy in maximizing enzymatic performance, thereby providing a better alternative for enzyme immobilization onto E. coli biofilms.
ESTHER : Dong_2021_ACS.Appl.Mater.Interfaces__
PubMedSearch : Dong_2021_ACS.Appl.Mater.Interfaces__
PubMedID: 33499600

Title : Hormetic Effects of Dimethachlone on Mycelial Growth and Virulence of Sclerotinia sclerotiorum - Hu_2021_Phytopathology_111_1166
Author(s) : Hu S , Li J , Wang P , Zhu F
Ref : Phytopathology , 111 :1166 , 2021
Abstract : Fungicide hormesis has implications for the application of fungicides to control plant diseases. We investigated the hormetic effects of the dicarboximide fungicide dimethachlone on mycelial growth and virulence of the necrotrophic plant pathogen Sclerotinia sclerotiorum. Dimethachlone at sublethal doses in potato dextrose agar (PDA) increased the mycelial growth of S. sclerotiorum. After the growth-stimulated mycelia were subcultured on fresh PDA and inoculated on rapeseed leaves, increased mycelial growth and virulence were observed, indicating that hormetic traits were passed down to the next generation. Dimethachlone applied to leaves at 0.002 to 500 microg/ml stimulated virulence, with a maximum stimulation amplitude (MSA) of 31.4% for the isolate HLJ4, which occurred at 2 microg/ml. Dimethachlone-resistant isolates and transformants had a mean virulence MSA of 30.4%, which was significantly higher (P = 0.008) than the MSA for sensitive isolates (16.2%). Negative correlations were detected between MSA and virulence in the absence of any fungicide (r = -0.872, P < 0.001) and between MSA and mycelial growth on PDA (r = -0.794, P = 0.002). Studies on hormetic mechanisms indicated that dimethachlone had no significant effects on expression levels of three virulence-associated genes, that is, a cutinase-encoding gene SsCut, a polygalacturonase gene SsPG1, or an oxaloacetate acetylhydrolase gene SsOah1. The results will contribute to understanding hormesis and have implications for the judicious application of fungicides to control plant diseases.
ESTHER : Hu_2021_Phytopathology_111_1166
PubMedSearch : Hu_2021_Phytopathology_111_1166
PubMedID: 33107780

Title : Epigallocatechin-3-Gallate Provides Protection Against Alzheimer's Disease-Induced Learning and Memory Impairments in Rats - Nan_2021_Drug.Des.Devel.Ther_15_2013
Author(s) : Nan S , Wang P , Zhang Y , Fan J
Ref : Drug Des Devel Ther , 15 :2013 , 2021
Abstract : PURPOSE: Recent evidence has highlighted the anti-inflammatory properties of the constituent of Green Tea Polyphenols (GTP), epigallocatechin-3-gallate (EGCG) which has been suggested to exert a neuroprotective effect on Alzheimer's disease (AD). The current study aimed to elucidate the effect of EGCG on memory function in rats with AD. METHODS: AD rat models were initially established through an injection with Abeta 25-35 solution, followed by gavage with EGCG at varying doses to determine the effect of EGCG on learning and cognitive deficits in AD. Morris water maze test was conducted to evaluate the spatial memory function of the rats. Immunohistochemistry and Western blot analysis were performed to identify Tau phosphorylation. The expression of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA and protein in rat hippocampus was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Acetylcholinesterase (AchE) activity, Abeta1-42 expression and Ach content were all detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: EGCG intervention brought about a decrease in the escape latency period while increasing the time at the target quadrant among the AD rats. EGCG decreased the hyperphosphorylation of Tau in hippocampus. BACE1 expression and activity as well as the expression of Abeta1-42 were suppressed by EGCG. Moreover, EGCG promoted Ach content by diminishing the activity of AchE. CONCLUSION: The current study demonstrates that EGCG may diminish the hyperphosphorylation of the Tau protein, downregulate BACE1 and Abeta1-42 expression to improve the antioxidant system and learning and memory function of rats with AD.
ESTHER : Nan_2021_Drug.Des.Devel.Ther_15_2013
PubMedSearch : Nan_2021_Drug.Des.Devel.Ther_15_2013
PubMedID: 34012254

Title : Decrease of an intracellular organic osmolyte contributes to the cytotoxicity of organophosphate in neuroblastoma cells in vitro - Wang_2021_Toxicology__152725
Author(s) : Wang P , Wu YJ , Sun ML
Ref : Toxicology , :152725 , 2021
Abstract : Organophosphorus compounds (OP) causes prominent delayed peripheral neuropathy in vivo and cytotoxicity to neuronal cells in vitro. The primary target protein of OP's neurotoxicity is neuropathy target esterase (NTE), which can convert phosphatidylcholine (PC) to glycerophosphocholine (GPC). Recent studies reveal that autophagic cell death is important for the initiation and progression of OP-induced neurotoxicity both in vivo and in vitro. However, the mechanism of how OP induces autophagic cell death is unknown. Here it is found that GPC is an important organic osmolyte in the neuroblastoma cells, and treatment with tri-o-cresyl phosphate (TOCP), a representative OP, leads to the decrease of GPC and imbalance of extracellular and intracellular osmolality. Knockdown of GPC metabolizing enzyme glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) reverses TOCP-induced autophagic cell death, which further supports the notion that the reduced GPC level leads to the autophagic cell death. Furthermore, it is found that autophagic cell death is due to the induction of reactive oxygen species (ROS) and mitochondrial damage by imbalance of osmolality with TOCP treatment. In summary, this study reveals that TOCP treatment decreases GPC level and intracellular osmolality, which induces ROS and mitochondrial damage and leads to the cell death and neurite degradation by autophagy. This study lays the foundation for further investigations on the potential therapeutic approaches for OP neurotoxicity or NTE mutation-related neurological diseases.
ESTHER : Wang_2021_Toxicology__152725
PubMedSearch : Wang_2021_Toxicology__152725
PubMedID: 33617914

Title : Prolonged Soluble Epoxide Hydrolase Reactivity in Brain Endothelial Cells Is Associated with Long Cognitive Deficits in Sepsis - Wang_2020_Mol.Neurobiol__
Author(s) : Wang P , Wang W , Hu Y , Li Y
Ref : Molecular Neurobiology , : , 2020
Abstract : Sepsis-associated encephalopathy (SAE) is known to cause long-term cognitive deficits which are related to sustained microglial activation, but the mechanisms are unclear. Recently, studies have shown soluble epoxide hydrolase (sEH) affects the chronic cognitive function or participates in long-term neuropsychiatric illness. We hypothesized that sEH may be involved in the long-term cognitive deficits of SAE. Male C57BL/6 mice were subjected to cecal ligation and puncture (CLP) and were administered vehicle or sEH inhibitor TPPU. CLP induced prolonged endothelial sEH reactivity and sustained activation of microglia in close vicinity to blood vessels at 14 days. We also observed that persistent loss of endothelial BBB function at 14 days following CLP. However, TPPU-treated septic mice exhibited improved BBB function and declined neuro-inflammation. We confirmed these beneficial effects in vitro, which indicated TPPU resulted in a significant improvement in IL-1beta-induced loss of BBB integrity on hCMEC/D3 cell monolayers. Animals were also given a behavior test at 14 days after CLP. Mice showed normal basal locomotor activity in the open field compared with sham-operated animals, but performed fewer entries to the center zone, indicating increased anxiety-like behavior as avoidance of the center. TPPU-treated CLP mice showed normal crossing into the center zone during an open-field test and improved recovery of the ability to learn the novel object recognition (NOR) task compared with saline-treated CLP animals. Our data indicated that prolonged sEH reactivity in brain endothelial cells is associated with long cognitive deficits in sepsis. sEHIs such as TPPU can improve the endothelial barrier function and decrease CLP-induced long-term encephalopathy, at least in part, through anti-inflammatory effects.
ESTHER : Wang_2020_Mol.Neurobiol__
PubMedSearch : Wang_2020_Mol.Neurobiol__
PubMedID: 32378122

Title : Computational design of new enzymes for hydrolysis and synthesis of third-generation cephalosporin antibiotics - Xue_2020_Enzyme.Microb.Technol_140_109649
Author(s) : Xue J , Wang P , Kuang J , Zhu Y
Ref : Enzyme Microb Technol , 140 :109649 , 2020
Abstract : Engineering active sites in inert scaffolds to catalyze chemical transformations with unnatural substrates is still a great challenge for enzyme catalysis. In this research, a p-nitrobenzyl esterase from Bacillus subtilis was identified from the structural database, and a double mutant E115A/E188A was designed to afford catalytic activities toward the hydrolysis of ceftizoxime. A quadruple mutant E115A/E188A/L362S/I270A with enhanced catalytic efficiency was created to catalyze the condensation reaction of ethyl-2-methoxy-amino-2-(2-aminothiazole-4-yl) acetate with 7-amino-3-nor-cephalosporanic acid to produce ceftizoxime in a fully aqueous medium. The catalytic efficiencies of the computationally designed mutants E115A/E188A/L362S/I270A and E115A/Y118 K/E188 V/I270A/L362S can be taken as starting points to further improve their properties towards the practical application in designing more ecology-friendly production of third-generation cephalosporins.
ESTHER : Xue_2020_Enzyme.Microb.Technol_140_109649
PubMedSearch : Xue_2020_Enzyme.Microb.Technol_140_109649
PubMedID: 32912699

Title : Organophosphate Diesters (Di-OPEs) Play a Critical Role in Understanding Global Organophosphate Esters (OPEs) in Fishmeal - Li_2020_Environ.Sci.Technol_54_12130
Author(s) : Li X , Zhao N , Fu J , Liu Y , Zhang W , Dong S , Wang P , Su X
Ref : Environ Sci Technol , 54 :12130 , 2020
Abstract : Organophosphate triesters (tri-OPEs) have recently been widely identified in aquatic ecosystems, but information on their organophosphate diester (di-OPE) metabolites is sparsely available. Herein, uniform fishmeal products were collected across the globe (the U.S., China, Europe, South America, and Southeast Asia). Sixteen representative tri-OPEs and eight di-OPEs were investigated to reveal whether industrial production, metabolism, environmental persistence, or physicochemical properties are the key factors influencing their environmental burden and distribution. Tri-OPEs and di-OPEs were 100% detected in fishmeal, with bis(2-chloroethyl) hydrogen phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at discernible levels in marine fauna for the first time. Average concentration of di-OPEs (49.6 +/- 27.5 ng/g dw) was of the same order of magnitude as that of tri-OPEs (59.3 +/- 92.2 ng/g dw). Geographical-specific distributions of tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), triphenyl phosphate (TPhP), tris(2-butoxyethyl) phosphate (TBOEP), and 2-ethylhexyl diphenyl phosphate (EHDPP) were statistically significant (p < 0.05). Mean concentration ratios ranged from 0.087 for the BCEP-TCEP pair to 507 for the dimethyl phosphate (DMP)-trimethyl phosphate (TMP) pair. Only the TPhP-diphenyl phosphate (DPhP) pair presented a strong positive linear correlation (r = 0.731; p < 0.01), and DPhP was proved a degradation origin. Commercial sources had a significant overall impact on distribution patterns of the DMP-TMP and the dibutyl phosphate (DnBP) - tri-n-butyl phosphate (TnBP) pairs, whereas biotic transformation and abiotic stability profoundly influenced the bis(2-ethylhexyl) phosphate (BEHP)-tris(2-ethylhexyl) phosphate (TEHP), the bis(1-chloro-2-propyl) phosphate (BCIPP)-TCIPP, and the BCEP-TCEP pairs. Di-OPEs are critical to understand environmental behavior of tri-OPEs in marine fauna.
ESTHER : Li_2020_Environ.Sci.Technol_54_12130
PubMedSearch : Li_2020_Environ.Sci.Technol_54_12130
PubMedID: 32936633

Title : Metal-Organic Frameworks Conjugated Lipase with Enhanced Bio-catalytic Activity and Stability - Zou_2020_Appl.Biochem.Biotechnol__
Author(s) : Zou B , Zhang L , Xia J , Wang P , Yan Y , Wang X , Adesanya IO
Ref : Appl Biochem Biotechnol , : , 2020
Abstract : Covalent immobilization of lipase onto a solid carrier is an effective way to enhance stability. Immobilization inhibits the activity of lipase due to decreased flexibility of enzyme structure via the covalent bond. In this study, monomer of the metal-organic frameworks (MOFs) material ZIF-8 (2-methyl imidazole-4-carboxylic acid) was innovatively used as a chemical modifier of Candida nrugosa lipase (CRL). The circular dichroism spectra results show that the CRL molecule was altered by chemical modification and thus its catalytic activity was 1.3 times higher than that of the free CRL. The modified CRL molecule was further immobilized in the "skeleton" of ZIF-8 through the monomer while in situ forming the cell skeleton of the MOFs, which prevent the active center from being destroyed. The results show that conjugation of chemical modification and immobilized enzymes ensure that there was no obvious reduction in the activity of CRL after immobilization and the stability of CRL was improved. Especially, the organic solvent stability of the modified immobilization CRL in isopropanol was significantly improved and retained more than 148% of its activity.
ESTHER : Zou_2020_Appl.Biochem.Biotechnol__
PubMedSearch : Zou_2020_Appl.Biochem.Biotechnol__
PubMedID: 32323142

Title : Characterization of a novel hyper-thermostable and chlorpyrifos-hydrolyzing carboxylesterase EstC: A representative of the new esterase family XIX - Wang_2020_Pestic.Biochem.Physiol_170_104704
Author(s) : Wang B , Wu S , Chang X , Chen J , Ma J , Wang P , Zhu G
Ref : Pestic Biochem Physiol , 170 :104704 , 2020
Abstract : Carboxylesterases have widely been used in a series of industrial applications, especially, the detoxification of pesticide residues. In the present study, EstC, a novel carboxylesterase from Streptomyces lividans TK24, was successfully heterogeneously expressed, purified and characterized. Phylogenetic analysis showed that EstC can be assigned as the first member of a novel family XIX. Multiple sequence alignment indicated that EstC has highly conserved structural features, including a catalytic triad formed by Ser155, Asp248 and His278, as well as a canonical Gly-His-Ser-Ala-Gly pentapeptide. Biochemical characterization indicated that EstC exhibited maximal activity at pH 9.0 (Tris-HCl buffer) and 55 degC. It also showed higher activity towards short-chain substrates, with the highest activity for p-nitrophenyl acetate (pNPA2) (K(m) = 0.31 +/- 0.02 mM, k(cat)/K(m) = 1923.35 +/- 9.62 s(-1) mM(-1)) compared to other pNP esters used in this experiment. Notably, EstC showed hyper-thermostability and good alkali stability. The activity of EstC had no significant changes when it was incubated under 55 degC for 100 h and reached half-life after incubation at 100 degC for 8 h. Beyond that, EstC also showed stability at pH ranging from 6.0 to 11.0 and about 90% residual activity still reserved after treatment at pH 8.0 or 9.0 for 26 h, especially. Furthermore, EstC had outstanding potential for bioremediation of chlorpyrifos-contaminated environment. The recombinant enzyme (0.5 U mL(-1)) could hydrolyze 79.89% chlorpyrifos (5 mg L(-1)) at 37 degC within 80 min. These properties will make EstC have a potential application value in various industrial productions and detoxification of chlorpyrifos residues.
ESTHER : Wang_2020_Pestic.Biochem.Physiol_170_104704
PubMedSearch : Wang_2020_Pestic.Biochem.Physiol_170_104704
PubMedID: 32980065
Gene_locus related to this paper: strco-estli

Title : Bioluminescent Sensor Reveals that Carboxylesterase 1A is a Novel Endoplasmic Reticulum-Derived Serologic Indicator for Hepatocyte Injury - Wang_2020_ACS.Sens_5_1987
Author(s) : Wang DD , Zou LW , Jin Q , Guan XQ , Yu Y , Zhu YD , Huang J , Gao P , Wang P , Ge GB , Yang L
Ref : ACS Sens , 5 :1987 , 2020
Abstract : Discovery of novel liver injury indicators and development of practical assays to detect target indicator(s) would strongly facilitate the diagnosis of liver disorders. Herein, an alternative biomarker discovery strategy was applied to find suitable endoplasmic reticulum-resident protein(s) as serologic indicator(s) for hepatocyte injury via analysis of the human proteome database among plasma and various organs. Both database searching and preliminary experiments suggested that human carboxylesterase 1A (CES1A), one of the most abundant and hepatic-restricted proteins, could serve as a good serologic indicator for hepatocyte injury. Then, a highly selective and practical bioluminescent sensor was developed for real-time sensing of CES1A in various biological systems including plasma. With the help of this bioluminescent sensor, the release of hepatic CES1A into the extracellular medium or the circulation system could be directly monitored. Further investigations demonstrated that serum activity levels of CES1A were elevated dramatically in mice with liver injury or patients with liver diseases. Collectively, this study provided solid evidence to support that CES1A was a novel serological indicator for hepatocyte injury. Furthermore, the strategy used in this study paved a new way for the rational discovery of practical indicators to monitor the dynamic progression of injury in a given tissue or organ.
ESTHER : Wang_2020_ACS.Sens_5_1987
PubMedSearch : Wang_2020_ACS.Sens_5_1987
PubMedID: 32529833

Title : GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine - Liu_2020_Brain.Behav__e01602
Author(s) : Liu Z , Qin G , Mana L , Dong Y , Huang S , Wang Y , Wu Y , Shi J , Tian J , Wang P
Ref : Brain Behav , :e01602 , 2020
Abstract : BACKGROUND: Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear. METHODS: Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC-MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step-down passive-avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T-SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining. RESULTS: After one-half or 1 month of intragastric administration, GAPT can ameliorate scopolamine-induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine-treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB. CONCLUSIONS: GAPT can improve the learning and memory ability of scopolamine-induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury.
ESTHER : Liu_2020_Brain.Behav__e01602
PubMedSearch : Liu_2020_Brain.Behav__e01602
PubMedID: 32174034

Title : Biofilm polysaccharide display platform: A natural, renewable, and biocompatible material for improved lipase performance - Dong_2020_J.Agric.Food.Chem__
Author(s) : Dong H , Zhang W , Wang Y , Liu D , Wang P
Ref : Journal of Agricultural and Food Chemistry , : , 2020
Abstract : Most of microorganisms can form biofilms, which makes biofilms become an abundant bioresource to be exploited. Due to the application limitations of current immobilization methods onto biofilms, we developed an immobilization method called the Biofilm Polysaccharides Display (BPD) strategy while maintaining the native biofilm structure and catalytic microenvironment of C. acetobutylicum B3. Lipase Lip181 showed significant improvements in stability after chemical immobilization. For example, immobilized Lip181 retained 74.23% of its original activity after incubation for 14 days while free Lip181 was totally deactivated. In addition, immobilized Lip181 maintained high residual activity (pH 5.0pH 11.0), which showed improved resistance to pH changes. Notably, this method did not decrease but slightly increased the relative activity of Lip181 from 6.39 to 6.78 U/mg. Immobilized Lip181 was used to prepare cinnamyl acetate, and it showed a maximum yield of 85.09%. Overall, this biofilm immobilization method may promote the development of biocatalysis and biofilm materials.
ESTHER : Dong_2020_J.Agric.Food.Chem__
PubMedSearch : Dong_2020_J.Agric.Food.Chem__
PubMedID: 31927950

Title : Genome sequencing of the Australian wild diploid species Gossypium australe highlights disease resistance and delayed gland morphogenesis - Cai_2020_Plant.Biotechnol.J_18_814
Author(s) : Cai Y , Cai X , Wang Q , Wang P , Zhang Y , Cai C , Xu Y , Wang K , Zhou Z , Wang C , Geng S , Li B , Dong Q , Hou Y , Wang H , Ai P , Liu Z , Yi F , Sun M , An G , Cheng J , Shi Q , Xie Y , Shi X , Chang Y , Huang F , Chen Y , Hong S , Mi L , Sun Q , Zhang L , Zhou B , Peng R , Zhang X , Liu F
Ref : Plant Biotechnol J , 18 :814 , 2020
Abstract : The diploid wild cotton species Gossypium australe possesses excellent traits including resistance to disease and delayed gland morphogenesis, and has been successfully used for distant breeding programmes to incorporate disease resistance traits into domesticated cotton. Here, we sequenced the G. australe genome by integrating PacBio, Illumina short read, BioNano (DLS) and Hi-C technologies, and acquired a high-quality reference genome with a contig N50 of 1.83 Mb and a scaffold N50 of 143.60 Mb. We found that 73.5% of the G. australe genome is composed of various repeat sequences, differing from those of G. arboreum (85.39%), G. hirsutum (69.86%) and G. barbadense (69.83%). The G. australe genome showed closer collinear relationships with the genome of G. arboreum than G. raimondii and has undergone less extensive genome reorganization than the G. arboreum genome. Selection signature and transcriptomics analyses implicated multiple genes in disease resistance responses, including GauCCD7 and GauCBP1, and experiments revealed induction of both genes by Verticillium dahliae and by the plant hormones strigolactone (GR24), salicylic acid (SA) and methyl jasmonate (MeJA). Experiments using a Verticillium-resistant domesticated G. barbadense cultivar confirmed that knockdown of the homologues of these genes caused a significant reduction in resistance against Verticillium dahliae. Moreover, knockdown of a newly identified gland-associated gene GauGRAS1 caused a glandless phenotype in partial tissues using G. australe. The G. australe genome represents a valuable resource for cotton research and distant relative breeding as well as for understanding the evolutionary history of crop genomes.
ESTHER : Cai_2020_Plant.Biotechnol.J_18_814
PubMedSearch : Cai_2020_Plant.Biotechnol.J_18_814
PubMedID: 31479566
Gene_locus related to this paper: gosra-a0a0d2pzd7

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

Title : Synthesis, Molecular Docking Simulation, and Enzymatic Degradation of AB-Type Indole-Based Polyesters with Improved Thermal Properties - Wang_2020_Biomacromolecules_21_1078
Author(s) : Wang P , Linares-Pasten JA , Zhang B
Ref : Biomacromolecules , 21 :1078 , 2020
Abstract : We report the facile synthesis of a series of indole-based hydroxyl-carboxylate (AB-type) monomers by a one-step procedure. These monomers were successfully polymerized by melt polycondensation to yield AB-type polyesters with a varied number of flexible methylene units in the backbones. These indole-based AB-polyesters showed decent thermal stability according to the TGA results (onset thermal degradation temperature of >330 degC), and their glass transition temperatures are dependent on the length of the methylene bridge (T(g) = 62-102 degC) according to the DSC results. Furthermore, DSC and WAXD measurements revealed that these polymers did not crystallize from melt, but the ones with flexible structures could crystallize from solution. Molecular docking simulations showed favorable interactions between indole-based polyesters and polyethylene terephthalate hydrolase (PETase) from Ideonella sakaiensis. This was corroborated by the experimental results, which indicated that the PETase enzyme has degrading activity on the indole-based AB polyesters except for the one with the highest degree of crystallinity.
ESTHER : Wang_2020_Biomacromolecules_21_1078
PubMedSearch : Wang_2020_Biomacromolecules_21_1078
PubMedID: 31951388

Title : Schizophreniaassociated microRNA148b3p regulates COMT and PRSS16 expression by targeting the ZNF804A gene in human neuroblastoma cells - Wu_2020_Mol.Med.Rep_22_1429
Author(s) : Wu S , Wang P , Tao R , Yang P , Yu X , Li Y , Shao Q , Nie F , Ha J , Zhang R , Tian Y , Ma J
Ref : Mol Med Rep , 22 :1429 , 2020
Abstract : Zinc finger protein 804A (ZNF804A) has been identified by genomewide association studies as a robust risk gene in schizophrenia, but how ZNF804A contributes to schizophrenia and its upstream regulation remains unknown. Previous studies have indicated that microRNAs (miRs) are key factors that regulate the expression levels of their target genes. The present study revealed significantly increased expression of miR148b3p in the peripheral blood of patients with firstonset schizophrenia compared with healthy controls, and bioinformatics analysis predicted that the ZNF804A gene is a target of miR148b3p. Therefore, the present study investigated the possible upstream regulation of ZNF804A by miR148b3p in the human neuroblastoma SHSY5Y cell line, and assessed the implications for schizophrenia. The results revealed significantly reversed expression levels of miR148b3p (P=0.0051) and ZNF804A (P=0.0218) in the peripheral blood of patients with firstonset schizophrenia compared with healthy individuals. Furthermore, it was demonstrated that miR148b3p directly targeted ZNF804A via binding to conserved target sites in the 3'untranslated region of ZNF804A mRNA, where it inhibited the endogenous expression of ZNF804A at both the mRNA (P=0.048) and protein levels (P=0.013) in SHSY5Y cells. Furthermore, miR148b3p was revealed to regulate the expression levels of catecholOmethyltransferase (COMT) and serine protease 16 (PRSS16) by targeting ZNF804A in SHSY5Y cells. Collectively, the present results indicated that there was a direct upstream regulation of the schizophrenia risk gene ZNF804A by miR148b3p, which contributed to the regulation of the downstream genes COMT and PRSS16. Thus, the miR148b3p/ZNF804A/COMT/PRSS16 pathway may play an important role in the pathophysiology of schizophrenia, and may serve as a potential target in drug discovery and gene therapy for this disorder.
ESTHER : Wu_2020_Mol.Med.Rep_22_1429
PubMedSearch : Wu_2020_Mol.Med.Rep_22_1429
PubMedID: 32626976
Gene_locus related to this paper: human-PRSS16

Title : SNHG20\/miR-140-5p\/NDRG3 axis contributes to 5-fluorouracil resistance in gastric cancer - Yu_2019_Oncol.Lett_18_1337
Author(s) : Yu J , Shen J , Qiao X , Cao L , Yang Z , Ye H , Xi C , Zhou Q , Wang P , Gong Z
Ref : Oncol Lett , 18 :1337 , 2019
Abstract : 5-fluorouracil (5-FU)-based chemotherapy is the first line treatment for advanced gastric cancer. However, the effectiveness of 5-FU is limited by drug resistance. The N-myc downstream-regulated gene, family member 3 (NDRG3) is a member of the NDRG family and has been implicated in numerous types of cancer. However, the role of NDRG3 in gastric cancer remains unclear. In the present study, NDRG3 mRNA expression in gastric cancer and adjacent normal tissues was analyzed using the Gene Expression Profiling Interactive Analysis web tool. NDRG3 expression was silenced using short hairpin RNAs to examine the effect of NDRG3 on the growth of gastric cancer cells. Potential regulators of NDRG3 were identified using the TargetScan and MicroRNA tools and verified by a luciferase assay and reverse transcription-quantitative PCR analysis. The current study demonstrated that NDRG3 was upregulated in gastric cancer specimens and promoted cell proliferation in gastric cancer cell lines. Furthermore, the present study revealed that the small nucleolar RNA host gene 20 (SNHG20)/microRNA (miR)-140-5p signaling pathway may regulate the expression of NDRG3. SNHG20 was revealed to be involved in mediating resistance to 5-FU in gastric cancer cell lines via NDRG3. In conclusion, the results of the present study suggest that the SNHG20/miR-140-5p/NDRG3 axis may be involved in mediating resistance to 5-FU in gastric cancer.
ESTHER : Yu_2019_Oncol.Lett_18_1337
PubMedSearch : Yu_2019_Oncol.Lett_18_1337
PubMedID: 31423195
Gene_locus related to this paper: human-NDRG3

Title : Association between EPHX1 polymorphisms and carbamazepine metabolism in epilepsy: a meta-analysis - Zhao_2019_Int.J.Clin.Pharm_41_1414
Author(s) : Zhao GX , Shen ML , Zhang Z , Wang P , Xie CX , He GH
Ref : Int J Clin Pharm , 41 :1414 , 2019
Abstract : Background: EPHX1 gene polymorphisms were recently acknowledged as an important source of individual variability in carbamazepine metabolism, but the result of that association still remains controversial. Aim of the review To obtain a more precise estimation of the associations between EPHX1 polymorphisms and carbamazepine metabolism and resistance. Methods: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc and Wan fang Database were searched for appropriate studies regarding the rs1051740 and rs2234922 polymorphisms of EPHX1 up to September 2019. The meta-analysis was carried out using the Review Manager 5.3 software. The mean difference and 95% confidence interval were applied to assess the strength of the relationship. Results: A total of 7 studies involving 1118 related epilepsy patients were included. EPHX1 rs1051740 polymorphism was significantly associated with adjusted concentrations of both carbamazepine (CC vs. TT: P = 0.02; CC vs. CT + TT: P = 0.005) and carbamazepine-10,11-epoxide (CC vs. CT + TT: P = 0.03). Furthermore, EPHX1 rs2234922 polymorphism was also observed to be significantly associated with decreased adjusted concentrations of carbamazepine-10,11-trans dihydrodiol (GG vs. GA + AA: P = 0.04) and CBZD:CBZE ratio (GG vs. AA: P = 0.008; GG vs. GA + AA: P = 0.0008). Nevertheless, the pooled analysis showed that the EPHX1 polymorphisms had no significant effect on CBZ resistance. Conclusion EPHX1 rs1051740 and rs2234922 polymorphisms may affect the carbamazepine metabolism; but carbamazepine resistance was not related to any of the single nucleotide polymorphisms investigated. These findings provided further evidence for individualized therapy of epilepsy patients in clinics.
ESTHER : Zhao_2019_Int.J.Clin.Pharm_41_1414
PubMedSearch : Zhao_2019_Int.J.Clin.Pharm_41_1414
PubMedID: 31650507

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

Title : Functional analysis of the GbDWARF14 gene associated with branching development in cotton - Wang_2019_PeerJ_7_e6901
Author(s) : Wang P , Zhang S , Qiao J , Sun Q , Shi Q , Cai C , Mo J , Chu Z , Yuan Y , Du X , Miao Y , Zhang X , Cai Y
Ref : PeerJ , 7 :e6901 , 2019
Abstract : Plant architecture, including branching pattern, is an important agronomic trait of cotton crops. In recent years, strigolactones (SLs) have been considered important plant hormones that regulate branch development. In some species such as Arabidopsis, DWARF14 is an unconventional receptor that plays an important role in the SL signaling pathway. However, studies on SL receptors in cotton are still lacking. Here, we cloned and analysed the structure of the GbD14 gene in Gossypium barbadense and found that it contains the domains necessary for a SL receptor. The GbD14 gene was expressed primarily in the roots, leaves and vascular bundles, and the GbD14 protein was determined via GFP to localize to the cytoplasm and nucleus. Gene expression analysis revealed that the GbD14 gene not only responded to SL signals but also was differentially expressed between cotton plants whose types of branching differed. In particular, GbD14 was expressed mainly in the axillary buds of normal-branching cotton, while it was expressed the most in the leaves of nulliplex-branch cotton. In cotton, the GbD14 gene can be induced by SL and other plant hormones, such as indoleacetic acid, abscisic acid, and jasmonic acid. Compared with wild-type Arabidopsis, GbD14-overexpressing Arabidopsis responded more rapidly to SL signals. Moreover, we also found that GbD14 can rescue the multi-branched phenotype of Arabidopsis Atd14 mutants. Our results indicate that the function of GbD14 is similar to that of AtD14, and GbD14 may be a receptor for SL in cotton and involved in regulating branch development. This research provides a theoretical basis for a profound understanding of the molecular mechanism of branch development and ideal plant architecture for cotton breeding improvements.
ESTHER : Wang_2019_PeerJ_7_e6901
PubMedSearch : Wang_2019_PeerJ_7_e6901
PubMedID: 31143538

Title : Effects of Bread Yeast Cell Wall Beta-Glucans on Mice with Loperamide-Induced Constipation - Chen_2019_J.Med.Food_22_1009
Author(s) : Chen Z , Lin S , Jiang Y , Liu L , Jiang J , Chen S , Tong Y , Wang P
Ref : J Med Food , 22 :1009 , 2019
Abstract : Constipation is a common gastrointestinal disorder characterized by changes in intestinal habits. Increasing evidence indicates that long-term use of irritant laxatives causes serious side effects. Meanwhile, more than 50% of patients are dissatisfied with sense of use of non-prescriptional laxatives. beta-glucans are natural polysaccharides widely found in yeast, fungus, and plants, which have been reported to exhibit various pharmacological effects. The aim of this study was to characterize the effect of beta-glucans extracted from the bread yeast cell wall on loperamide-induced constipation mice. Forty mice were fed with loperamide (10 mg/kg) to make the constipation model and a diet supplemented with 2.5, 5, and 10 mg/kg beta-glucan. We assessed the defecation frequency, intestinal transit function of mice, as well as used high-throughput sequencing to analyze the intestinal microbiota composition and functional biological profiles data. Meanwhile, we detected expression of neurotransmitters including acetylcholinesterase, substance P, and serotonin (5-HT) and expression of tight junction protein (TJP) including zonula occludens-1 and mucin-2 in distal colon to characterize the possible molecular mechanisms. beta-glucans significantly enhanced intestinal motility and provided a possibility to regulate the expression of neurotransmitters and TJP in mice. The intestinal microecological portion of the treatment group partially recovered and was closer to the normal group. This study showed that beta-glucans can influence the intestinal microbiota and restore microecological balance to regulate the express of neurotransmitters and TJP to recover intestinal epithelial mechanical barrier. We suggested that beta-glucans could be used as an active nutritional supplement to protect the damaged intestinal barrier and help patients who have constipation complications and dysbiosis.
ESTHER : Chen_2019_J.Med.Food_22_1009
PubMedSearch : Chen_2019_J.Med.Food_22_1009
PubMedID: 31536448

Title : Fluorescence sensor for facile and visual detection of organophosphorus pesticides using AIE fluorogens-SiO2-MnO2 sandwich nanocomposites - Wu_2019_Talanta_198_8
Author(s) : Wu X , Wang P , Hou S , Wu P , Xue J
Ref : Talanta , 198 :8 , 2019
Abstract : Organophosphorus pesticides (OPs) are frequently for pest control in the agriculture industry. Accumulation of OPs is harmful to the environment and human health. Thus, facile and portable detection of organophosphorus pesticides is of great importance. Among these methods, the fluorescence assay holds the advantages of high sensitivity, simplicity, nondestructive properties. Conventional fluorophores have the drawbacks of poor photostability and low signal-to-noise ratio due to their aggregation-caused quenching drawbacks at high concentration or in the aggregate state. Aggregation-induced emission fluorogens (AIEgens) are one key to develop next-generation fluorescence sensor due to their high emission efficiency in the aggregated state. 1,2-bis[4-(3-sulfonatopropoxyl) phenyl]-1,2-diphenylethene (BSPOTPE) is a typical AIE molecule containing two hydroxyl group. In this study, a fluorescence sensor based on BSPOTPE-SiO2-MnO2 sandwich nanocomposites was fabricated. Thiocholine (TCh), which produced from acetylthiocholine(ATCh) by the hydrolysis of acetylcholinesterase (AChE), can "turn on" the fluorescence sensor. Based on the inhibition effect of OPs on AChE activity and the corresponding "turn off" effect on the fluorescence sensor, an AIE-based assay for OPs determination was developed. The fabricated sensor for paraoxon determination has a good linear relationship in the range of 1-100mug/L and the LOD of 1mug/L. Moreover, a simple, convenient fluorescence strip for visual semi-quantitative of OPs was fabricated, indicating this "on-off" fluorescent sensor is promising for on-site and infield detection.
ESTHER : Wu_2019_Talanta_198_8
PubMedSearch : Wu_2019_Talanta_198_8
PubMedID: 30876606

Title : Time-Course Changes in Urine Metabolic Profiles of Rats Following 90-Day Exposure to Propoxur - Liang_2019_Sci.Rep_9_16989
Author(s) : Liang YJ , Wang P , Wang HP , Long DX , Sun YJ , Wu YJ
Ref : Sci Rep , 9 :16989 , 2019
Abstract : As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing (1)H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.
ESTHER : Liang_2019_Sci.Rep_9_16989
PubMedSearch : Liang_2019_Sci.Rep_9_16989
PubMedID: 31740703

Title : Combined toxicity of organophosphate flame retardants and cadmium to Corbicula fluminea in aquatic sediments - Li_2018_Environ.Pollut_243_645
Author(s) : Li D , Wang P , Wang C , Fan X , Wang X , Hu B
Ref : Environ Pollut , 243 :645 , 2018
Abstract : Organophosphate flame retardants (OPFRs), as alternatives to polybrominated biphenyl ethers (PBDEs), are frequently detected in various environmental matrices. Owing to urbanization and industrial pollution, co-contamination of OPFRs and heavy metals is ubiquitous in the environment. The toxicity of OPFRs in aqueous phase is a significant concern, but uncertainty still exists regarding the co-toxicity to benthic organisms of OPFRs and metals in sediments. Hence, we explored the physiological response of Corbicula fluminea to OPFRs and Cd in sediments. The results indicated that the antioxidant system in the clams was stimulated in the presence of OPFRs and Cd, and the oxidative stress increased with increasing concentrations of OPFRs. In contrast, the cytochrome P450 (CYP450) content and acetylcholinesterase (AChE) activity were reduced by exposure to both OPFRs and Cd. The cytochrome P450 4 family (CYP4) mRNA expression and OPFR toxicity were lower than those in previously reported experiments conducted in the water phase. Moreover, the expression levels of metallothionein (MT) and AChE mRNA decreased when OPFRs and Cd were present together. The highest integrated biomarker response (IBR) index (IBR=15.41) was observed in the presence of 45mgkg(-1) Cd + 200 mg kg(-1) OPFRs, rather than the 45mgkg(-1) Cd + 400 mg kg(-1) OPFRs treatment (IBR=9.48). In addition, CYP450 and AChE in the digestive glands of C. fluminea exhibited significant correlations with the concentration of the OPFR/Cd mixture (p<0.01) and could be effective biomarkers for OPFR and Cd co-contamination. The results potentially contribute to more realistic predictions and evaluations of the environmental risks posed by OPFRs in aquatic sediments contaminated with heavy metals, particularly with respect to the risk to benthic organisms.
ESTHER : Li_2018_Environ.Pollut_243_645
PubMedSearch : Li_2018_Environ.Pollut_243_645
PubMedID: 30219590

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein - Zhang_2018_Cell.Rep_24_441
Author(s) : Zhang S , Zhou P , Wang P , Li Y , Jiang L , Jia W , Wang H , Fan A , Wang D , Shi X , Fang X , Hammel M , Wang S , Wang X , Zhang L
Ref : Cell Rep , 24 :441 , 2018
Abstract : The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the beta5-beta6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.
ESTHER : Zhang_2018_Cell.Rep_24_441
PubMedSearch : Zhang_2018_Cell.Rep_24_441
PubMedID: 29996104

Title : Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage - Zou_2018_Aging.Dis_9_51
Author(s) : Zou J , Chen Z , Liang C , Fu Y , Wei X , Lu J , Pan M , Guo Y , Liao X , Xie H , Wu D , Li M , Liang L , Wang P , Wang Q
Ref : Aging Dis , 9 :51 , 2018
Abstract : Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson's disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. METHODS: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. RESULTS: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores' distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. CONCLUSIONS: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD.
ESTHER : Zou_2018_Aging.Dis_9_51
PubMedSearch : Zou_2018_Aging.Dis_9_51
PubMedID: 29392081

Title : Association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed workers - Ding_2018_Ecotoxicol.Environ.Saf_161_563
Author(s) : Ding M , Yang Y , Duan X , Wang S , Feng X , Wang T , Wang P , Liu S , Li L , Liu J , Tang L , Niu X , Zhang Y , Li G , Yao W , Cui L , Wang W
Ref : Ecotoxicology & Environmental Safety , 161 :563 , 2018
Abstract : Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P<0.001). Multivariate analysis indicates that exposure group (b=-1.016, P<0.001), agender (b=0.365, P<0.001), drinking (b=0.271, P=0.004) and TERF1rs3863242 (b=-0.368, P=0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate.
ESTHER : Ding_2018_Ecotoxicol.Environ.Saf_161_563
PubMedSearch : Ding_2018_Ecotoxicol.Environ.Saf_161_563
PubMedID: 29929132

Title : Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2 - Weng_2018_Bioorg.Chem_77_320
Author(s) : Weng ZM , Ge GB , Dou TY , Wang P , Liu PK , Tian XH , Qiao N , Yu Y , Zou LW , Zhou Q , Zhang WD , Hou J
Ref : Bioorg Chem , 77 :320 , 2018
Abstract : Human carboxylesterases (hCEs) are key enzymes from the serine hydrolase superfamily. Among all identified hCEs, human carboxylesterase 2 (hCE2) plays crucial roles in the metabolic activation of ester drugs including irinotecan and flutamide. Selective and potent hCE2 inhibitors could be used to alleviate the toxicity induced by hCE2-substrate drugs. In this study, more than fifty flavonoids were collected to assay their inhibitory effects against hCE2 using a fluorescence-based method. The results demonstrated that C3 and C6 hydroxy groups were essential for hCE2 inhibition, while O-glycosylation or C-glycosylation would lead to the loss of hCE2 inhibition. Among all tested flavonoids, 5,6-dihydroxyflavone displayed the most potent inhibitory effect against hCE2 with the IC50 value of 3.50muM. The inhibition mechanism of 5,6-dihydroxyflavone was further investigated by both experimental and docking simulations. All these findings are very helpful for the medicinal chemists to design and develop more potent and highly selective flavonoid-type hCE2 inhibitors.
ESTHER : Weng_2018_Bioorg.Chem_77_320
PubMedSearch : Weng_2018_Bioorg.Chem_77_320
PubMedID: 29421708

Title : Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate - Duan_2018_R.Soc.Open.Sci_5_172357
Author(s) : Duan X , Yang Y , Wang S , Feng X , Wang T , Wang P , Yao W , Cui L , Wang W
Ref : R Soc Open Sci , 5 :172357 , 2018
Abstract : Cholinesterase activity (ChA), the effective biomarker for organophosphate pesticide exposure, is possibly affected by single nucleotide polymorphisms (SNPs) in cell-cycle-related genes. One hundred and eighty workers with long-term exposure to omethoate and 115 healthy controls were recruited to explore the gene-gene and gene-environment interactions. The acetylthiocholine and dithio-bis-(nitrobenzoic acid) method was used to detect the cholinesterase activities in whole blood, erythrocytes and plasma. Genetic polymorphisms were determined by the PCR-RFLP and direct PCR electrophoresis methods. Statistical results showed that the cholinesterase activities of whole blood, erythrocytes and plasma in the exposure group were significantly lower than those in the control group (p < 0.001), and erythrocyte cholinesterase activities were associated with gender, smoking and drinking in the exposure group (p < 0.05). Single-locus analyses showed that there is a statistically significant difference in the ChA among the genotypes CC, CA and AA of the p21 rs1801270 locus in the control group (p = 0.033), but not in the exposure group. A significant interaction between genes and environmental factors (i.e. p53, p21, mdm2, gender, smoking and drinking) affecting ChA was found through a generalized multifactor dimensionality reduction analysis. These obtained markers will be useful in further marker-assisted selection in workers with exposure to omethoate.
ESTHER : Duan_2018_R.Soc.Open.Sci_5_172357
PubMedSearch : Duan_2018_R.Soc.Open.Sci_5_172357
PubMedID: 29892419

Title : A Novel Subfamily Esterase with a Homoserine Transacetylase-like Fold but no Transferase Activity - Li_2017_Appl.Environ.Microbiol_83_e00131
Author(s) : Li PY , Yao QQ , Wang P , Zhang Y , Li Y , Zhang YQ , Hao J , Zhou BC , Chen XL , Shi M , Zhang YZ , Zhang XY
Ref : Applied Environmental Microbiology , 83 :e00131\ , 2017
Abstract : Microbial esterases play important roles in deep-sea organic carbon degradation and cycling. Though sharing similar catalytic triads and oxyanion holes, esterases are hydrolases, and homoserine transacetylases (HTAs) are transferases. Because two HTA homologs were identified as acetyl esterases, the HTA family was divided into the bonafide acetyltransferase subfamily and the acetyl esterase subfamily recently. Here, we identified and characterized a novel HTA-like esterase, Est22, from a deep-sea sedimentary metagenomic library. Est22 could efficiently hydrolyze esters with acyl length of up to six carbon atoms, but had no transacetylase activity, which is different from HTAs and HTA-like acetyl esterases. Phylogenetic analysis also showed that Est22 and its homologs form a separate branch in the HTA family. We solved the structures of Est22 and its mutant L374D and modeled the structure of L374D with p-nitrophenyl butyrate. Based on structural, mutational and biochemical analyses, Phe71 and Met176 in the oxyanion hole and Arg294 are revealed to be the key substrate-binding residues. A detailed structural comparison indicated that differences in their catalytic tunnels lead to the different substrate specificities of Est22 and the other two HTA subfamilies. Biochemical and sequence analyses suggested that Est22 homologs may share the same substrate recognition and catalysis mechanism with Est22. Due to the significant differences in sequence, structure and substrate specificity between Est22 (and its homologs) and the other two HTA subfamilies, we suggest that Est22 and its homologs represent a new subfamily in the HTA family.IMPORTANCE Microbial esterases play important roles in the turnover of organic carbon in deep sea. Esterases and homoserine transacetylases (HTAs) represent two groups of alpha/beta hydrolases. Esterases catalyze the hydrolysis of simple esters and are widely used in pharmaceutical and agrochemical industries, while HTAs catalyze the transfer of acetyl group from acetyl-CoA to homoserine and are essential for microbial growth. Here, we reported a novel HTA-like esterase, Est22, from a deep-sea sediment. Because of the significant differences in sequence, structure and substrate specificity from HTAs and HTA-like acetyl esterases, Est22 together with its homologs represent a new subfamily in the HTA family. This study offers new knowledge on marine esterases.
ESTHER : Li_2017_Appl.Environ.Microbiol_83_e00131
PubMedSearch : Li_2017_Appl.Environ.Microbiol_83_e00131
PubMedID: 28235874
Gene_locus related to this paper: 9bact-a0a1b1h1k0

Title : Improved catalytic properties of Penicillium notatum lipase immobilized in nanoscale silicone polymeric films - Rehman_2017_Int.J.Biol.Macromol_97_279
Author(s) : Rehman S , Wang P , Bhatti HN , Bilal M , Asgher M
Ref : Int J Biol Macromol , 97 :279 , 2017
Abstract : Lipases are one of the most proficient biocatalysts having enormous biotechnological prospective. Immobilization offers a potential solution to improve the stability and recycling characteristics of lipases. An extracellular lipase from Penicillium notatum (PNL) was immobilized in silicon polymers (SiP) through entrapment, and subsequently coated this matrix on the network of fibers in the sponges. The silicone polymers-immobilized lipase (SiP-lipase) displayed highest apparent activity and entrapment efficiency of 1.19Ug-1 polymers and 92.3%, respectively. It also exhibited greater catalytic activity in broad-working pHs and higher temperature than equivalent free-state of enzyme. Immobilization caused an improvement in thermo-stability of the lipase with an increase in energy of activation. The recycling potential of SiP-lipase was investigated. After reusing the sponge pieces for ten reaction cycles, the SiP preserved its structure without leakage of enzyme, and retained around 90% of its original activity. The SiP surface analysis was envisaged by scanning electron microscopy that further confirmed the recycling efficiency of SiP-lipase. Overall, SiP-lipase displayed a number of useful properties that make it a promising candidate for future applications in different chemical processes.
ESTHER : Rehman_2017_Int.J.Biol.Macromol_97_279
PubMedSearch : Rehman_2017_Int.J.Biol.Macromol_97_279
PubMedID: 28089928

Title : Severe hypertriglyceridemia due to two novel loss-of-function lipoprotein lipase gene mutations (C310R\/E396V) in a Chinese family associated with recurrent acute pancreatitis - Lun_2017_Oncotarget_8_47741
Author(s) : Lun Y , Sun X , Wang P , Chi J , Hou X , Wang Y
Ref : Oncotarget , 8 :47741 , 2017
Abstract : Lipoprotein lipase (LPL) is widely expressed in skeletal muscles, cardiac muscles as well as adipose tissue and involved in the catabolism of triglyceride. Herein we have systematically characterized two novel loss-of-function mutations in LPL from a Chinese family in which afflicted members were manifested by severe hypertriglyceridemia and recurrent pancreatitis. DNA sequencing revealed that the proband was a heterozygote carrying a novel c.T928C (p.C310R) mutation in exon 6 of the LPL gene. Another member of the family was detected to be a compound heterozygote who along with the c.T928C mutation also carried a novel missense mutation c.A1187T (p.E396V) in exon 8 of the LPL gene. Furthermore, COS-1 cells were transfected with lentiviruses containing the mutant LPL genes. While C310R markedly reduced the overall LPL protein level, COS-1 cells carrying E396V or double mutations contained similar overall LPL protein levels to the wild-type. The specific activity of the LPL mutants remained at comparable magnitude to the wild-type. However, few LPL were detected in the culture medium for the mutants, suggesting that both mutations caused aberrant triglyceride catabolism. More specifically, E396V and double mutations dampened the transport of LPL to the cell surface, while for the C310R mutation, reducing LPL protein level might be involved. By characterizing these two novel LPL mutations, this study has expanded our understanding on the pathogenesis of familial hypertriglyceridemia (FHTG).
ESTHER : Lun_2017_Oncotarget_8_47741
PubMedSearch : Lun_2017_Oncotarget_8_47741
PubMedID: 28548960
Gene_locus related to this paper: human-LPL

Title : Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1 - Zou_2017_Front.Pharmacol_8_435
Author(s) : Zou LW , Dou TY , Wang P , Lei W , Weng ZM , Hou J , Wang DD , Fan YM , Zhang WD , Ge GB , Yang L
Ref : Front Pharmacol , 8 :435 , 2017
Abstract : Human carboxylesterase 1 (hCE1), one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs) were assayed using D-Luciferin methyl ester (DME) and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB) as specific optical substrate for hCE1, and hCE2, respectively. Following screening of a series of natural triterpenoids, oleanolic acid (OA), and ursolic acid (UA) were found with strong inhibitory effects on hCE1 and relative high selectivity over hCE2. In order to get the highly selective and potent inhibitors of hCE1, a series of OA and UA derivatives were synthesized from OA and UA by chemical modifications including oxidation, reduction, esterification, and amidation. The inhibitory effects of these derivatives on hCEs were assayed and the structure-activity relationships of tested triterpenoids as hCE1 inhibitors were carefully investigated. The results demonstrated that the carbonyl group at the C-28 site is essential for hCE1 inhibition, the modifications of OA or UA at this site including esters, amides and alcohols are unbeneficial for hCE1 inhibition. In contrast, the structural modifications on OA and UA at other sites, such as converting the C-3 hydroxy group to 3-O-beta-carboxypropionyl (compounds 20 and 22), led to a dramatically increase of the inhibitory effects against hCE1 and very high selectivity over hCE2. 3D-QSAR analysis of all tested triterpenoids including OA and UA derivatives provide new insights into the fine relationships linking between the inhibitory effects on hCE1 and the steric-electrostatic properties of triterpenoids. Furthermore, both inhibition kinetic analyses and docking simulations demonstrated that compound 22 was a potent competitive inhibitor against hCE1-mediated DME hydrolysis. All these findings are very helpful for medicinal chemists to design and develop highly selective and more potent hCE1 inhibitors for biomedical applications.
ESTHER : Zou_2017_Front.Pharmacol_8_435
PubMedSearch : Zou_2017_Front.Pharmacol_8_435
PubMedID: 28713276

Title : Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors - Zaghloul_2017_Front.Immunol_8_1673
Author(s) : Zaghloul N , Addorisio ME , Silverman HA , Patel HL , Valdes-Ferrer SI , Ayasolla KR , Lehner KR , Olofsson PS , Nasim M , Metz CN , Wang P , Ahmed M , Chavan SS , Diamond B , Tracey KJ , Pavlov VA
Ref : Front Immunol , 8 :1673 , 2017
Abstract : Sepsis, a complex disorder characterized by immune, metabolic, and neurological dysregulation, is the number one killer in the intensive care unit. Mortality remains alarmingly high even in among sepsis survivors discharged from the hospital. There is no clear strategy for managing this lethal chronic sepsis illness, which is associated with severe functional disabilities and cognitive deterioration. Providing insight into the underlying pathophysiology is desperately needed to direct new therapeutic approaches. Previous studies have shown that brain cholinergic signaling importantly regulates cognition and inflammation. Here, we studied the relationship between peripheral immunometabolic alterations and brain cholinergic and inflammatory states in mouse survivors of cecal ligation and puncture (CLP)-induced sepsis. Within 6 days, CLP resulted in 50% mortality vs. 100% survival in sham-operated controls. As compared to sham controls, sepsis survivors had significantly lower body weight, higher serum TNF, interleukin (IL)-1beta, IL-6, CXCL1, IL-10, and HMGB1 levels, a lower TNF response to LPS challenge, and lower serum insulin, leptin, and plasminogen activator inhibitor-1 levels on day 14. In the basal forebrain of mouse sepsis survivors, the number of cholinergic [choline acetyltransferase (ChAT)-positive] neurons was significantly reduced. In the hippocampus and the cortex of mouse sepsis survivors, the activity of acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, as well as the expression of its encoding gene were significantly increased. In addition, the expression of the gene encoding the M1 muscarinic acetylcholine receptor was decreased in the hippocampus. In parallel with these forebrain cholinergic alterations, microglial activation (in the cortex) and increased Il1b and Il6 gene expression (in the cortex), and Il1b gene expression (in the hippocampus) were observed in mouse sepsis survivors. Furthermore, microglial activation was linked to decreased cortical ChAT protein expression and increased AChE activity. These results reinforce the notion of persistent inflammation-immunosuppression and catabolic syndrome in sepsis survivors and characterize a previously unrecognized relationship between forebrain cholinergic dysfunction and neuroinflammation in sepsis survivors. This insight is of interest for new therapeutic approaches that focus on brain cholinergic signaling for patients with chronic sepsis illness, a problem with no specific treatment.
ESTHER : Zaghloul_2017_Front.Immunol_8_1673
PubMedSearch : Zaghloul_2017_Front.Immunol_8_1673
PubMedID: 29326685

Title : A highly specific ratiometric two-photon fluorescent probe to detect dipeptidyl peptidase IV in plasma and living systems - Zou_2017_Biosens.Bioelectron_90_283
Author(s) : Zou LW , Wang P , Qian XK , Feng L , Yu Y , Wang DD , Jin Q , Hou J , Liu ZH , Ge GB , Yang L
Ref : Biosensors & Bioelectronics , 90 :283 , 2017
Abstract : In this study, a highly specific ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized to monitor dipeptidyl peptidase IV in plasma and living systems. GP-BAN was designed on the basis of the catalytic properties and substrate preference of DPP-IV, and it could be readily hydrolyzed upon addition of DPP-IV under physiological conditions. Both reaction phenotyping and inhibition assays demonstrated that GP-BAN displayed good reactivity and high selectivity towards DPP-IV over other human serine hydrolases including FAP, DPP-VIII, and DPP-IX. The probe was successfully used to monitor the real activities of DPP-IV in complex biological systems including diluted plasma, while it could be used for high throughput screening of DPP-IV inhibitors by using human plasma or tissue preparations as enzyme sources. As a two-photon fluorescent probe, GP-BAN was also successfully used for two-photon imaging of endogenous DPP-IV in living cells and tissues, and showed high ratiometric imaging resolution and deep-tissue penetration ability. Taken together, a ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized for highly selective and sensitive detection of DPP-IV in complex biological systems, which could serve as a promising imaging tool to explore the biological functions and physiological roles of this key enzyme in living systems.
ESTHER : Zou_2017_Biosens.Bioelectron_90_283
PubMedSearch : Zou_2017_Biosens.Bioelectron_90_283
PubMedID: 27923191

Title : Structural and Mechanistic Insights into the Improvement of the Halotolerance of a Marine Microbial Esterase by Increasing Intra- and Interdomain Hydrophobic Interactions - Li_2017_Appl.Environ.Microbiol_83_
Author(s) : Li PY , Zhang Y , Xie BB , Zhang YQ , Hao J , Wang Y , Wang P , Li CY , Qin QL , Zhang XY , Su HN , Shi M , Zhang YZ , Chen XL
Ref : Applied Environmental Microbiology , 83 : , 2017
Abstract : Halotolerant enzymes are beneficial for industrial processes requiring high salt concentrations and low water activity. Most halophilic proteins are evolved to have reduced hydrophobic interactions on the surface and in the hydrophobic cores for their haloadaptation. However, in this study, we improved the halotolerance of a thermolabile esterase, E40, by increasing intraprotein hydrophobic interactions. E40 was quite unstable in buffers containing more than 0.3 M NaCl, and its kcat and substrate affinity were both significantly reduced in 0.5 M NaCl. By introducing hydrophobic residues in loop 1 of the CAP domain and/or alpha7 of the catalytic domain in E40, we obtained several mutants with improved halotolerance, and the M3 S202W I203F mutant was the most halotolerant. ("M3" represents a mutation in loop 1 of the CAP domain in which residues R22-K23-T24 of E40 are replaced by residues Y22-K23-H24-L25-S26 of Est2.) Then we solved the crystal structures of the S202W I203F and M3 S202W I203F mutants to reveal the structural basis for their improved halotolerance. Structural analysis revealed that the introduction of hydrophobic residues W202 and F203 in alpha7 significantly improved E40 halotolerance by strengthening intradomain hydrophobic interactions of F203 with W202 and other residues in the catalytic domain. By further introducing hydrophobic residues in loop 1, the M3 S202W I203F mutant became more rigid and halotolerant due to the formation of additional interdomain hydrophobic interactions between the introduced Y22 in loop 1 and W204 in alpha7. These results indicate that increasing intraprotein hydrophobic interactions is also a way to improve the halotolerance of enzymes with industrial potential under high-salt conditions.IMPORTANCE Esterases and lipases for industrial application are often subjected to harsh conditions such as high salt concentrations, low water activity, and the presence of organic solvents. However, reports on halotolerant esterases and lipases are limited, and the underlying mechanism for their halotolerance is still unclear due to the lack of structures. In this study, we focused on the improvement of the halotolerance of a salt-sensitive esterase, E40, and the underlying mechanism. The halotolerance of E40 was significantly improved by introducing hydrophobic residues. Comparative structural analysis of E40 and its halotolerant mutants revealed that increased intraprotein hydrophobic interactions make these mutants more rigid and more stable than the wild type against high concentrations of salts. This study shows a new way to improve enzyme halotolerance, which is helpful for protein engineering of salt-sensitive enzymes.
ESTHER : Li_2017_Appl.Environ.Microbiol_83_
PubMedSearch : Li_2017_Appl.Environ.Microbiol_83_
PubMedID: 28733281
Gene_locus related to this paper: 9bact-E40

Title : Display of fungal hydrophobin on the Pichia pastoris cell surface and its influence on Candida antarctica lipase B - Wang_2016_Appl.Microbiol.Biotechnol_100_5883
Author(s) : Wang P , He J , Sun Y , Reynolds M , Zhang L , Han S , Liang S , Sui H , Lin Y
Ref : Applied Microbiology & Biotechnology , 100 :5883 , 2016
Abstract : To modify the Pichia pastoris cell surface, two classes of hydrophobins, SC3 from Schizophyllum commune and HFBI from Trichoderma reesei, were separately displayed on the cell wall. There was an observable increase in the hydrophobicity of recombinant strains. Candida antarctica lipase B (CALB) was then co-displayed on the modified cells, generating strains GS115/SC3-61/CALB-51 and GS115/HFBI-61/CALB-51. Interestingly, the hydrolytic and synthetic activities of strain GS115/HFBI-61/CALB-51 increased by 37 and 109 %, respectively, but decreased by 26 and 43 %, respectively, in strain GS115/SC3-61/CALB-51 compared with the hydrophobin-minus recombinant strain GS115/CALB-GCW51. The amount of glycerol by-product from the transesterification reaction adsorbed on the cell surface was significantly decreased following hydrophobin modification, removing the glycerol barrier and allowing substrates to access the active sites of lipases. Electron micrographs indicated that the cell wall structures of both recombinant strains appeared altered, including changes to the inner glucan layer and outer mannan layer. These results suggest that the display of hydrophobins can change the surface structure and hydrophobic properties of P. pastoris and affect the catalytic activities of CALB displayed on the surface of P. pastoris cells.
ESTHER : Wang_2016_Appl.Microbiol.Biotechnol_100_5883
PubMedSearch : Wang_2016_Appl.Microbiol.Biotechnol_100_5883
PubMedID: 26969039

Title : Bioconcentration and metabolism of ketoconazole and effects on multi-biomarkers in crucian carp (Carassius auratus) - Liu_2016_Chemosphere_150_145
Author(s) : Liu J , Lu G , Yang H , Yan Z , Wang Y , Wang P
Ref : Chemosphere , 150 :145 , 2016
Abstract : The tissue distribution, bioconcentration, metabolism and biological effects of the antifungal medication ketoconazole were investigated in fish, crucian carp (Carassius auratus) were exposed to a series of nominal concentrations (0.2, 2 and 20 mug/L) for 14 days. The ultra-high performance liquid chromatography tandem triple quadrupole mass spectroscopy (UPLC/MS/MS) analysis was used to determine the bioconcentration of ketoconazole and its metabolites in fish. The highest tissue concentration of ketoconazole was observed in the liver with the bioconcentration factor of 257.2, which is lower than the estimated BCF value. The ability of crucian carp to metabolize ketoconazole was confirmed and the results pointed out the existence of seven metabolites likely formed via oxidation of imidazole ring and the metabolic alteration of the piperazine rings. In addition, acetylcholinesterase, 7-ethoxyresorufin O-deethylase, superoxide dismutase and glutathione S-transferase changed significantly after 3, 7 and 14 days of exposure (P < 0.05), which indicated that the accumulation and metabolism of ketoconazole in fish tissues may account for the biological effects.
ESTHER : Liu_2016_Chemosphere_150_145
PubMedSearch : Liu_2016_Chemosphere_150_145
PubMedID: 26901470

Title : Design, synthesis, and structure-activity relationship study of glycyrrhetinic acid derivatives as potent and selective inhibitors against human carboxylesterase 2 - Zou_2016_Eur.J.Med.Chem_112_280
Author(s) : Zou LW , Li YG , Wang P , Zhou K , Hou J , Jin Q , Hao DC , Ge GB , Yang L
Ref : Eur Journal of Medicinal Chemistry , 112 :280 , 2016
Abstract : Human carboxylesterase 2 (hCE2), one of the major carboxylesterases in the human intestine and various tumour tissues, plays important roles in the oral bioavailability and treatment outcomes of ester- or amide-containing drugs or prodrugs, such as anticancer agents CPT-11 (irinotecan) and LY2334737 (gemcitabine). In this study, 18beta-glycyrrhetinic acid (GA), the most abundant pentacyclic triterpenoid from natural source, was selected as a reference compound for the development of potent and specific inhibitors against hCE2. Simple semi-synthetic modulation on GA was performed to obtain a series of GA derivatives. Structure-activity relationship analysis brought novel insights into the structure modification of GA. Converting the 11-oxo-12-ene of GA to 12-diene moiety, and C-3 hydroxyl and C-30 carboxyl group to 3-O-beta-carboxypropionyl and ethyl ester respectively, led to a significant enhancement of the inhibitory effect on hCE2 and the selectivity over hCE1. These exciting findings inspired us to design and synthesize the more potent compound 15 (IC50 0.02 muM) as a novel and highly selective inhibitor against hCE2, which was 3463-fold more potent than the parent compound GA and demonstrated excellent selectivity (>1000-fold over hCE1). The molecular docking study of compound 15 and the active site of hCE1 and hCE2 demonstrated that the potent and selective inhibition of compound 15 toward hCE2 could partially be attributed to its relatively stronger interactions with hCE2 than with hCE1.
ESTHER : Zou_2016_Eur.J.Med.Chem_112_280
PubMedSearch : Zou_2016_Eur.J.Med.Chem_112_280
PubMedID: 26900660

Title : Sesquiterpenoids from Chinese Agarwood Induced by Artificial Holing - Li_2016_Molecules_21_274
Author(s) : Li W , Liao G , Dong WH , Kong FD , Wang P , Wang H , Mei WL , Dai HF
Ref : Molecules , 21 :274 , 2016
Abstract : Two new sesquiterpenoids, 3-oxo-7-hydroxylholosericin A (1) and 1,5;8,12-diepoxy-guaia-12-one (2), together with seven known sesquiterpenoids 3-9, were isolated from Chinese agarwood induced by artificial holing originating from Aquilaria sinensis (Lour.) Gilg. Their structures were identified by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The absolute configuration of compound 1 was determined by comparison of its measured CD curve with that of calculated data for 1 and ent-1. The NMR data of 3 were reported in this study for the first time. Compounds 1, 2, 4-6, together with the EtOAc extract showed moderate inhibitory activities against acetylcholinesterase, and compounds 4-6, 8 exhibited antibacterial activities against Staphylococcus aureus or Ralstonia solanacearum.
ESTHER : Li_2016_Molecules_21_274
PubMedSearch : Li_2016_Molecules_21_274
PubMedID: 26927047

Title : Rapid eye movement sleep behavior disorder in patients with probable Alzheimer's disease - Wang_2016_Aging.Clin.Exp.Res_28_951
Author(s) : Wang P , Wing YK , Xing J , Liu Y , Zhou B , Zhang Z , Yao H , Guo Y , Shang Y , Zhang X
Ref : Aging Clin Exp Res , 28 :951 , 2016
Abstract : BACKGROUND AND AIMS: Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with neurodegenerative disorders characterized by alpha-synuclein deposition, including Parkinson's disease, multiple system atrophy, and Lewy body dementia. However, this tendency in tauopathy-mediated diseases is rare and only sporadically reported. We systematically illustrate the occurrence of RBD and sleep features among a cohort of patients with Alzheimer's disease (AD), a non-synucleinopathy.
METHODS: We recruited 105 clinically probable AD patients. Fifteen clinically probable AD patients with suspected RBD underwent a video-polysomnography (vPSG) examination.
RESULTS: Five patients with probable AD exhibited RBD. One of the patients performed repeated touching of the head and the face with his hands and flailed his arms. Three patients exhibited hand twisting, exploring, prominent limb kicking, and jerking. The fifth patient exhibited all of the characteristics of RBD (he recalled a dream about fighting animals), and his wife was awakened by his screaming. Of these five patients, one patient took the acetylcholinesterase inhibitor drug donepezil. The patients with AD + RBD demonstrated increases in both tonic and phasic electromyography activity during REM sleep, but sleep architecture did not differ between the AD + RBD and AD-alone groups. CONCLUSION: RBD can occur in patients with AD. The occurrence of RBD does not change the sleep architecture of AD patients.
ESTHER : Wang_2016_Aging.Clin.Exp.Res_28_951
PubMedSearch : Wang_2016_Aging.Clin.Exp.Res_28_951
PubMedID: 26022447

Title : Interdomain hydrophobic interactions modulate the thermostability of microbial esterases from the hormone-sensitive lipase family - Li_2015_J.Biol.Chem_290_11188
Author(s) : Li PY , Chen XL , Ji P , Li CY , Wang P , Zhang Y , Xie BB , Qin QL , Su HN , Zhou BC , Zhang YZ , Zhang XY
Ref : Journal of Biological Chemistry , 290 :11188 , 2015
Abstract : Microbial hormone-sensitive lipases (HSLs) contain a CAP domain and a catalytic domain. However, it remains unclear how the CAP domain interacts with the catalytic domain to maintain the stability of microbial HSLs. Here, we isolated an HSL esterase, E40, from a marine sedimental metagenomic library. E40 exhibited the maximal activity at 45 degrees C and was quite thermolabile, with a half-life of only 2 min at 40 degrees C, which may be an adaptation of E40 to the permanently cold sediment environment. The structure of E40 was solved to study its thermolability. Structural analysis showed that E40 lacks the interdomain hydrophobic interactions between loop 1 of the CAP domain and alpha7 of the catalytic domain compared with its thermostable homologs. Mutational analysis showed that the introduction of hydrophobic residues Trp(202) and Phe(203) in alpha7 significantly improved E40 stability and that a further introduction of hydrophobic residues in loop 1 made E40 more thermostable because of the formation of interdomain hydrophobic interactions. Altogether, the results indicate that the absence of interdomain hydrophobic interactions between loop 1 and alpha7 leads to the thermolability of E40. In addition, a comparative analysis of the structures of E40 and other thermolabile and thermostable HSLs suggests that the interdomain hydrophobic interactions between loop 1 and alpha7 are a key element for the thermostability of microbial HSLs. Therefore, this study not only illustrates the structural element leading to the thermolability of E40 but also reveals a structural determinant for HSL thermostability.
ESTHER : Li_2015_J.Biol.Chem_290_11188
PubMedSearch : Li_2015_J.Biol.Chem_290_11188
PubMedID: 25771540
Gene_locus related to this paper: 9bact-E40

Title : Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients - Li_2015_Eur.Neurol_74_86
Author(s) : Li Z , Yu Z , Zhang J , Wang J , Sun C , Wang P
Ref : Eur Neurol , 74 :86 , 2015
Abstract : BACKGROUND: The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. SUBJECTS AND
METHODS: Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups.
RESULTS: The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). CONCLUSION: This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients.
ESTHER : Li_2015_Eur.Neurol_74_86
PubMedSearch : Li_2015_Eur.Neurol_74_86
PubMedID: 26288230

Title : A Two-Photon Ratiometric Fluorescent Probe for Imaging Carboxylesterase 2 in Living Cells and Tissues - Jin_2015_ACS.Appl.Mater.Interfaces_7_28474
Author(s) : Jin Q , Feng L , Wang DD , Dai ZR , Wang P , Zou LW , Liu ZH , Wang JY , Yu Y , Ge GB , Cui JN , Yang L
Ref : ACS Appl Mater Interfaces , 7 :28474 , 2015
Abstract : In this study, a two-photon ratiometric fluorescent probe NCEN has been designed and developed for highly selective and sensitive sensing of human carboxylesterase 2 (hCE2) based on the catalytic properties and substrate preference of hCE2. Upon addition of hCE2, the probe could be readily hydrolyzed to release 4-amino-1,8-naphthalimide (NAH), which brings remarkable red-shift in fluorescence (90 nm) spectrum. The newly developed probe exhibits good specificity, ultrahigh sensitivity, and has been successfully applied to determine the real activities of hCE2 in complex biological samples such as cell and tissue preparations. NCEN has also been used for two-photon imaging of intracellular hCE2 in living cells as well as in deep-tissues for the first time, and the results showed that the probe exhibited high ratiometric imaging resolution and deep-tissue imaging depth. All these findings suggested that this probe holds great promise for applications in bioimaging of endogenous hCE2 in living cells and in exploring the biological functions of hCE2 in complex biological systems.
ESTHER : Jin_2015_ACS.Appl.Mater.Interfaces_7_28474
PubMedSearch : Jin_2015_ACS.Appl.Mater.Interfaces_7_28474
PubMedID: 26641926

Title : Fructus Psoraleae contains natural compounds with potent inhibitory effects towards human carboxylesterase 2 - Li_2015_Fitoterapia_101_99
Author(s) : Li YG , Hou J , Li SY , Lv X , Ning J , Wang P , Liu ZM , Ge GB , Ren JY , Yang L
Ref : Fitoterapia , 101 :99 , 2015
Abstract : Fructus Psoraleae (FP) is an edible Chinese herbal which is widely used in Asia for the treatment of various diseases including asthma, diarrhea, and osteoporosis. This study aimed to investigate the inhibitory effects of the crude ethanol extract from FP on human carboxylesterase 2 (hCE2), as well as to identity and characterize the naturally occurring inhibitors of hCE2 in FP. Our results demonstrated that the ethanol extract of FP displayed potent inhibitory effects towards hCE2, while five major bioactive constitutes in FP were efficiently identified by LC-DAD-ESI-MS/MS, with the aid of LC-based activity profiling. The identified bioactive compounds including neobavaisoflavone, isobavachalcone, bavachinin, corylifol A and bakuchiol were found to be naturally occurring potent inhibitors of hCE2, with low Ki values ranging from 0.62muM to 3.89muM. This is the first report of the chemical constitutes in FP as potent inhibitors of hCE2.
ESTHER : Li_2015_Fitoterapia_101_99
PubMedSearch : Li_2015_Fitoterapia_101_99
PubMedID: 25596095

Title : A Ric8\/Synembryn Homolog Promotes Gpa1 and Gpa2 Activation To Respectively Regulate Cyclic AMP and Pheromone Signaling in Cryptococcus neoformans - Gong_2014_Eukaryot.Cell_13_1290
Author(s) : Gong J , Grodsky JD , Zhang Z , Wang P
Ref : Eukaryot Cell , 13 :1290 , 2014
Abstract : The G protein alpha subunits Gpa1, Gpa2, and Gpa3 mediate signal transduction and are important in the growth and virulence of Cryptococcus neoformans. To understand how Gpa1 functions without a conventional Gbeta subunit, we characterized a resistance to inhibitors of cholinesterase 8 (Ric8) homolog from C. neoformans, which shares amino acid sequence homology with other Ric8 proteins that exhibit guanine nucleotide exchange factor (GEF) activity toward Galpha. We found that the ric8 mutant was reduced in capsule size and melanin formation, which could be suppressed by cyclic AMP (cAMP) supplementation or by introducing the activated GPA1(Q284L) allele. Consistent with the fact that Ric8 participates in cAMP signaling to regulate virulence, the ric8 mutant was attenuated in virulence toward mice. Interestingly, disruption of RIC8 also resulted in opposing effects on pheromone signaling, as the ric8 mutant showed reduced mating but an enhanced ability to induce the pheromone response in the mating partner. To identify Ric8 functional mechanisms, we examined the interactions between Ric8 and the three Galpha proteins. Ric8 interacted with Gpa1 and Gpa2, but not Gpa3. The presence of Gpa1(Q284L) negatively affected its interaction with Ric8, whereas the activated Gpa2(Q203L) allele abolished the interaction. Collectively, these findings suggest that Ric8 functions as a GEF to facilitate the activation of Gpa1-cAMP signaling and to promote Gpa2, affecting mating efficiency. Our study highlights the distinct and conserved characteristics associated with G protein signaling and contributes to our overall understanding of how G protein alpha subunits function with or without a canonical Gbeta partner in C. neoformans.
ESTHER : Gong_2014_Eukaryot.Cell_13_1290
PubMedSearch : Gong_2014_Eukaryot.Cell_13_1290
PubMedID: 25084863

Title : Generation of Dipeptidyl Peptidase-IV-Inhibiting Peptides from beta-Lactoglobulin Secreted by Lactococcus lactis - Shigemori_2014_Biomed.Res.Int_2014_393598
Author(s) : Shigemori S , Oshiro K , Wang P , Yamamoto Y , Wang Y , Sato T , Uyeno Y , Shimosato T
Ref : Biomed Res Int , 2014 :393598 , 2014
Abstract : Previous studies showed that hydrolysates of beta-lactoglobulin (BLG) prepared using gastrointestinal proteases strongly inhibit dipeptidyl peptidase-IV (DPP-IV) activity in vitro. In this study, we developed a BLG-secreting Lactococcus lactis strain as a delivery vehicle and in situ expression system. Interestingly, trypsin-digested recombinant BLG from L. lactis inhibited DPP-IV activity, suggesting that BLG-secreting L. lactis may be useful in the treatment of type 2 diabetes mellitus.
ESTHER : Shigemori_2014_Biomed.Res.Int_2014_393598
PubMedSearch : Shigemori_2014_Biomed.Res.Int_2014_393598
PubMedID: 25157356

Title : Optimized inhibitors of soluble epoxide hydrolase improve in vitro target residence time and in vivo efficacy - Lee_2014_J.Med.Chem_57_7016
Author(s) : Lee KS , Liu JY , Wagner KM , Pakhomova S , Dong H , Morisseau C , Fu SH , Yang J , Wang P , Ulu A , Mate CA , Nguyen LV , Hwang SH , Edin ML , Mara AA , Wulff H , Newcomer ME , Zeldin DC , Hammock BD
Ref : Journal of Medicinal Chemistry , 57 :7016 , 2014
Abstract : Diabetes is affecting the life of millions of people. A large proportion of diabetic patients suffer from severe complications such as neuropathic pain, and current treatments for these complications have deleterious side effects. Thus, alternate therapeutic strategies are needed. Recently, the elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) was shown to reduce diabetic neuropathic pain in rodents. In this report, we describe a series of newly synthesized sEH inhibitors with at least 5-fold higher potency and doubled residence time inside both the human and rodent sEH enzyme than previously reported inhibitors. These inhibitors also have better physical properties and optimized pharmacokinetic profiles. The optimized inhibitor selected from this new series displayed improved efficacy of almost 10-fold in relieving pain perception in diabetic neuropathic rats as compared to the approved drug, gabapentin, and previously published sEH inhibitors. Therefore, these new sEH inhibitors could be an attractive alternative to treat diabetic neuropathy in humans.
ESTHER : Lee_2014_J.Med.Chem_57_7016
PubMedSearch : Lee_2014_J.Med.Chem_57_7016
PubMedID: 25079952
Gene_locus related to this paper: human-EPHX2

Title : Novel Multipotent AChEI-CCB Attenuates Hyperhomocysteinemia-Induced Memory Deficits and Neuropathologies in Rats - Xia_2014_J.Alzheimers.Dis_42_1029
Author(s) : Xia Y , Liu R , Chen R , Tian Q , Zeng K , Hu J , Liu X , Wang Q , Wang P , Wang XC , Wang JZ
Ref : J Alzheimers Dis , 42 :1029 , 2014
Abstract : Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive cause remains unclear and the therapeutic strategies have been elusive. Combination therapy, as one of the promising treatments, has been studied for years and may exert synergistic beneficial effects on AD through polytherapeutic targets. In this study, we tested the effects of a synthesized juxtaposition (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat model, and found that SCR1693 remarkably improved the HHcy-induced memory deficits and preserved dendrite morphologies as well as spine density by upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple AD-associated sites by regulating the activity of protein phosphatase-2A and glycogen synthase kinase-3beta. Furthermore, SCR1693 was more effective than individual administration of both donepezil and nilvadipine which were used as AChEI and CCB, respectively, in the clinical practice. In conclusion, our data suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a promising therapeutic candidate for AD.
ESTHER : Xia_2014_J.Alzheimers.Dis_42_1029
PubMedSearch : Xia_2014_J.Alzheimers.Dis_42_1029
PubMedID: 25024319

Title : Construction of genetically engineered bacteria that degrades organophosphorus pesticide residues and can be easily detected by the fluorescence - Li_2014_Environ.Technol_35_556
Author(s) : Li Q , Wang P , Chen R , Li W , Wu YJ
Ref : Environ Technol , 35 :556 , 2014
Abstract : Organophosphorus compounds (OPs) are widely used in agriculture and industry and there is increased concern about their toxicological effects in the environment. Bioremediation can offer an efficient and cost-effective option for the removal of OPs. Herein, we describe the construction of a genetically engineered microorganism (GEM) that can degrade OPs and be directly detected and monitored in the environment using an enhanced green fluorescent protein (EGFP) fusion strategy. The coding regions of EGFP, a reporter protein that can fluoresce by itself, and organophosphorus hydrolase (OPH), which has a broad substrate specificity and is able to hydrolyse a number of organophosphorus pesticides, were cloned into the expression vector pET-28b. The fusion protein of EGFP-OPH was expressed in E. coli BL21 (DE3) and the protein expression reached the highest level at 11 h after isopropyl beta-D-thiogalactopyranoside induction. The fluorescence of the GEM was detected by fluorescence spectrophotometry and microscopy, and its ability to degrade OPs was determined by OPH activity assay. Those GEM that express the fusion protein (EGFP and OPH) exhibited strong fluorescence intensity and also potent hydrolase activity, which could be used to degrade organophosphorus pesticide residues in the environment and can also be directly monitored by fluorescence.
ESTHER : Li_2014_Environ.Technol_35_556
PubMedSearch : Li_2014_Environ.Technol_35_556
PubMedID: 24645434

Title : Frster resonance energy transfer competitive displacement assay for human soluble epoxide hydrolase - Lee_2013_Anal.Biochem_434_259
Author(s) : Lee KS , Morisseau C , Yang J , Wang P , Hwang SH , Hammock BD
Ref : Analytical Biochemistry , 434 :259 , 2013
Abstract : The soluble epoxide hydrolase (sEH), responsible for the hydrolysis of various fatty acid epoxides to their corresponding 1,2-diols, is becoming an attractive pharmaceutical target. These fatty acid epoxides, particularly epoxyeicosatrienoic acids (EETs), play an important role in human homeostatic and inflammation processes. Therefore, inhibition of human sEH, which stabilizes EETs in vivo, brings several beneficial effects to human health. Although there are several catalytic assays available to determine the potency of sEH inhibitors, measuring the in vitro inhibition constant (K(i)) for these inhibitors using catalytic assay is laborious. In addition, k(off), which has been recently suggested to correlate better with the in vivo potency of inhibitors, has never been measured for sEH inhibitors. To better measure the potency of sEH inhibitors, a reporting ligand, 1-(adamantan-1-yl)-3-(1-(2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetyl) piperidin-4-yl)urea (ACPU), was designed and synthesized. With ACPU, we have developed a Forster resonance energy transfer (FRET)-based competitive displacement assay using intrinsic tryptophan fluorescence from sEH. In addition, the resulting assay allows us to measure the K(i) values of very potent compounds to the picomolar level and to obtain relative k(off) values of the inhibitors. This assay provides additional data to evaluate the potency of sEH inhibitors.
ESTHER : Lee_2013_Anal.Biochem_434_259
PubMedSearch : Lee_2013_Anal.Biochem_434_259
PubMedID: 23219719

Title : Characterization of streptonigrin biosynthesis reveals a cryptic carboxyl methylation and an unusual oxidative cleavage of a N-C bond - Xu_2013_J.Am.Chem.Soc_135_1739
Author(s) : Xu F , Kong D , He X , Zhang Z , Han M , Xie X , Wang P , Cheng H , Tao M , Zhang L , Deng Z , Lin S
Ref : Journal of the American Chemical Society , 135 :1739 , 2013
Abstract : Streptonigrin (STN, 1) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activity. Here, we reported the biosynthetic gene cluster of STN identified by genome scanning of a STN producer Streptomyces flocculus CGMCC4.1223. This cluster consists of 48 genes determined by a series of gene inactivations. On the basis of the structures of intermediates and shunt products accumulated from five specific gene inactivation mutants and feeding experiments, the biosynthetic pathway was proposed, and the sequence of tailoring steps was preliminarily determined. In this pathway, a cryptic methylation of lavendamycin was genetically and biochemically characterized to be catalyzed by a leucine carboxyl methyltransferase StnF2. A [2Fe-2S](2+) cluster-containing aromatic ring dioxygenase StnB1/B2 system was biochemically characterized to catalyze a regiospecific cleavage of the N-C8' bond of the indole ring of the methyl ester of lavendamycin. This work provides opportunities to illuminate the enzymology of novel reactions involved in this pathway and to create, using genetic and chemo-enzymatic methods, new streptonigrinoid analogues as potential therapeutic agents.
ESTHER : Xu_2013_J.Am.Chem.Soc_135_1739
PubMedSearch : Xu_2013_J.Am.Chem.Soc_135_1739
PubMedID: 23301954
Gene_locus related to this paper: 9actn-l7pij2

Title : Characterization of HOVI-MEH1, a microsomal epoxide hydrolase from the glassy-winged sharpshooter Homalodisca vitripennis - Kamita_2013_Arch.Insect.Biochem.Physiol_83_171
Author(s) : Kamita SG , Oshita GH , Wang P , Morisseau C , Hammock BD , Nandety RS , Falk BW
Ref : Archives of Insect Biochemistry & Physiology , 83 :171 , 2013
Abstract : Epoxide hydrolase (EH) is an enzyme in the alpha/beta-hydrolase fold superfamily that uses a water molecule to transform an epoxide to its corresponding diol. In insects, EHs metabolize among other things critical developmental hormones called juvenile hormones (JHs). EHs also play roles in the detoxification of toxic compounds that are found in the insect's diet or environment. In this study, a full-length cDNA encoding an epoxide hydrolase, Hovi-mEH1, was obtained from the xylem-feeding insect Homalodisca vitripennis. H. vitripennis, commonly known as the glassy-winged sharpshooter, is an economically important vector of plant pathogenic bacteria such as Xylella fastidiosa. Hovi-mEH1 hydrolyzed the general EH substrates cis-stilbene oxide and trans-diphenylpropene oxide with specific activities of 47.5 +/- 6.2 and 1.3 +/- 0.5 nmol of diol formed min(-1) mg(-1) , respectively. Hovi-mEH1 metabolized JH III with a Vmax of 29.3 +/- 1.6 nmol min(-1) mg(-1) , kcat of 0.03 s(-1) , and KM of 13.8 +/- 2.0 muM. These Vmax and kcat values are similar to those of known JH metabolizing EHs from lepidopteran and coleopteran insects. Hovi-mEH1 showed 99.1% identity to one of three predicted EH-encoding sequences that were identified in the transcriptome of H. vitripennis. Of these three sequences only Hovi-mEH1 clustered with known JH metabolizing EHs. On the basis of biochemical, phylogenetic, and transcriptome analyses, we hypothesize that Hovi-mEH1 is a biologically relevantJH-metabolizing enzyme in H. vitripennis.
ESTHER : Kamita_2013_Arch.Insect.Biochem.Physiol_83_171
PubMedSearch : Kamita_2013_Arch.Insect.Biochem.Physiol_83_171
PubMedID: 23704009

Title : High-resolution structures of AidH complexes provide insights into a novel catalytic mechanism for N-acyl homoserine lactonase - Gao_2013_Acta.Crystallogr.D.Biol.Crystallogr_69_82
Author(s) : Gao A , Mei GY , Liu S , Wang P , Tang Q , Liu YP , Wen H , An XM , Zhang LQ , Yan XX , Liang DC
Ref : Acta Crystallographica D Biol Crystallogr , 69 :82 , 2013
Abstract : Many pathogenic bacteria that infect humans, animals and plants rely on a quorum-sensing (QS) system to produce virulence factors. N-Acyl homoserine lactones (AHLs) are the best-characterized cell-cell communication signals in QS. The concentration of AHL plays a key role in regulating the virulence-gene expression and essential biological functions of pathogenic bacteria. N-Acyl homoserine lactonases (AHL-lactonases) have important functions in decreasing pathogenicity by degrading AHLs. Here, structures of the AHL-lactonase from Ochrobactrum sp. (AidH) in complex with N-hexanoyl homoserine lactone, N-hexanoyl homoserine and N-butanoyl homoserine are reported. The high-resolution structures together with biochemical analyses reveal convincing details of AHL degradation. No metal ion is bound in the active site, which is different from other AHL-lactonases, which have a dual Lewis acid catalysis mechanism. AidH contains a substrate-binding tunnel between the core domain and the cap domain. The conformation of the tunnel entrance varies with the AHL acyl-chain length, which contributes to the binding promiscuity of AHL molecules in the active site. It also supports the biochemical result that AidH is a broad catalytic spectrum AHL-lactonase. Taken together, the present results reveal the catalytic mechanism of the metal-independent AHL-lactonase, which is a typical acid-base covalent catalysis.
ESTHER : Gao_2013_Acta.Crystallogr.D.Biol.Crystallogr_69_82
PubMedSearch : Gao_2013_Acta.Crystallogr.D.Biol.Crystallogr_69_82
PubMedID: 23275166
Gene_locus related to this paper: 9rhiz-d2j2t6

Title : Complete genome sequence of Bacillus thuringiensis subsp. kurstaki strain HD73 - Liu_2013_Genome.Announc_1_e0008013
Author(s) : Liu G , Song L , Shu C , Wang P , Deng C , Peng Q , Lereclus D , Wang X , Huang D , Zhang J , Song F
Ref : Genome Announc , 1 :e0008013 , 2013
Abstract : Bacillus thuringiensis is a Gram-positive bacterium that produces intracellular protein crystals toxic to a wide variety of insect larvae. We report the complete genome sequence of Bacillus thuringiensis subsp. kurstaki strain HD73 from the Centre OILB (Institut Pasteur, France), which belongs to serotype 3ab and is toxic to lepidopteran larvae.
ESTHER : Liu_2013_Genome.Announc_1_e0008013
PubMedSearch : Liu_2013_Genome.Announc_1_e0008013
PubMedID: 23516207

Title : Draft genome sequence of Alicyclobacillus hesperidum strain URH17-3-68 - Wang_2012_J.Bacteriol_194_6348
Author(s) : Wang P , Li L , Chen X , Jiang N , Liu G , Chen L , Xu J , Song H , Chen Z , Ma Y
Ref : Journal of Bacteriology , 194 :6348 , 2012
Abstract : Alicyclobacillus hesperidum is a thermoacidophilic bacterium. We isolated strain URH17-3-68 from hot spring sludge in Tengchong, Yunnan province, China. Its extracellular products include heat- and acid-stable enzymes which are important for industrial applications. Here we report the draft genome of this strain.
ESTHER : Wang_2012_J.Bacteriol_194_6348
PubMedSearch : Wang_2012_J.Bacteriol_194_6348
PubMedID: 23105079
Gene_locus related to this paper: 9bacl-h2esd6 , 9bacl-j9e7t9

Title : Examining the interactome of huperzine A by magnetic biopanning - Guo_2012_PLoS.One_7_e37098
Author(s) : Guo W , Liu S , Peng J , Wei X , Sun Y , Qiu Y , Gao G , Wang P , Xu Y
Ref : PLoS ONE , 7 :e37098 , 2012
Abstract : Huperzine A is a bioactive compound derived from traditional Chinese medicine plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple neuroprotective effects. In addition to being a potent acetylcholinesterase inhibitor, it was thought to act through other mechanisms such as antioxidation, antiapoptosis, etc. However, the molecular targets involved with these mechanisms were not identified. In this study, we attempted to exam the interactome of Huperzine A using a cDNA phage display library and also mammalian brain tissue extracts. The drugs were chemically linked on the surface of magnetic particles and the interactive phages or proteins were collected and analyzed. Among the various cDNA expressing phages selected, one was identified to encode the mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and the target phages and target proteins were confirmed. Another enriched phage clone was identified as mitochondria ATP synthase, which was also panned out from the proteome of mouse brain tissue lysate. These data indicated the possible involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's pharmacological effects. Such involvement had been suggested by previous studies based on enzyme activity changes. Our data supported the new mechanism. Overall we demonstrated the feasibility of using magnetic biopanning as a simple and viable method for investigating the complex molecular mechanisms of bioactive molecules.
ESTHER : Guo_2012_PLoS.One_7_e37098
PubMedSearch : Guo_2012_PLoS.One_7_e37098
PubMedID: 22615909

Title : Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins - Han_2012_Brain.Res_1470_59
Author(s) : Han RW , Zhang RS , Chang M , Peng YL , Wang P , Hu SQ , Choi CL , Yin M , Wang R , Han YF
Ref : Brain Research , 1470 :59 , 2012
Abstract : Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice. Under the same experimental condition, the anti-amnesic effect of tacrine was also compared. Briefly, in both tasks, scopolamine (0.1-0.6 mg/kg, ip) dose-dependently impaired learning and memory functions. B3C (1.5-2.5 mumol/kg), B7C (0.4-0.6 mumol/kg) or tacrine (8-12 mumol/kg), each administered ip, dose-dependently mitigated scopolamine-induced learning and memory impairments in both tasks. Our present results show, for the first time, that B3C and B7C reverse cognitive impairment resulted from scopolamine in both water maze and object recognition tasks; and under the same condition, the relative potency of B3C and B7C to improve cognitive capacity was 5-20 folds over that of tacrine. These novel in vivo findings further demonstrate that both B3C and B7C may potentially be developed as Alzheimer's therapeutic drugs for different severities of neurodegenerations.
ESTHER : Han_2012_Brain.Res_1470_59
PubMedSearch : Han_2012_Brain.Res_1470_59
PubMedID: 22750583

Title : A novel Escherichia coli O157:H7 clone causing a major hemolytic uremic syndrome outbreak in China - Xiong_2012_PLoS.One_7_e36144
Author(s) : Xiong Y , Wang P , Lan R , Ye C , Wang H , Ren J , Jing H , Wang Y , Zhou Z , Bai X , Cui Z , Luo X , Zhao A , Zhang S , Sun H , Wang L , Xu J
Ref : PLoS ONE , 7 :e36144 , 2012
Abstract : An Escherichia coli O157:H7 outbreak in China in 1999 caused 177 deaths due to hemolytic uremic syndrome. Sixteen outbreak associated isolates were found to belong to a new clone, sequence type 96 (ST96), based on multilocus sequence typing of 15 housekeeping genes. Whole genome sequencing of an outbreak isolate, Xuzhou21, showed that the isolate is phylogenetically closely related to the Japan 1996 outbreak isolate Sakai, both of which share the most recent common ancestor with the US outbreak isolate EDL933. The levels of IL-6 and IL-8 of peripheral blood mononuclear cells induced by Xuzhou21 and Sakai were significantly higher than that induced by EDL933. Xuzhou21 also induced a significantly higher level of IL-8 than Sakai while both induced similar levels of IL-6. The expression level of Shiga toxin 2 in Xuzhou21 induced by mitomycin C was 68.6 times of that under non-inducing conditions, twice of that induced in Sakai (32.7 times) and 15 times higher than that induced in EDL933 (4.5 times). Our study shows that ST96 is a novel clone and provided significant new insights into the evolution of virulence of E. coli O157:H7.
ESTHER : Xiong_2012_PLoS.One_7_e36144
PubMedSearch : Xiong_2012_PLoS.One_7_e36144
PubMedID: 22558360
Gene_locus related to this paper: ecoli-ycfp , ecoli-YFBB , ecoli-yqia , ecoli-Z1341

Title : Complete genome sequence of Bacillus thuringiensis serovar finitimus strain YBT-020 - Zhu_2011_J.Bacteriol_193_2379
Author(s) : Zhu Y , Shang H , Zhu Q , Ji F , Wang P , Fu J , Deng Y , Xu C , Ye W , Zheng J , Zhu L , Ruan L , Peng D , Sun M
Ref : Journal of Bacteriology , 193 :2379 , 2011
Abstract : Bacillus thuringiensis is a gram-positive, spore-forming bacterium that forms parasporal crystals at the onset of the sporulation phase of its growth. Here, we report the complete genome sequence of B. thuringiensis serovar finitimus strain YBT-020, whose parasporal crystals consist of Cry26Aa and Cry28Aa crystal proteins and are located between the exosporium and the spore coat and remain adhering to the spore after sporulation.
ESTHER : Zhu_2011_J.Bacteriol_193_2379
PubMedSearch : Zhu_2011_J.Bacteriol_193_2379
PubMedID: 21398543
Gene_locus related to this paper: bacan-BA2392 , bacan-BA5009 , bacan-BA5110 , bacan-DHBF , bacce-BC2141 , bacce-BC4862 , bacce-BC5130 , bacce-BCE3188 , bacce-PHAC , bacce-q72yu1 , baccn-a7guq6 , baccr-pepx , bacce-c2qdt4

Title : Complete genome sequence of Bacillus subtilis BSn5, an endophytic bacterium of Amorphophallus konjac with antimicrobial activity for the plant pathogen Erwinia carotovora subsp. carotovora - Deng_2011_J.Bacteriol_193_2070
Author(s) : Deng Y , Zhu Y , Wang P , Zhu L , Zheng J , Li R , Ruan L , Peng D , Sun M
Ref : Journal of Bacteriology , 193 :2070 , 2011
Abstract : Here, we present the complete genome sequence of Bacillus subtilis strain BSn5, isolated from Amorphophallus konjac calli tissue and showing strong inhibitory activity to Erwinia carotovora subsp. carotovora, which causes Amorphophallus soft rot disease and affects the industry development of this organism.
ESTHER : Deng_2011_J.Bacteriol_193_2070
PubMedSearch : Deng_2011_J.Bacteriol_193_2070
PubMedID: 21317323
Gene_locus related to this paper: bacpu-pnbae , bacsu-CAH , bacsu-lip , bacsu-LIPB , bacsu-PPSE , bacsu-YBAC , bacsu-YDEN , bacsu-YTPA , bacsu-ytxm , bacsu-YVAK

Title : Isolation and characterization of a ferulic acid esterase (Fae1A) from the rumen fungus Anaeromyces mucronatus - Qi_2011_J.Appl.Microbiol_110_1341
Author(s) : Qi M , Wang P , Selinger LB , Yanke LJ , Forster RJ , McAllister TA
Ref : J Appl Microbiol , 110 :1341 , 2011
Abstract : AIMS: A novel ferulic acid esterase gene from rumen fungus Anaeromyces mucronatus was cloned, heteroexpressed in Escherichia coli and characterized. METHODS AND
RESULTS: A total of 30 clones exhibiting activity on alpha-naphthyl acetate (alpha-NA) were isolated from an A. mucronatus YE505 cDNA library. Sequence analysis revealed that these clones represented two esterase-coding sequences. The gene, fae1A, showed highest amino acid sequence identity to CE family 1 esterases from anaerobic micro-organisms such as Orpinomyces sp., Ruminococcus albus and Clostridium thermocellum. The gene comprised 828 nucleotides encoding a polypeptide of 275 amino acids. The coding sequence was cloned into the pET30a expression vector and overexpressed in E. coli BL21 (DE3). Gene product Fae1A was found to exhibit activity against a number of substrates including naphthyl fatty acid esters, p-nitrophenyl fatty acid esters and hydroxylcinnamic acid esters.
CONCLUSIONS: Fae1A exhibited a lower K(m) and higher catalytic efficiency (k(cat) /K(m) ) on ferulic acid esters than on alpha-NA or p-nitrophenyl acetate, suggesting that it has a higher affinity for ethyl and methyl ferulate than for the acetyl esters. It releases ferulic acid and p-coumaric acid from barley straw. Activity of Fae1A was inhibited by the serine-specific protease inhibitor, phenylmethylsulfonyl fluoride, indicating that a serine residue plays a role in its activity. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report of characterization of carbohydrate esterase gene from the genus of Anaeromyces.
ESTHER : Qi_2011_J.Appl.Microbiol_110_1341
PubMedSearch : Qi_2011_J.Appl.Microbiol_110_1341
PubMedID: 21362116
Gene_locus related to this paper: 9fung-f2ycb6

Title : Emergence of a new multidrug-resistant serotype X variant in an epidemic clone of Shigella flexneri - Ye_2010_J.Clin.Microbiol_48_419
Author(s) : Ye C , Lan R , Xia S , Zhang J , Sun Q , Zhang S , Jing H , Wang L , Li Z , Zhou Z , Zhao A , Cui Z , Cao J , Jin D , Huang L , Wang Y , Luo X , Bai X , Wang P , Xu Q , Xu J
Ref : J Clin Microbiol , 48 :419 , 2010
Abstract : Shigella spp. are the causative agent of shigellosis with Shigella flexneri serotype 2a being the most prevalent in developing countries. Epidemiological surveillance in China found that a new serotype of S. flexneri appeared in 2001 and replaced serotype 2a in 2003 as the most prevalent serotype in Henan Province. The new serotype also became the dominant serotype in 7 of the 10 other provinces under surveillance in China by 2007. The serotype was identified as a variant of serotype X. It differs from serotype X by agglutination to the monovalent anti-IV type antiserum and the group antigen-specific monoclonal antibody MASF IV-I. Genome sequencing of a serotype X variant isolate, 2002017, showed that it acquired a Shigella serotype conversion island, also as an SfX bacteriophage, containing gtr genes for type X-specific glucosylation. Multilocus sequence typing of 15 genes from 37 serotype X variant isolates and 69 isolates of eight other serotypes, 1a, 2a, 2b, 3a, 4a, 5b, X, and Y, found that all belong to a new sequence type (ST), ST91. Pulsed-field gel electrophoresis revealed 154 pulse types with 655 S. flexneri isolates analyzed and identified 57 serotype switching events. The data suggest that S. flexneri epidemics in China have been caused by a single epidemic clone, ST91, with frequent serotype switching to evade infection-induced immunity to serotypes to which the population was exposed previously. The clone has also acquired resistance to multiple antibiotics. These findings underscore the challenges to the current vaccine development and control strategies for shigellosis.
ESTHER : Ye_2010_J.Clin.Microbiol_48_419
PubMedSearch : Ye_2010_J.Clin.Microbiol_48_419
PubMedID: 19955273
Gene_locus related to this paper: shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-S2753 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-ycfp , shifl-YFBB , shifl-YHET , shifl-YJFP , shifl-YPFH , shiss-yqia

Title : Dual response surface-optimized synthesis of L-menthyl conjugated linoleate in solvent-free system by Candida rugosa lipase - Li_2010_Bioresour.Technol_101_1305
Author(s) : Li Z , Wang Y , Li J , Wang P , Wei W , Gao Y , Fu C , Dong W
Ref : Bioresour Technol , 101 :1305 , 2010
Abstract : Lipase-catalyzed synthesis of L-menthyl conjugated linoleate in solvent-free system was studied in this paper. Duel response surface methodology was employed to explore the factors which would influence the reaction conversion by a range of independent experiments. The conditions of reaction temperature, reaction time, enzyme amount, substrate molar ratio and water content were symmetrically investigated. When the substrates were 1 mmol CLA and 1 mmol L-menthol, the maximum conversion (79.1+/-0.8%) was obtained at 30 degrees C, Candida rugosa lipase of 33.7% (w/w by weight of L-menthol), water content of 32% (w/w by weight of L-menthol), reaction time of 43 h. The product isomers (9Z,11E-/10E,12Z-=63/37) were analyzed by GC/MS. The similarity between the oleic acid and 9Z,11E-CLA conformations which were obtained by molecular modeling could account for the specific catalyzed by C. rugosa lipase.
ESTHER : Li_2010_Bioresour.Technol_101_1305
PubMedSearch : Li_2010_Bioresour.Technol_101_1305
PubMedID: 19833506

Title : Facile synthesis of three bidesmosidic oleanolic acid saponins with strong inhibitory activity on pancreatic lipase - Guo_2009_Carbohydr.Res_344_1167
Author(s) : Guo T , Liu Q , Wang P , Zhang L , Zhang W , Li Y
Ref : Carbohydr Res , 344 :1167 , 2009
Abstract : The first synthesis of scabiosaponins E (1), F (2), and G (3), three new oleanolic acid saponins with strong inhibitory activity on pancreatic lipase isolated from the Chinese traditional medicinal herb Scabiosa tschiliensis, was efficiently achieved in an one-pot strategy under the combined use of glycosyl trichloroacetimidates and p-toluene 1-thioglycosides (STol) as donors.
ESTHER : Guo_2009_Carbohydr.Res_344_1167
PubMedSearch : Guo_2009_Carbohydr.Res_344_1167
PubMedID: 19463989

Title : Comparing the relative toxicity of malathion and malaoxon in blue catfish Ictalurus furcatus - Aker_2008_Environ.Toxicol_23_548
Author(s) : Aker WG , Hu X , Wang P , Hwang HM
Ref : Environ Toxicol , 23 :548 , 2008
Abstract : Malathion inhibits the critical body enzyme, acetylcholinesterase (AChE). This capability requires that malathion should first be converted to malaoxon to become an active anticholinesterase agent. Conversion can be caused by oxidation in mammals, insects, plants, and in sunlight. In this study, the effects of malathion and malaoxon on catfish Ictalurus furcatus were evaluated. After 96-h exposures, the LC(50) (concentration that causes 50% mortality) and IC(50) (concentration that causes 50% enzyme inhibition) for malaoxon were lower than corresponding values for malathion. The overall mean 96-h LC(50) is 17.0 ppm for malathion and 3.1 ppm for malaoxon. IC(50) values for malathion are 8.5 ppm for brain, 10.3 ppm for liver, and 16.6 ppm for muscle. Corresponding values for malaoxon are 2.3, 3.7, and 6.8 ppm, respectively. All the AChE activities in malathion- and malaoxon-exposed catfish brain showed significant inhibition. The oxidation product malaoxon demonstrated higher inhibition on AChE activity than did malathion. Moreover, malaoxon showed significant inhibition on butyrylcholinesterase (BChE) in the liver if the concentrations were increased to more than 1 ppm. Malathion showed no difference between treatment group and control group. Compared with malathion, malaoxon showed higher inhibition on monoamine activity than that of malathion. The results indicated that the oxidative product malaoxon is more toxic than the parent compound malathion. AChE, BChE, and monoamine activities are confirmed as bioindicators of malathion exposure in blue catfish, I. furcatus.
ESTHER : Aker_2008_Environ.Toxicol_23_548
PubMedSearch : Aker_2008_Environ.Toxicol_23_548
PubMedID: 18247417

Title : Novel alkaloids from the roots of Stemona sessilifolia - Wang_2007_Chem.Biodivers_4_523
Author(s) : Wang P , Liu AL , An Z , Li ZH , Du GH , Qin HL
Ref : Chem Biodivers , 4 :523 , 2007
Abstract : Four new Stemona alkaloids, sessilistemonamines A-C (1-3, resp.) and dihydrostemoninine (4), were isolated from the roots of Stemona sessilifolia. Their structures and relative configurations were elucidated by means of in-depth 1D- and 2D-NMR-spectroscopic as well as mass-spectrometric experiments; and the structure of 4 was solved by X-ray single-crystal diffraction. The stereoisomeric compounds 1-3 share an unprecedented tetracyclic decahydro-1H-furo[2',3':4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus. Compounds 1 and 2 were found to be moderately active in terms of acetylcholinesterase (AchE) inhibition, with IC50 values of 68.8+/-9.5 and 17.1+/-2.5 microM, resp.
ESTHER : Wang_2007_Chem.Biodivers_4_523
PubMedSearch : Wang_2007_Chem.Biodivers_4_523
PubMedID: 17372955

Title : An organic soluble lipase for water-free synthesis of biodiesel - Zhao_2007_Appl.Biochem.Biotechnol_143_236
Author(s) : Zhao X , El-Zahab B , Brosnahan R , Perry J , Wang P
Ref : Appl Biochem Biotechnol , 143 :236 , 2007
Abstract : Lipase AK was modified with short alkyl chains to form a highly organic soluble enzyme and was used to catalyze the synthesis of biodiesel from soybean oil in organic media. The effects of several key factors including water content, temperature, and solvent were examined for the solubilized enzyme in comparison with several other commercially available lipases. Whereas native lipases showed no activity in the absence of water, the organic soluble lipase demonstrated reaction rates of up to 33 g-product/g-enzyme h. The biocatalyst remains soluble in the biodiesel product, and therefore, there is no need to be removed because it is expected to be burned along with the diesel in combustion engines. This provides a promising one-pot mix-and-use strategy for biodiesel production.
ESTHER : Zhao_2007_Appl.Biochem.Biotechnol_143_236
PubMedSearch : Zhao_2007_Appl.Biochem.Biotechnol_143_236
PubMedID: 18057451

Title : Enzymatic synthesis of galactosyl lactic ethyl ester and its polymer for use as biomaterials - Jia_2007_J.Biotechnol_132_314
Author(s) : Jia H , Wang P
Ref : J Biotechnol , 132 :314 , 2007
Abstract : Lactate-based chemicals and polymers including poly(lactic acid) (PLA) are highly valuable materials for biomedical, food and general-purpose applications. Chemical synthesis, albeit the high reaction velocities achieved with it, often leaves chemical residues that are subject to health and safety concerns. Alternative biosynthesis is preferred in order to overcome these problems. Herein we report a novel enzymatic synthesis for the preparation of beta-d-galactosyl-l-lactic acid ethyl ester (GLAEE). Such a product, which may find applications in food and personal care products, is generally difficult to synthesize via traditional chemical routes because the reactions have to be highly selective due to the multiple hydroxyl groups of sugars. We further explore the enzymatic polymerization of GLAEE to form a unique biopolymer, poly(beta-d-galactoside-co-l-lactic acid) (PGLA). Novozyme 435 was found efficient in catalyzing the polymerization reaction in acetone with a conversion yield of 60% within 100 h. The molecular weight of the polymer product ranged from about 800-2000 as analyzed by using ESI-MS. It is expected that a variety of sugar-hydroxyl acids copolymers can be prepared through the same approach and a new class of biomaterials can thus be developed.
ESTHER : Jia_2007_J.Biotechnol_132_314
PubMedSearch : Jia_2007_J.Biotechnol_132_314
PubMedID: 17689799

Title : Evolutionary and biomedical insights from the rhesus macaque genome - Gibbs_2007_Science_316_222
Author(s) : Gibbs RA , Rogers J , Katze MG , Bumgarner R , Weinstock GM , Mardis ER , Remington KA , Strausberg RL , Venter JC , Wilson RK , Batzer MA , Bustamante CD , Eichler EE , Hahn MW , Hardison RC , Makova KD , Miller W , Milosavljevic A , Palermo RE , Siepel A , Sikela JM , Attaway T , Bell S , Bernard KE , Buhay CJ , Chandrabose MN , Dao M , Davis C , Delehaunty KD , Ding Y , Dinh HH , Dugan-Rocha S , Fulton LA , Gabisi RA , Garner TT , Godfrey J , Hawes AC , Hernandez J , Hines S , Holder M , Hume J , Jhangiani SN , Joshi V , Khan ZM , Kirkness EF , Cree A , Fowler RG , Lee S , Lewis LR , Li Z , Liu YS , Moore SM , Muzny D , Nazareth LV , Ngo DN , Okwuonu GO , Pai G , Parker D , Paul HA , Pfannkoch C , Pohl CS , Rogers YH , Ruiz SJ , Sabo A , Santibanez J , Schneider BW , Smith SM , Sodergren E , Svatek AF , Utterback TR , Vattathil S , Warren W , White CS , Chinwalla AT , Feng Y , Halpern AL , Hillier LW , Huang X , Minx P , Nelson JO , Pepin KH , Qin X , Sutton GG , Venter E , Walenz BP , Wallis JW , Worley KC , Yang SP , Jones SM , Marra MA , Rocchi M , Schein JE , Baertsch R , Clarke L , Csuros M , Glasscock J , Harris RA , Havlak P , Jackson AR , Jiang H , Liu Y , Messina DN , Shen Y , Song HX , Wylie T , Zhang L , Birney E , Han K , Konkel MK , Lee J , Smit AF , Ullmer B , Wang H , Xing J , Burhans R , Cheng Z , Karro JE , Ma J , Raney B , She X , Cox MJ , Demuth JP , Dumas LJ , Han SG , Hopkins J , Karimpour-Fard A , Kim YH , Pollack JR , Vinar T , Addo-Quaye C , Degenhardt J , Denby A , Hubisz MJ , Indap A , Kosiol C , Lahn BT , Lawson HA , Marklein A , Nielsen R , Vallender EJ , Clark AG , Ferguson B , Hernandez RD , Hirani K , Kehrer-Sawatzki H , Kolb J , Patil S , Pu LL , Ren Y , Smith DG , Wheeler DA , Schenck I , Ball EV , Chen R , Cooper DN , Giardine B , Hsu F , Kent WJ , Lesk A , Nelson DL , O'Brien W E , Prufer K , Stenson PD , Wallace JC , Ke H , Liu XM , Wang P , Xiang AP , Yang F , Barber GP , Haussler D , Karolchik D , Kern AD , Kuhn RM , Smith KE , Zwieg AS
Ref : Science , 316 :222 , 2007
Abstract : The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.
ESTHER : Gibbs_2007_Science_316_222
PubMedSearch : Gibbs_2007_Science_316_222
PubMedID: 17431167
Gene_locus related to this paper: macmu-3neur , macmu-ACHE , macmu-BCHE , macmu-f6rul6 , macmu-f6sz31 , macmu-f6the6 , macmu-f6unj2 , macmu-f6wtx1 , macmu-f6zkq5 , macmu-f7aa58 , macmu-f7ai42 , macmu-f7aim4 , macmu-f7buk8 , macmu-f7cfi8 , macmu-f7cnr2 , macmu-f7cu68 , macmu-f7flv1 , macmu-f7ggk1 , macmu-f7hir7 , macmu-g7n054 , macmu-KANSL3 , macmu-TEX30 , macmu-Y4neur , macmu-g7n4x3 , macmu-i2cy02 , macmu-f7ba84 , macmu-CES2 , macmu-h9er02 , macmu-a0a1d5rbr3 , macmu-a0a1d5q4k5 , macmu-g7mxj6 , macmu-f7dn71 , macmu-f7hkw9 , macmu-f7hm08 , macmu-g7mke4 , macmu-a0a1d5rh04 , macmu-h9fud6 , macmu-f6qwx1 , macmu-f7h4t2 , macmu-h9zaw9 , macmu-f7h550 , macmu-a0a1d5q9w1 , macmu-f7gkb9 , macmu-f7hp78 , macmu-a0a1d5qvu5

Title : Effect of alcohols and temperature on the direct chiral resolutions of fipronil, isocarbophos and carfentrazone-ethyl - Wang_2005_Biomed.Chromatogr_19_454
Author(s) : Wang P , Jiang S , Liu D , Jia G , Wang Q , Zhou Z
Ref : Biomedical Chromatography , 19 :454 , 2005
Abstract : The enantiomeric separations of three pesticides fipronil (asymmetric nitrogen), isocarbophos (asymmetric phosphorus) and carfentrazone-ethyl (asymmetric carbon) were studied on cellulose-tri(3,5-dimethylphenylcarbamate) chiral stationary phase using high-performance liquid chromatography under normal phase. The mobile phase was n-hexane with alcohols including ethanol, n-propanol, iso-propanol, n-butanol and iso-butanol as polar modifiers. The flow rate was 1.0 mL/min with UV detection at 280, 225 and 230 nm for fipronil, isocarbophos and carfentrazone-ethyl respectively. The influence of the modifiers and their volume content and temperature from 0 to 50 degrees C on the separations was investigated. The chiral stationary phase showed excellent stereoselectivity for the two enantiomers of fipronil and isocarbophos and certain chiral recognition for carfentrazone-ethyl. Iso-propanol was more suitable for the chiral separation of isocarbophos and carfentrazone-ethyl, and iso-butanol was better for fipronil. The resolutions increased with the decreasing modifier content and temperature for all the three chiral pesticides.
ESTHER : Wang_2005_Biomed.Chromatogr_19_454
PubMedSearch : Wang_2005_Biomed.Chromatogr_19_454
PubMedID: 16037928

Title : Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis - Hui_2005_Proc.Natl.Acad.Sci.U.S.A_102_5210
Author(s) : Hui E , Bai J , Wang P , Sugimori M , Llinas RR , Chapman ER
Ref : Proc Natl Acad Sci U S A , 102 :5210 , 2005
Abstract : Synaptotagmins (syts) are a family of membrane proteins present on a variety of intracellular organelles. In vertebrates, 16 isoforms of syt have been identified. The most abundant isoform, syt I, appears to function as a Ca2+ sensor that triggers the rapid exocytosis of synaptic vesicles from neurons. The functions of the remaining syt isoforms are less well understood. The cytoplasmic domain of syt I binds membranes in response to Ca2+, and this interaction has been proposed to play a key role in secretion. Here, we tested the Ca(2+)-triggered membrane-binding activity of the cytoplasmic domains of syts I-XII; eight isoforms tightly bound to liposomes that contained phosphatidylserine as a function of the concentration of Ca2+. We then compared the disassembly kinetics of Ca2+.syt.membrane complexes upon rapid mixing with excess Ca2+ chelator and found that syts can be classified into three distinct kinetic groups. syts I, II, and III constitute the fast group; syts V, VI, IX, and X make up the medium group; and syt VII exhibits the slowest kinetics of disassembly. Thus, isoforms of syt, which have much slower disassembly kinetics than does syt I, might function as Ca2+ sensors for asynchronous release, which occurs after Ca2+ domains have collapsed. We also compared the temperature dependence of Ca2+.syt.membrane assembly and disassembly reactions by using squid and rat syt I. These results indicate that syts have diverged to release Ca2+ and membranes with distinct kinetics.
ESTHER : Hui_2005_Proc.Natl.Acad.Sci.U.S.A_102_5210
PubMedSearch : Hui_2005_Proc.Natl.Acad.Sci.U.S.A_102_5210
PubMedID: 15793006

Title : [Expression and characterization of carboxylesterase A2 in E. coli] - Huang_2002_Shi.Yan.Sheng.Wu.Xue.Bao_35_77
Author(s) : Huang J , Qiao CL , Zhao Q , Wang P
Ref : Shi Yan Sheng Wu Xue Bao , 35 :77 , 2002
Abstract : The most commonly observed change that has been linked to resistance development is the increase in activity of carboxylesterases. The putative mechanism involves an overproduction of this enzyme for the sequestration and the hydroxylation of various organophosphate and carbamate insecticides. Carboxylesterases A2 cDNA was amplified from Culex quinquefasciatus by RT-PCR and sequenced consequently. Target gene was inserted into pET-28a to create prokaryotic expression plasmid pET-EstA2. When pET-EstA2 was transformed into E. coli BL21, the recombinant was induced by IPTG. A pure recombinant protein was obtained by affinity purification. Compared with carboxylesterase A2 purified from Culex quinquefasciatus, carboxylesterase A2, purified from the product of the transgenic of E. coli, has the same Km, but the Vm was higher than that of it, which shows that carboxylesterase A2, purified from the product of E. coli by affinity, is purer than that from Culex quinquefasciatus. The study on the expression and characterization of carboxylesterase A2 in E. coli is more useful for its future application.
ESTHER : Huang_2002_Shi.Yan.Sheng.Wu.Xue.Bao_35_77
PubMedSearch : Huang_2002_Shi.Yan.Sheng.Wu.Xue.Bao_35_77
PubMedID: 15344323

Title : ERK activation and cellular proliferation in response to muscarinic acetylcholine receptor agonists -
Author(s) : Wang P , Dhanasekaran N , Luthin GR
Ref : Annals of the New York Academy of Sciences , 812 :182 , 1997
PubMedID: 9186737

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

Title : Human prostate muscarinic receptor subtypes - Ruggieri_1995_J.Pharmacol.Exp.Ther_274_976
Author(s) : Ruggieri MR , Colton MD , Wang P , Wang J , Smyth RJ , Pontari MA , Luthin GR
Ref : Journal of Pharmacology & Experimental Therapeutics , 274 :976 , 1995
Abstract : The alpha adrenergic receptor subtypes of the human prostate have been intensively investigated, while the muscarinic receptor subtypes and their function have yet to be determined in this tissue. [3H]-QNB binding to muscarinic receptors was performed on membrane homogenates of adenoma from six prostatectomy specimens resulting in an average total receptor density of 46 fMol/mg protein. Pirenzepine, hexahydrosiladifenidol, and para-fluoro-hexahydrosiladifenidol, drugs with high affinity for the M1 subtype, were significantly more potent inhibitors of [3H]-QNB binding than the M2 selective drug methoctramine. Immunoprecipitation studies were done using antisera raised to individual M1-M5 receptor subtypes. Approximately 75% of the solubilized receptors in the adenoma specimens were immunoprecipitated with the anti-M1 antibody, in contrast to 5% or less with antibodies against M2, M3 or M4 subtypes. These immunoprecipitation studies confirm the preponderance of the M1 subtype in prostate adenoma suggested by the high affinity pirenzepine binding. M1 receptors, when incubated with agonist, coimmunoprecipitated with the alpha subunits of the guanine nucleotide binding regulatory proteins Gi alpha, Gq/11 alpha and G16 alpha. Immunohistochemical staining with the anti-M1 antibody demonstrates the M1 receptor to be localized to the glandular epithelium. The human prostate is the first peripheral tissue in which a preponderance of the M1 subtype of muscarinic receptors has been demonstrated.
ESTHER : Ruggieri_1995_J.Pharmacol.Exp.Ther_274_976
PubMedSearch : Ruggieri_1995_J.Pharmacol.Exp.Ther_274_976
PubMedID: 7636762

Title : Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins - Wang_1995_J.Pharmacol.Exp.Ther_273_959
Author(s) : Wang P , Luthin GR , Ruggieri MR
Ref : Journal of Pharmacology & Experimental Therapeutics , 273 :959 , 1995
Abstract : Activation of muscarinic acetylcholine receptors is primarily responsible for urinary bladder emptying. Because multiple subtypes of muscarinic receptors exist, we wished to characterize those present in bladder and ultimately to attribute function to those that regulate bladder contractility, neurotransmitter release and perhaps other cholinergic functions in this tissue. Although the m2 and m3 subtypes could be immunoprecipitated after solubilization from human, rat, rabbit and guinea pig bladder membranes, the m1, m4 and m5 subtypes could not. The m2:m3 ratio was 9:1 in rat bladder but was only 3:1 in the other species examined. Immunoprecipitation of the m2 subtype correlated with the relative levels of high-affinity agonist binding sites measured by competition of carbachol for [3H]N-methylscopolamine binding or measured directly using [3H]oxotremorine-M. In the presence of agonist, but not antagonist, GTP binding proteins could be immunoprecipitated in concert with the m2 or m3 receptors using anti-receptor antibodies. These proteins were members of the Gi and Gq/11 subfamilies for both the m2 and the m3 receptor subtypes. In spite of the preponderance of the m2 receptor in all species studied, Schild analysis using somewhat selective antagonists showed that the pharmacologically defined m3 receptor mediated contractility in strips of rat and rabbit bladder. Thus acetylcholine activates bladder smooth muscle via the m3 receptor subtype, and subsequent contractility may be transduced by guanine nucleotide binding proteins such as the Gi and Gq/11 subfamilies.
ESTHER : Wang_1995_J.Pharmacol.Exp.Ther_273_959
PubMedSearch : Wang_1995_J.Pharmacol.Exp.Ther_273_959
PubMedID: 7752101

Title : Purification of human liver cytosolic epoxide hydrolase and comparison to the microsomal enzyme - Wang_1982_Biochemistry_21_5769
Author(s) : Wang P , Meijer J , Guengerich FP
Ref : Biochemistry , 21 :5769 , 1982
Abstract : Epoxide hydrolase (EC was purified to electrophoretic homogeneity from human liver cytosol by using hydrolytic activity toward trans-8-ethylstyrene 7,8-oxide (TESO) as an assay. The overall purification was 400-fold. The purified enzyme has an apparent monomeric molecular weight of 58 000, significantly greater than the 50 000 found for human (or rat) liver microsomal epoxide hydrolase or for another TESO-hydrolyzing enzyme also isolated from human liver cytosol. Purified cytosolic TESO hydrolase catalyzes the hydrolysis of cis-8-ethylstyrene 7,8-oxide 10 times more rapidly than does the microsomal enzyme, catalyzes the hydrolysis of TESO and trans-stilbene oxide as rapidly as the microsomal enzyme, but catalyzes the hydrolysis of styrene 7,8-oxide, p-nitrostyrene 7,8-oxide, and naphthalene 1,2-oxide much less effectively than does the microsomal enzyme. Purified cytosolic TESO hydrolase does not hydrolyze benzo[a]pyrene 4,5-oxide, a substrate for the microsomal enzyme. The activities of the purified enzymes can explain the specific activities observed with subcellular fractions. Anti-human liver microsomal epoxide hydrolase did not recognize cytosolic TESO hydrolase in purified form or in cytosol, as judged by double-diffusion immunoprecipitin analysis, precipitation of enzymatic activity, and immunoelectrophoretic techniques. Cytosolic TESO hydrolase and microsomal epoxide hydrolase were also distinguished by peptide mapping. The results provide evidence that physically different forms of epoxide hydrolase exist in different subcellular fractions and can have markedly different substrate specificities.
ESTHER : Wang_1982_Biochemistry_21_5769
PubMedSearch : Wang_1982_Biochemistry_21_5769
PubMedID: 6185139
Gene_locus related to this paper: human-EPHX1 , human-EPHX2