Chen S

General

Full name : Chen Sibao

First name : Sibao

Mail : State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen 518057\; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences Beijing

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Country : China

Email : sibao.chen@polyu.edu.hk

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References (137)

Title : A rare case of anti-DPPX encephalitis combined with neuroleptospirosis - Jin_2024_BMC.Neurol_24_34
Author(s) : Jin Y , Lan W , Chen X , Liu W , Luo W , Chen S
Ref : BMC Neurol , 24 :34 , 2024
Abstract : BACKGROUND: Neuroleptospirosis and anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis are both very rare and have only been reported in the form of respective case reports. There are no reports of anti-DPPX encephalitis combined with neuroleptospirosis in the literature. We reported the first case of neuroleptospirosis combined with elevated DPPX antibodies in serum and cerebrospinal fluid (CSF). CASE PRESENTATION: A previously healthy 53-year-old Chinese male farmer with a history of drinking raw stream water and flood sewage exposure was brought to the hospital due to an acute onset of neuropsychiatric symptoms. No fever or meningeal irritation signs were detected on physical examination. Routine laboratory investigations, including infection indicators, leukocyte and protein in CSF, electroencephalogram and gadolinium-enhanced magnetic resonance imaging of the brain, all revealed normal. While metagenomic next-generation sequencing (mNGS) identified the DNA genome of Leptospira interrogans in the CSF. Anti-DPPX antibody was detected both in blood and in CSF. A diagnosis of neuroleptospirosis combined with autoimmune encephalitis associated with DPPX-Ab was eventually made. He resolved completely after adequate amount of penicillin combined with immunotherapy. CONCLUSION: We highlight that in patients with acute or subacute behavioral changes, even in the absence of fever, if the most recent freshwater exposure is clear, physicians should pay attention to leptospirosis. Due to the low sensitivity of routine microscopy, culture, polymerase chain reaction and antibody testing, mNGS may have more advantages in diagnosing neuroleptospirosis. As autoimmune encephalitis can be triggered by various infections, neuroleptospirosis may be one of the causes of autoimmune encephalitis. Since neuronal antibody measurements themselves are not that common in neuroleptospirosis, future studies are needed to determine whether the detection of anti-DPPX antibodies is a rare event in leptospirosis. Early identification of autoimmune encephalitis and timely administration of immunotherapy may lead to a better outcome.
ESTHER : Jin_2024_BMC.Neurol_24_34
PubMedSearch : Jin_2024_BMC.Neurol_24_34
PubMedID: 38243162
Gene_locus related to this paper: human-DPP6

Title : Biodegradation of phthalic acid esters (PAEs) by Janthinobacterium sp. strain E1 under stress conditions - Zhang_2024_J.Gen.Appl.Microbiol__
Author(s) : Zhang K , Zhou H , Ke J , Feng H , Lu C , Chen S , Liu A
Ref : J Gen Appl Microbiol , : , 2024
Abstract : Phthalates esters (PAEs) are a kind of polymeric material additives widely been added into plastics to improve products' flexibility. It can easily cause environmental pollution which are hazards to public health. In this study, we isolated an efficient PAEs degrading strain, Janthinobacterium sp. E1, and determined its degradation effect of di-2-ethylhexyl phthalate (DEHP) under stress conditions. Strain E1 showed an obvious advantage in pollutants degradation under various environmental stress conditions. Degradation halo clearly occurred around the colony of strain E1 on agar plate supplemented with triglyceride. Strain E1's esterase is a constitutively expressed intracellular enzyme. The esterase purified from strain E1 showed a higher catalytic effect on short-chain PAEs than long-chain PAEs. The input of DEHP, DBP (dibutyl phthalate) and DMP (dimethyl phthalate) into the tested soil did not change the species composition of soil prokaryotic community, but altered the dominant species in specific environmental conditions. And the community diversity and richness decreased to a certain extent. However, the diversity and richness of the microbial community were improved after the contaminated soil was treated with the strain E1. Our results also suggested that strain E1 exhibited a tremendous potential in environmental bioremediation in the real environment, which provides a new insight into the elimination of the pollutants contamination in the urban environment.
ESTHER : Zhang_2024_J.Gen.Appl.Microbiol__
PubMedSearch : Zhang_2024_J.Gen.Appl.Microbiol__
PubMedID: 38220211

Title : Leafhopper salivary carboxylesterase suppresses JA-Ile synthesis to facilitate initial arbovirus transmission in rice phloem - Chi_2024_Plant.Commun__100939
Author(s) : Chi Y , Zhang H , Chen S , Cheng Y , Zhang X , Jia D , Chen Q , Chen H , Wei T
Ref : Plant Commun , :100939 , 2024
Abstract : Plant jasmonoyl-L-isoleucine (JA-Ile) is a major defense signal against insect feeding, but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in plant phloem remains elusive. Insect carboxylesterases (CarEs) are the third major family of detoxification enzymes. Here, we identify a new leafhopper CarE10 that specifically expressed in salivary glands and is secreted into rice phloem as the saliva component. Leafhopper CarE10 directly binds and promotes rice Jasmonate resistant 1 (JAR1) degradation by the proteasome system. Moreover, the direct association of CarE10 with JAR1 obviously impairs JAR1 enzyme activity for JA conversion to JA-Ile in in-vitro JA-Ile synthesis system. A devastating rice reovirus activates and promotes co-secretion of virions and CarE10 by virus-induced vesicles into saliva-stored salivary cavities of leafhopper vectors and ultimately into rice phloem to establish initial infection. Furthermore, virus-mediated increase of CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes the reduced levels of JAR1 and thus suppresses JA-Ile synthesis, thereby promoting host attractiveness to insect vectors and facilitating initial viral transmission. Our findings provide insights into how insect salivary protein CarE10 suppresses host JA-Ile synthesis to benefit initial virus transmission in rice phloem.
ESTHER : Chi_2024_Plant.Commun__100939
PubMedSearch : Chi_2024_Plant.Commun__100939
PubMedID: 38725245

Title : Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024 - Chen_2024_Mar.Drugs_22_
Author(s) : Chen X , Chen S , Guo H , Lu X , Shen H , Liu L , Wang L , Chen B , Zhang Y , Liu Y
Ref : Mar Drugs , 22 : , 2024
Abstract : Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (-)-nigrosporine C (-)-3, together with eight known compounds (4-11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1-3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher's method, and X-ray single-crystal diffraction technique using Cu Kalpha radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 micromol/L and without cytotoxicity in a concentration of 100.0 micromol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC(50) values of 103.7 micromol/L. Compound 5 exhibited moderate antioxidant activity with EC(50) values of 167.0 micromol/L.
ESTHER : Chen_2024_Mar.Drugs_22_
PubMedSearch : Chen_2024_Mar.Drugs_22_
PubMedID: 38786605

Title : A Novel Bacillus Velezensis for Efficient Degradation of Zearalenone - Li_2024_Foods_13_
Author(s) : Li Y , Chen S , Yu Z , Yao J , Jia Y , Liao C , Chen J , Wei Y , Guo R , He L , Ding K
Ref : Foods , 13 : , 2024
Abstract : Zearalenone (ZEN) is considered one of the most serious mycotoxins contaminating grains and their by-products, causing significant economic losses in the feed and food industries. Biodegradation pathways are currently considered the most efficient solution to remove ZEN contamination from foods. However, low degradation rates and vulnerability to environmental impacts limit the application of biodegradation pathways. Therefore, the main research objective of this article was to screen strains that can efficiently degrade ZEN and survive under harsh conditions. This study successfully isolated a new strain L9 which can efficiently degrade ZEN from 108 food ingredients. The results of sequence alignment showed that L9 is Bacillus velezensis. Meanwhile, we found that the L9 degradation rate reached 91.14% at 24 h and confirmed that the primary degradation mechanism of this strain is biodegradation. The strain exhibits resistance to high temperature, acid, and 0.3% bile salts. The results of whole-genome sequencing analysis showed that, it is possible that the strain encodes the key enzyme, such as chitinase, carboxylesterases, and lactone hydrolase, that work together to degrade ZEN. In addition, 227 unique genes in this strain are primarily involved in its replication, recombination, repair, and protective mechanisms. In summary, we successfully excavated a ZEN-degrading, genetically distinct strain of Bacillus velezensis that provides a solid foundation for the detoxification of feed and food contamination in the natural environment.
ESTHER : Li_2024_Foods_13_
PubMedSearch : Li_2024_Foods_13_
PubMedID: 38397507

Title : Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients - Zhang_2024_BMC.Cardiovasc.Disord_24_251
Author(s) : Zhang S , Wang J , Chen S , Zhang Y , He R , Wang X , Ding F , Hu W , Dai Y , Lu L , Zhang R , Ni J , Chen Q
Ref : BMC Cardiovasc Disord , 24 :251 , 2024
Abstract : BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.
ESTHER : Zhang_2024_BMC.Cardiovasc.Disord_24_251
PubMedSearch : Zhang_2024_BMC.Cardiovasc.Disord_24_251
PubMedID: 38745157

Title : MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity - Zhou_2024_Theranostics_14_1583
Author(s) : Zhou S , Ling X , Zhu J , Liang Y , Feng Q , Xie C , Li J , Chen Q , Chen S , Miao J , Zhang M , Li Z , Shen W , Li X , Wu Q , Wang X , Liu R , Wang C , Hou FF , Kong Y , Liu Y , Zhou L
Ref : Theranostics , 14 :1583 , 2024
Abstract : Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/beta-catenin signaling. beta-catenin knockout blocked 2-AG/CB2-induced fatty acid beta-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.
ESTHER : Zhou_2024_Theranostics_14_1583
PubMedSearch : Zhou_2024_Theranostics_14_1583
PubMedID: 38389852
Gene_locus related to this paper: human-MGLL , mouse-MGLL

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

Title : Phthalate biomarkers composition in relation to fatty liver: evidence from epidemiologic and in vivo studies - Chen_2024_Sci.Total.Environ__171607
Author(s) : Chen S , Liu H , Sun Y , Li S , Shi Y , Cheng Z , Zhu H , Sun H
Ref : Sci Total Environ , :171607 , 2024
Abstract : Phthalates, classified as environmental endocrine disruptors, pose potential toxicity risks to human health. Metabolic dysfunction-associated fatty liver disease is one of the most widespread liver diseases globally. Compared to studies focusing on metabolic disorders in relation to pollutants exposure, the impact of individual factors such as fatty liver on the in vivo metabolism of pollutants is always overlooked. Therefore, this study measured concentrations and composition of phthalate monoesters (mPAEs) in human urine samples, particularly those from fatty liver patients. Furthermore, we induced fatty liver in male Wistar rats by formulating a high-fat diet for twelve weeks. After administering a single dose of DEHP at 500 mg/kg bw through gavage, we compared the levels of di-2-ethylhexyl phthalate (DEHP), its metabolites (mDEHPs) and three hepatic metabolic enzymes, namely cytochrome P450 enzymes (CYP450), UDP glucuronosyltransferase 1 (UGT1), and carboxylesterase 1 (CarE1), between the normal and fatty liver rat groups. Compared to healthy individuals (n = 75), fatty liver patients (n = 104) exhibited significantly lower urinary concentrations of mPAEs (median: 106 vs. 166 ng/mL), but with a higher proportion of mono-2-ethylhexyl phthalate in mDEHPs (25.7 % vs. 9.9 %) (p < 0.05). In the animal experiment, we found that fatty liver in rats prolonged the elimination half-life of DEHP (24.61 h vs. 18.89 h) and increased the contents of CYP450, CarE1, and UGT1, implying the common but differentiated metabolism of DEHP as excess lipid accumulation in liver cells. This study provides valuable information on how to distinguish populations in biomonitoring studies across a diverse population and in assigning exposure classifications of phthalates or similar chemicals in epidemiologic studies.
ESTHER : Chen_2024_Sci.Total.Environ__171607
PubMedSearch : Chen_2024_Sci.Total.Environ__171607
PubMedID: 38461993

Title : Rapid prediction method of ZIF-8 immobilized Candida rugosa lipase activity by near-infrared spectroscopy - Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123072
Author(s) : Chen S , Ma M , Peng J , He X , Wang Q , Chu G
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 302 :123072 , 2023
Abstract : Candida rugosa lipase (CRL, EC3.1.1.3) is one of the main enzymes synthesizing esters, and ZIF-8 was chosen as an immobilization carrier for lipase. Enzyme activity testing often requires expensive reagents as substrates, and the experiment processes are time-consuming and inconvenient. As a result, a novel approach based on near-infrared spectroscopy (NIRs) was developed for predicting CRL/ZIF-8 enzyme activity. The absorbance of the immobilized enzyme catalytic system was evaluated using UV-Vis spectroscopy to investigate the amount of CRL/ZIF-8 enzyme activity. The powdered samples' near-infrared spectra were obtained. The sample's enzyme activity data were linked with each sample's original NIR spectra to establish the NIR model. A partial least squares (PLS) model of immobilized enzyme activity was developed by coupling spectral preprocessing with a variable screening technique. The experiments were completed within 48 h to eliminate inaccuracies between the reduction in enzyme activity with increasing laying-aside time throughout the test and the NIRs modeling. The root-mean-square error of cross-validation (RMSECV), the correlation coefficient of validation set (R) value, and the ratio of prediction to deviation (RPD) value were employed as assessment model indicators. The near-infrared spectrum model was developed by merging the best 2nd derivative spectral preprocessing with the Competitive Adaptive Reweighted Sampling (CARS) variable screening method. This model's root-mean-square error of cross-validation (RMSECV) was 0.368 U/g, the correlation coefficient of calibration set (R_cv) value was 0.943, the root-mean-square error of prediction (RMSEP) set was 0.414 U/g, the correlation coefficient of validation set (R) value was 0.952, and the ratio of prediction to deviation (RPD) was 3.0. The model demonstrates that the fitting relationship between the predicted and the reference enzyme activity value of the NIRs is satisfactory. The findings revealed a strong relationship between NIRs and CRL/ZIF-8 enzyme activity. As a result, the established model could be implemented to quantify the enzyme activity of CRL/ZIF-8 quickly by including more variations of natural samples. The prediction method is simple, rapid, and adaptable to be the theoretical and practical basis for further studying other interdisciplinary research work in enzymology and spectroscopy.
ESTHER : Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123072
PubMedSearch : Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123072
PubMedID: 37390722

Title : Discovery of novel carboxylesterase 2 inhibitors for the treatment of delayed diarrhea and ulcerative colitis - Cao_2023_Biochem.Pharmacol__115742
Author(s) : Cao Z , Liu Y , Chen S , Wang W , Yang Z , Chen Y , Jiao S , Huang W , Chen L , Sun L , Li Z , Zhang L
Ref : Biochemical Pharmacology , :115742 , 2023
Abstract : Human carboxylesterase 2 (hCES2) is an enzyme that metabolizes irinotecan to SN-38, a toxic metabolite considered a significant source of side effects (lethal delayed diarrhea). The hCES2 inhibitors could block the hydrolysis of irinotecan in the intestine and thus reduce the exposure of intestinal SN-38, which may alleviate irinotecan-associated diarrhea. However, existing hCES2 inhibitors (except loperamide) are not used in clinical applications due to lack of validity or acceptable safety. Therefore, developing more effective and safer drugs for treating delayed diarrhea is urgently needed. This study identified a lead compound 1 with a novel scaffold by high-throughput screening in our in-house library. After a comprehensive structure-activity relationship study, the optimal compound 24 was discovered as an efficient and highly selective hCES2 inhibitor (hCES2: IC(50) = 6.72 microM; hCES1: IC(50) > 100 microM). Further enzyme kinetics study indicated that compound 24 is a reversible inhibitor of hCES2 with competitive inhibition mode (Ki = 6.28 microM). The cell experiments showed that compound 24 could reduce the level of hCES2 in living cells (IC(50) = 6.54 microM). The modeling study suggested that compound 24 fitted very well with the binding pocket of hCES2 by forming multiple interactions. Notably, compound 24 can effectively treat irinotecan-induced delayed diarrhea and DSS-induced ulcerative colitis, and its safety has also been verified in subtoxic studies. Based on the overall pharmacological and preliminary safety profiles, compound 24 is worthy of further evaluation as a novel agent for irinotecan-induced delayed diarrhea.
ESTHER : Cao_2023_Biochem.Pharmacol__115742
PubMedSearch : Cao_2023_Biochem.Pharmacol__115742
PubMedID: 37567318

Title : The MAX2-KAI2 module promotes salicylic acid-mediated immune responses in Arabidopsis - Zheng_2023_J.Integr.Plant.Biol__
Author(s) : Zheng X , Liu F , Yang X , Li W , Chen S , Yue X , Jia Q , Sun X
Ref : J Integr Plant Biol , : , 2023
Abstract : Arabidopsis MORE AXILLARY GROWTH2 (MAX2) is a key component in the strigolactone (SL) and karrikin (KAR) signaling pathways and regulates the degradation of SUPPRESSOR OF MAX2 1/SMAX1-like (SMAX1/SMXL) proteins, which are transcriptional co-repressors that regulate plant architecture, as well as abiotic and biotic stress responses. The max2 mutation reduces resistance against Pseudomonas syringae pv. tomato (Pst). To uncover the mechanism of MAX2-mediated resistance, we evaluated the resistance of various SL and KAR signaling pathway mutants. The resistance of SL-deficient mutants and of dwarf 14 (d14) was similar to that of the wild type, whereas the resistance of the karrikin insensitive 2 (kai2) mutant was compromised, demonstrating that the KAR signaling pathway, not the SL signaling pathway, positively regulates the immune response. We measured the resistance of smax1 and smxl mutants, as well as the double, triple, and quadruple mutants with max2, which revealed that both the smax1 mutant and smxl6/7/8 triple mutant rescue the low resistance phenotype of max2 and that SMAX1 accumulation diminishes resistance. The susceptibility of smax1D, containing a degradation-insensitive form of SMAX1, further confirmed the SMAX1 function in the resistance. The relationship between the accumulation of SMAX1/SMXLs and disease resistance suggested that the inhibitory activity of SMAX1 to resistance requires SMXL6/7/8. Moreover, exogenous application of KAR2 enhanced resistance against Pst, but KAR-induced resistance depended on salicylic acid (SA) signaling. Inhibition of karrikin signaling delayed SA-mediated defense responses and inhibited pathogen-induced protein biosynthesis. Together, we propose that the MAX2-KAI2-SMAX1 complex regulates resistance with the assistance of SMXL6/7/8 and SA signaling and that SMAX1/SMXLs possibly form a multimeric complex with their target transcription factors to fine-tune immune responses. This article is protected by copyright. All rights reserved.
ESTHER : Zheng_2023_J.Integr.Plant.Biol__
PubMedSearch : Zheng_2023_J.Integr.Plant.Biol__
PubMedID: 36738234

Title : Design, synthesis, and biological evaluation studies of novel carboxylesterase 2 inhibitors for the treatment of irinotecan-induced delayed diarrhea - Yang_2023_Bioorg.Chem_138_106625
Author(s) : Yang Z , Cao Z , Wang W , Chen Y , Huang W , Jiao S , Chen S , Chen L , Liu Y , Mao J , Zhang L , Li Z
Ref : Bioorg Chem , 138 :106625 , 2023
Abstract : Human carboxylesterase 2 (hCES2A), one of the most important serine hydrolases distributed in the small intestine and colon, plays a crucial role in the hydrolysis of various prodrugs and esters. Accumulating evidence has demonstrated that the inhibition of hCES2A effectively alleviate the side effects induced by some hCES2A-substrate drugs, including delayed diarrhea caused by the anticancer drug irinotecan. Nonetheless, there is a scarcity of selective and effective inhibitors that are suitable for irinotecan-induced delayed diarrhea. Following screening of the in-house library, the lead compound 01 was identified with potent inhibition on hCES2A, which was further optimized to obtain LK-44 with potent inhibitory activity (IC(50) = 5.02 +/- 0.67 microM) and high selectivity on hCES2A. Molecular docking and molecular dynamics simulations indicated that LK-44 can formed stable hydrogen bonds with amino acids surrounding the active cavity of hCES2A. The results of inhibition kinetics studies unveiled that LK-44 inhibited hCES2A-mediated FD hydrolysis in a mixed inhibition manner, with a K(i) value of 5.28 microM. Notably, LK-44 exhibited low toxicity towards HepG2 cells according to the MTT assay. Importantly, in vivo studies showed that LK-44 significantly reduced the side effects of irinotecan-induced diarrhea. These findings suggested that LK-44 is a potent inhibitor of hCES2A with high selectivity against hCES1A, which has potential as a lead compound for the development of more effective hCES2A inhibitors to mitigate irinotecan-induced delayed diarrhea.
ESTHER : Yang_2023_Bioorg.Chem_138_106625
PubMedSearch : Yang_2023_Bioorg.Chem_138_106625
PubMedID: 37300962
Gene_locus related to this paper: human-CES2

Title : Genome-wide identification and expression of monoacylglycerol lipase (MAGL) gene family in peanut (Arachis hypogaea L.) and functional analysis of AhMGATs in neutral lipid metabolism - Zhan_2023_Int.J.Biol.Macromol_243_125300
Author(s) : Zhan Y , Wu T , Zhao X , Wang J , Guo S , Chen S , Qu S , Zheng Z
Ref : Int J Biol Macromol , 243 :125300 , 2023
Abstract : Monoacylglycerol lipase (MAGL) involved in regulating plant growth and development and stress responses, hydrolyzes monoacylglycerol (MAG) into free fatty acid and glycerol, which is the last step of triacylglycerol (TAG) breakdown. Here, a genome-wide characterization of MAGL gene family from cultivated peanut (Arachis hypogaea L.) was performed. In total, 24 MAGL genes were identified and unevenly distributed on 14 chromosomes, encoding 229-414 amino acids with molecular weights ranging from 25.91 to 47.01 kDa. Spatiotemporal and stress-induced expression was analyzed by qRT-PCR. Multiple sequence alignment revealed that AhMAGL1a/b and AhMAGL3a/b were the only four bifunctional enzymes with conserved regions of hydrolase and acyltransferase, which could also be named as AhMGATs. GUS histochemical assay showed that AhMAGL1a and -1b were strongly expressed in all tissues of the plants; whereas both AhMAGL3a and -3b were weakly expressed in plants. Subcellular localization analysis indicated that AhMGATs were localized in the endoplasmic reticulum and/or Golgi complex. Seed-specific overexpression of AhMGATs in Arabidopsis decreased the oil content of the seeds and altered the fatty acid compositions, indicating that AhMGATs were involved in TAG breakdown but not TAG biosynthesis in plant seeds. This study lays the foundation for better understanding AhMAGL genes biological function in planta.
ESTHER : Zhan_2023_Int.J.Biol.Macromol_243_125300
PubMedSearch : Zhan_2023_Int.J.Biol.Macromol_243_125300
PubMedID: 37315669
Gene_locus related to this paper: arahy-h9lbh7

Title : Novel miR-108 and miR-234 target juvenile hormone esterase to regulate the response of Plutella xylostella to Cry1Ac protoxin - Yang_2023_Ecotoxicol.Environ.Saf_254_114761
Author(s) : Yang J , Chen S , Xu X , Lin S , Wu J , Lin G , Bai J , Song Q , You M , Xie M
Ref : Ecotoxicology & Environmental Safety , 254 :114761 , 2023
Abstract : Insect hormones, such as juvenile hormone (JH), precisely regulate insect life-history traits. The regulation of JH is tightly associated with the tolerance or resistance to Bacillus thuringiensis (Bt). JH esterase (JHE) is a primary JH-specific metabolic enzyme which plays a key role in regulating JH titer. Here, we characterized a JHE gene from Plutella xylostella (PxJHE), and found it was differentially expressed in the Bt Cry1Ac resistant and susceptible strains. Suppression of PxJHE expression with RNAi increased the tolerance of P. xylostella to Cry1Ac protoxin. To investigate the regulatory mechanism of PxJHE, two target site prediction algorithms were applied to predict the putative miRNAs targeting PxJHE, and the resulting putative miRNAs were subsequently verified for their function targeting PxJHE using luciferase reporter assay and RNA immunoprecipitation. MiR-108 or miR-234 agomir delivery dramatically reduced PxJHE expression in vivo, whilst only miR-108 overexpression consequently increased the tolerance of P. xylostella larvae to Cry1Ac protoxin. By contrast, reduction of miR-108 or miR-234 dramatically increased PxJHE expression, accompanied by the decreased tolerance to Cry1Ac protoxin. Furthermore, injection of miR-108 or miR-234 led to developmental defects in P. xylostella, whilst injection of antagomir did not cause any obvious abnormal phenotypes. Our results indicated that miR-108 or miR-234 can be applied as potential molecular targets to combat P. xylostella and perhaps other lepidopteran pests, providing novel insights into miRNA-based integrated pest management.
ESTHER : Yang_2023_Ecotoxicol.Environ.Saf_254_114761
PubMedSearch : Yang_2023_Ecotoxicol.Environ.Saf_254_114761
PubMedID: 36907089

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 : Characterisation of AMB-FUBINACA metabolism and CB(1)-mediated activity of its acid metabolite - Webb_2023_Forensic.Toxicol_41_114
Author(s) : Webb HDJ , Finlay DB , Chen S , Vernall AJ , Sparkes E , Banister SD , Rosengren RJ , Glass M
Ref : Forensic Toxicol , 41 :114 , 2023
Abstract : PURPOSE: AMB-FUBINACA is a synthetic cannabinoid receptor agonist (SCRA) which is primarily metabolised by hepatic enzymes producing AMB-FUBINACA carboxylic acid. The metabolising enzymes associated with this biotransformation remain unknown. This study aimed to determine if AMB-FUBINACA metabolism could be reduced in the presence of carboxylesterase (CES) inhibitors and recreational drugs commonly consumed with it. The affinity and activity of the AMB-FUBINACA acid metabolite at the cannabinoid type-1 receptor (CB(1)) was investigated to determine the activity of the metabolite. METHODS: The effect of CES1 and CES2 inhibitors, and delta-9-tetrahydrocannabinol (delta(9)-THC) on AMB-FUBINACA metabolism were determined using both human liver microsomes (HLM) and recombinant carboxylesterases. Radioligand binding and cAMP assays comparing AMB-FUBINACA and AMB-FUBINACA acid were carried out in HEK293 cells expressing human CB(1). RESULTS: AMB-FUBINACA was rapidly metabolised by HLM in the presence and absence of NADPH. Additionally, CES1 and CES2 inhibitors both significantly reduced AMB-FUBINACA metabolism. Furthermore, digitonin (100smicroM) significantly inhibited CES1-mediated metabolism of AMB-FUBINACA by ~ 56%, while the effects elicited by delta(9)-THC were not statistically significant. AMB-FUBINACA acid produced only 26% radioligand displacement consistent with low affinity binding. In cAMP assays, the potency of AMB-FUBINACA was ~ 3000-fold greater at CB(1) as compared to the acid metabolite. CONCLUSIONS: CES1A1 was identified as the main hepatic enzyme responsible for the metabolism of AMB-FUBINACA to its less potent carboxylic acid metabolite. This biotransformation was significantly inhibited by digitonin. Since other xenobiotics may also inhibit similar SCRA metabolic pathways, understanding these interactions may elucidate why some users experience high levels of harm following SCRA use.
ESTHER : Webb_2023_Forensic.Toxicol_41_114
PubMedSearch : Webb_2023_Forensic.Toxicol_41_114
PubMedID: 36652070

Title : Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study - Chen_2022_PLoS.Med_19_e1004124
Author(s) : Chen S , Price AC , Cardinal RN , Moylett S , Kershenbaum AD , FitzGerald J , Mueller C , Stewart R , O'Brien JT
Ref : PLoS Med , 19 :e1004124 , 2022
Abstract : BACKGROUND: Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality. METHODS AND FINDINGS: We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results. CONCLUSION: In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.
ESTHER : Chen_2022_PLoS.Med_19_e1004124
PubMedSearch : Chen_2022_PLoS.Med_19_e1004124
PubMedID: 36472984

Title : Structural Basis for the Regiospecificity of a Lipase from Streptomyces sp. W007 - Zhao_2022_Int.J.Mol.Sci_23_5822
Author(s) : Zhao Z , Chen S , Xu L , Cai J , Wang J , Wang Y
Ref : Int J Mol Sci , 23 :5822 , 2022
Abstract : The efficiency and accuracy of the synthesis of structural lipids are closely related to the regiospecificity of lipases. Understanding the structural mechanism of their regiospecificity contributes to the regiospecific redesign of lipases for meeting the technological innovation needs. Here, we used a thermostable lipase from Streptomyces sp. W007 (MAS1), which has been recently reported to show great potential in industry, to gain an insight into the structural basis of its regiospecificity by molecular modelling and mutagenesis experiments. The results indicated that increasing the steric hindrance of the site for binding a non-reactive carbonyl group of TAGs could transform the non-specific MAS1 to a alpha-specific lipase, such as the mutants G40E, G40F, G40Q, G40R, G40W, G40Y, N45Y, H108W and T237Y (PSI > 80). In addition, altering the local polarity of the site as well as the conformational stability of its composing residues could also impact the regiospecificity. Our present study could not only aid the rational design of the regiospecificity of lipases, but open avenues of exploration for further industrial applications of lipases.
ESTHER : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedSearch : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedID: 35628632
Gene_locus related to this paper: 9actn-h0b8d4

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

Title : Construction of a copper nanocluster\/MnO(2) nanosheet-based fluorescent platform for butyrylcholinesterase activity detection and anti-Alzheimer's drug screening - Chen_2022_J.Mater.Chem.B__
Author(s) : Chen S , Li Z , Huang Z , Jia Q
Ref : J Mater Chem B , : , 2022
Abstract : An abnormal level of butyrylcholinesterase (BChE) activity is highly connected with hepatic damage and Alzheimer's disease. Herein, a facile and efficient method was proposed for BChE detection by incorporating polyethyleneimine-capped copper nanoclusters (PEI-CuNCs) with manganese dioxide (MnO(2)) nanosheets. The emission of PEI-CuNCs can be significantly quenched by MnO(2) nanosheets via the inner filter effect. With the addition of BChE, the hydrolysis of butyrylthiocholine iodide produces thiocholine which can reduce MnO(2) nanosheets to Mn(2+), thus resulting in the fluorescence recovery of PEI-CuNCs. Based on that, a fluorescence "turn-on" sensing platform for BChE activity determination was constructed with a detection limit of 2.26 U L(-1). This sensing method is able to detect BChE in human serum samples and identify the serums of normal persons and cirrhotic patients effectively, indicating its great potential in the clinical diagnosis of liver diseases. Furthermore, the approach can also be used to screen BChE inhibitors, which are promising medications to alleviate the symptoms of Alzheimer's disease.
ESTHER : Chen_2022_J.Mater.Chem.B__
PubMedSearch : Chen_2022_J.Mater.Chem.B__
PubMedID: 35343562

Title : Predictive Value of Perioperative Cytokine Levels on the Risk for In-Stent Restenosis in Acute Myocardial Infarction Patients - Chen_2022_Contrast.Media.Mol.Imaging_2022_7832564
Author(s) : Chen D , Xie X , Lu Y , Chen S , Lin S
Ref : Contrast Media Mol Imaging , 2022 :7832564 , 2022
Abstract : To investigate the value of perioperative cytokine levels in predicting the risk for in-stent restenosis in patients with acute myocardial infarction. 452 patients with acute myocardial infarction admitted to our hospital between June 2018 and June 2020 were prospectively selected as subjects. All patients underwent percutaneous coronary intervention. The baseline data of the patients were collected. Venous blood was taken before, 24 hours, and 3 days after the operation to detect the levels of related cytokines. Follow-up was performed for 1 year. The patients were assigned to restenosis and nonrestenosis groups according to the presence and absence of restenosis. Multivariate logistic analysis was used to explore the influencing factors of the risk for in-stent restenosis in patients with acute myocardial infarction. By July 1, 2021, 449 cases had been followed up. Of them, 44 cases suffered from in-stent restenosis and 405 cases did not affect in-stent restenosis. The incidence of in-stent restenosis was 9.80%. Before, 24 hours, and 3 days after the operation, the lipoprotein-associated phospholipase A2 (Lp-PLA2) level was significantly higher in the restenosis group than that in the nonrestenosis group. At 3 days after the operation, the interleukin 6 (IL-6) level was significantly higher in the restenosis group than that in the nonrestenosis group (P < 0.05). Multivariate logistic analysis displayed that Lp-PLA2 level preoperatively (OR = 1.048, 95% CI 1.029-1.068), Lp-PLA2 level 24 hours postoperatively (OR = 1.013, 95% CI 1.007-1.019), Lp-PLA2 level 3 days postoperatively (OR = 1.032, 95% CI 1.015-1.048), and IL-6 level 3 days postoperatively (OR = 1.020, 95% CI 1.000-1.040) were risk factors for in-stent restenosis (all P < 0.05). IL-6 and Lp-PLA2 levels can predict the risk for in-stent restenosis in patients with acute myocardial infarction in the perioperative period.
ESTHER : Chen_2022_Contrast.Media.Mol.Imaging_2022_7832564
PubMedSearch : Chen_2022_Contrast.Media.Mol.Imaging_2022_7832564
PubMedID: 35542755

Title : Populus euphratica Phospholipase Ddelta Increases Salt Tolerance by Regulating K(+)\/Na(+) and ROS Homeostasis in Arabidopsis - Zhang_2022_Int.J.Mol.Sci_23_4911
Author(s) : Zhang Y , Yao J , Yin K , Liu Z , Deng C , Liu J , Hou S , Zhang H , Yu D , Zhao N , Zhao R , Chen S
Ref : Int J Mol Sci , 23 :4911 , 2022
Abstract : Phospholipase Dalpha (PLDalpha), which produces signaling molecules phosphatidic acid (PA), has been shown to play a critical role in plants adapting to salt environments. However, it is unclear whether phospholipase Ddelta (PLDdelta) can mediate the salt response in higher plants. PePLDdelta was isolated from salt-resistant Populus euphratica and transferred to Arabidopsis thaliana to testify the salt tolerance of transgenic plants. The NaCl treatment (130 mM) reduced the root growth and whole-plant fresh weight of wild-type (WT) A. thaliana, vector controls (VC) and PePLDdelta-overexpressed lines, although a less pronounced effect was observed in transgenic plants. Under salt treatment, PePLDdelta-transgenic Arabidopsis exhibited lower electrolyte leakage, malondialdehyde content and H(2)O(2) levels than WT and VC, resulting from the activated antioxidant enzymes and upregulated transcripts of genes encoding superoxide dismutase, ascorbic acid peroxidase and peroxidase. In addition, PePLDdelta-overexpressed plants increased the transcription of genes encoding the plasma membrane Na(+)/H(+) antiporter (AtSOS1) and H(+)-ATPase (AtAHA2), which enabled transgenic plants to proceed with Na(+) extrusion and reduce K(+) loss under salinity. The capacity to regulate reactive oxygen species (ROS) and K(+)/Na(+) homeostasis was associated with the abundance of specific PA species in plants overexpressing PePLDdelta. PePLDdelta-transgenic plants retained a typically higher abundance of PA species, 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2), 36:5 (18:2-18:3) and 36:6 (18:3-18:3), under control and saline conditions. It is noteworthy that PA species 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2) and 36:5 (18:2-18:3) markedly increased in response to NaCl in transgenic plants. In conclusion, we suppose that PePLDdelta-derived PA enhanced the salinity tolerance by regulating ROS and K(+)/Na(+) homeostasis in Arabidopsis.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_4911
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_4911
PubMedID: 35563299

Title : Potentially tunable ratiometric electrochemiluminescence sensing based on conjugated polymer nanoparticle for organophosphorus pesticides detection - He_2022_J.Hazard.Mater_432_128699
Author(s) : He Y , Yang G , Zhao J , Tan K , Yuan R , Chen S
Ref : J Hazard Mater , 432 :128699 , 2022
Abstract : In general, suitable double luminophores and their coreactants are necessary for constructing electrochemiluminescence (ECL) ratio strategy. However, the complexity of matching double luminophores and the stability and repeatability problem suffered by introducing exogenous coreactant would greatly limit the application of ratio detection. An original single-luminophore-based ECL ratio sensing was developed excluding any exogenous coreactants in this work. The poly [9,9-bis(3'-(N,N-dimethylamino)propyl)- 2,7-fluorene]-alt-2,7-(9,9-dioctylfluorene)] nanoparticles (PFN NPs) were explored to emit two anodic ECL signals. One centered at + 1.25 V (ECL-1) with the scanning potential of 0 ~ + 1.25 V and the other at + 1.95 V (ECL-2) with the scanning potential of 0 ~ + 1.95 V. ECL-1 showed a very strong emission without any exogenous coreactant. Importantly, hydrogen peroxide (H(2)O(2)) was able to efficiently weaken ECL-1 but strengthen ECL-2. When organophosphorus pesticides (OPs) were absent, the immobilized acetylcholinesterase-choline oxidase (AChE-ChOx) would catalyze the substrate acetylthiocholine chloride (ATCl) to produce H(2)O(2), resulting in a quenched ECL-1 and an enhanced ECL-2. With the introduction of OPs, ECL-1 increased while ECL-2 accordingly decreased as OPs prohibited production of H(2)O(2) by inhibiting activity of AChE. Highly sensitive ECL ratio detection for OPs was realized based on the change of the ratio of two signals. The dual anode emission properties of PFN NPs coupled with the opposite regulation of H(2)O(2) on the two signals paved a new avenue for potentially tunable ECL ratio sensing strategy, and showed enormous potential applications for OPs analysis.
ESTHER : He_2022_J.Hazard.Mater_432_128699
PubMedSearch : He_2022_J.Hazard.Mater_432_128699
PubMedID: 35325864

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

Title : Chemical profile, anti-hepatoma activity, anti-acetylcholinesterase and antioxidant activity of aerial part of Aconitum carmichaeli Debx - Yu_2022_Nat.Prod.Res__1
Author(s) : Yu J , Xia J , Xu J , Chen S , Zhang Y , Yin F , Fang J , Cai L , Zhang B , Zhan Y , Zhang X , Zeng Z , Liang Z
Ref : Nat Prod Res , :1 , 2022
Abstract : Five extracts of the aerial parts of Aconitum carmichaeli were obtained by different solvent extraction or macroporous adsorption resin purification: ethyl acetate layer extract (EAE), n-butanol layer extract (BuE), water layer extract (WE), extract eluted by 10% ethanol from macroporous resin (10%EE), extract eluted by 80% ethanol from macroporous resin (80%EE). Antioxidant activities of the five extracts were determined by ABTS, DPPH, FRAP assays, anti-AChE activities by modified Ellman's method, insvitro anti-hepatoma activities by CCK-8 assay, and chemical constituents of 80%EE were identified by UPLC-QE-Orbitrap-MS. The results demonstrated that the 80%EE showed the best insvitro anti-hepatoma activity on Huh-7 cell line with an IC(50) of 103.91 +/- 11.02 microg/mL. 10%EE and 80%EE gave the highest antioxidant activity. Furthermore, current findings demonstrated that the aerial part of Aconitum carmichaeli Debx. has high medicinal value and may be a good natural medicine.
ESTHER : Yu_2022_Nat.Prod.Res__1
PubMedSearch : Yu_2022_Nat.Prod.Res__1
PubMedID: 36503283

Title : The adverse effects of fluxapyroxad on the neurodevelopment of zebrafish embryos - Yu_2022_Chemosphere_307_135751
Author(s) : Yu H , Zhang J , Chen Y , Chen J , Qiu Y , Zhao Y , Li H , Xia S , Chen S , Zhu J
Ref : Chemosphere , 307 :135751 , 2022
Abstract : Fluxapyroxad (Flu), one of the succinate dehydrogenase-inhibited (SDHI) fungicides, has been extensively used in crop fungal disease control. Despite its increasing use in modern agriculture and long-term retention in the environment, the potentially toxic effects of Flu in vivo, especially on neurodevelopment, remain under-evaluated. In this study, zebrafish embryos were exposed to Flu at concentrations of 0.5, 0.75, and 1 mg/L for 96 h to evaluate the neurotoxicity of Flu. The results showed that Flu caused concentration-dependent malformations, including shorter body length, smaller head and eyes, and yolk sac edema. After exposure to Flu, larval zebrafish exhibited severe motor aberrations. Flu at a concentration of 1 mg/L significantly decreased dopamine level and notably altered acetylcholinesterase (AChE) activity and acetylcholine (ACh) content. Abnormal central nervous system (CNS) neurogenesis and disordered motor neuron development were observed in Tg (HUC-GFP) and Tg (hb9-GFP) zebrafish in Flu-treated groups. The expression of key genes involved in neurotransmission and neurodevelopment further proved that Flu impaired the zebrafish nervous system. This work contributes to our understanding of the neurotoxic effects and mechanisms induced by Flu in zebrafish and may help us take precautions against the neurotoxicity of Flu.
ESTHER : Yu_2022_Chemosphere_307_135751
PubMedSearch : Yu_2022_Chemosphere_307_135751
PubMedID: 35863420

Title : Production of Red Pigments by a Newly Isolated Talaromyces aurantiacus Strain with LED Stimulation for Screen Printing - Gong_2022_Indian.J.Microbiol_62_280
Author(s) : Gong X , Luo H , Wu X , Liu H , Sun C , Chen S
Ref : Indian J Microbiol , 62 :280 , 2022
Abstract : Microbial pigments have been widely applied to printing in food, textile, and paper industries as a sustainable alternative to synthetic dyes. Herein, we isolated a novel Talaromyces aurantiacus strain with a strong ability to produce red pigments. We further studied pigment production conditions, stability, screen printing application, and bioactivities. Our results showed that sucrose was a favourable carbon source and the addition of l-histidine significantly enhanced the production of red pigments. Pigment production was strictly photo-regulated with effective wavelengths around 450 nm (blue light). We mixed the red pigments with cellulosic materials and explored their application potentials for screen printing on paper, cotton fabrics, and polymeric carriers. The printing density was significantly improved from 0.3 to 0.7 by overlay printing. T. aurantiacus pigments could be stably stored at pH 5-11, temperature - 10 to 70 degreesC, and redox potential - 200 to 300 mV. Moreover, the stable ranges were extended to pH 1-11 and temperature over 100 degreesC after screen-printed on paper. The red pigments exhibited antioxidant activity towards 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (IC(50) 10.4 mg L(-1) in solution). Our results further indicated the red pigments by T. aurantiacus was environmentally friendly based on acetylcholinesterase activity assay. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-022-01008-x.
ESTHER : Gong_2022_Indian.J.Microbiol_62_280
PubMedSearch : Gong_2022_Indian.J.Microbiol_62_280
PubMedID: 35462713

Title : Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower of Clitoria ternatea L - Li_2022_Molecules_27_6336
Author(s) : Li C , Tang W , Chen S , He J , Li X , Zhu X , Li H , Peng Y
Ref : Molecules , 27 :6336 , 2022
Abstract : Phenolic compounds from the flower of Clitoria ternatea L. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower of Clitoria ternatea L. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS(+), and superoxide anion radical scavenging activities. They can also significantly inhibit lipase, alpha-amylase, and alpha-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods.
ESTHER : Li_2022_Molecules_27_6336
PubMedSearch : Li_2022_Molecules_27_6336
PubMedID: 36234873

Title : Unexpected Findings During Double-blind Discontinuation of Acetylcholinesterase Inhibitor Medications - Moo_2021_Clin.Ther__
Author(s) : Moo LR , Martinez E , Padala K , Dunay MA , Scali RR , Chen S , Thielke SM
Ref : Clin Ther , : , 2021
Abstract : PURPOSE: The long-term effects of acetylcholinesterase inhibitors (AChEIs) used in the treatment of patients with various types of dementia remain unclear, largely due to challenges in the study of their discontinuation. We present several unexpected results from a discontinuation trial that might merit further investigation. METHODS: This double-blind, placebo-controlled study of the discontinuation of AChEI medications was conducted in 62 US veterans. Participants were randomized to receive continued treatment with their medication (sham-taper group) or to treatment discontinuation via tapering (real-taper group), over a period of 6 weeks. The primary end point was the patient's/family caregiver's decision to discontinue the study medication. FINDINGS: The study was underpowered to detect a significant between-group difference in the primary end point, but examination of the discontinuation process generated several unexpected results: (1) recruitment proved extremely challenging for a variety of reasons, with <5% of potentially eligible participants enrolled; (2) all 3 patients with Parkinson disease-associated dementia showed a worsening of symptoms when they discontinued their AChEI medication, but they showed improvement after they restarted it; (3) changes in symptom-scale scores varied quite broadly across participants, regardless of treatment arm; (4) unusual effects were noted in the sham-taper arm; and (5) the only significant predictor of the decision to discontinue the study medication was a worsening in the caregiver's mood. IMPLICATIONS: These findings argue for the use of caution in discontinuing AChEIs in patients with Parkinson disease-associated dementia, although there may be potential benefits of a "drug holiday." The findings also urge the consideration of distress on the part of the caregiver while making medication treatment decisions in dementia. Future research must address challenges with recruitment and symptom fluctuations. (Clin Ther. 2021;43:XXX-XXX) 2021 Elsevier Inc.
ESTHER : Moo_2021_Clin.Ther__
PubMedSearch : Moo_2021_Clin.Ther__
PubMedID: 34127273

Title : Identification of rare, transient post-mitotic cell states that are induced by injury and required for whole-body regeneration in Schmidtea mediterranea - Benham-Pyle_2021_Nat.Cell.Biol_23_939
Author(s) : Benham-Pyle BW , Brewster CE , Kent AM , Mann FG, Jr. , Chen S , Scott AR , Box AC , Sanchez Alvarado A
Ref : Nat Cell Biol , 23 :939 , 2021
Abstract : Regeneration requires the coordination of stem cells, their progeny and distant differentiated tissues. Here, we present a comprehensive atlas of whole-body regeneration in Schmidtea mediterranea and identify wound-induced cell states. An analysis of 299,998 single-cell transcriptomes captured from regeneration-competent and regeneration-incompetent fragments identified transient regeneration-activated cell states (TRACS) in the muscle, epidermis and intestine. TRACS were independent of stem cell division with distinct spatiotemporal distributions, and RNAi depletion of TRACS-enriched genes produced regeneration defects. Muscle expression of notum, follistatin, evi/wls, glypican-1 and junctophilin-1 was required for tissue polarity. Epidermal expression of agat-1/2/3, cyp3142a1, zfhx3 and atp1a1 was important for stem cell proliferation. Finally, expression of spectrinbeta and atp12a in intestinal basal cells, and lrrk2, cathepsinB, myosin1e, polybromo-1 and talin-1 in intestinal enterocytes regulated stem cell proliferation and tissue remodelling, respectively. Our results identify cell types and molecules that are important for regeneration, indicating that regenerative ability can emerge from coordinated transcriptional plasticity across all three germ layers.
ESTHER : Benham-Pyle_2021_Nat.Cell.Biol_23_939
PubMedSearch : Benham-Pyle_2021_Nat.Cell.Biol_23_939
PubMedID: 34475533

Title : Extraction and purification of total flavonoids from Eupatorium lindleyanum DC. and evaluation of their antioxidant and enzyme inhibitory activities - Li_2021_Food.Sci.Nutr_9_2349
Author(s) : Li C , Chen S , Sha J , Cui J , He J , Fu J , Shen Y
Ref : Food Sci Nutr , 9 :2349 , 2021
Abstract : The health benefits and promising medical treatment potential of total flavonoids from Eupatorium lindleyanum DC. (TFELDC) have been recognized. The process parameters of extracting total flavonoids from Eupatorium lindleyanum DC. by ultrasonic-microwave synergistic extraction (UMSE) were optimized, and they were purified by AB-8 macroporous resin in the current study. In addition, the antioxidant and enzyme inhibitory activities of the purified TFELDC (PTFELDC) were evaluated. The results showed that the optimal parameters of UMSE were as follows: ethanol volume fraction 71.5%, L/S ratio 12.2 ml/g, microwave power 318 W, and extraction time 143 s. After TFELDC were purified by AB-8 macroporous resin, the total flavonoid contents of PTFELDC increased from 208.18 +/- 1.60 to 511.19 +/- 3.21 mg RE/g FDS. Compared with TFELDC, the content of total flavonoids in PTFELDC was increased by 2.46 times. The antioxidant activities of PTFELDC were assessed using DPPH radical, superoxide anion radical, reducing power, and ferric reducing antioxidant power assays, and the IC(50) values were found to be 37.13, 19.62, 81.22, and 24.72 microg/ml, respectively. The enzyme inhibitory activities of PTFELDC were measured using lipase, alpha-amylase, alpha-glucosidase, and acetylcholinesterase assays with the IC(50) values 1.38, 2.08, 1.63, and 0.58 mg/ml, respectively. By comparing with their positive controls, it was found that PTFELDC had good antioxidant activities, and lipase, alpha-amylase, and alpha-glucosidase inhibitory activities, However, the acetylcholinesterase inhibitory activity was relatively weaker. These results suggested that PTFELDC have a promising potential as natural antioxidant, antilipidemic, and hypoglycemic drugs used in functional foods or pharmaceuticals.
ESTHER : Li_2021_Food.Sci.Nutr_9_2349
PubMedSearch : Li_2021_Food.Sci.Nutr_9_2349
PubMedID: 34026054

Title : Accelerated biodegradation of polyethylene terephthalate by Thermobifida fusca cutinase mediated by Stenotrophomonas pavanii - Huang_2021_Sci.Total.Environ__152107
Author(s) : Huang QS , Yan ZF , Chen XQ , Du YY , Li J , Liu ZZ , Xia W , Chen S , Wu J
Ref : Sci Total Environ , :152107 , 2021
Abstract : Polyethylene terephthalate (PET) is a general plastic that produces a significant amount of waste due to its non-degradable properties. We obtained four bacteria (Stenotrophomonas pavanii JWG-G1, Comamonas thiooxydans CG-1, Comamonas koreensis CG-2 and Fulvimonas soli GM-1) that utilize PET as a sole carbon source through a novel stepwise screening and verification strategy. PET films pretreated with S. pavanii JWG-G1 exhibited weight loss of 91.4% following subsequent degradation by Thermobifida fusca cutinase (TfC). S. pavanii JWG-G1 was able to colonize the PET surface and maintain high cell viability (over 50%) in biofilm, accelerating PET degradation. Compared with PET films with no pretreatment, pretreatment with S. pavanii JWG-G1 caused the PET surface to be significantly rougher with greater hydrophilicity (contact angle of 86.3 +/- 2 degrees vs. 96.6 +/- 2 degrees), providing better opportunities for TfC to contact and act on PET. Our study indicates that S. pavanii JWG-G1 could be used as a novel pretreatment for efficiently accelerating PET biodegradation by TfC.
ESTHER : Huang_2021_Sci.Total.Environ__152107
PubMedSearch : Huang_2021_Sci.Total.Environ__152107
PubMedID: 34864034

Title : Recombinant expression and surface display of a zearalenone lactonohydrolase from Trichoderma aggressivum in Escherichia coli - Chen_2021_Protein.Expr.Purif_187_105933
Author(s) : Chen S , Pan L , Liu S , Li X , Wang B
Ref : Protein Expr Purif , 187 :105933 , 2021
Abstract : Zearalenone (ZEN), one of the most dangerous mycotoxins, causes enormous economic losses in the food and feed industries. To solve the problem of ZEN pollution, ZEN detoxifying enzymes are in emergent need. In this study, a zearalenone lactonohydrolase from Trichoderma aggressivum, denoted as ZHD-P, was heterologously expressed and characterized. The intracellular ZHD-P from E. coli BL21(DE3) exhibited high activity for ZEN degradation (191.94 U/mg), with the optimal temperature and pH of 45 degreesC and 7.5-9.0, respectively. With excellent temperature stability, the intracellular ZHD-P retained 100% activity when it was incubated at 25-40 degreesC for 1 h. Furthermore, we firstly constructed an E. coli cell surface display system for ZHD-P. The surface-displayed ZHD-P exhibited high activity against ZEN and showed optimal activity at 40 degreesC and pH 9.0. With superior pH stability, the surface-displayed ZHD-P retained 80% activity when it was incubated at pH 5.0-11.0 for 12 h. Interestingly, the metal ions tolerance of the surface-displayed ZHD-P was better than the intracellular form. Additionally, the surface-displayed ZHD-P could be reused four times with the residual enzyme activity of more than 50%. The biotoxicity assessment using P. phosphoreum T3 indicated that ZEN could be degraded into hypotoxic products by the intracellular or surface-displayed ZHD-P. ZHD-P could be feasible for ZEN detoxification.
ESTHER : Chen_2021_Protein.Expr.Purif_187_105933
PubMedSearch : Chen_2021_Protein.Expr.Purif_187_105933
PubMedID: 34273541

Title : A loss-of-function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA\/VSD) and tetralogy of Fallot (TOF) - Peng_2021_FEBS.Open.Bio_11_375
Author(s) : Peng J , Wang Q , Meng Z , Wang J , Zhou Y , Zhou S , Song W , Chen S , Chen AF , Sun K
Ref : FEBS Open Bio , 11 :375 , 2021
Abstract : Pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital heart disease (CHD) characterized by a lack of luminal continuity and blood flow from either the right ventricle or the pulmonary artery, together with VSDs. The prevalence of PA/VSD is about 0.2% of live births and approximately 2% of CHDs. PA/VSD is similar to tetralogy of Fallot (TOF) in terms of structural and pathological characteristics. The pathogenesis of these two CHDs remains incompletely understood. It was previously reported that N-myc downstream-regulated gene (NDRG)4 is required for myocyte proliferation during early cardiac development. In the present study, we enrolled 80 unrelated patients with PA/VSD or TOF and identified a probably damaging variant p.T256M of NDRG4. The p.T256M variant impaired the proliferation ability of human cardiac myocytes (hCM). Furthermore, the p.T256M variant resulted in G1 and G2 arrest of hCM, followed by an increase in p27 and caspase-9 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell-cycle arrest and likely contributes towards the pathogenesis of PA/VSD and TOF.
ESTHER : Peng_2021_FEBS.Open.Bio_11_375
PubMedSearch : Peng_2021_FEBS.Open.Bio_11_375
PubMedID: 33211401
Gene_locus related to this paper: human-NDRG4

Title : Discovery of 7-O-1, 2, 3-triazole hesperetin derivatives as multi-target-directed ligands against Alzheimer's disease - Wang_2021_Chem.Biol.Interact__109489
Author(s) : Wang M , Fang L , Liu T , Chen X , Zheng Y , Zhang Y , Chen S , Li Z
Ref : Chemico-Biological Interactions , :109489 , 2021
Abstract : The development of multi-target-directed ligands (MTDLs) may improve complex central nervous system diseases such as Alzheimer's disease (AD). Here, a series of 7-O-1, 2, 3-triazole hesperetin derivatives was evaluated for their inhibition of cholinesterase, anti-neuroinflammatory, and neuroprotective activity. Among the hesperetin derivatives, compound a8 (7-O-((1-(3-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)hesperetin) possessed excellent anti-butyrylcholinesterase activity (IC(50) = 3.08 +/- 0.29 microM) and exhibited good anti-neuroinflammatory activity (IC(50) = 2.91 +/- 0.47 microM) against NO production through remarkably blocking the NF-kappaB signaling pathway and inhibiting the phosphorylation of P65. In addition, a8 showed a remarkable neuroprotective effect and lacked neurotoxicity up to 50 microM concentration. Furthermore, possessing significant self-mediated Abeta(1-42) aggregation inhibitory activity, chelated biometals and reduced ROS production were found in compound a8. In the bi-directional transport assay, a8 exhibited a blood-brain barrier penetrating ability. In this study, the Morris water maze task showed that compound a8 significantly improved the learning and memory impairment of the scopolamine-induced AD mice model. Results highlighted the potential of compound a8 to be a potential MTDL for the development of anti-AD agents.
ESTHER : Wang_2021_Chem.Biol.Interact__109489
PubMedSearch : Wang_2021_Chem.Biol.Interact__109489
PubMedID: 33905740

Title : Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology - Li_2021_Drug.Des.Devel.Ther_15_1883
Author(s) : Li S , Wang Y , Li C , Yang N , Yu H , Zhou W , Chen S , Yang S , Li Y
Ref : Drug Des Devel Ther , 15 :1883 , 2021
Abstract : BACKGROUND: Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. METHODS: In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. RESULTS: Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10-13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5'-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. CONCLUSION: These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.
ESTHER : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedSearch : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedID: 33976539

Title : Comparative Analyses of Sperm DNA Methylomes Among Three Commercial Pig Breeds Reveal Vital Hypomethylated Regions Associated With Spermatogenesis and Embryonic Development - Chen_2021_Front.Genet_12_740036
Author(s) : Chen S , Liu S , Mi S , Li W , Zhang S , Ding X , Yu Y
Ref : Front Genet , 12 :740036 , 2021
Abstract : Identifying epigenetic changes is essential for an in-depth understanding of phenotypic diversity and pigs as the human medical model for anatomizing complex diseases. Abnormal sperm DNA methylation can lead to male infertility, fetal development failure, and affect the phenotypic traits of offspring. However, the whole genome epigenome map in pig sperm is lacking to date. In this study, we profiled methylation levels of cytosine in three commercial pig breeds, Landrace, Duroc, and Large White using whole-genome bisulfite sequencing (WGBS). The results showed that the correlation of methylation levels between Landrace and Large White pigs was higher. We found that 1,040-1,666 breed-specific hypomethylated regions (HMRs) were associated with embryonic developmental and economically complex traits for each breed. By integrating reduced representation bisulfite sequencing (RRBS) public data of pig testis, 1743 conservated HMRs between sperm and testis were defined, which may play a role in spermatogenesis. In addition, we found that the DNA methylation patterns of human and pig sperm showed high similarity by integrating public data from WGBS and chromatin immunoprecipitation sequencing (ChIP-seq) in other mammals, such as human and mouse. We identified 2,733 conserved HMRs between human and pig involved in organ development and brain-related traits, such as NLGN1 (neuroligin 1) containing a conserved-HMR between human and pig. Our results revealed the similarities and diversity of sperm methylation patterns among three commercial pig breeds and between human and pig. These findings are beneficial for elucidating the mechanism of male fertility, and the changes in commercial traits that undergo strong selection.
ESTHER : Chen_2021_Front.Genet_12_740036
PubMedSearch : Chen_2021_Front.Genet_12_740036
PubMedID: 34691153

Title : Design, synthesis, and biological evaluation of novel (4-(1,2,4-oxadiazol-5-yl)phenyl)-2-aminoacetamide derivatives as multifunctional agents for the treatment of Alzheimer's disease - Liu_2021_Eur.J.Med.Chem_227_113973
Author(s) : Liu T , Chen S , Du J , Xing S , Li R , Li Z
Ref : Eur Journal of Medicinal Chemistry , 227 :113973 , 2021
Abstract : On the basis of our previous work, a novel series of (4-(1,2,4-oxadiazol-5-yl)phenyl)-2-aminoacetamide derivatives were synthesized and evaluated as multifunctional ligands for the treatment of Alzheimer's disease (AD). Biological evaluations indicated that the derivatives can be used as anti-AD drugs that have multifunctional properties, inhibit the activity of butyrylcholinesterase (BuChE), inhibit neuroinflammation, have neuroprotective properties, and inhibit the self-aggregation of Abeta. Compound f9 showed good potency in BuChE inhibition (IC(50): 1.28 +/- 0.18 microM), anti-neuroinflammatory potency (NO, IL-1beta, TNF-alpha; IC(50): 0.67 +/- 0.14, 1.61 +/- 0.21, 4.15 +/- 0.44 microM, respectively), and inhibited of Abeta self-aggregation (51.91 +/- 3.90%). Preliminary anti-inflammatory mechanism studies indicated that the representative compound f9 blocked the activation of the NF-kappaB signaling pathway. Moreover, f9 exhibited 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect, and an inhibitory effect on the production of intracellular reactive oxygen species (ROS). In the bi-directional transport assay, f9 displayed proper blood-brain barrier (BBB) permeability. In addition, the title compound improved memory and cognitive functions in a mouse model induced by scopolamine. Hence, the compound f9 can be considered as a promising lead compound for further investigation in the treatment of AD.
ESTHER : Liu_2021_Eur.J.Med.Chem_227_113973
PubMedSearch : Liu_2021_Eur.J.Med.Chem_227_113973
PubMedID: 34752955

Title : Bifunctional Moderator-Powered Ratiometric Electrochemiluminescence Enzymatic Biosensors for Detecting Organophosphorus Pesticides Based on Dual-Signal Combined Nanoprobes - He_2021_Anal.Chem__
Author(s) : He Y , Hu F , Zhao J , Yang G , Zhang Y , Chen S , Yuan R
Ref : Analytical Chemistry , : , 2021
Abstract : The bifunctional moderator is urgently needed in the field of ratiometric electrochemiluminescence (ECL) sensing since it can mediate simultaneously two ECL signals to conveniently realize their opposite change trend. This work designed a novel dual-signal combined nanoprobe with carboxyl-functionalized poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] nanoparticles (c-PFBT NPs) as the anodic ECL probe and L-cysteine capped CdS quantum dots (L-CdS QDs) as the cathodic ECL probe, which performed a dual-signal output capability without any additional coreactants. More importantly, hydrogen peroxide (H(2)O(2)) produced in situ by enzyme-catalyzed reaction was developed as a bifunctional moderator for simultaneously regulating two signals. The dual-signal combined nanoprobe (c-PFBT NPs@CdS QDs) served as the matrix to immobilize acetylcholinesterase (AChE) and choline oxidase for organophosphorus (OPs) analysis. In the absence of OPs, H(2)O(2) was produced by catalyzing the substrate acetylthiocholine (ATCl) with enzymes and it quenched the anodic ECL signal from c-PFBT NPs and simultaneously promoted the cathodic ECL signal from L-CdS QDs. When OPs was present, the activity of AChE was inhibited, the anodic signal would increase, and the cathodic signal would accordingly decrease. The integration of the bifunctional moderator H(2)O(2) and dual-signal combined nanoprobe c-PFBT NPs@CdS QDs not only provides an attractive ECL platform for enzymatic sensing involving the generation or consumption of H(2)O(2) but also paves a new pathway for other ratiometric ECL systems involving enzyme catalytic amplification for detecting antigens, antibodies, DNA, RNA, etc.
ESTHER : He_2021_Anal.Chem__
PubMedSearch : He_2021_Anal.Chem__
PubMedID: 34133127

Title : Dammarane Sapogenins Improving Simulated Weightlessness-Induced Depressive-Like Behaviors and Cognitive Dysfunction in Rats - Wang_2021_Front.Psychiatry_12_638328
Author(s) : Wang Q , Dong L , Wang M , Chen S , Li S , Chen Y , He W , Zhang H , Zhang Y , Pires Dias AC , Yang S , Liu X
Ref : Front Psychiatry , 12 :638328 , 2021
Abstract : Background: Our studies demonstrated that the space environment has an impact on the brain function of astronauts. Numerous ground-based microgravity and social isolation showed that the space environment can induce brain function damages in humans and animals. Dammarane sapogenins (DS), an active fraction from oriental ginseng, possesses neuropsychic protective effects and has been shown to improve depression and memory. This study aimed to explore the effects and mechanisms of DS in attenuating depressive-like behaviors and cognitive deficiency induced by simulated weightlessness and isolation [hindlimb suspension and isolation (HLSI)] in rats. Methods: Male rats were orally administered with two different doses of DS (37.5, 75 mg/kg) for 14 days, and huperzine-A (1 mg/kg) served as positive control. Rats were subjected to HLSI for 14 days except the control group during drug administration. The depressive-like behaviors were then evaluated by the open-field test, the novel object recognition test, and the forced swimming test. The spatial memory and working memory were evaluated by the Morris water maze (MWM) test, and the related mechanism was further explored by analyzing the activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and superoxide dismutase (SOD) in the hippocampus of rats. Results: The results showed that DS treatment significantly reversed the HLSI-induced depressive-like behaviors in the open-field test, the novel object recognition test, and the forced swimming test and improved the HLSI-induced cognitive impairment in the MWM test. Furthermore, after DS treatment, the ChAT and SOD activities of HLSI rats were increased while AChE activity was significantly suppressed. Conclusions: These findings clearly demonstrated that DS might exert a significant neuropsychic protective effect induced by spaceflight environment, driven in part by the modulation of cholinergic system and anti-oxidation in the hippocampus.
ESTHER : Wang_2021_Front.Psychiatry_12_638328
PubMedSearch : Wang_2021_Front.Psychiatry_12_638328
PubMedID: 33841208

Title : Effects of perioperative interventions for preventing postoperative delirium: A protocol for systematic review and meta-analysis of randomized controlled trials - Li_2021_Medicine.(Baltimore)_100_e26662
Author(s) : Li X , Wang Y , Liu J , Xiong Y , Chen S , Han J , Xie W , Wu Q
Ref : Medicine (Baltimore) , 100 :e26662 , 2021
Abstract : BACKGROUND: Postoperative delirium (POD) not only increases the medical burden but also adversely affects patient prognosis. Although some cases of delirium can be avoided by early intervention, there is no clear evidence indicating whether any of these measures can effectively prevent POD in specific patient groups. OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of the existing preventive measures for managing POD. METHODS: The PubMed, OVID (Embase and MEDLINE), Web of Science, and the Cochrane Library databases were searched for articles published before January 2020. The relevant randomized controlled trials (RCTs) were selected based on the inclusion and exclusion criteria. Data extraction and methodological quality assessment were performed according to a predesigned data extraction form and scoring system, respectively. The interventions were compared on the basis of the primary outcome like incidence of POD, and secondary outcomes like duration of delirium and the length of intensive care unit and hospital stay. RESULTS: Sixty-three RCTs were included in the study, covering interventions like surgery, anesthesia, analgesics, intraoperative blood glucose control, cholinesterase inhibitors, anticonvulsant drugs, antipsychotic drugs, sleep rhythmic regulation, and multi-modal nursing. The occurrence of POD was low in 4 trials that monitored the depth of anesthesia with bispectral index during the operation (P<.0001). Two studies showed that supplementary analgesia was useful for delirium prevention (P=.002). Seventeen studies showed that perioperative sedation with alpha2-adrenergic receptor agonists prevented POD (P=.0006). Six studies showed that both typical and atypical antipsychotic drugs can reduce the incidence of POD (P=.002). Multimodal nursing during the perioperative period effectively reduced POD in 6 studies (P<.00001). Furthermore, these preventive measures can reduce the duration of delirium, as well as the total and postoperative length of hospitalized stay for non-cardiac surgery patients. For patients undergoing cardiac surgery, effective prevention can only reduce the length of intensive care unit stay. CONCLUSION: Measures including intraoperative monitoring of bispectral index, supplemental analgesia, alpha2-adrenergic receptor agonists, antipsychotic drugs, and multimodal care are helpful to prevent POD effectively. However, larger, high-quality RCTs are needed to verify these findings and develop more interventions and drugs for preventing postoperative delirium.
ESTHER : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedSearch : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedID: 34398027

Title : Insights into the microbial degradation and catalytic mechanisms of chlorpyrifos - Huang_2021_Environ.Res_194_110660
Author(s) : Huang Y , Zhang W , Pang S , Chen J , Bhatt P , Mishra S , Chen S
Ref : Environ Research , 194 :110660 , 2021
Abstract : Chlorpyrifos is extensively used worldwide as an insecticide to control various insect pests. Long-term and irregular applications of chlorpyrifos have resulted in large-scale soil, groundwater, sediment, and air pollution. Numerous studies have shown that chlorpyrifos and its major intermediate metabolite 3,5,6-trichloropyridinol (TCP) accumulate in non-target organisms through biomagnification and have a strong toxic effect on non-target organisms, including human beings. Bioremediation based on microbial metabolism is considered an eco-friendly and efficient strategy to remove chlorpyrifos residues. To date, a variety of bacterial and fungal species have been isolated and characterized for the biodegradation of chlorpyrifos and TCP. The metabolites and degradation pathways of chlorpyrifos have been investigated. In addition, the chlorpyrifos-degrading enzymes and functional genes in microbes have been reported. Hydrolases can catalyze the first step in ester-bond hydrolysis, and this initial regulatory metabolic reaction plays a key role in the degradation of chlorpyrifos. Previous studies have shown that the active site of hydrolase contains serine residues, which can initiate a catalytic reaction by nucleophilic attack on the P-atom of chlorpyrifos. However, few reviews have focused on the microbial degradation and catalytic mechanisms of chlorpyrifos. Therefore, this review discusses the deep understanding of chlorpyrifos degradation mechanisms with microbial strains, metabolic pathways, catalytic mechanisms, and their genetic basis in bioremediation.
ESTHER : Huang_2021_Environ.Res_194_110660
PubMedSearch : Huang_2021_Environ.Res_194_110660
PubMedID: 33387540

Title : Intestinal UGT1A1 and protection against Irinotecan-induced toxicity in a novel UGT1A1 tissue-specific humanized mouse model - Mennillo_2021_Drug.Metab.Dispos__
Author(s) : Mennillo E , Yang X , Weber AA , Maruo Y , Verreault M , Barbier O , Chen S , Tukey RH
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2021
Abstract : The human UDP-glucuronosyltransferases (UGTs) represent an important family of drug-metabolizing enzymes, with UGT1A1 targeting the conjugation and detoxification of many exogenous substances including pharmaceutical drugs. In this study we generated humanized UGT1A1 mice expressing the human UGT1A1 gene in either liver (hUGT1A1(HEP) ) or intestine (hUGT1A1(GI) ), enabling experiments to examine tissue-specific properties of UGT1A1 specific glucuronidation. Hepatic and intestinal tissue-specific expression and function of UGT1A1 were demonstrated. Although the liver is considered a major organ for detoxification, intestinal UGT1A1 is an important contributor for drug clearance. Mice were challenged with irinotecan (CPT-11), a prodrug hydrolyzed by carboxylesterases to form the active metabolite SN-38 and detoxified by UGT1A1. Humanized UGT1A1(HEP) mice, that have no intestinal UGT1A1, displayed a greater lethality rate when exposed to CPT-11 than hUGT1A1(GI) mice. When exposed to a low dose of CPT-11 (10 mg/kg), hUGT1A1(HEP) mice displayed greater intestinal inflammatory (IL-1beta and IL-6) insult in addition to p53-triggered apoptotic responses. In vitro studies with intestinal crypt organoids exposed to CPT-11 confirmed the results observed in vivo and indicated that CPT-11 impacts stemness, apoptosis, and ER stress in organoids deficient UGT1A1. When we examined the induction of ER stress in organoids with thapsigargin (TGN), an inhibitor of sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), apoptosis and the caspase surge that occurred in hUGT1A1(HEP) mice were blocked in hUGT1A1(GI) organoids. This study reveals the importance of intestinal UGT1A1 in preventing inflammation, apoptosis, and loss of intestinal stemness capacity upon systemic challenge with an important chemotherapeutic agent. Significance Statement Hepatic and intestinal UGT1A1 play a key role in the metabolism and detoxification of endogenous and exogenous compounds. The use of tissue-specific humanized models expressing UGT1A1 in liver or intestine has confirmed the relevance of the intestinal tract in the detoxification of irinotecan. Mechanistic studies using intestinal organoids highlighted the importance of UGT1A1 in reducing inflammation, apoptosis, and loss of stemness. These new models provide valuable tools for studying tissue-specific glucuronidation of substances that are metabolized by human UGT1A1.
ESTHER : Mennillo_2021_Drug.Metab.Dispos__
PubMedSearch : Mennillo_2021_Drug.Metab.Dispos__
PubMedID: 34697081

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

Title : Exposure of Helicoverpa armigera Larvae to Plant Volatile Organic Compounds Induces Cytochrome P450 Monooxygenases and Enhances Larval Tolerance to the Insecticide Methomyl - Wu_2021_Insects_12_
Author(s) : Wu C , Ding C , Chen S , Wu X , Zhang L , Song Y , Li W , Zeng R
Ref : Insects , 12 : , 2021
Abstract : Plants release an array of volatile chemicals into the air to communicate with other organisms in the environment. Insect attack triggers emission of herbivore-induced plant volatiles (HIPVs). How insect herbivores use these odors to plan their detoxification systems is vital for insect adaptation to environmental xenobiotics. Here we show that the larvae of Helicoverpa armigera (Hubner), a broadly polyphagous lepidopteran herbivore, have the capacity to use plant volatiles as cues to upregulate multiple detoxification systems, including cytochrome P450 monooxygenases (P450s), for detoxification of insecticides. Olfactory exposure of the fifth instars to two terpene volatiles limonene and nerolidol, and two green-leaf volatiles 2-heptanone and cis-3-hexenyl acetate significantly reduced larval susceptibility to the insecticide methomyl. However, larval pretreatment with piperonyl butoxide (PBO), a known P450 inhibitor, neutralized the effects of volatile exposure. Furthermore, larval exposure to the four plant volatiles enhanced activities of P450 enzymes in midguts and fatbodies, and upregulated expression of CYP6B2, CYP6B6 and CYP6B7, P450s involved in detoxification of the insecticide. Larval exposure to 2-heptanone and limonene volatiles also enhanced activities of glutathione-s-transferase and carboxylesterase. Our findings suggest that olfactory exposure to HIPVs enhances larval insecticide tolerance via induction of detoxification P450s.
ESTHER : Wu_2021_Insects_12_
PubMedSearch : Wu_2021_Insects_12_
PubMedID: 33808968

Title : A dual-mode nanoprobe for the determination of parathion methyl based on graphene quantum dots modified silver nanoparticles - Li_2020_Anal.Bioanal.Chem_412_5583
Author(s) : Li Y , Chen S , Lin D , Chen Z , Qiu P
Ref : Anal Bioanal Chem , 412 :5583 , 2020
Abstract : We developed a highly sensitive and selective method for double-signal analysis (fluorescence and ultraviolet-visible spectrophotometry) of organophosphorus pesticides (OPs), based on reversible quenching of graphene quantum dots (GQDs; fluorophores) with silver nanoparticles (AgNPs; absorbers). We used acetylcholinesterase to catalytically convert acetylthiocholine into thiocholine. In turn, by competitive binding to the AgNPs, the produced thiocholine displaces AgNPs from the GQDs and thus induces fluorescence recovery. However, OP analytes inhibit the activity of acetylcholinesterase and, in so doing, retain the silver-graphene nanoparticle complex and fluorescence quenching. The degree of quenching is proportional to the concentration of OPs; the detection limit is as low as 0.017 microg/L. The ultraviolet-visible absorption of GQDs/AgNPs at 390 nm decreases-because of AgNP aggregation that occurs after desorption from the GQDs-and the absorbance is linearly proportional to the OP concentration. Our system has good selectivity to substances that are commonly present in water and vegetables. We successfully applied our method to OP analysis in water, apple, and carrot samples.
ESTHER : Li_2020_Anal.Bioanal.Chem_412_5583
PubMedSearch : Li_2020_Anal.Bioanal.Chem_412_5583
PubMedID: 32572544

Title : Enzymatic Synthesis of beta-Sitosterol Laurate by Candida rugosa Lipase AY30 in the Water\/AOT\/Isooctane Reverse Micelle - Chen_2020_Appl.Biochem.Biotechnol__
Author(s) : Chen S , Li J , Fu Z , Wei G , Li H , Zhang B , Zheng L , Deng Z
Ref : Appl Biochem Biotechnol , : , 2020
Abstract : Phytosterols are regarded as compounds able to reduce total and low-density lipoprotein cholesterol in the blood, and their esterified derivatives could help to improve the effectiveness of this function. In the present study, the water/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/isooctane reverse micelle (RM) system was set up as a reaction medium for Candida rugosa lipase AY30 (CRL AY30) to synthesize beta-sitosterol laurate (beta-SLE). The product was identified by TLC, FT-IR, and HPLC-APCI-QqQ-MS/MS and quantified by HPLC. Through stepwise optimization, it was found that CRL AY30 had the highest activity in the water/AOT/isooctane RM system where 50 mM PBS with a pH of 7.5 was adopted as water core to carry CRL AY30, and the proportion of [CRL AY30] (mg/mL), [water] (mM), and [AOT] (mM) was set in 3:375:25, respectively, in isooctane. After screened with single-factor experiments, the esterification reaction conditions in the CRL AY30-water/AOT/isooctane RM system were further optimized by the response surface method as follows: the mole ratio of beta-sitosterol to lauric acid of 1:3.5 (25 mM beta-sitosterol), the enzyme load of 18% (w/w total reactants), the reaction temperature of 47 degrees C, and the reaction time of 48 h. As a result, the maximum esterification rate was up to 88.12 +/- 0.79%.
ESTHER : Chen_2020_Appl.Biochem.Biotechnol__
PubMedSearch : Chen_2020_Appl.Biochem.Biotechnol__
PubMedID: 32388606

Title : Runx2 Regulates Mouse Tooth Root Development Via Activation of WNT Inhibitor NOTUM - Wen_2020_J.Bone.Miner.Res_35_2252
Author(s) : Wen Q , Jing J , Han X , Feng J , Yuan Y , Ma Y , Chen S , Ho TV , Chai Y
Ref : J Bone Miner Res , 35 :2252 , 2020
Abstract : Progenitor cells are crucial in controlling organ morphogenesis. Tooth development is a well-established model for investigating the molecular and cellular mechanisms that regulate organogenesis. Despite advances in our understanding of how tooth crown formation is regulated, we have limited understanding of tooth root development. Runt-related transcription factor 2 (RUNX2) is a well-known transcription factor in osteogenic differentiation and early tooth development. However, the function of RUNX2 during tooth root formation remains unknown. We revealed in this study that RUNX2 is expressed in a subpopulation of GLI1+ root progenitor cells, and that loss of Runx2 in these GLI1+ progenitor cells and their progeny results in root developmental defects. Our results provide in vivo evidence that Runx2 plays a crucial role in tooth root development and in regulating the differentiation of root progenitor cells. Furthermore, we identified that Gli1, Pcp4, NOTUM, and Sfrp2 are downstream targets of Runx2 by integrating bulk and single-cell RNA sequencing analyses. Specifically, ablation of Runx2 results in downregulation of WNT inhibitor NOTUM and upregulation of canonical WNT signaling in the odontoblastic site, which disturbs normal odontoblastic differentiation. Significantly, exogenous NOTUM partially rescues the impaired root development in Runx2 mutant molars. Collectively, our studies elucidate how Runx2 achieves functional specificity in regulating the development of diverse organs and yields new insights into the network that regulates tooth root development. 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
ESTHER : Wen_2020_J.Bone.Miner.Res_35_2252
PubMedSearch : Wen_2020_J.Bone.Miner.Res_35_2252
PubMedID: 32569388

Title : New insights into the microbial degradation and catalytic mechanism of synthetic pyrethroids - Zhan_2020_Environ.Res_182_109138
Author(s) : Zhan H , Huang Y , Lin Z , Bhatt P , Chen S
Ref : Environ Research , 182 :109138 , 2020
Abstract : The significant applications of pyrethroid insecticides in agro-ecosystem and household environments have raised serious environmental concerns. Environmental bioremediation has emerged as an effective and eco-friendly approach to remove or neutralize hazardous compounds. Bioaugmentation accelerates pyrethroid degradation in liquid cultures and soil. Pyrethroid-degrading microorganisms have been extensively studied to cope with pyrethroid residues. Microorganisms primarily hydrolyze the ester bonds of pyrethroids, and their degradation pathways have been elaborated. The functional genes and enzymes involved in microbial degradation have also been screened and studied. Carboxylesterase plays a key role in pyrethroid degradation by cleaving its carboxylester linkage. The catalytic mechanism is dependent on a specific catalytic triad, consisting of three amino acid residues (glutamine, histidine, and serine) within the active site of the carboxylesterase enzyme. Pyrethroid-degrading strains and enzymes have proven to be effective for the bioremediation of pyrethroid-contaminated environments. In this review, we have summarized newly isolated pyrethroid-degrading strains and proposed the degradation pathways along with key functional genes/enzymes. To develop an efficient bioremediation strategy, pyrethroid-degrading microorganisms should be comprehensively explored.
ESTHER : Zhan_2020_Environ.Res_182_109138
PubMedSearch : Zhan_2020_Environ.Res_182_109138
PubMedID: 32069744

Title : Degradation of Acephate and Its Intermediate Methamidophos: Mechanisms and Biochemical Pathways - Lin_2020_Front.Microbiol_11_2045
Author(s) : Lin Z , Pang S , Zhang W , Mishra S , Bhatt P , Chen S
Ref : Front Microbiol , 11 :2045 , 2020
Abstract : Acephate is an organophosphate pesticide that has been widely used to control insect pests in agricultural fields for decades. However, its use has been partially restricted in many countries due to its toxic intermediate product methamidophos. Long term exposure to acephate and methamidophos in non-target organisms results in severe poisonous effects, which has raised public concern and demand for the removal of these pollutants from the environment. In this paper, the toxicological effects of acephate and/or methamidophos on aquatic and land animals, including humans are reviewed, as these effects promote the necessity of removing acephate from the environment. Physicochemical degradation mechanisms of acephate and/or methamidophos are explored and explained, such as photo-Fenton, ultraviolet/titanium dioxide (UV/TiO(2)) photocatalysis, and ultrasonic ozonation. Compared with physicochemical methods, the microbial degradation of acephate and methamidophos is emerging as an eco-friendly method that can be used for large-scale treatment. In recent years, microorganisms capable of degrading methamidophos or acephate have been isolated, including Hyphomicrobium sp., Penicillium oxalicum, Luteibacter jiangsuensis, Pseudomonas aeruginosa, and Bacillus subtilis. Enzymes related to acephate and/or methamidophos biodegradation include phosphotriesterase, paraoxonase 1, and carboxylesterase. Furthermore, several genes encoding organophosphorus degrading enzymes have been identified, such as opd, mpd, and ophc2. However, few reviews have focused on the biochemical pathways and molecular mechanisms of acephate and methamidophos. In this review, the mechanisms and degradation pathways of acephate and methamidophos are summarized in order to provide a new way of thinking for the study of the degradation of acephate and methamidophos.
ESTHER : Lin_2020_Front.Microbiol_11_2045
PubMedSearch : Lin_2020_Front.Microbiol_11_2045
PubMedID: 33013750

Title : Esterase is a powerful tool for the biodegradation of pyrethroid insecticides - Bhatt_2020_Chemosphere_244_125507
Author(s) : Bhatt P , Bhatt K , Huang Y , Lin Z , Chen S
Ref : Chemosphere , 244 :125507 , 2020
Abstract : Agricultural and household applications of pyrethroid insecticides have significantly increased residual concentrations in living cells and environments. The enhanced concentration is toxic for living beings. Pyrethroid hydrolase enzyme (pyrethroid catalyzing esterase) regulates pyrethroid degradation, and has been well reported in various organisms (bacteria, fungi, insects and animals). Hydrolysis mechanisms of these esterases are different from others and properly function at factors viz., optimum temperature, pH and physicochemical environment. Active site of the enzyme contains common amino acids that play important role in pyrethroid catalysis. Immobilization technology emphasizes the development of better reusable efficiency of pyrethroid hydrolases to carry out large-scale applications for complete degradation of pyrethroids from the environments. In this review we have attempted to provide insights of pyrethroid-degrading esterases in different living systems along with complete mechanisms.
ESTHER : Bhatt_2020_Chemosphere_244_125507
PubMedSearch : Bhatt_2020_Chemosphere_244_125507
PubMedID: 31835049

Title : Antioxidant and pancreatic lipase inhibitory effects of flavonoids from different citrus peel extracts: An in vitro study - Huang_2020_Food.Chem_326_126785
Author(s) : Huang R , Zhang Y , Shen S , Zhi Z , Cheng H , Chen S , Ye X
Ref : Food Chem , 326 :126785 , 2020
Abstract : Obesity and oxidative damage are two important risk factors associated closely with metabolic syndrome. Utilization of functional food ingredients is considered as a feasible way to tackle these challenges. In the present study, eight representative species of citrus peel extracts (CPEs) were evaluated and compared for their flavonoid profiles, antioxidant activities, and pancreatic lipase (PL) inhibitory capacities and mechanisms. Results indicated that hesperidin, naringin, neohesperidin, narirutin and eriocitrin were the five major flavonoids in CPEs, among which hesperidin was the main active PL inhibitor. Moreover, hesperidin could interact with PL by hydrogen bonds and van der Waals forces, and the interaction would not obviously change the secondary structure of PL. Overall, ponkan peel extract, having the strongest overall antioxidant activity, the highest content of hesperidin and total phenolic compounds among all tested CPEs, is a promising natural ingredient to scavenge free radicals and manage obesity.
ESTHER : Huang_2020_Food.Chem_326_126785
PubMedSearch : Huang_2020_Food.Chem_326_126785
PubMedID: 32438224

Title : Anti-dipeptidyl-peptidase-like protein 6 encephalitis, a rare cause of reversible rapid progressive dementia and insomnia - Zhou_2020_J.Neuroimmunol_339_577114
Author(s) : Zhou Q , Zhu X , Meng H , Zhang M , Chen S
Ref : Journal of Neuroimmunology , 339 :577114 , 2020
Abstract : Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare type of autoimmune encephalitis. We present a case of a 72-year-old male with anti-DPPX encephalitis who developed rapidly progressive cognitive decline, psychiatric and sleep problems, severe abdominal pain and diarrhea. Antibodies against DPPX were positive both in serum and cerebrospinal fluid. (18)F-FDG PET-MR imaging indicated hypometabolism in the bilateral temporal lobes and thalamus. No related tumors were found, and the patient responded to immunotherapy without relapse at the 3-year follow-up. The present case enriches the understanding of the clinical, imaging manifestations and prognosis of anti-DPPX encephalitis.
ESTHER : Zhou_2020_J.Neuroimmunol_339_577114
PubMedSearch : Zhou_2020_J.Neuroimmunol_339_577114
PubMedID: 31775073
Gene_locus related to this paper: human-DPP6

Title : Enhanced Contextual Fear Memory and Elevated Astroglial Glutamate Synthase Activity in Hippocampal CA1 BChE shRNA Knockdown Mice - Chen_2020_Front.Psychiatry_11_564843
Author(s) : Chen S , Lin Z , Tan KL , Chen R , Su W , Zhao H , Tan Q , Tan W
Ref : Front Psychiatry , 11 :564843 , 2020
Abstract : Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.
ESTHER : Chen_2020_Front.Psychiatry_11_564843
PubMedSearch : Chen_2020_Front.Psychiatry_11_564843
PubMedID: 33061920

Title : Carbofuran toxicity and its microbial degradation in contaminated environments - Mishra_2020_Chemosphere_259_127419
Author(s) : Mishra S , Zhang W , Lin Z , Pang S , Huang Y , Bhatt P , Chen S
Ref : Chemosphere , 259 :127419 , 2020
Abstract : Carbofuran is one of the most toxic broad-spectrum and systemic N-methyl carbamate pesticide, which is extensively applied as insecticide, nematicide and acaricide for agricultural, domestic and industrial purposes. It is extremely lethal to mammals, birds, fish and wildlife due to its anticholinesterase activity, which inhibits acetyl-cholinesterase and butyrylcholinesterse activity. In humans, carbofuran is associated with endocrine disrupting activity, reproductive disorders, cytotoxic and genotoxic abnormalities. Therefore, cleanup of carbofuran-contaminated environments is of utmost concern and urgently needs an adequate, advanced and effective remedial technology. Microbial technology (bacterial, fugal and algal species) is a very potent, pragmatic and ecofriendly approach for the removal of carbofuran. Microbial enzymes and their catabolic genes exhibit an exceptional potential for bioremediation strategies. To understand the specific mechanism of carbofuran degradation and involvement of carbofuran hydrolase enzymes and genes, highly efficient genomic approaches are required to provide reliable information and unfold metabolic pathways. This review briefly discusses the carbofuran toxicity and its toxicological impact into the environment, in-depth understanding of carbofuran degradation mechanism with microbial strains, metabolic pathways, molecular mechanisms and genetic basis involved in degradation.
ESTHER : Mishra_2020_Chemosphere_259_127419
PubMedSearch : Mishra_2020_Chemosphere_259_127419
PubMedID: 32593003

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 : Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis - Shang_2019_Cancer.Res_79_5513
Author(s) : Shang S , Ji X , Zhang L , Chen J , Li C , Shi R , Xiang W , Kang X , Zhang D , Yang F , Dai R , Chen P , Chen S , Chen Y , Li Y , Miao H
Ref : Cancer Research , 79 :5513 , 2019
Abstract : Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg.
ESTHER : Shang_2019_Cancer.Res_79_5513
PubMedSearch : Shang_2019_Cancer.Res_79_5513
PubMedID: 31439546
Gene_locus related to this paper: human-ABHD5

Title : Synthesis and biological evaluation of genistein-O-alkylamine derivatives as potential multifunctional anti-Alzheimer agents - Hong_2019_Chem.Biol.Drug.Des_93_188
Author(s) : Hong C , Guo HY , Chen S , Lv JW , Zhang X , Yang YC , Huang K , Zhang YJ , Tian ZY , Luo W , Chen YP
Ref : Chemical Biology Drug Des , 93 :188 , 2019
Abstract : A series of genistein derivatives were synthesized and evaluated as multifunctional anti-Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC50 value (0.034 muM) much lower than that of rivastigmine (6.53 muM). A Lineweaver-Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal-chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 muM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD.
ESTHER : Hong_2019_Chem.Biol.Drug.Des_93_188
PubMedSearch : Hong_2019_Chem.Biol.Drug.Des_93_188
PubMedID: 30299583

Title : Synthetic and biological approaches to map substrate specificities of proteases - Chen_2019_Biol.Chem_401_165
Author(s) : Chen S , Yim JJ , Bogyo M
Ref : Biol Chem , 401 :165 , 2019
Abstract : Proteases are regulators of diverse biological pathways including protein catabolism, antigen processing and inflammation, as well as various disease conditions, such as malignant metastasis, viral infection and parasite invasion. The identification of substrates of a given protease is essential to understand its function and this information can also aid in the design of specific inhibitors and active site probes. However, the diversity of putative protein and peptide substrates makes connecting a protease to its downstream substrates technically difficult and time-consuming. To address this challenge in protease research, a range of methods have been developed to identify natural protein substrates as well as map the overall substrate specificity patterns of proteases. In this review, we highlight recent examples of both synthetic and biological methods that are being used to define the substrate specificity of protease so that new protease-specific tools and therapeutic agents can be developed.
ESTHER : Chen_2019_Biol.Chem_401_165
PubMedSearch : Chen_2019_Biol.Chem_401_165
PubMedID: 31639098

Title : Biodegradation of mycotoxin fumonisin B1 by a novel bacterial consortium SAAS79 - Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
Author(s) : Zhao Z , Zhang Y , Gong A , Liu N , Chen S , Zhao X , Li X , Chen L , Zhou C , Wang J
Ref : Applied Microbiology & Biotechnology , 103 :7129 , 2019
Abstract : Fumonisin B1 (FB1) contamination in cereals and cereal products remains an important aspect of food safety because of its wide distribution and the potential health hazard. However, only a few microorganisms have been reported to effectively degrade FB1. In this present study, a bacterial consortium SAAS79 with highly FB1-degrading activity was isolated from the spent mushroom compost. The combination of antibiotic-driven selection and 16S rDNA sequencing identified the Pseudomonas genus as the key FB1-degrading member. The microbial consortium could degrade more than 90% of 10 microg/mL FB1 after incubation for 24 h at pH of 5-7 and temperature of 28-35 degreesC. The enzymes from the intracellular space were proved to be responsible for FB1 degradation, which eliminated about 90% of 10 microg/mL FB1 in 3 h. Besides, liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) analysis identified two degradation products of FB1, and their toxicity on the monkey kidney cells (MARC-145) was significantly lower (p < 0.05) compared with the parent FB1. Overall, the consortium SAAS79 and its crude enzymes may be a potential choice for the decontamination of FB1 in the feed and food industry. Also, the bacterial consortium provides a new source of genes for the development of enzymatic detoxification agent.
ESTHER : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedSearch : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedID: 31230101

Title : Insecticide Resistance Status and Mechanisms of Anopheles sinensis (Diptera: Culicidae) in Wenzhou, an Important Coastal Port City in China - Chen_2019_J.Med.Entomol_56_803
Author(s) : Chen S , Qin Q , Zhong D , Fang X , He H , Wang L , Dong L , Lin H , Zhang M , Cui L , Yan G
Ref : Journal of Medical Entomology , 56 :803 , 2019
Abstract : Although scaled-up interventions and effective control efforts have drastically reduced malaria morbidity and mortality, malaria remains a serious threat to public health worldwide. Anopheles sinensis Wiedemann 1828 is a historically important vector of Plasmodium vivax (Haemosporida: Plasmodiidae) malaria in China. Insecticide resistance has become a major obstacle to vector-borne disease control. However, little is known about the insecticide resistance of An. sinensis in Wenzhou, an important coastal port city in Zhejiang province, China. The aim of this study was to examine insecticide resistance and mechanisms in An. sinensis field mosquito populations. Evidence of multiple insecticide resistance was found in An. sinensis adult female populations. Medium to high frequencies of target site kdr together with fixed ace-1 mutations was detected in both the Ruian and Yongjia populations. Both populations showed an association between kdr L1014 mutation and resistance phenotype when tested against deltamethrin and DDT. Significantly different metabolic enzyme activities were found between the susceptible laboratory strain and field-collected mosquitoes from both Ruian and Yongjia. Both field collected An. sinensis populations exhibited significantly higher P450 enzyme activity compared with the laboratory strain, while the field-collected resistant mosquitoes exhibited various GST and COE enzyme activities. These results indicate multiple resistance mechanisms in An. sinensis field populations. Effective implementation of insecticide resistance management strategies is urgently needed. The data collected in this study will be valuable for modeling insecticide resistance spread and vector-control interventions.
ESTHER : Chen_2019_J.Med.Entomol_56_803
PubMedSearch : Chen_2019_J.Med.Entomol_56_803
PubMedID: 30715428

Title : Insight Into Microbial Applications for the Biodegradation of Pyrethroid Insecticides - Bhatt_2019_Front.Microbiol_10_1778
Author(s) : Bhatt P , Huang Y , Zhan H , Chen S
Ref : Front Microbiol , 10 :1778 , 2019
Abstract : Pyrethroids are broad-spectrum insecticides and presence of chiral carbon differentiates among various forms of pyrethroids. Microbial approaches have emerged as a popular solution to counter pyrethroid toxicity to marine life and mammals. Bacterial and fungal strains can effectively degrade pyrethroids into non-toxic compounds. Different strains of bacteria and fungi such as Bacillus spp., Raoultella ornithinolytica, Psudomonas flourescens, Brevibacterium sp., Acinetobactor sp., Aspergillus sp., Candida sp., Trichoderma sp., and Candia spp., are used for the biodegradation of pyrethroids. Hydrolysis of ester bond by enzyme esterase/carboxyl esterase is the initial step in pyrethroid biodegradation. Esterase is found in bacteria, fungi, insect and mammalian liver microsome cells that indicates its hydrolysis ability in living cells. Biodegradation pattern and detected metabolites reveal microbial consumption of pyrethroids as carbon and nitrogen source. In this review, we aim to explore pyrethroid degrading strains, enzymes and metabolites produced by microbial strains. This review paper covers in-depth knowledge of pyrethroids and recommends possible solutions to minimize their environmental toxicity.
ESTHER : Bhatt_2019_Front.Microbiol_10_1778
PubMedSearch : Bhatt_2019_Front.Microbiol_10_1778
PubMedID: 31428072

Title : Plant allelochemicals affect tolerance of polyphagous lepidopteran pest Helicoverpa armigera (Hubner) against insecticides - Chen_2019_Pestic.Biochem.Physiol_154_32
Author(s) : Chen S , Elzaki MEA , Ding C , Li ZF , Wang J , Zeng RS , Song YY
Ref : Pestic Biochem Physiol , 154 :32 , 2019
Abstract : Cotton bollworm, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae), is a polyphagous lepidopteran pest distributed worldwide with a broad spectrum of host plants. However, the mechanism of H. armigera adaptation to various insecticides and defensive allelochemicals in its host plants is not fully understood. Therefore, this study examined the influence of consumption of plant allelochemicals on larval tolerance to methomyl and chlorpyrifos insecticides in H. armigera and its possible mechanism. Twelve plant allelochemicals were screened to evaluate their effects on larval sensitivity to methomyl. Of which flavone, coumarin, DIMBOA (2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one) and visnagin significantly reduced larval sensitivity to methomyl. Application of cytochrome P450 inhibitor piperonyl butoxide (PBO) significantly increased the mortality of methomyl-treated larvae. In contrast, PBO addition significantly decreased the mortality of chlorpyrifos-treated larvae. Moreover, allelochemical consumption enhanced the activities of glutathione S-transferase, carboxylesterase, cytochrome P450 and acetylcholinesterase in the midgut and fat body. The qRT-PCR analysis confirms that P450 genes, CYP6B2, CYP6B6 and CYP6B7 were induced by the four allelochemicals in the midguts and the fat bodies. In conclusion, the generalist H. armigera can take benefit of plant allelochemicals from its host plants to elaborate its defense against insecticides.
ESTHER : Chen_2019_Pestic.Biochem.Physiol_154_32
PubMedSearch : Chen_2019_Pestic.Biochem.Physiol_154_32
PubMedID: 30765054

Title : Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity - Feng_2019_Fitoterapia__104378
Author(s) : Feng Z , Chen S , Wang W , Feng L , Dong Y , Zou Y , Ke C , Tang C , Yao S , Zhang H , Gan L , Ye Y , Lin L
Ref : Fitoterapia , :104378 , 2019
Abstract : Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the whole plants of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525+/-0.140muM, which was comparable with the positive control, huperzine A (IC50=0.143+/-0.029muM).
ESTHER : Feng_2019_Fitoterapia__104378
PubMedSearch : Feng_2019_Fitoterapia__104378
PubMedID: 31676395

Title : An ultrasensitive signal-on electrochemiluminescence biosensor based on Au nanoclusters for detecting acetylthiocholine - Zhang_2019_Anal.Bioanal.Chem_411_905
Author(s) : Zhang C , Fan Y , Zhang H , Chen S , Yuan R
Ref : Anal Bioanal Chem , 411 :905 , 2019
Abstract : For improving the sensitivity of the electrochemiluminescent (ECL) detection and extending the applications of luminophore, the development of coreactant accelerator is one of the important ways. In this work, Au nanoclusters (Au NCs) were chosen as the luminescent material, and thiocholine, which was in situ generated by enzymatic reaction, was found to serve as a coreactant accelerator for Au NC-S2O8(2-) ECL system. Based on this discovery, a highly sensitive detection of acetylthiocholine (ATCl) was achieved using the acetylcholinesterase (AChE) biosensor. CeO2 nanowires (CeO2 NWs) were used to improve the stability of Au NCs on the glassy carbon electrode (GCE) due to the large specific surface area and good film-forming properties of CeO2 NWs. ATCl was catalyzed by acetylcholinesterase (AChE) to produce thiocholine, which served as the coreactant accelerator to improve the ECL signal of Au NC-S2O8(2-) system. The biosensor obtained a low detection limit of 0.17 nM. The integration of thiocholine and Au NCs would provide a new ECL platform for bioanalysis. Graphical abstract .
ESTHER : Zhang_2019_Anal.Bioanal.Chem_411_905
PubMedSearch : Zhang_2019_Anal.Bioanal.Chem_411_905
PubMedID: 30565170

Title : Neuroprotective Effect of Resveratrol via Activation of Sirt1 Signaling in a Rat Model of Combined Diabetes and Alzheimer's Disease - Ma_2019_Front.Neurosci_13_1400
Author(s) : Ma X , Sun Z , Han X , Li S , Jiang X , Chen S , Zhang J , Lu H
Ref : Front Neurosci , 13 :1400 , 2019
Abstract : Background: Alzheimer's disease (AD) and diabetes mellitus (DM) often coexist in patients because having one of these conditions increases risk for the other. These two diseases share several pathophysiological mechanisms, such as specific inflammatory signaling pathways, oxidative stress, and cell apoptosis. It is still unclear exactly which mechanisms associated with DM are responsible for increased AD risk. Studies have found that even transient elevation of brain Abeta levels can allow T2DM to slightly disrupt the neural milieu in a way that encourages pathologies associated with the onset of memory deficits and AD. A recent study argues that a potential common pathogenetic mechanism underlying both DM and AD is evidenced by the cooccurrence of amyloid brain legions and deposits containing both tau and Abeta in pancreatic beta cells. Given these links, an investigation detailing disease mechanisms as well as treatment options for patients with cooccurring DM and AD is urgently needed. The biological effects of resveratrol relevant to DM and AD treatment include its abilities to modulate oxidative stress and reduce inflammation. A rat model of DM and concomitant AD was created for this study using intraperitoneal injection of streptozotocin and hippocampal injection of Abeta1-40 to characterize resveratrol's potential protective action. Results: Resveratrol significantly increased the Sirt1 expression, inhibited the memory impairment, the increased acetylcholinesterase, malondialdehyde, interleukin-1beta and interleukin 6 levels, and the decreased levels of choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione in this rat model of diabetes and concomitant AD. The Sirt 1 inhibitor EX527 partially reversed the effects of resveratrol. Conclusion: This study suggests that resveratrol may have a neuroprotective action through activation of Sirt1 signaling in diabetes and AD with concurrent onset.
ESTHER : Ma_2019_Front.Neurosci_13_1400
PubMedSearch : Ma_2019_Front.Neurosci_13_1400
PubMedID: 32038127

Title : Coreactant-free electrochemiluminescence biosensor for the determination of organophosphorus pesticides - He_2019_Biosens.Bioelectron__111898
Author(s) : He Y , Du J , Luo J , Chen S , Yuan R
Ref : Biosensors & Bioelectronics , :111898 , 2019
Abstract : Poly [(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] (PFBT) was functionalized with carboxyl groups via nanoprecipitation method to prepare polymer nanoparticles (PNPs). Remarkable electrochemiluminescence (ECL) was observed at PFBT PNPs without any external species or dissolved O2 as coreactants. Furthermore, such an ECL emission could be efficiently quenched by hydrogen peroxide (H2O2). A coreactant-free ECL enzyme-based biosensor is making use of PFBT PNPs as luminophore for detecting organophosphorus (OPs) pesticides. In the absence of OPs, H2O2 stemmed from the enzymatic reaction would quench the ECL signal of PFBT PNPs, resulting in an ECL signal-off state. In the presence of OPs, the ECL signal obviously increased because the enzyme activity of the acetylcholinesterase (AChE) was inhibited by OPs. The linear range for OPs detection was 1.0 x 10(-12)-1.0 x 10(-7) M and the detection limit was low as 1.5 x 10(-13) M. Such a coreactant-free ECL strategy could avoid the drawbacks resulted from the addition of exogenous species or dissolved O2 as coreactant. More importantly, H2O2 was released by many oxidases-induced reactions, and its quenching effect on the ECL of PFBT PNPs would pave a new avenue for constructing coreactant-free enzyme-based ECL biosensor for environmental monitoring and biological analysis.
ESTHER : He_2019_Biosens.Bioelectron__111898
PubMedSearch : He_2019_Biosens.Bioelectron__111898
PubMedID: 31767347

Title : LncRNA ABHD11-AS1 promotes the development of endometrial carcinoma by targeting cyclin D1 - Liu_2018_J.Cell.Mol.Med_22_3955
Author(s) : Liu Y , Wang LL , Chen S , Zong ZH , Guan X , Zhao Y
Ref : J Cell Mol Med , 22 :3955 , 2018
Abstract : To investigate the expression, role and mechanism of action of long non-coding RNA (lncRNA) ABHD11-AS1 in endometrial carcinoma. The expression of lncRNA ABHD11-AS1 was quantified by qRT-PCR in human endometrial carcinoma (n = 89) and normal endometrial tissues (n = 27). LncRNA ABHD11-AS1 was stably overexpressed or knocked-down in endometrial carcinoma cell lines to examine the cellular phenotype and expression of related molecules. Compared to normal endometrial tissue, lncRNA ABHD11-AS1 was significantly overexpressed in endometrial carcinoma. Overexpression of lncRNA ABHD11-AS1 promoted the proliferation, G1-S progression, invasion and migration of endometrial cancer cells; inhibited apoptosis; up-regulated cyclin D1, CDK1, CDK2, CDK4, Bcl-xl and VEGFA; and down-regulated p16, while ABHD11-AS1 down-regulation has the opposite effect. RNA pull down demonstrated that lncRNA ABHD11-AS1 binds directly to cyclin D1. Knockdown of cyclin D1 can reverse the effect of ABHD11-AS1. Overexpression of lncRNA ABHD11-AS1 increased the tumorigenicity and up-regulated cyclin D1 in an in vivo model of endometrial cancer in nude mice. LncRNA ABHD11-AS1 functions as an oncogene to promote cell proliferation and invasion in endometrial carcinoma by positively targeting cyclin D1.
ESTHER : Liu_2018_J.Cell.Mol.Med_22_3955
PubMedSearch : Liu_2018_J.Cell.Mol.Med_22_3955
PubMedID: 29799152
Gene_locus related to this paper: human-ABHD11

Title : Enhanced Poly(ethylene terephthalate) Hydrolase Activity by Protein Engineering - Ma_2018_Engineering.(Beijing)_4_888
Author(s) : Ma Y , Yao M , Li B , Ding M , He B , Chen S , Zhou X , Yuan Y
Ref : Engineering (Beijing) , 4 :888 , 2018
Abstract : Poly(ethylene terephthalate) hydrolase (PETase) from Ideonella sakaiensis exhibits a strong ability to degrade poly(ethylene terephthalate) (PET) at room temperature, and is thus regarded as a potential tool to solve the issue of polyester plastic pollution. Therefore, we explored the interaction between PETase and the substrate (a dimer of the PET monomer ethylene terephthalate, 2PET), using a model of PETase and its substrate. In this study, we focused on six key residues around the substrate-binding groove in order to create novel high-efficiency PETase mutants through protein engineering. These PETase mutants were designed and tested. The enzymatic activities of the R61A, L88F, and I179F mutants, which were obtained with a rapid cell-free screening system, exhibited 1.4 fold, 2.1 fold, and 2.5 fold increases, respectively, in comparison with wild-type PETase. The I179F mutant showed the highest activity, with the degradation rate of a PET film reaching 22.5 mg per micromol/L PETase per day. Thus, this study has created enhanced artificial PETase enzymes through the rational protein engineering of key hydrophobic sites, and has further illustrated the potential of biodegradable plastics.
ESTHER : Ma_2018_Engineering.(Beijing)_4_888
PubMedSearch : Ma_2018_Engineering.(Beijing)_4_888
PubMedID:
Gene_locus related to this paper: idesa-peth

Title : A pooled analysis of mesenchymal stem cell-based therapy for liver disease - Zhao_2018_Stem.Cell.Res.Ther_9_72
Author(s) : Zhao L , Chen S , Shi X , Cao H , Li L
Ref : Stem Cell Res Ther , 9 :72 , 2018
Abstract : BACKGROUND: Liver disease is a major cause of death and disability. Mesenchymal stem cells (MSCs) show promise for the treatment of liver disease. However, whether MSC-based therapy is more effective than conventional treatment is unclear, as are the optimal MSC source, the administration frequency, and the most effective MSC delivery route. We therefore undertook a systematic review and meta-analysis of the therapeutic efficacy of MSCs against liver disease and the related factors. METHODS: We systematically searched Medline (PubMed), Cochrane Library, EMBASE, ClinicalTrials.gov, and SinoMed CBM to identify studies published up to June 2017 involving liver disease patients receiving MSC-based therapy and which reported estimates of liver function during the follow-up period. RESULTS: Thirty-nine studies were selected from 672 publications. According to a meta-analysis of 23 controlled studies, compared with conventional treatment MSC therapy significantly improves liver function in patients with liver disease in terms of the model of end-stage liver disease score, albumin, alanine aminotransferase, and total bilirubin levels, and prothrombin time, up to 6 months after administration. However, it has no beneficial effects in terms of prothrombin activity, international normalized ratio, or cholinesterase level. Considerable heterogeneity was identified at most time points. Subgroup analyses showed that a single MSC injection was more effective than multiple injections, MSC administration was more effective via the hepatic artery than the peripheral vein, and MSCs derived from bone marrow were more effective than those derived from the umbilical cord. CONCLUSIONS: MSC-based therapy is relatively safe and improves liver function during the first 6 months after administration. A single injection administration via the hepatic artery and MSCs derived from bone marrow are optimal in terms of improving liver function. However the significant heterogeneity among studies and discontinuous results of the subgroup meta-analysis should be addressed; moreover the long-term efficacy of MSC therapy warrants further investigation.
ESTHER : Zhao_2018_Stem.Cell.Res.Ther_9_72
PubMedSearch : Zhao_2018_Stem.Cell.Res.Ther_9_72
PubMedID: 29562935

Title : Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice - Lu_2018_Phytother.Res_32_1056
Author(s) : Lu C , Lv J , Dong L , Jiang N , Wang Y , Wang Q , Li Y , Chen S , Fan B , Wang F , Liu X
Ref : Phytother Res , 32 :1056 , 2018
Abstract : 20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 mumol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory-related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine-induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory-improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease.
ESTHER : Lu_2018_Phytother.Res_32_1056
PubMedSearch : Lu_2018_Phytother.Res_32_1056
PubMedID: 29468740

Title : Carboxylesterase-involved metabolism of di-n-butyl phthalate in pumpkin (Cucurbita moschata) seedlings - Lin_2017_Environ.Pollut_220_421
Author(s) : Lin Q , Chen S , Chao Y , Huang X , Wang S , Qiu R
Ref : Environ Pollut , 220 :421 , 2017
Abstract : Uptake and accumulation by plants is a significant pathway in the migration and transformation of phthalate esters (PAEs) in the environment. However, limited information is available on the mechanisms of PAE metabolism in plants. Here, we investigated the metabolism of di-n-butyl phthalate (DnBP), one of the most frequently detected PAEs, in pumpkin (Cucurbita moschata) seedlings via a series of hydroponic experiments with an initial concentration of 10 mg L(-1). DnBP hydrolysis occurred primarily in the root, and two of its metabolites, mono-n-butyl phthalate (MnBP) and phthalic acid (PA), were detected in all plant tissues. The MnBP concentration was an order of magnitude higher than that of PA in shoots, which indicated MnBP was more readily transported to the shoot than was PA because of the former's dual hydrophilic and lipophilic characteristics. More than 80% of MnBP and PA were located in the cell water-soluble component except that 96% of MnBP was distributed into the two solid cellular fractions (i.e., cell wall and organelles) at 96 h. A 13-20% and 29-54% increase of carboxylesterase (CXE) activity shown in time-dependent and concentration-dependent experiments, respectively, indicated the involvement of CXEs in plant metabolism of DnBP. The level of CXE activity in root subcellular fractions was in the order: the cell water-soluble component (88-94%) >> cell wall (3-7%) > cell organelles (3-4%), suggesting that the cell water-soluble component is the dominant locus of CXE activity and also the domain of CXE-catalyzed hydrolysis of DnBP. The addition of triphenyl phosphate, a CXE inhibitor, led to 43-56% inhibition of CXE activity and 16-25% increase of DnBP content, which demonstrated the involvement of CXEs in plant metabolism of DnBP. This study contributes to our understanding of enzymitic mechanisms of PAE transformation in plants.
ESTHER : Lin_2017_Environ.Pollut_220_421
PubMedSearch : Lin_2017_Environ.Pollut_220_421
PubMedID: 27697378

Title : Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC - Wu_2017_Mol.Cancer_16_138
Author(s) : Wu DD , Chen X , Sun KX , Wang LL , Chen S , Zhao Y
Ref : Mol Cancer , 16 :138 , 2017
Abstract : BACKGROUND: There is increasing evidence in support of the role of lncRNAs in tumor cell proliferation, differentiation and apoptosis. METHODS: We examined the expression of the lncRNA ABHD11-AS(1) in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues by real-time quantitative PCR (qRT-PCR). After inducing ABHD11-AS(1) downregulation by small interfering RNA (siRNA) or ABHD11-AS(1) overexpression by plasmid transfection, we examined the EOC cell phenotypes and expression of related molecules. RESULTS: Expression of the lncRNA ABHD11-AS(1) in EOC tissues was higher than that in normal ovarian tissue. It was positively associated with the tumor stage (stage I/II vs. stage III/IV), and it was lower in the well-differentiated group than in the poorly/moderately differentiated group. Overexpression of ABHD11-AS(1) in the ovarian cancer cell lines A2780 and OVCAR3 promoted ovarian cancer cell proliferation, invasion and migration, and inhibited apoptosis. Silencing of ABHD11-AS(1) had the opposite effect. Subcutaneous injection of tumor cells in nude mice showed that ABHD11-AS(1) could significantly promote tumor growth. In addition, intraperitoneal injection of tumor cells in the nude mice resulted in an increase in the metastatic ability of the tumor. Further, overexpression of ABHD11-AS(1) upregulated the expression of RhoC and its downstream molecules P70s6k, MMP2 and BCL-xL. Silencing of ABHD11-AS(1) had the opposite effect. The RNA pull-down assay showed that ABHD11-AS(1) can combine directly with RhoC. Silencing of RhoC was found to inhibit the cancer-promoting effects of lncRNA ABHD11-AS(1). Thus, it seems that RhoC is a major target of the lncRNA ABHD11-AS(1). CONCLUSIONS: This is the first study to demonstrate the role of RhoC in the tumor-promoting effects of the lncRNA ABHD11-AS(1). The present findings shed light on new therapeutic targets for ovarian cancer treatment.
ESTHER : Wu_2017_Mol.Cancer_16_138
PubMedSearch : Wu_2017_Mol.Cancer_16_138
PubMedID: 28818073
Gene_locus related to this paper: human-ABHD11

Title : Genome sequence of Talaromyces piceus 9-3 provides insights into lignocellulose degradation - He_2017_3.Biotech_7_368
Author(s) : He R , Bai X , Cai P , Sun C , Zhang D , Chen S
Ref : 3 Biotech , 7 :368 , 2017
Abstract : Many species of Penicillium have exhibited great potential for lignocellulose hydrolysis. The filamentous fungus Talaromyces piceus 9-3 (anamorph: Penicillium piceum), which was isolated from compost wastes in China, was sequenced in this study. Compared with the cellulase producer T. reesei, T. piceus 9-3 processes a lignocellulolytic enzyme system comprising more diverse enzymatic components, especially hemicellulases. This report will facilitate the use of this strain for biomass degradation.
ESTHER : He_2017_3.Biotech_7_368
PubMedSearch : He_2017_3.Biotech_7_368
PubMedID: 29062678
Gene_locus related to this paper: 9euro-a0a2d2agx5

Title : Novel Double-Potential Electrochemiluminescence Ratiometric Strategy in Enzyme-Based Inhibition Biosensing for Sensitive Detection of Organophosphorus Pesticides - Chen_2017_Anal.Chem_89_2823
Author(s) : Chen H , Zhang H , Yuan R , Chen S
Ref : Analytical Chemistry , 89 :2823 , 2017
Abstract : Generally, electrochemiluminescence (ECL) ratiometric assays were based on the energy transfer (ET) between an emitter and a metal nanomaterial or between two different emitters. The choice of suitable energy donor-acceptor pair and the distance dependence of ET would greatly limit the practical application of ratiometric assays. This work explored a novel double-potential ECL ratiometry without the ET for organophosphorus pesticides (OPs) analysis, in which, reduced graphene oxide-CdTe quantum dots (RGO-CdTe QDs) and carboxyl-conjugated polymer dots (PFO dots) were chosen as cathodic and anodic ECL emitters, and the reactant (dissolved O2) and the product (H2O2) in enzymatic reactions served as their coreactants, respectively. With the occurrence of the enzymatic reactions induced by the acetylcholinesterase (AChE) and choline oxidase (ChOx), the cathodic ECL signal from RGO-CdTe QDs was at "signal off" state due to the consumption of dissolved O2. Meanwhile, the anodic ECL signal from PFO dots was at "signal on" state due to the in situ generation of H2O2. In the presence of OPs, the cathodic ECL signal would increase while the anodic ECL signal would decline correspondingly due to the inhibition of OPs on the activity of AChE. Using the reactant and the product in enzymatic reactions as the coreactants of two different ECL emitters, we conveniently achieved the opposite change trend in two ECL signals for the ratiometric detection of OPs, which exhibited a greatly improved accuracy, reliability and sensitivity, thus, showing a great attraction for developing ECL ratiometric systems for the bioanalysis.
ESTHER : Chen_2017_Anal.Chem_89_2823
PubMedSearch : Chen_2017_Anal.Chem_89_2823
PubMedID: 28192982

Title : Bacterial cellulose synthesis mechanism of facultative anaerobe Enterobacter sp. FY-07 - Ji_2016_Sci.Rep_6_21863
Author(s) : Ji K , Wang W , Zeng B , Chen S , Zhao Q , Chen Y , Li G , Ma T
Ref : Sci Rep , 6 :21863 , 2016
Abstract : Enterobacter sp. FY-07 can produce bacterial cellulose (BC) under aerobic and anaerobic conditions. Three potential BC synthesis gene clusters (bcsI, bcsII and bcsIII) of Enterobacter sp. FY-07 have been predicted using genome sequencing and comparative genome analysis, in which bcsIII was confirmed as the main contributor to BC synthesis by gene knockout and functional reconstitution methods. Protein homology, gene arrangement and gene constitution analysis indicated that bcsIII had high identity to the bcsI operon of Enterobacter sp. 638; however, its arrangement and composition were same as those of BC synthesizing operon of G. xylinum ATCC53582 except for the flanking sequences. According to the BC biosynthesizing process, oxygen is not directly involved in the reactions of BC synthesis, however, energy is required to activate intermediate metabolites and synthesize the activator, c-di-GMP. Comparative transcriptome and metabolite quantitative analysis demonstrated that under anaerobic conditions genes involved in the TCA cycle were downregulated, however, genes in the nitrate reduction and gluconeogenesis pathways were upregulated, especially, genes in three pyruvate metabolism pathways. These results suggested that Enterobacter sp. FY-07 could produce energy efficiently under anaerobic conditions to meet the requirement of BC biosynthesis.
ESTHER : Ji_2016_Sci.Rep_6_21863
PubMedSearch : Ji_2016_Sci.Rep_6_21863
PubMedID: 26911736
Gene_locus related to this paper: 9entr-a0a127l3e1

Title : Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice - Qiu_2016_Behav.Brain.Res_312_212
Author(s) : Qiu G , Chen S , Guo J , Wu J , Yi YH
Ref : Behavioural Brain Research , 312 :212 , 2016
Abstract : Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (alpha)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with alpha-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of alpha-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with alpha-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, alpha-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of alpha-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity.
ESTHER : Qiu_2016_Behav.Brain.Res_312_212
PubMedSearch : Qiu_2016_Behav.Brain.Res_312_212
PubMedID: 27316341

Title : Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes - Wu_2016_ACS.Med.Chem.Lett_7_498
Author(s) : Wu WL , Hao J , Domalski M , Burnett DA , Pissarnitski D , Zhao Z , Stamford A , Scapin G , Gao YD , Soriano A , Kelly TM , Yao Z , Powles MA , Chen S , Mei H , Hwa J
Ref : ACS Med Chem Lett , 7 :498 , 2016
Abstract : In our efforts to develop second generation DPP-4 inhibitors, we endeavored to identify distinct structures with long-acting (once weekly) potential. Taking advantage of X-ray cocrystal structures of sitagliptin and other DPP-4 inhibitors, such as alogliptin and linagliptin bound to DPP-4, and aided by molecular modeling, we designed several series of heterocyclic compounds as initial targets. During their synthesis, an unexpected chemical transformation provided a novel tricyclic scaffold that was beyond our original design. Capitalizing on this serendipitous discovery, we have elaborated this scaffold into a very potent and selective DPP-4 inhibitor lead series, as highlighted by compound 17c.
ESTHER : Wu_2016_ACS.Med.Chem.Lett_7_498
PubMedSearch : Wu_2016_ACS.Med.Chem.Lett_7_498
PubMedID: 27190600
Gene_locus related to this paper: human-DPP4

Title : Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning - Tang_2016_Respir.Care_61_965
Author(s) : Tang W , Ruan F , Chen Q , Chen S , Shao X , Gao J , Zhang M
Ref : Respir Care , 61 :965 , 2016
Abstract : BACKGROUND: Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis.
METHODS: The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors.
RESULTS: Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value.
CONCLUSIONS: High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis.
ESTHER : Tang_2016_Respir.Care_61_965
PubMedSearch : Tang_2016_Respir.Care_61_965
PubMedID: 27048625

Title : Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism - Hu_2016_Mol.Cell.Endocrinol_423_60
Author(s) : Hu X , Chen R , Fu C , Fan X , Wang J , Qian J , Yi S , Li C , Luo J , Su J , Zhang S , Xie B , Zheng H , Lai Y , Chen Y , Li H , Gu X , Chen S , Shen Y
Ref : Mol Cell Endocrinol , 423 :60 , 2016
Abstract : Mutations in Thyroglobulin (TG) are common genetic causes of congenital hypothyroidism (CH). But the TG mutation spectrum and its frequency in Chinese CH patients have not been investigated. Here we conducted a genetic screening of TG gene in a cohort of 382 Chinese CH patients. We identified 22 rare non-polymorphic variants including six truncating variants and 16 missense variants of unknown significance (VUS). Seven patients carried homozygous pathogenic variants, and three patients carried homozygous or compound heterozygous VUS. 48 out of 382 patients carried one of 18 heterozygous VUS which is significantly more often than their occurrences in control cohort (P < 0.0001). Unique to Asian population, the c.274+2T>G variant is the most common pathogenic variant with an allele frequency of 0.021. The prevalence of CH due to TG gene defect in Chinese population was estimated to be approximately 1/101,000. Our study uncovered ethnicity specific TG mutation spectrum and frequency.
ESTHER : Hu_2016_Mol.Cell.Endocrinol_423_60
PubMedSearch : Hu_2016_Mol.Cell.Endocrinol_423_60
PubMedID: 26777470
Gene_locus related to this paper: human-TG

Title : Highly sensitive electrochemiluminescenc assay of acetylcholinesterase activity based on dual biomarkers using Pd-Au nanowires as immobilization platform - Ye_2015_Biosens.Bioelectron_79_34
Author(s) : Ye C , Wang MQ , Zhong X , Chen S , Chai Y , Yuan R
Ref : Biosensors & Bioelectronics , 79 :34 , 2015
Abstract : One-dimensional Pd-Au nanowires (Pd-Au NWs) were prepared and applied to fabricate an electrochemiluminescence (ECL) biosensor for the detection of acetylcholinesterase (AChE) activity. Compared with single-component of Pd or Au, the bimetallic nanocomposite of Pd-Au NWs offers a larger surface area for the immobilization of enzyme, and displays superior electrocatalytic activity and efficient electron transport capacity. In the presence of AChE and choline oxidase (ChOx), acetylcholine (ATCl) is hydrolyzed by AChE to generate thiocholine, then thiocholine is catalyzed by ChOx to produce H2O2in situ, which serves as the coreactant to effectively enhance the ECL intensity in luminol-ECL system. The detection principle is based on the inhibited AChE and reactivated AChE as dual biomarkers, in which AChE was inhibited by organophosphorus (OP) agents, and then reactivated by obidoxime. Such dual biomarkers method can achieve credible evaluation for AChE activity via providing AChE activity before and after reactivation. The liner range for AChE activity detection was from 0.025UL-1 to 25KUL-1 with a low detection limit down to 0.0083UL-1.
ESTHER : Ye_2015_Biosens.Bioelectron_79_34
PubMedSearch : Ye_2015_Biosens.Bioelectron_79_34
PubMedID: 26686921

Title : Discovery and expression of a Pseudomonas sp. esterase as a novel biocatalyst for the efficient biosynthesis of a chiral intermediate of pregabalin -
Author(s) : Xu F , Chen S , Xu G , Wu J , Yang L
Ref : Biotechnol Bioprocess Eng , 20 :473 , 2015
PubMedID:

Title : Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US - Saint-Laurent_2015_J.Med.Econ_18_930
Author(s) : Saint-Laurent Thibault C , Ozer Stillman I , Chen S , Getsios D , Proskorovsky I , Hernandez L , Dixit S
Ref : J Med Econ , 18 :930 , 2015
Abstract : OBJECTIVE: This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US.
METHODS: A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum.
RESULTS: Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. CONCLUSION: Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.
ESTHER : Saint-Laurent_2015_J.Med.Econ_18_930
PubMedSearch : Saint-Laurent_2015_J.Med.Econ_18_930
PubMedID: 26086535

Title : The Effect of Rifampin on the Pharmacokinetics of Edoxaban in Healthy Adults - Mendell_2015_Clin.Drug.Investig_35_447
Author(s) : Mendell J , Chen S , He L , Desai M , Parasramupria DA
Ref : Clin Drug Investig , 35 :447 , 2015
Abstract : BACKGROUND AND OBJECTIVE: The oral direct factor Xa inhibitor edoxaban is a P-glycoprotein (P-gp) substrate metabolized via carboxylesterase-1 and cytochrome P450 (CYP) 3A4/5. The effect of rifampin-induced induction of P-gp and CYP3A4/5 on transport and metabolism of edoxaban through the CYP3A4/5 pathway was investigated in a single-dose edoxaban study.
METHODS: This was a phase 1, open-label, two-treatment, two-period, single-sequence drug interaction study in healthy adults. All subjects received a single oral 60 mg edoxaban dose in period 1, and 7 days of 600 mg rifampin (2 x 300 mg capsules once daily) with a single oral edoxaban 60 mg dose administered concomitantly on day 7 in period 2. A 6-day washout period separated the treatments. Plasma concentrations of edoxaban and its metabolites M4 and M6 were measured, and limited assessments of pharmacodynamic markers of coagulation were performed.
RESULTS: In total, 34 healthy subjects were enrolled; 32 completed the study. Coadministration of rifampin with edoxaban decreased edoxaban exposure but increased active metabolite exposure. Rifampin increased apparent oral clearance of edoxaban by 33 % and decreased its half-life by 50 %. Anticoagulant effects based on the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) with and without rifampin at early time points were maintained to a greater-than-expected degree than with edoxaban exposure alone, presumably because of an increased contribution from the active metabolites. Edoxaban was well tolerated in this healthy adult population.
CONCLUSIONS: Rifampin reduced exposure to edoxaban while increasing exposure to its active metabolites M4 and M6. PT and aPTT at early time points did not change appreciably; however, the data should be interpreted with caution.
ESTHER : Mendell_2015_Clin.Drug.Investig_35_447
PubMedSearch : Mendell_2015_Clin.Drug.Investig_35_447
PubMedID: 26068927

Title : Deciphering the venomic transcriptome of killer-wasp Vespa velutina - Liu_2015_Sci.Rep_5_9454
Author(s) : Liu Z , Chen S , Zhou Y , Xie C , Zhu B , Zhu H , Liu S , Wang W , Chen H , Ji Y
Ref : Sci Rep , 5 :9454 , 2015
Abstract : Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world.
ESTHER : Liu_2015_Sci.Rep_5_9454
PubMedSearch : Liu_2015_Sci.Rep_5_9454
PubMedID: 25896434
Gene_locus related to this paper: vesve-pa1

Title : Comparative genomic analysis of N2-fixing and non-N2-fixing Paenibacillus spp.: organization, evolution and expression of the nitrogen fixation genes - Xie_2014_PLoS.Genet_10_e1004231
Author(s) : Xie JB , Du Z , Bai L , Tian C , Zhang Y , Xie JY , Wang T , Liu X , Chen X , Cheng Q , Chen S , Li J
Ref : PLoS Genet , 10 :e1004231 , 2014
Abstract : We provide here a comparative genome analysis of 31 strains within the genus Paenibacillus including 11 new genomic sequences of N2-fixing strains. The heterogeneity of the 31 genomes (15 N2-fixing and 16 non-N2-fixing Paenibacillus strains) was reflected in the large size of the shell genome, which makes up approximately 65.2% of the genes in pan genome. Large numbers of transposable elements might be related to the heterogeneity. We discovered that a minimal and compact nif cluster comprising nine genes nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV encoding Mo-nitrogenase is conserved in the 15 N2-fixing strains. The nif cluster is under control of a sigma(70)-depedent promoter and possesses a GlnR/TnrA-binding site in the promoter. Suf system encoding [Fe-S] cluster is highly conserved in N2-fixing and non-N2-fixing strains. Furthermore, we demonstrate that the nif cluster enabled Escherichia coli JM109 to fix nitrogen. Phylogeny of the concatenated NifHDK sequences indicates that Paenibacillus and Frankia are sister groups. Phylogeny of the concatenated 275 single-copy core genes suggests that the ancestral Paenibacillus did not fix nitrogen. The N2-fixing Paenibacillus strains were generated by acquiring the nif cluster via horizontal gene transfer (HGT) from a source related to Frankia. During the history of evolution, the nif cluster was lost, producing some non-N2-fixing strains, and vnf encoding V-nitrogenase or anf encoding Fe-nitrogenase was acquired, causing further diversification of some strains. In addition, some N2-fixing strains have additional nif and nif-like genes which may result from gene duplications. The evolution of nitrogen fixation in Paenibacillus involves a mix of gain, loss, HGT and duplication of nif/anf/vnf genes. This study not only reveals the organization and distribution of nitrogen fixation genes in Paenibacillus, but also provides insight into the complex evolutionary history of nitrogen fixation.
ESTHER : Xie_2014_PLoS.Genet_10_e1004231
PubMedSearch : Xie_2014_PLoS.Genet_10_e1004231
PubMedID: 24651173
Gene_locus related to this paper: 9bacl-x4zf35 , 9bacl-x4zxj9 , 9bacl-x5a3k6 , 9bacl-x4zet8

Title : Genome sequence and transcriptome analyses of the thermophilic zygomycete fungus Rhizomucor miehei - Zhou_2014_BMC.Genomics_15_294
Author(s) : Zhou P , Zhang G , Chen S , Jiang Z , Tang Y , Henrissat B , Yan Q , Yang S , Chen CF , Zhang B , Du Z
Ref : BMC Genomics , 15 :294 , 2014
Abstract : BACKGROUND: The zygomycete fungi like Rhizomucor miehei have been extensively exploited for the production of various enzymes. As a thermophilic fungus, R. miehei is capable of growing at temperatures that approach the upper limits for all eukaryotes. To date, over hundreds of fungal genomes are publicly available. However, Zygomycetes have been rarely investigated both genetically and genomically.
RESULTS: Here, we report the genome of R. miehei CAU432 to explore the thermostable enzymatic repertoire of this fungus. The assembled genome size is 27.6-million-base (Mb) with 10,345 predicted protein-coding genes. Even being thermophilic, the G + C contents of fungal whole genome (43.8%) and coding genes (47.4%) are less than 50%. Phylogenetically, R. miehei is more closerly related to Phycomyces blakesleeanus than to Mucor circinelloides and Rhizopus oryzae. The genome of R. miehei harbors a large number of genes encoding secreted proteases, which is consistent with the characteristics of R. miehei being a rich producer of proteases. The transcriptome profile of R. miehei showed that the genes responsible for degrading starch, glucan, protein and lipid were highly expressed.
CONCLUSIONS: The genome information of R. miehei will facilitate future studies to better understand the mechanisms of fungal thermophilic adaptation and the exploring of the potential of R. miehei in industrial-scale production of thermostable enzymes. Based on the existence of a large repertoire of amylolytic, proteolytic and lipolytic genes in the genome, R. miehei has potential in the production of a variety of such enzymes.
ESTHER : Zhou_2014_BMC.Genomics_15_294
PubMedSearch : Zhou_2014_BMC.Genomics_15_294
PubMedID: 24746234

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

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

Title : Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle - Chen_2014_Nat.Genet_46_253
Author(s) : Chen S , Zhang G , Shao C , Huang Q , Liu G , Zhang P , Song W , An N , Chalopin D , Volff JN , Hong Y , Li Q , Sha Z , Zhou H , Xie M , Yu Q , Liu Y , Xiang H , Wang N , Wu K , Yang C , Zhou Q , Liao X , Yang L , Hu Q , Zhang J , Meng L , Jin L , Tian Y , Lian J , Yang J , Miao G , Liu S , Liang Z , Yan F , Li Y , Sun B , Zhang H , Zhu Y , Du M , Zhao Y , Schartl M , Tang Q , Wang J
Ref : Nat Genet , 46 :253 , 2014
Abstract : Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
ESTHER : Chen_2014_Nat.Genet_46_253
PubMedSearch : Chen_2014_Nat.Genet_46_253
PubMedID: 24487278
Gene_locus related to this paper: cynse-a0a3p8wch2 , cynse-a0a3p8vd14 , cynse-a0a3p8w747 , cynse-a0a3p8wq40 , cynse-a0a3p8wul3 , cynse-a0a3p8vqr4 , cynse-a0a3p8vmz4

Title : Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes - You_2014_Nat.Commun_5_5594
Author(s) : You X , Bian C , Zan Q , Xu X , Liu X , Chen J , Wang J , Qiu Y , Li W , Zhang X , Sun Y , Chen S , Hong W , Li Y , Cheng S , Fan G , Shi C , Liang J , Tom Tang Y , Yang C , Ruan Z , Bai J , Peng C , Mu Q , Lu J , Fan M , Yang S , Huang Z , Jiang X , Fang X , Zhang G , Zhang Y , Polgar G , Yu H , Li J , Liu Z , Ravi V , Coon SL , Yang H , Venkatesh B , Shi Q
Ref : Nat Commun , 5 :5594 , 2014
Abstract : Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates.
ESTHER : You_2014_Nat.Commun_5_5594
PubMedSearch : You_2014_Nat.Commun_5_5594
PubMedID: 25463417
Gene_locus related to this paper: 9gobi-a0a3b4bh68 , 9gobi-a0a3b4bmj6 , 9gobi-a0a3b4alj9 , 9gobi-a0a3b4biy6 , 9gobi-a0a3b4ah01 , 9gobi-a0a3b3z8m7 , 9gobi-a0a3b4aaj5 , 9gobi-a0a3b4b6y7

Title : Morphological diversity of GABAergic and cholinergic interneurons in the striatal dorsolateral and ventromedial regions of rats - Ma_2014_Cell.Mol.Neurobiol_34_351
Author(s) : Ma Y , Feng Q , Ouyang L , Mu S , Liu B , Li Y , Chen S , Lei W
Ref : Cellular Molecular Neurobiology , 34 :351 , 2014
Abstract : The striatum plays a fundamental role in sensorimotor and cognitive functions of the body, and different sub-regions control different physiological functions. The striatal interneurons play important roles in the striatal function, yet their specific functions are not clearly elucidated so far. The present study aimed to investigate the morphological properties of the GABAergic interneurons expressing neuropeptide Y (NPY), calretinin (Cr), and parvalbumin (Parv) as well as the cholinergic interneurons expressing choline acetyltransferase (ChAT) in the striatal dorsolateral (DL) and ventromedial (VM) regions of rats using immunohistochemistry and Western blot. The present results showed that the somatic size of Cr+ was the smallest, while ChAT+ was the largest among the four types of interneurons. There was no regional difference in neuronal somatic size of all types of interneurons. Cr+ and Parv+ neurons were differentially distributed in the striatum. Moreover, Parv+ had the longest primary dendrites in the DL region, while NPY+ had the longest ones in the VM region of striatum. But there was regional difference in the length of primary dendrites of Parv. The numbers of primary dendrites of Parv+ were the largest in both DL and VM regions of striatum. Both Cr+ and Parv+ primary dendrites displayed regional difference in the striatum. Western blot further confirmed the regional differences in the protein expression level of Cr and Parv. Hence, the present study indicates that GABAergic and cholinergic interneurons might be involved in different physiological functions based on their morphological and distributional diversity in different regions of the rat striatum.
ESTHER : Ma_2014_Cell.Mol.Neurobiol_34_351
PubMedSearch : Ma_2014_Cell.Mol.Neurobiol_34_351
PubMedID: 24343377

Title : Association of lipoprotein lipase polymorphism rs2197089 with serum lipid concentrations and LPL gene expression - Mo_2013_J.Hum.Genet_58_160
Author(s) : Mo X , Liu X , Wang L , Lu X , Chen S , Li H , Huang J , Chen J , Cao J , Li J , Tang Y , Gu D
Ref : J Hum Genet , 58 :160 , 2013
Abstract : Many single-nucleotide polymorphisms (SNPs) have been reported to be associated with lipid concentrations in recent genome-wide association studies. The aim of this study was to validate the associations of rs2197089 in the lipoprotein lipase (LPL) gene with serum lipid concentrations and gene expression levels in the Chinese Han population and examine the potential interactions. A total of 9339 participants were recruited and genotyped for rs2197089. Gene expression levels of LPL in blood cells of 309 participants were evaluated by real-time PCR. We observed significant associations between rs2197089 and decreased triglycerides (TG) (P=0.0006), but not high-density lipoprotein cholesterol (HDL-C) concentration (P=0.0881). However, weak evidence of interaction between cigarette smoking and rs2197089 was detected (P=0.0362). In smokers, significant association between rs2197089 and increased HDL-C concentration was found (P=0.0068). Participants with the minor allele A had higher expression levels of LPL (P=0.0243). The results of our study indicated that rs2197089 was significantly associated with TG but it was associated with HDL-C only in smokers. This SNP seemed to have influence on the expression level of LPL.
ESTHER : Mo_2013_J.Hum.Genet_58_160
PubMedSearch : Mo_2013_J.Hum.Genet_58_160
PubMedID: 23344322

Title : In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor - Podolin_2013_Prostaglandins.Other.Lipid.Mediat_104-105_25
Author(s) : Podolin PL , Bolognese BJ , Foley JF , Long E, 3rd , Peck B , Umbrecht S , Zhang X , Zhu P , Schwartz B , Xie W , Quinn C , Qi H , Sweitzer S , Chen S , Galop M , Ding Y , Belyanskaya SL , Israel DI , Morgan BA , Behm DJ , Marino JP, Jr. , Kurali E , Barnette MS , Mayer RJ , Booth-Genthe CL , Callahan JF
Ref : Prostaglandins Other Lipid Mediat , 104-105 :25 , 2013
Abstract : Soluble epoxide hydrolase (sEH, EPHX2) metabolizes eicosanoid epoxides, including epoxyeicosatrienoic acids (EETs) to the corresponding dihydroxyeicosatrienoic acids (DHETs), and leukotoxin (LTX) to leukotoxin diol (LTX diol). EETs, endothelium-derived hyperpolarizing factors, exhibit potentially beneficial properties, including anti-inflammatory effects and vasodilation. A novel, potent, selective inhibitor of recombinant human, rat and mouse sEH, GSK2256294A, exhibited potent cell-based activity, a concentration-dependent inhibition of the conversion of 14,15-EET to 14,15-DHET in human, rat and mouse whole blood in vitro, and a dose-dependent increase in the LTX/LTX diol ratio in rat plasma following oral administration. Mice receiving 10 days of cigarette smoke exposure concomitant with oral administration of GSK2256294A exhibited significant, dose-dependent reductions in pulmonary leukocytes and keratinocyte chemoattractant (KC, CXCL1) levels. Mice receiving oral administration of GSK2256294A following 10 days of cigarette smoke exposure exhibited significant reductions in pulmonary leukocytes compared to vehicle-treated mice. These data indicate that GSK2256294A attenuates cigarette smoke-induced inflammation by both inhibiting its initiation and/or maintenance and promoting its resolution. Collectively, these data indicate that GSK2256294A would be an appropriate agent to evaluate the role of sEH in clinical studies, for example in diseases where cigarette smoke is a risk factor, such as chronic obstructive pulmonary disease (COPD) and cardiovascular disease.
ESTHER : Podolin_2013_Prostaglandins.Other.Lipid.Mediat_104-105_25
PubMedSearch : Podolin_2013_Prostaglandins.Other.Lipid.Mediat_104-105_25
PubMedID: 23434473

Title : The anti-inflammatory effect of donepezil on experimental autoimmune encephalomyelitis in C57 BL\/6 mice - Jiang_2013_Neuropharmacol_73C_415
Author(s) : Jiang Y , Zou Y , Chen S , Zhu C , Wu A , Liu Y , Ma L , Zhu D , Ma X , Liu M , Kang Z , Pi R , Peng F , Wang Q , Chen X
Ref : Neuropharmacology , 73C :415 , 2013
Abstract : Donepezil is a potent and selective acetylcholinesterase inhibitor. It has been reported to restore cognitive performance in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) mice, an established model of MS. However, there are no reports about the anti-inflammatory effects of donepezil on EAE. In this study, the donepezil treatments on EAE mice were initiated at day 7 post immunization (7 p.i., subclinical periods, early donepezil treatment) and day 13 p.i. (clinical periods, late donepezil treatment) with the dosage of 1, 2 and 4 mg/kg/d respectively and the treatments persisted throughout the experiments. Blood-brain barrier (BBB) permeability was detected by Evan's blue content, the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, Akt and phosphorylated Akt (p-Akt) as well as nerve growth factor (NGF) and its precursor form (proNGF) in the brains of EAE mice were detected by Western blot, and the levels of interferon-gamma and interleukin-4 in the splenocytes culture supernatants and brains of EAE mice were evaluated by ELISA. The results showed that the 2 mg/kg/d late donepezil treatment was the optimal dosage and could ameliorate clinical and pathological parameters, improve magnetic resonance imaging outcomes, reduce the permeability of BBB, inhibit the production of MMP-2 and MMP-9, modulate the expression of NGF and proNGF, increase Th2 bias and the phosphorylation of Akt in the brains of EAE mice. Our data suggested that the anti-inflammatory effects of donepezil may be a novel mechanism on treating EAE and provided further insights to understand the donepezil's neuroprotective activities in MS.
ESTHER : Jiang_2013_Neuropharmacol_73C_415
PubMedSearch : Jiang_2013_Neuropharmacol_73C_415
PubMedID: 23831366

Title : Cutinase: Characteristics, preparation, and application - Chen_2013_Biotechnol.Adv_31_1754
Author(s) : Chen S , Su L , Chen J , Wu J
Ref : Biotechnol Adv , 31 :1754 , 2013
Abstract : Cutinases (E.C. 3.1.1.74) belong to the alpha/beta-hydrolase superfamily. They were initially discovered because they are secreted by fungi to hydrolyze the ester bonds of the plant polymer cutin. Since then, they have been shown to catalyze the hydrolysis of a variety of polymers, insoluble triacylglycerols, and low-molecular-weight soluble esters. Cutinases are also capable of catalyzing esterification and transesterification reactions. These relatively small, versatile, secreted catalysts have shown promise in a number of industrial applications. This review begins by describing the characteristics of cutinases, pointing out key differences among cutinases, esterases and lipases, and reviewing recent progress in engineering improved cutinases. It continues with a review of the methods used to produce cutinases, with the goal of obtaining sufficient quantities of material for use in industrial processes. Finally, the uses of cutinases in the textile industry are described. The studies presented here demonstrate that the cutinases are poised to become important industrial catalysts, replacing older technologies with more environmentally friendly processes.
ESTHER : Chen_2013_Biotechnol.Adv_31_1754
PubMedSearch : Chen_2013_Biotechnol.Adv_31_1754
PubMedID: 24055682

Title : Intestinal glucuronidation protects against chemotherapy-induced toxicity by irinotecan (CPT-11) - Chen_2013_Proc.Natl.Acad.Sci.U.S.A_110_19143
Author(s) : Chen S , Yueh MF , Bigo C , Barbier O , Wang K , Karin M , Nguyen N , Tukey RH
Ref : Proc Natl Acad Sci U S A , 110 :19143 , 2013
Abstract : Camptothecin (CPT)-11 (irinotecan) has been used widely for cancer treatment, particularly metastatic colorectal cancer. However, up to 40% of treated patients suffer from severe late diarrhea, which prevents CPT-11 dose intensification and efficacy. CPT-11 is a prodrug that is hydrolyzed by hepatic and intestinal carboxylesterase to form SN-38, which in turn is detoxified primarily through UDP-glucuronosyltransferase 1A1 (UGT1A1)-catalyzed glucuronidation. To better understand the mechanism associated with toxicity, we generated tissue-specific Ugt1 locus conditional knockout mouse models and examined the role of glucuronidation in protecting against irinotecan-induced toxicity. We targeted the deletion of the Ugt1 locus and the Ugt1a1 gene specifically in the liver (Ugt1(DeltaHep)) and the intestine (Ugt1(DeltaGI)). Control (Ugt1(F/F)), Ugt1(DeltaHep), and Ugt1(DeltaGI) adult male mice were treated with different concentrations of CPT-11 daily for four consecutive days. Toxicities were evaluated with regard to tissue glucuronidation potential. CPT-11-treated Ugt1(DeltaHep) mice showed a similar lethality rate to the CPT-11-treated Ugt1(F/F) mice. However, Ugt1(DeltaGI) mice were highly susceptible to CPT-11-induced diarrhea, developing severe and lethal mucositis at much lower CPT-11 doses, a result of the proliferative cell loss and inflammation in the intestinal tract. Comparative expression levels of UGT1A1 in intestinal tumors and normal surrounding tissue are dramatically different, providing for the opportunity to improve therapy by differential gene regulation. Intestinal expression of the UGT1A proteins is critical toward the detoxification of SN-38, whereas induction of the UGT1A1 gene may serve to limit toxicity and improve the efficacy associated with CPT-11 treatment.
ESTHER : Chen_2013_Proc.Natl.Acad.Sci.U.S.A_110_19143
PubMedSearch : Chen_2013_Proc.Natl.Acad.Sci.U.S.A_110_19143
PubMedID: 24191041

Title : Extracellular overexpression of recombinant Thermobifida fusca cutinase by alpha-hemolysin secretion system in E. coli BL21(DE3) - Su_2012_Microb.Cell.Fact_11_8
Author(s) : Su L , Chen S , Yi L , Woodard RW , Chen J , Wu J
Ref : Microb Cell Fact , 11 :8 , 2012
Abstract : BACKGROUND: Extracellular expression of proteins has an absolute advantage in a large-scale industrial production. In our previous study, Thermobifida fusca cutinase, an enzyme mainly utilized in textile industry, was expressed via type II secretory system in Escherichia coli BL21(DE3), and it was found that parts of the expressed protein was accumulated in the periplasmic space. Due to the fact that alpha-hemolysin secretion system can export target proteins directly from cytoplasm across both cell membrane of E. coli to the culture medium, thus in the present study we investigated the expression of cutinase using this alpha-hemolysin secretion system. RESULTS: T. fusca cutinase was fused with the specific signal peptide of alpha-hemolysin scretion system and expressed in E. coli BL21(DE3). In addition, HlyB and HlyD, strain-specific translocation components of alpha-hemolysin secretion system, were coexpressed to facilitate the enzyme expression. The cultivation of this engineered cell showed that cutinase activity in the culture medium reached 334 U/ml, which is 2.5 times that from type II secretion pathway under the same culture condition. The recombinant cutinase was further purified. Biochemical characterization of purified enzyme, which had an alpha-hemolysin secretion pathway signal peptide attached, had substrate specificity, pH and temperature profile, as well as application capability in bioscouring similar to that of wild-type cutinase. CONCLUSIONS: In the present study, T. fusca cutinase was successfully secreted to the culture media by alpha-hemolysin secretion system. This is the first report of cutinase being efficiently secreted by this pathway. Due to the limited cases of successful expression of industrial enzyme by E. coli alpha-hemolysin secretion system, our study further explored the utilization of this pathway in industrial enzymes.
ESTHER : Su_2012_Microb.Cell.Fact_11_8
PubMedSearch : Su_2012_Microb.Cell.Fact_11_8
PubMedID: 22239833

Title : Functional characterization of lipase in the pathogenesis of Staphylococcus aureus - Hu_2012_Biochem.Biophys.Res.Commun_419_617
Author(s) : Hu C , Xiong N , Zhang Y , Rayner S , Chen S
Ref : Biochemical & Biophysical Research Communications , 419 :617 , 2012
Abstract : During infection, Staphylococcus aureus produces multiple enzymes that enable it to invade and destroy host tissues and metastasize to other sites. One such enzyme, lipase, has been recognized for its relationship in the virulence of S. aureus. However, a direct involvement of lipase in the pathogenesis of S. aureus remains to be demonstrated. Our prior study indicated that anti-lipase serum inhibits biofilm formation in S. aureus clinical strains. The aim of this study was to further characterize the roles of lipase in the pathogenesis in S. aureus. We found that deletion of the lipase-coding gene reduced biofilm formation relative to the wild-type strain. This was shown by culture in 96-well plates coated with collagen to resemble the in vivo infection process. Intraperitoneal inoculation of mice with a lipase mutant strain showed defective formation of peritoneal abscesses, and bacterial loads in different organs were much lower compared with the wild-type. Importantly, active immunization with recombinant lipase protected mice against a lethal challenge with S. aureus. Altogether, our data provide evidence that S. aureus lipase plays important roles in the pathogenesis of S. aureus.
ESTHER : Hu_2012_Biochem.Biophys.Res.Commun_419_617
PubMedSearch : Hu_2012_Biochem.Biophys.Res.Commun_419_617
PubMedID: 22369949

Title : Enantiomeric separation and toxicity of an organophosporus insecticide, pyraclofos - Zhang_2012_J.Agric.Food.Chem_60_6953
Author(s) : Zhang H , Chen S , Zhou S
Ref : Journal of Agricultural and Food Chemistry , 60 :6953 , 2012
Abstract : Despite the fact that the biological processes of chiral pesticides are enantioselective, knowledge of the toxicities of pyraclofos due to enantiospecificity is scarce. In this study, the optical isomers of pyraclofos were separated and their toxicities to butyrylcholinesterase (BChE) and Daphnia magna were assessed. Baseline resolution of the enantiomers was obtained on both Chiralcel OD and Chiralpak AD columns. The effect of the mobile phase composition and column temperature were then discussed. The resolved enantiomers were characterized by their optical rotation and circular dichroism signs. The anti-BChE tests demonstrated that (-)-pyraclofos was about 15 times more potent than its (+)-form. However, acute aquatic assays suggested that (+)-pyraclofos was about 6 times more toxic than its antipode. Moreover, the joint toxicity of pyraclofos enantiomers to D. magna was found to be an additive effect. These results demonstrated that the overall toxicity of pyraclofos should be assessed using the individual enantiomers.
ESTHER : Zhang_2012_J.Agric.Food.Chem_60_6953
PubMedSearch : Zhang_2012_J.Agric.Food.Chem_60_6953
PubMedID: 22708718

Title : Identification of Human Butyrylcholinesterase Organophosphate-Resistant Variants through a Novel Mammalian Enzyme Functional Screen - Zhang_2012_J.Pharmacol.Exp.Ther_343_673
Author(s) : Zhang J , Chen S , Ralph EC , Dwyer MA , Cashman JR
Ref : Journal of Pharmacology & Experimental Therapeutics , 343 :673 , 2012
Abstract : Human butyrylcholinesterase (hBChE) is currently being developed as a detoxication enzyme for the catalytic hydrolysis or stoichiometric binding of organophosphates (OPs). Previously, rationally designed hBChE mutants (G117H and E197Q) were reported in the literature and showed the feasibility of engineering OP hydrolytic functional activity into hBChE. However, the OP hydrolysis rate for G117H is too low for clinical utility. Additional OP-resistant hBChE variants with greater hydrolysis rates are needed as OP nerve-agent countermeasures for therapeutic utility. As described herein, a directed molecular evolution process was used to identify amino acid residues that contribute to OP-resistant functional activity of hBChE variants. In this article, we describe the development and validation of a novel method to identify hBChE variants with OP-resistant functional activity (decreased rate of OP inhibition). The method reported herein used an adenoviral protein expression system combined with a functional screening protocol of OP nerve-agent model compounds that have been shown to have functional properties similar to authentic OP nerve-agent compounds. The hBChE screening method was robust for transfection efficiency, library diversity, and reproducibility of positive signals. The screening approach not only identified the previously reported hBChE G117H variant, but also identified a series of additional hBChE variants, including hBChE G117N, G117R, E197C, and L125V, that exhibited OP-resistant functional activities not reported previously. The mammalian functional screening approach can serve as a cornerstone for further optimization and screening for OP-resistant hBChEs for potential therapeutic applications.
ESTHER : Zhang_2012_J.Pharmacol.Exp.Ther_343_673
PubMedSearch : Zhang_2012_J.Pharmacol.Exp.Ther_343_673
PubMedID: 22956723

Title : Engineered Thermobifida fusca cutinase with increased activity on polyester substrates - Silva_2011_Biotechnol.J_6_1230
Author(s) : Silva C , Da S , Silva N , Matama T , Araujo R , Martins M , Chen S , Chen J , Wu J , Casal M , Cavaco-Paulo A
Ref : Biotechnol J , 6 :1230 , 2011
Abstract : A bacterial cutinase from Thermobifida fusca, named Tfu_0883, was genetically modified by site-directed mutagenesis to enhance its activity on poly(ethylene terephthalate) (PET). The new mutations tailored the catalytic site for PET, increasing the affinity of cutinase to this hydrophobic substrate and the ability to hydrolyze it. The mutation I218A was designed to create space and the double mutation Q132A/T101A was designed both to create space and to increase hydrophobicity. The activity of the double mutant on the soluble substrate p-nitrophenyl butyrate increased two-fold compared to wild-type cutinase, while on PET both single and double mutants exhibited considerably higher hydrolysis efficiency. The replacement of specific amino acids at the active site was an effective approach for the improvement of the Tfu_0883 cutinase capacity to hydrolyze polyester surfaces. Thus, this study provides valuable insight on how the function and stability of enzymes can be improved by molecular engineering for their application in synthetic fiber biotransformation.
ESTHER : Silva_2011_Biotechnol.J_6_1230
PubMedSearch : Silva_2011_Biotechnol.J_6_1230
PubMedID: 21751386
Gene_locus related to this paper: thefu-q6a0i4

Title : Effect of Silent Mutations in Translational Initial Region on the Production of Recombinant Cutinase in Escherichia coli - Liu_2011_Curr.Microbiol_62_1302
Author(s) : Liu ZG , Zhu L , Zhu KL , Chen S , Chen J , Wu J
Ref : Curr Microbiol , 62 :1302 , 2011
Abstract : Translational Initial Region (TIR) is the threshold of an intracellular translation process, and tiny alterations in this region are reported to intensely influence the downstream expression. Such property provides a potential utilization in extracellular production of recombinant enzyme. As an esterase, cutinase is an essential catalyst in the process of textile scouring, and has a potential application in food and chemical industry. In the present study, a bacterial cutinase (Tfu_0883) from Thermobifida fusca was expressed in Escherichia coli with pelB as its signal peptide using trc as its promoter. A subsequent TIR degeneracy mutagenesis was then carried out in the initial sequence of pelB. A fast screening method for these mutants was developed and a series of strains with different expression strengths were accordingly obtained. Among these mutants, a high cutinase production level of 38.0 U/ml was achieved, which is three times that of the control group. This study explored the potential utilization of TIR degeneracy mutagenesis in the production of industrial enzymes.
ESTHER : Liu_2011_Curr.Microbiol_62_1302
PubMedSearch : Liu_2011_Curr.Microbiol_62_1302
PubMedID: 21212953

Title : Structural diversity of bacterial flagellar motors - Chen_2011_EMBO.J_30_2972
Author(s) : Chen S , Beeby M , Murphy GE , Leadbetter JR , Hendrixson DR , Briegel A , Li Z , Shi J , Tocheva EI , Muller A , Dobro MJ , Jensen GJ
Ref : EMBO Journal , 30 :2972 , 2011
Abstract : The bacterial flagellum is one of nature's most amazing and well-studied nanomachines. Its cell-wall-anchored motor uses chemical energy to rotate a microns-long filament and propel the bacterium towards nutrients and away from toxins. While much is known about flagellar motors from certain model organisms, their diversity across the bacterial kingdom is less well characterized, allowing the occasional misrepresentation of the motor as an invariant, ideal machine. Here, we present an electron cryotomographical survey of flagellar motor architectures throughout the Bacteria. While a conserved structural core was observed in all 11 bacteria imaged, surprisingly novel and divergent structures as well as different symmetries were observed surrounding the core. Correlating the motor structures with the presence and absence of particular motor genes in each organism suggested the locations of five proteins involved in the export apparatus including FliI, whose position below the C-ring was confirmed by imaging a deletion strain. The combination of conserved and specially-adapted structures seen here sheds light on how this complex protein nanomachine has evolved to meet the needs of different species.
ESTHER : Chen_2011_EMBO.J_30_2972
PubMedSearch : Chen_2011_EMBO.J_30_2972
PubMedID: 21673657
Gene_locus related to this paper: 9burk-f3kvd4 , 9firm-f7njq4

Title : Complete sequencing and pan-genomic analysis of Lactobacillus delbrueckii subsp. bulgaricus reveal its genetic basis for industrial yogurt production - Hao_2011_PLoS.One_6_e15964
Author(s) : Hao P , Zheng H , Yu Y , Ding G , Gu W , Chen S , Yu Z , Ren S , Oda M , Konno T , Wang S , Li X , Ji ZS , Zhao G
Ref : PLoS ONE , 6 :e15964 , 2011
Abstract : Lactobacillus delbrueckii subsp. bulgaricus (Lb. bulgaricus) is an important species of Lactic Acid Bacteria (LAB) used for cheese and yogurt fermentation. The genome of Lb. bulgaricus 2038, an industrial strain mainly used for yogurt production, was completely sequenced and compared against the other two ATCC collection strains of the same subspecies. Specific physiological properties of strain 2038, such as lysine biosynthesis, formate production, aspartate-related carbon-skeleton intermediate metabolism, unique EPS synthesis and efficient DNA restriction/modification systems, are all different from those of the collection strains that might benefit the industrial production of yogurt. Other common features shared by Lb. bulgaricus strains, such as efficient protocooperation with Streptococcus thermophilus and lactate production as well as well-equipped stress tolerance mechanisms may account for it being selected originally for yogurt fermentation industry. Multiple lines of evidence suggested that Lb. bulgaricus 2038 was genetically closer to the common ancestor of the subspecies than the other two sequenced collection strains, probably due to a strict industrial maintenance process for strain 2038 that might have halted its genome decay and sustained a gene network suitable for large scale yogurt production.
ESTHER : Hao_2011_PLoS.One_6_e15964
PubMedSearch : Hao_2011_PLoS.One_6_e15964
PubMedID: 21264216
Gene_locus related to this paper: lacda-q1g8l1 , lacdl-pip

Title : Study on improvement of extracellular production of recombinant Thermobifida fusca cutinase by Escherichia coli - Chen_2011_Appl.Biochem.Biotechnol_165_666
Author(s) : Chen S , Liu Z , Chen J , Wu J
Ref : Appl Biochem Biotechnol , 165 :666 , 2011
Abstract : Escherichia coli is one of the most commonly used host strains for recombinant protein production. More and more research works on the production of recombinant protein indicate that extracellular production throughout a culture medium is more convenient and attractive compared to intracellular production. In present work, inducing temperature and isopropyl beta-D: -1-thiogalactopyranoside (IPTG) concentration were investigated to decrease the formation of inclusion body and increase the amount of soluble recombinant cutinase initially. Enzyme activity in the culture medium reached to 118.9 U/ml at 64 h of culture, and no inclusion body was detected in cytoplasm under the inducement condition of 0.2 mM IPTG and 30 degrees C. In addition, it was found that a large amount of cutinase had been accumulated in periplasm since 16-h cultivation under the same inducement condition. Therefore, glycine and surfactant sodium taurodeoxycholate (TDOC) were further used to promote the leakage of recombinant cutinase from periplasm. Supplied with 100 mM glycine and 1 mM TDOC, the amount of cutinase in periplasm decreased remarkably, and the activity in the culture medium reached to 146.2 and 149.2 U/ml after 54 h of culturing, respectively.
ESTHER : Chen_2011_Appl.Biochem.Biotechnol_165_666
PubMedSearch : Chen_2011_Appl.Biochem.Biotechnol_165_666
PubMedID: 21594592

Title : Complete genome sequence of Bifidobacterium longum subsp. longum BBMN68, a new strain from a healthy chinese centenarian - Hao_2011_J.Bacteriol_193_787
Author(s) : Hao Y , Huang D , Guo H , Xiao M , An H , Zhao L , Zuo F , Zhang B , Hu S , Song S , Chen S , Ren F
Ref : Journal of Bacteriology , 193 :787 , 2011
Abstract : Bifidobacterium longum subsp. longum BBMN68 was isolated from the feces of a healthy centenarian living in an area of BaMa, Guangxi, China, known for longevity. Here we report the main genome features of B. longum strain BBMN68 and the identification of several predicted proteins associated with the ecological niche of longevity.
ESTHER : Hao_2011_J.Bacteriol_193_787
PubMedSearch : Hao_2011_J.Bacteriol_193_787
PubMedID: 21097614
Gene_locus related to this paper: biflo-BL0073 , biflo-BL0336 , biflo-BL0581 , biflo-BL0582 , biflo-BL0682 , biflo-BL0787 , biflo-BL0807 , biflo-BL1109 , biflo-BL1514 , biflo-PAP , biflo-PTRB

Title : Highly pure phospholipids based brain docosahexaenoic Acid transporters - Chen_2010_Recent.Pat.CNS.Drug.Discov_5_135
Author(s) : Chen S
Ref : Recent Pat CNS Drug Discov , 5 :135 , 2010
Abstract : The most common age-dependent neurodegenerative disorders such as dementia and Alzheimer's disease have become an urgent public health problem in the most areas of the world. The strategy of the current therapy focuses on increasing availability of brain acetylcholine concentration, and use of acetylcholinesterase inhibitors has become the main approach to symptomatic treatment. However, an ideal drug for the disorders should enable to both simultaneously delay or halt the underlying pathological process and improve memory. The present paper describes an alterative cholinergic strategy to memory enhancement by the exogenous introduction of highly enriched docosahexaenoic acid (DHA)--containing molecular species of highly pure phospholipids and highly pure ether phospholipids based brain DHA transporters to promote survival of aged basal forebrain cholinergic neurons (BFCNs) through reversing abnormal levels of neural membrane DHA aminophospholipids. This results in significantly improving neural membrane fluidity and gap capacity leading to further recovering the expression of the p75 neurotrophin receptor and then failed retrograde nerve growth factor signaling, followed by promoting the choline acetyltransferase activity in the BFCNs. The pre-clinical results shown in published patents and recent applications to support the proposed therapeutic mechanism of the brain DHA transporters are summarized. The advantage of the potential drugs in both the prevention and treatment of age-dependent basal forebrain cholinergic dysfunction related neurodegenerative disorders is further discussed.
ESTHER : Chen_2010_Recent.Pat.CNS.Drug.Discov_5_135
PubMedSearch : Chen_2010_Recent.Pat.CNS.Drug.Discov_5_135
PubMedID: 19832689

Title : Characterization of Thermobifida fusca cutinase-carbohydrate-binding module fusion proteins and their potential application in bioscouring - Zhang_2010_Appl.Environ.Microbiol_76_6870
Author(s) : Zhang Y , Chen S , Xu M , Cavaco-Paulo A , Wu J , Chen J
Ref : Applied Environmental Microbiology , 76 :6870 , 2010
Abstract : Cutinase from Thermobifida fusca is thermally stable and has potential application in the bioscouring of cotton in the textile industry. In the present study, the carbohydrate-binding modules (CBMs) from T. fusca cellulase Cel6A (CBM(Cel6A)) and Cellulomonas fimi cellulase CenA (CBM(CenA)) were fused, separately, to the carboxyl terminus of T. fusca cutinase. Both fusion enzymes, cutinase-CBM(Cel6A) and cutinase-CBM(CenA), were expressed in Escherichia coli and purified to homogeneity. Enzyme characterization showed that both displayed similar catalytic properties and pH stabilities in response to T. fusca cutinase. In addition, both fusion proteins displayed an activity half-life of 53 h at their optimal temperature of 50 degrees C. Compared to T. fusca cutinase, in the absence of pectinase, the binding activity on cotton fiber was enhanced by 2% for cutinase-CBM(Cel6A) and by 28% for cutinase-CBM(CenA), whereas in the presence of pectinase, the binding activity was enhanced by 40% for the former and 45% for the latter. Notably, a dramatic increase of up to 3-fold was observed in the amount of released fatty acids from cotton fiber by both cutinase-CBM fusion proteins when acting in concert with pectinase. This is the first report of improving the scouring efficiency of cutinase by fusing it with CBM. The improvement in activity and the strong synergistic effect between the fusion proteins and pectinase suggest that they may have better applications in textile bioscouring than the native cutinase.
ESTHER : Zhang_2010_Appl.Environ.Microbiol_76_6870
PubMedSearch : Zhang_2010_Appl.Environ.Microbiol_76_6870
PubMedID: 20729325

Title : Biochemical characterization of the cutinases from Thermobifida fusca - Chen_2010_J.Mol.Catal.B.Enzym_63_121
Author(s) : Chen S , Su L , Billig S , Zimmermann W , Chen J , Wu J
Ref : J Mol Catal B Enzym , 63 :121 , 2010
Abstract : Thermobifida fusca produces two cutinases which share 93% identity in amino acid sequence. In the present study, we investigated the detailed biochemical properties of T. fusca cutinases for the first time. For a better comparison between bacterial and fungal cutinases, recombinant Fusarium solani pisi cutinase was subjected to the similar analysis. The results showed that both bacterial and fungal cutinases are monomeric proteins in solution. The bacterial cutinases exhibited a broad substrate specificity against plant cutin, synthetic polyesters, insoluble triglycerides, and soluble esters. In addition, the two isoenzymes of T. fusca and the F.solani pisi cutinase are similar in substrate kinetics, the lack of interfacial activation, and metal ion requirements. However, the T.fusca cutinases showed higher stability in the presence of surfactants and organic solvents. Considering the versatile hydrolytic activity, good tolerance to surfactants, superior stability in organic solvents, and thermostability demonstrated by T. fusca cutinases, they may have promising applications in related industries.
ESTHER : Chen_2010_J.Mol.Catal.B.Enzym_63_121
PubMedSearch : Chen_2010_J.Mol.Catal.B.Enzym_63_121
PubMedID:
Gene_locus related to this paper: thefu-q6a0i4 , thefu-q6a0i3

Title : Genome sequencing and analysis of the model grass Brachypodium distachyon. -
Author(s) : Vogel JP , Garvin DF , Mockler TC , Schmutz J , Rokhsar D , Bevan MW , Barry K , Lucas S , Harmon-Smith M , Lail K , Tice H , Grimwood J , McKenzie N , Huo N , Gu YQ , Lazo GR , Anderson OD , You FM , Luo MC , Dvorak J , Wright J , Febrer M , Idziak D , Hasterok R , Lindquist E , Wang M , Fox SE , Priest HD , Filichkin SA , Givan SA , Bryant DW , Chang JH , Wu H , Wu W , Hsia AP , Schnable PS , Kalyanaraman A , Barbazuk B , Michael TP , Hazen SP , Bragg JN , Laudencia-Chingcuanco D , Weng Y , Haberer G , Spannagl M , Mayer K , Rattei T , Mitros T , Lee SJ , Rose JK , Mueller LA , York TL , Wicker T , Buchmann JP , Tanskanen J , Schulman AH , Gundlach H , Bevan M , de Oliveira AC , Maia Lda C , Belknap W , Jiang N , Lai J , Zhu L , Ma J , Sun C , Pritham E , Salse J , Murat F , Abrouk M , Bruggmann R , Messing J , Fahlgren N , Sullivan CM , Carrington JC , Chapman EJ , May GD , Zhai J , Ganssmann M , Gurazada SG , German M , Meyers BC , Green PJ , Tyler L , Wu J , Thomson J , Chen S , Scheller HV , Harholt J , Ulvskov P , Kimbrel JA , Bartley LE , Cao P , Jung KH , Sharma MK , Vega-Sanchez M , Ronald P , Dardick CD , De Bodt S , Verelst W , Inz D , Heese M , Schnittger A , Yang X , Kalluri UC , Tuskan GA , Hua Z , Vierstra RD , Cui Y , Ouyang S , Sun Q , Liu Z , Yilmaz A , Grotewold E , Sibout R , Hematy K , Mouille G , Hofte H , Michael T , Pelloux J , O'Connor D , Schnable J , Rowe S , Harmon F , Cass CL , Sedbrook JC , Byrne ME , Walsh S , Higgins J , Li P , Brutnell T , Unver T , Budak H , Belcram H , Charles M , Chalhoub B , Baxter I
Ref : Nature , 463 :763 , 2010
PubMedID: 20148030
Gene_locus related to this paper: bradi-i1grm0 , bradi-i1gx82 , bradi-i1hb80 , bradi-i1hkv6 , bradi-i1hpu6 , bradi-i1i3e4 , bradi-i1i9i0 , bradi-i1i435 , bradi-i1ix93 , bradi-i1gsk6 , bradi-i1hk44 , bradi-i1hk45 , bradi-i1hnk7 , bradi-i1hsd5 , bradi-i1huy4 , bradi-i1huy9 , bradi-i1huz0 , bradi-i1gxx9 , bradi-i1hl25 , bradi-i1hcw7 , bradi-i1hyv6 , bradi-i1hyb5 , bradi-i1hvr8 , bradi-i1hmu2 , bradi-i1hf05 , bradi-i1gry7 , bradi-i1hf06 , bradi-i1i5z8 , bradi-i1icy3 , bradi-i1j1h3 , bradi-i1h1e3 , bradi-i1hvr9 , bradi-a0a0q3r7i7 , bradi-i1i377 , bradi-i1hjg5 , bradi-i1h3i9 , bradi-i1gsg5 , bradi-a0a0q3mph9 , bradi-i1h682 , bradi-a0a0q3lc91 , bradi-i1gx49 , bradi-i1i839 , bradi-a0a2k2dsp5 , bradi-i1gsb5

Title : Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study - Hou_2009_Hum.Genet_125_11
Author(s) : Hou L , Chen S , Yu H , Lu X , Chen J , Wang L , Huang J , Fan Z , Gu D
Ref : Hum Genet , 125 :11 , 2009
Abstract : The human PLA2G7 gene encodes lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an emerging risk factor for cardiovascular diseases. In the present study, seven single nucleotide polymorphisms (SNPs) in the PLA2G7 gene were genotyped in 827 patients with coronary heart disease (CHD), of which 512 were patients with myocardial infarction (MI), and 947 age- and gender-matched controls in a Chinese Han population. Plasma Lp-PLA(2) activity was measured in 416 randomly selected controls and 689 randomly selected CHD patients, including 423 MI patients. Lp-PLA(2) activity in CHD and MI cases was significantly higher (233.42+/-57.66 and 234.27+/-59.51 nmol ml(-1) min(-1), respectively) than in controls (211.47+/-58.61 nmol ml(-1) min(-1)). After adjusting for traditional risk factors by logistic regression, the odds ratios for CHD and MI per 1 standard deviation increment of Lp-PLA(2) activity were 1.27 (95% CI, 1.07-1.50) and 1.27 (95% CI, 1.05-1.54), respectively. Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA(2) activity, but neither was associated with increased CHD risk. Both univariate and multivariate analyses, adjusting effects of conventional factors, indicated that the rs13210554 T allele increased the risk of MI in this Chinese Han population. In summary, an independent association of increased plasma Lp-PLA(2) activity with CHD and MI existed in this Chinese Han Population. Although V279F and I198T mutations significantly decreased the activity of Lp-PLA(2), only the promoter rs13210554 polymorphism was associated with MI. Lp-PLA(2) activity appears to influence the CHD and MI risk in Chinese Han population.
ESTHER : Hou_2009_Hum.Genet_125_11
PubMedSearch : Hou_2009_Hum.Genet_125_11
PubMedID: 19034521
Gene_locus related to this paper: human-PLA2G7

Title : Interaction of sortase A and lipase 2 in the inhibition of Staphylococcus aureus biofilm formation - Xiong_2009_Arch.Microbiol_191_879
Author(s) : Xiong N , Hu C , Zhang Y , Chen S
Ref : Arch Microbiol , 191 :879 , 2009
Abstract : Recombinant sortase A (SrtA) was used to immune rabbit, and the inhibitory activity of anti-SrtA serum on Staphylococcus aureus biofilm formation was tested. Biofilm formation was inhibited by anti-SrtA rabbit serum in S. aureus ATCC25923 and two clinical isolated strains. The antiserum was separated into two fractions, and the main component with the inhibitory activity was demonstrated to be the IgG fraction. Two proteins interact with the IgG fraction were identified by using an in vitro pull-down assay and were confirmed to be lipase 2 and gamma-hemolysin by mass spectrometry. Cross-interaction between SrtA and lipase 2 was further confirmed by Western blotting. Addition of anti-lipase 2 serum in the culture medium also showed inhibitory effect against biofilm formation. Together, our study suggests anti-SrtA serum inhibits S. aureus biofilm formation and lipase 2 is one of the targets of anti-SrtA serum in this inhibition process. This is the first study to demonstrate the roles of antisera against SrtA and lipase 2 in the inhibition of biofilm formation in S. aureus.
ESTHER : Xiong_2009_Arch.Microbiol_191_879
PubMedSearch : Xiong_2009_Arch.Microbiol_191_879
PubMedID: 19838678

Title : Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region - Zhang_2008_Gene_417_5
Author(s) : Zhang J , Chen S , Zhang W , Liu X , Shi H , Che H , Wang W , Li F , Yao L
Ref : Gene , 417 :5 , 2008
Abstract : N-Myc downstream-regulated gene 1 (ndrg1) is up-regulated in N-Myc knockout mouse embryos. The human NDRG family consists of 4 highly homologous members and human Ndrg1 exhibits approximately 94% homology with mouse ndrg1. However, the regulatory mechanism of NDRG1 via Myc repression is as yet unknown. We previously identified human NDRG2 and demonstrated that this gene is transcriptionally down-regulated by Myc via Miz-1-dependent interaction with the core promoter region of NDRG2. Here, we provide evidence that human NDRG1 is regulated by Myc in a manner similar to NDRG2. We found that Ndrg1 expression levels were enhanced as Myc expression declined in differentiated cells, but were down-regulated following Myc induction. The data revealed that both N-Myc and c-Myc can repress human NDRG1 at the transcriptional level. We further determined that the core promoter region of human NDRG1 is required for Myc repression, and verified the interaction of Myc with the core promoter region. However, the presence of the protein synthesis inhibitor cycloheximide could reverse the repression of Myc, indicating the indirect repression of human NDRG1 by Myc. Moreover, we found that c-Myc-mediated repression can be inhibited by TSA, an HDACs inhibitor, which suggests the involvement of HDACs in the repression process. Taken together, our results demonstrate that, in common with NDRG2, human NDRG1 can be indirectly transcriptionally down-regulated by Myc via interaction with the NDRG1 core promoter.
ESTHER : Zhang_2008_Gene_417_5
PubMedSearch : Zhang_2008_Gene_417_5
PubMedID: 18455888

Title : Polymorphisms of the lipoprotein lipase gene are associated with atherosclerotic cerebral infarction in the Chinese - Xu_2008_Neurosci_155_403
Author(s) : Xu E , Li W , Zhan L , Guan G , Wang X , Chen S , Shi Y
Ref : Neuroscience , 155 :403 , 2008
Abstract : BACKGROUND: Lipoprotein lipase (LPL), which plays an essential role in plasma lipoprotein metabolism and transportation, appears to be a risk factor for ischemic vascular diseases. Several studies have recently reported the presence of relationship between HindIII, PvuII, Ser447Ter (C-->G) polymorphisms of LPL and ischemic vascular diseases. PURPOSE: We first studied the relationship between LPL polymorphisms and the risk of atherosclerotic cerebral infarction (CI) by detecting the frequencies of LPL HindIII, PvuII and Ser447Ter genotypes and combined genotypes in the Chinese. METHODS: We recruited 185 CI patients, confirmed by cranial computed tomography or magnetic resonance imaging/angiography, or both, and 186 control subjects. Polymerase chain reaction-restriction fragment length polymorphisms technique was used to detect HindIII, PvuII and Ser447Ter polymorphisms of the LPL gene. RESULTS: The frequencies of the H+H+ genotype and H+ allele did not differ between CI and control groups. The frequencies of the P+P+ genotype and P+ allele gene were significantly higher in the CI group (P=0.040, P=0.015). The frequencies of CG+GG genotype and G allele were lower in the CI group (P<0.001, P<0.001). In the CI group, the individuals with P+P+ genotype had a significantly higher level of plasma triglyceride (TG) and a lower level of plasma high density lipoprotein cholesterol (HDL-c). CG+GG genotypes were correlated with significantly higher levels of plasma total cholesterol (TC), HDL-c and low density lipoprotein cholesterol (LDL-c) in the CI group. The frequencies of H+/C and P+/C combined genotypes were higher in the CI group than in controls (P<0.001, P<0.001). The frequency of H+/P+/C combined genotype was significantly higher in the CI group than in controls (P<0.001). CONCLUSIONS: Our study suggests that PvuII and Ser447Ter polymorphisms are associated with lipid profile and CI.
ESTHER : Xu_2008_Neurosci_155_403
PubMedSearch : Xu_2008_Neurosci_155_403
PubMedID: 18590804

Title : Identification and characterization of bacterial cutinase - Chen_2008_J.Biol.Chem_283_25854
Author(s) : Chen S , Tong X , Woodard RW , Du G , Wu J , Chen J
Ref : Journal of Biological Chemistry , 283 :25854 , 2008
Abstract : Cutinase, which exists in both fungi and bacteria, catalyzes the cleavage of the ester bonds of cutin. Fungal cutinases have been extensively studied, however, reports on bacterial cutinases have been limited due to the lack of knowledge concerning the identity of their open reading frames. In the present study, the cutinase from Thermobifida fusca was induced by cutin and purified to homogeneity by following p-nitrophenyl butyrate hydrolyzing activity. Peptide mass fingerprinting analysis of the wild-type enzyme matched two proteins, Tfu_0883 and Tfu_0882, which are 93% identical in sequence. Both proteins were cloned and overexpressed in their mature form. Recombinant Tfu_0883 and Tfu_0882 display very similar enzymatic properties and were confirmed to be cutinases by their capability to hydrolyze the ester bonds of cutin. Comparative characterization of Fusarium solani pisi and T. fusca cutinases indicated that they have similar substrate specificity and catalytic properties except that the T. fusca enzymes are thermally more stable. Homology modeling revealed that T. fusca cutinases adopt an alpha/beta-hydrolase fold that exhibits both similarities and variations from the fungal cutinase structure. A serine hydrolase catalytic mechanism involving a Ser(170)-His(248)-Asp(216) (Tfu_0883 numbering) catalytic triad was supported by active site-directed inhibition studies and mutational analyses. This is the first report of cutinase encoding genes from bacterial sources.
ESTHER : Chen_2008_J.Biol.Chem_283_25854
PubMedSearch : Chen_2008_J.Biol.Chem_283_25854
PubMedID: 18658138
Gene_locus related to this paper: thefu-q6a0i4 , thefu-q6a0i3

Title : Characterization of ST-4821 complex, a unique Neisseria meningitidis clone - Peng_2008_Genomics_91_78
Author(s) : Peng J , Yang L , Yang F , Yang J , Yan Y , Nie H , Zhang X , Xiong Z , Jiang Y , Cheng F , Xu X , Chen S , Sun L , Li W , Shen Y , Shao Z , Liang X , Xu J , Jin Q
Ref : Genomics , 91 :78 , 2008
Abstract : Ten outbreaks of a new serogroup C meningococcal disease emerged during 2003-2005 in China. The multilocus sequence typing results indicated that unique sequence type 4821 clone meningococci were responsible for these outbreaks. Herein, we determined the entire genomic DNA sequence of serogroup C isolate 053442, which belongs to ST-4821. Comparison of 053442 gene contents with other meningococcal genomes shows that they have similar characteristics, including thousands of repetitive elements and simple sequence repeats, numerous phase-variable genes, and similar virulence-related factors. However, many strain-specific regions were found in each genome. We also present the results of a genomic comparison of 28 ST-4821 complex isolates that were isolated from different serogroups using comparative genomic hybridization analysis. Genome comparison between the newly emerged hyperinvasive isolates belonging to different serogroups will further our understanding of their respective pathogenetic mechanisms.
ESTHER : Peng_2008_Genomics_91_78
PubMedSearch : Peng_2008_Genomics_91_78
PubMedID: 18031983
Gene_locus related to this paper: neigo-pip , neima-metx , neimb-q9k0t9 , neime-ESD , neime-NMA2216 , neime-NMB0276 , neime-NMB1877

Title : Development of acetylcholinesterase biosensor based on CdTe quantum dots\/gold nanoparticles modified chitosan microspheres interface - Du_2008_Biosens.Bioelectron_24_475
Author(s) : Du D , Chen S , Song D , Li H , Chen X
Ref : Biosensors & Bioelectronics , 24 :475 , 2008
Abstract : In this paper, a novel acetylcholinesterase (AChE) biosensor was constructed by modifying glassy carbon electrode with CdTe quantum dots (QDs) and excellent conductive gold nanoparticles (GNPs) though chitosan microspheres to immobilize AChE. Since GNPs have shown widespread use particularly for constructing electrochemical biosensors through their high electron-transfer ability, the combined AChE exhibited high affinity to its substrate and thus a sensitive, fast and cheap method for determination of monocrotophos. The combination of CdTe QDs and GNPs promoted electron transfer and catalyzed the electro-oxidation of thiocholine, thus amplifying the detection sensitivity. This novel biosensing platform based on CdTe QDs-GNPs composite responded even more sensitively than that on CdTe QDs or GNPs alone because of the presence of synergistic effects in CdTe-GNPs film. The inhibition of monocrotophos was proportional to its concentration in two ranges, from 1 to 1000 ng mL(-1) and from 2 to 15 microg mL(-1), with a detection limit of 0.3 ng mL(-1). The proposed biosensor showed good precision and reproducibility, acceptable stability and accuracy in garlic samples analysis.
ESTHER : Du_2008_Biosens.Bioelectron_24_475
PubMedSearch : Du_2008_Biosens.Bioelectron_24_475
PubMedID: 18640026

Title : Electrochemical pesticide sensitivity test using acetylcholinesterase biosensor based on colloidal gold nanoparticle modified sol-gel interface - Du_2008_Talanta_74_766
Author(s) : Du D , Chen S , Cai J , Zhang A
Ref : Talanta , 74 :766 , 2008
Abstract : Based on the change in electrochemical behavior of enzymatic activity induced by pesticide, a novel electrochemical method for investigation of pesticide sensitivity using acetylcholinesterase (AChE) biosensor was developed. The sol-gel-derived silicate network assembling gold nanoparticles (AuNPs-SiSG) provided a biocompatible microenvironment around the enzyme molecule to stabilize its biological activity and prevented them from leaking out of the interface. The composite was characterized using atomic force microscopy and proved to be chemically clean, porous and homogeneous. AuNPs promoted a conductive pathway for electron transfer and improved electrochemical reactions at a lower potential. Typical pesticides such as monocrotophos, methyl parathion and carbaryl were selected for pesticide sensitivity tests. Due to the inhibitions of pesticides, the electrochemical responses of substrate on AChE-sensors decreased greatly. The inhibition curves showed good correspondence with the results by UV spectrophotometry assay. The proposed electrochemical pesticide sensitivity test exhibited high sensitivity, desirable accuracy, low cost and simplified procedures. This method could be developed as a conventional method to select efficient enzyme inhibitors and investigate toxic compounds against to enzyme.
ESTHER : Du_2008_Talanta_74_766
PubMedSearch : Du_2008_Talanta_74_766
PubMedID: 18371707

Title : Phospholipid and fatty acid specificity of endothelial lipase: potential role of the enzyme in the delivery of docosahexaenoic acid (DHA) to tissues - Chen_2007_Biochim.Biophys.Acta_1771_1319
Author(s) : Chen S , Subbaiah PV
Ref : Biochimica & Biophysica Acta , 1771 :1319 , 2007
Abstract : Docosahexaenoic acid (DHA; 22:6 n-3) is an essential fatty acid required for the normal function of several tissues, especially the brain. Previous studies suggested that lysophosphatidylcholine (lysoPC) is a preferred carrier of DHA to the brain, although the pathways of the formation of DHA-containing lysophospholipids in plasma have not been delineated. We propose that endothelial lipase (EL), a phospholipase A1 that plays an important role in the metabolism of high density lipoproteins, may be responsible for the generation of DHA lysophospholipids in plasma. Here we studied the substrate specificity of EL using deuterium-labeled phospholipids with different polar head groups, as well as DHA-enriched natural phospholipids to test this hypothesis. Glycerol-stabilized phospholipids were treated with recombinant EL, and the products were analyzed by liquid chromatography/electrospray ionization mass spectrometry. EL showed the polar head group specificity in the order of phosphatidylethanolamine>phosphatidylcholine>phosphatidylserine>phosphatidic acid. Within the same phospholipid class, the enzyme showed preference for the species containing DHA at the sn-2 position, and was inactive in the hydrolysis of phospholipids containing an ether linkage. Since EL is known to be secreted by the cells of blood-brain barrier, we suggest that it plays an important role in the delivery of DHA lysophospholipid carriers to the brain.
ESTHER : Chen_2007_Biochim.Biophys.Acta_1771_1319
PubMedSearch : Chen_2007_Biochim.Biophys.Acta_1771_1319
PubMedID: 17905648
Gene_locus related to this paper: human-LIPG

Title : Immobilization of acetylcholinesterase on gold nanoparticles embedded in sol-gel film for amperometric detection of organophosphorous insecticide - Du_2007_Biosens.Bioelectron_23_130
Author(s) : Du D , Chen S , Cai J , Zhang A
Ref : Biosensors & Bioelectronics , 23 :130 , 2007
Abstract : A simple method to immobilize acetylcholinesterase (AChE) on silica sol-gel (SiSG) film assembling gold nanoparticles (AuNPs) was proposed, thus a sensitive, fast and stable amperometric sensor for quantitative determination of organophosphorous insecticide was developed. The large quantities of hydroxyl groups in the sol-gel composite provided a biocompatible microenvironment around enzyme molecule and stabilized its biological activity to a large extent. The immobilized AChE could catalyze the hydrolysis of acetylthiocholine chloride (ATCl) with a Kmapp value of 450 microM to form thiocholine, which was then oxidized to produce detectable single with a linear range of 10-1000 microM. AuNPs catalyzed the electro-oxidation of thiocholine, thus increasing detection sensitivity. Based on the inhibition of organophosphorous insecticide on the enzymatic activity of AChE, using monocrotophos as a model compound, the conditions for detection of the insecticide were optimized. The inhibition of monocrotophos was proportional to its concentration ranging from 0.001 to 1 microg/ml and 2 to 15 microg/ml, with the correlation coefficients of 0.9930 and 0.9985, respectively. The detection limit was 0.6 ng/ml at a 10% inhibition. The developed biosensor exhibited good reproducibility and acceptable stability, thus providing a new promising tool for analysis of enzyme inhibitors.
ESTHER : Du_2007_Biosens.Bioelectron_23_130
PubMedSearch : Du_2007_Biosens.Bioelectron_23_130
PubMedID: 17499494

Title : An amperometric acetylthiocholine sensor based on immobilization of acetylcholinesterase on a multiwall carbon nanotube-cross-linked chitosan composite - Du_2007_Anal.Bioanal.Chem_387_1059
Author(s) : Du D , Huang X , Cai J , Zhang A , Ding J , Chen S
Ref : Anal Bioanal Chem , 387 :1059 , 2007
Abstract : A simple method has been devised for immobilization of acetylcholinesterase (AChE)--covalent bonding to a multiwall carbon nanotube (MWNT)--cross-linked chitosan composite (CMC)-and a sensitive amperometric sensor for rapid detection of acetylthiocholine (ATCl) has been based on this. Fourier-transform infrared spectroscopy proved that the native structure of the immobilized enzyme was preserved on this chemically clean and homogeneous composite film, because of the excellent biocompatibility and non-toxicity of chitosan. Glutaraldehyde was used as cross-linker to covalently bond the AChE, and efficiently prevented leakage of the enzyme from the film. Because of the inherent conductive properties of the MWNT, the immobilized AChE had greater affinity for ATCl and excellent catalytic effect in the hydrolysis of ATCl, with a K(app)(m) value of 132 micromol L(-1), forming thiocholine, which was then oxidized to produce a detectable and rapid response. Under optimum conditions the amperometric current increased linearly with the increasing concentration of ATCl in the range 2.0-400 micromol L(-1), with a detection limit of 0.10 micromol L(-1). Fabrication reproducibility of the sensor was good and the stability was acceptable. The sensor is a promising new tool for characterization of enzyme inhibitors and for pesticide analysis. Abstract.
ESTHER : Du_2007_Anal.Bioanal.Chem_387_1059
PubMedSearch : Du_2007_Anal.Bioanal.Chem_387_1059
PubMedID: 17186224

Title : Current experimental therapy for Alzheimer's disease - Chen_2007_Curr.Neuropharmacol_5_127
Author(s) : Chen S , Zhang XJ , Li L , Le WD
Ref : Curr Neuropharmacol , 5 :127 , 2007
Abstract : In the past decade, enormous efforts have been devoted to understand the genetics and molecular pathogenesis of Alzheimer's disease (AD), which has been transferred into extensive experimental approaches aimed at reversing disease progression. The trend in future AD therapy has been shifted from traditional anti-acetylcholinesterase treatment to multiple mechanisms-based therapy targeting amyloid plaques formation and amyloid peptides (Abeta)-mediated cytotoxicity, and neurofibrillary tangles generation. This review will cover current experimental studies with the focus on secretases-based drug development, immunotherapy, and anti-neurofibrillary tangles intervention. The outcome of these on-going studies may provide high hope that AD can be cured in the future.
ESTHER : Chen_2007_Curr.Neuropharmacol_5_127
PubMedSearch : Chen_2007_Curr.Neuropharmacol_5_127
PubMedID: 18615180

Title : RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion - Ding_2006_Nat.Neurosci_9_832
Author(s) : Ding J , Guzman JN , Tkatch T , Chen S , Goldberg JA , Ebert PJ , Levitt P , Wilson CJ , Hamm HE , Surmeier DJ
Ref : Nat Neurosci , 9 :832 , 2006
Abstract : Parkinson disease is a neurodegenerative disorder whose symptoms are caused by the loss of dopaminergic neurons innervating the striatum. As striatal dopamine levels fall, striatal acetylcholine release rises, exacerbating motor symptoms. This adaptation is commonly attributed to the loss of interneuronal regulation by inhibitory D(2) dopamine receptors. Our results point to a completely different, new mechanism. After striatal dopamine depletion, D(2) dopamine receptor modulation of calcium (Ca(2+)) channels controlling vesicular acetylcholine release in interneurons was unchanged, but M(4) muscarinic autoreceptor coupling to these same channels was markedly attenuated. This adaptation was attributable to the upregulation of RGS4-an autoreceptor-associated, GTPase-accelerating protein. This specific signaling adaptation extended to a broader loss of autoreceptor control of interneuron spiking. These observations suggest that RGS4-dependent attenuation of interneuronal autoreceptor signaling is a major factor in the elevation of striatal acetylcholine release in Parkinson disease.
ESTHER : Ding_2006_Nat.Neurosci_9_832
PubMedSearch : Ding_2006_Nat.Neurosci_9_832
PubMedID: 16699510

Title : Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a - Nie_2006_BMC.Genomics_7_173
Author(s) : Nie H , Yang F , Zhang X , Yang J , Chen L , Wang J , Xiong Z , Peng J , Sun L , Dong J , Xue Y , Xu X , Chen S , Yao Z , Shen Y , Jin Q
Ref : BMC Genomics , 7 :173 , 2006
Abstract : BACKGROUND: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301).
RESULTS: The Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes. CONCLUSION: Our data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.
ESTHER : Nie_2006_BMC.Genomics_7_173
PubMedSearch : Nie_2006_BMC.Genomics_7_173
PubMedID: 16822325
Gene_locus related to this paper: shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PTRB , shifl-S2753 , shifl-SF1808 , shifl-SF3046 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-ycfp , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YIEL , shifl-YJFP , shifl-YPFH , shiss-yeiG , shiss-yqia

Title : Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery - Yang_2005_Nucleic.Acids.Res_33_6445
Author(s) : Yang F , Yang J , Zhang X , Chen L , Jiang Y , Yan Y , Tang X , Wang J , Xiong Z , Dong J , Xue Y , Zhu Y , Xu X , Sun L , Chen S , Nie H , Peng J , Xu J , Wang Y , Yuan Z , Wen Y , Yao Z , Shen Y , Qiang B , Hou Y , Yu J , Jin Q
Ref : Nucleic Acids Research , 33 :6445 , 2005
Abstract : The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.
ESTHER : Yang_2005_Nucleic.Acids.Res_33_6445
PubMedSearch : Yang_2005_Nucleic.Acids.Res_33_6445
PubMedID: 16275786
Gene_locus related to this paper: ecoli-yeiG , shidy-IROD , shidy-q67dv1 , shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-S2753 , shifl-SF1334 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-ycfp , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YJFP , shifl-YPFH , shiss-yaim , shiss-yeiG , shiss-yqia

Title : Neural adhesion molecules L1 and CHL1 are survival factors for motoneurons - Nishimune_2005_J.Neurosci.Res_80_593
Author(s) : Nishimune H , Bernreuther C , Carroll P , Chen S , Schachner M , Henderson CE
Ref : Journal of Neuroscience Research , 80 :593 , 2005
Abstract : Many neurotrophic factors with survival activity for motoneurons in vivo were first identified using cultures of purified embryonic motoneurons. The L1 neural cell adhesion molecule has multiple roles in brain development. We showed by in situ hybridization and RT-PCR that L1 mRNA was expressed at significant levels in motoneurons of embryonic and postnatal spinal cord. We therefore cultured purified motoneurons from E14 rat embryos in the absence of trophic factors but with L1-Fc and CHL1-Fc fusion proteins. L1-Fc prevented the death of approximately half of the motoneurons that were saved by BDNF in a dose-dependent manner (EC50 = 10 pM). CHL1-Fc saved the same number of motoneurons as did L1-Fc, whereas P0-Fc had little neurotrophic activity at the same concentrations. Survival induced by L1 and CHL1 was completely inhibited by 20 microM LY294002 and PD98059, indicating that both MEK and PI3K pathways are required for signaling by these molecules. L1 can signal in other cell types through the FGF receptor FGFR1. In cultures of motoneurons, effects of suboptimal concentrations of L1 and suboptimal concentrations of FGF-2 were additive, but the effects of optimal concentrations of FGF-2 (50 ng/ml) were not further increased in the presence of L1-Fc. Thus, in this system, too, FGF and L1 may use similar signaling pathways.
ESTHER : Nishimune_2005_J.Neurosci.Res_80_593
PubMedSearch : Nishimune_2005_J.Neurosci.Res_80_593
PubMedID: 15880726

Title : Robust axonal sprouting and synaptogenesis in organotypic slice cultures of rat cerebellum exposed to increased potassium chloride - Chen_2005_Brain.Res_1057_88
Author(s) : Chen S , Hirata K , Ren Y , Sugimori M , Llinas R , Hillman DE
Ref : Brain Research , 1057 :88 , 2005
Abstract : Organotypic slices of the rat cerebellum, cultured in physiological levels [K+]o (5 mM) for 14 days, loose the majority of granule cells in the anterior lobe resulting in few axons and atypical Purkinje cell dendrites with vacant spines. When the culture medium was switched from 5 mM to 20, 30 or 40 mM [K+]o during the last 7 days of cultures, slices developed axons with numerous vesicle-filled boutons that made synaptic contact with Purkinje cell spines. Most boutons had one or two spine profile contacts, while some were unusually large. Enlarged boutons abutted Purkinje cell somata or their dendrites, causing intervening spines to invaginate terminals to form rosette synaptic complexes. Calbindin immuno-labeling excluded Purkinje cell axonal collaterals as the source of rosette boutons and suggested a granule cell origin. Quantification of vacant spines as compared to those on boutons revealed a threshold for potassium, between 10 and 20 mM, where the number of synaptic spines increased and vacant spines decreased drastically. These findings suggest that elevated [K+]o triggers an activity-dependent plasticity in rat cerebellar slice cultures by promoting axonal sprouting with formation of vesicle-filled boutons and synaptogenesis on open receptor sites of Purkinje cell spines.
ESTHER : Chen_2005_Brain.Res_1057_88
PubMedSearch : Chen_2005_Brain.Res_1057_88
PubMedID: 16125152

Title : Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line - Shu_2004_Mol.Cell.Proteomics_3_279
Author(s) : Shu H , Chen S , Bi Q , Mumby M , Brekken DL
Ref : Mol Cell Proteomics , 3 :279 , 2004
Abstract : A major goal of the Alliance for Cellular Signaling is to elaborate the components of signal transduction networks in model cell systems, including murine B lymphocytes. Due to the importance of protein phosphorylation in many aspects of cell signaling, the initial efforts have focused on the identification of phosphorylated proteins. In order to identify serine- and threonine-phosphorylated proteins on a proteome-wide basis, WEHI-231 cells were treated with calyculin A, a serine/threonine phosphatase inhibitor, to induce high levels of protein phosphorylation. Proteins were extracted from whole-cell lysates and digested with trypsin. Phosphorylated peptides were then enriched using immobilized metal affinity chromatography and identified by liquid chromatography-tandem mass spectrometry. A total of 107 proteins and 193 phosphorylation sites were identified using these methods. Forty-two of these proteins have been reported to be phosphorylated, but only some of them have been detected in B cells. Fifty-four of the identified proteins were not previously known to be phosphorylated. The remaining 11 phosphoproteins have previously only been characterized as novel cDNA or genomic sequences. Many of the identified proteins were phosphorylated at multiple sites. The proteins identified in this study significantly expand the repertoire of proteins known to be phosphorylated in B cells. The number of newly identified phosphoproteins indicates that B cell signaling pathways utilizing protein phosphorylation are likely to be more complex than previously appreciated.
ESTHER : Shu_2004_Mol.Cell.Proteomics_3_279
PubMedSearch : Shu_2004_Mol.Cell.Proteomics_3_279
PubMedID: 14729942
Gene_locus related to this paper: mouse-dpp8

Title : Organizational and mutational analysis of a complete FR-008\/candicidin gene cluster encoding a structurally related polyene complex - Chen_2003_Chem.Biol_10_1065
Author(s) : Chen S , Huang X , Zhou X , Bai L , He J , Jeong KJ , Lee SY , Deng Z
Ref : Chemical Biology , 10 :1065 , 2003
Abstract : The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively.
ESTHER : Chen_2003_Chem.Biol_10_1065
PubMedSearch : Chen_2003_Chem.Biol_10_1065
PubMedID: 14652074
Gene_locus related to this paper: 9acto-q6w5p8 , strgr-pabt

Title : Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157 - Jin_2002_Nucleic.Acids.Res_30_4432
Author(s) : Jin Q , Yuan Z , Xu J , Wang Y , Shen Y , Lu W , Wang J , Liu H , Yang J , Yang F , Zhang X , Zhang J , Yang G , Wu H , Qu D , Dong J , Sun L , Xue Y , Zhao A , Gao Y , Zhu J , Kan B , Ding K , Chen S , Cheng H , Yao Z , He B , Chen R , Ma D , Qiang B , Wen Y , Hou Y , Yu J
Ref : Nucleic Acids Research , 30 :4432 , 2002
Abstract : We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.
ESTHER : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedSearch : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedID: 12384590
Gene_locus related to this paper: ecoli-Aes , ecoli-yafa , ecoli-ycfp , ecoli-yqia , ecoli-YfhR , shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-SF1334 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YIEL , shifl-YJFP , shifl-YPFH

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1

Title : Biological monitoring of combined exposure to organophosphates and pyrethroids - He_2002_Toxicol.Lett_134_119
Author(s) : He F , Chen S , Tang X , Gan W , Tao B , Wen B
Ref : Toxicol Lett , 134 :119 , 2002
Abstract : A total of 132 farmers were selected from two areas (J and S) for this study. In area J, the subgroups Ja (40 subjects) and Jb (36 subjects) sprayed on rice crops either the organophosphate (OP) insecticide methamidophos or the mixture methamidophos-deltamethrin (a pyrethroid, Pyr). In area S, the subgroups Sa (27 subjects) and Sb (29 subjects) sprayed on cottons either the OP methyl-parathion or the mixture methyl-parathion-deltamethrin. Groups Jc (22 subjects) and Sc (20 subjects) were non-exposed controls. Erythrocyte acetylcholinesterase (AChE) was measured by the Ellman's method before spraying, after 2-h exposure and 1 h later. Inhibition of AChE occurred after 2-h exposure to both single OP (Ja and Sa) and OP-containing mixtures (Jb and Sb) as compared with both pre-exposure and control values (Jc and Sc). A similar recovery was found in subgroups Ja, Jb, Sa and Sb 1 h after spraying, but all remained lower than the pre-exposure level. There was no difference in AChE inhibition and recovery between the single OP subgroups and the OP mixture subgroups. The inhibitory effect on AChE shown in subjects with combined OP-Pyr exposure was induced by the OP component of the insecticide mixture and to a similar extent as that induced by the single OP formulations. In addition to the fact that the OP is more potent than Pyrs, the above results might explain why the clinical manifestations of OP mixture poisonings are similar to those of single OP poisoning.
ESTHER : He_2002_Toxicol.Lett_134_119
PubMedSearch : He_2002_Toxicol.Lett_134_119
PubMedID: 12191869

Title : N-Acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal agents - Sun_2001_Bioorg.Med.Chem.Lett_11_1875
Author(s) : Sun X , Zeckner DJ , Current WL , Boyer R , McMillian C , Yumibe N , Chen S
Ref : Bioorganic & Medicinal Chemistry Lett , 11 :1875 , 2001
Abstract : We describe herein the synthesis, bioconversion, antifungal activity, and preliminary toxicology evaluation of a series of N-acyloxymethyl carbamate linked triprodrugs of pseudomycins. The syntheses of these prodrugs (3-6) were achieved via simple N-acylation of PSB (1) or PSC' (2) with various prodrug linkers (7-9). As expected, upon incubation with mouse and/or human plasma, many of these prodrugs (3, 5, and 6) were converted to the parent compound within a few hours. Of particular significance, two pseudomycin triprodrugs (5 and 6) showed excellent in vivo efficacy against systemic Candidiasis without tail vein irritation being observed.
ESTHER : Sun_2001_Bioorg.Med.Chem.Lett_11_1875
PubMedSearch : Sun_2001_Bioorg.Med.Chem.Lett_11_1875
PubMedID: 11459651

Title : Prodrugs of 3-amido bearing pseudomycin analogues: novel antifungal agents - Sun_2001_Bioorg.Med.Chem.Lett_11_1881
Author(s) : Sun X , Zeckner D , Zhang Y , Sachs RK , Current W , Rodriguez M , Chen S
Ref : Bioorganic & Medicinal Chemistry Lett , 11 :1881 , 2001
Abstract : With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B.
ESTHER : Sun_2001_Bioorg.Med.Chem.Lett_11_1881
PubMedSearch : Sun_2001_Bioorg.Med.Chem.Lett_11_1881
PubMedID: 11459652

Title : Engineering lipase at the molecular scale for cleaner biodiesel production - A review - Tan_2023_Mol.Catal_546_113271
Author(s) : Tan Z , Chen G , Chen S , Zhang J , Liu J , Ma X , Liao H , Hu Z , Ge F , Ju F , Shi H , Bilal M
Ref : Molecular Catalysis , 546 :113271
Abstract : Increasing environmental concerns and significant demand for industrial fuels necessitate the development of alternate and sustainable energy sources. Biodiesel is a renewable and environmentally friendly fuel produced by trans-esterifying a variety of feedstocks. Lipases are robust triacylglycerol ester hydrolases that catalyze hydrolysis, esterification, interesterification, transesterification, acylation, acidolysis, alcoholysis, aminolysis, and resolution of racemates. Although the lipase-assisted greener biosynthesis of biodiesel has numerous advantages over the traditional alkali-based process, low catalytic efficiency, marginal stability, and high cost of lipase enzymes limit its widespread industrial processability. Protein engineering methodologies such as directed evolution, semi-rational design, and rational design can effectively tailor or improve the biocatalytic characteristics of lipase enzymes used in biodiesel generation, such as thermostability, solvent tolerance, activity, and substrate specificity. These innovative techniques improved our ability to predict structure-function relationships, engineering qualities, computational tools for designing new biocatalysts, and functional screening to manipulate enzyme traits for application in prevalent industrial bioprocesses. Many recent studies have demonstrated improved lipase performance, such as activity, stability, and specificity via protein engineering. This review spotlights a current overview of lipase engineering at the molecular scale with robust biocatalytic properties for biodiesel synthesis.
ESTHER : Tan_2023_Mol.Catal_546_113271
PubMedSearch : Tan_2023_Mol.Catal_546_113271
PubMedID: