Chen Q

References (102)

Title : Upconversion fluorescence nanosensor based on enzymatic inhibited and copper-triggered o-phenylenediamine oxidation for the detection of dimethoate pesticides - Li_2024_Food.Chem_453_139666
Author(s) : Li S , Zhang S , Wu J , Khan IM , Chen M , Jiao T , Wei J , Chen X , Chen Q
Ref : Food Chem , 453 :139666 , 2024
Abstract : Pesticide residues in agricultural products pose a significant threat to human health. Herein, a sensitive fluorescence method employing upconversion nanoparticles was developed for detecting organophosphorus pesticides (OPs) based on the principle of enzyme inhibition and copper-triggered o-phenylenediamine (OPD) oxidation. Copper ions (Cu(2+)) oxidized the colorless OPD to a yellow 2,3-diaminophenazine (oxOPD). The yellow solution oxOPD quenched the fluorescence of upconversion nanoparticles due to the fluorescence resonance energy transfer. The high affinity of Cu(2+) for thiocholine reduced the level of oxOPD, resulting in almost no fluorescence quenching. The addition of dimethoate led to the inhibition of acetylcholinesterase activity and thus prevented the formation of thiocholine. Subsequently, Cu(2+) oxidized OPD to form oxOPD, which attenuated the fluorescence signal of the system. The detection system has a good linear range of 0.01 ng/mL to 50 ng/mL with a detection limit of 0.008 ng/mL, providing promising applications for rapid detection of dimethoate.
ESTHER : Li_2024_Food.Chem_453_139666
PubMedSearch : Li_2024_Food.Chem_453_139666
PubMedID: 38759443

Title : Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier - Zhang_2024_Dig.Dis.Sci__
Author(s) : Zhang JH , Lin AP , Zhang L , Ruan DD , Gao MZ , Chen Q , Yu HP , Liao LS , Lin XF , Fang ZT , Lin F , Lu SY , Luo JW , Zheng XL , Chen MS
Ref : Digestive Diseases & Sciences , : , 2024
Abstract : BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.
ESTHER : Zhang_2024_Dig.Dis.Sci__
PubMedSearch : Zhang_2024_Dig.Dis.Sci__
PubMedID: 38564148
Gene_locus related to this paper: human-LIPA

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 : 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 : Biodegradation of poly(ethylene terephthalate) through PETase surface-display: From function to structure - Han_2024_J.Hazard.Mater_461_132632
Author(s) : Han W , Zhang J , Chen Q , Xie Y , Zhang M , Qu J , Tan Y , Diao Y , Wang Y , Zhang Y
Ref : J Hazard Mater , 461 :132632 , 2024
Abstract : Polyethylene terephthalate (PET) is one of the most used plastics which has caused some environmental pollution and social problems. Although many newly discovered or modified PET hydrolases have been reported at present, there is still a lack of comparison between their hydrolytic capacities, as well as the need for new biotechnology to apply them for the PET treatment. Here, we systematically studied the surface-display technology for PET hydrolysis using several PET hydrolases. It is found that anchoring protein types had little influence on the surface-display result under T7 promoter, while the PET hydrolase types were more important. By contrast, the newly reported FAST-PETase showed the strongest hydrolysis effect, achieving 71.3% PET hydrolysis in 24 h by pGSA-FAST-PETase. Via model calculation, FAST-PETase indeed exhibited higher temperature tolerance and catalytic capacity. Besides, smaller particle size and lower crystallinity favored the hydrolysis of PET pellets. Through protein structure comparison, we summarized the common characteristics of efficient PET-hydrolyzing enzymes and proposed three main crystal structures of PET enzymes via crystal structural analysis, with ISPETase being the representative and main structure. Surface co-display of FAST-PETase and MHETase can promote the hydrolysis of PET, and the C-terminal of the fusion protein is crucial for PET hydrolysis. The results of our research can be helpful for PET contamination removal as well as other areas involving the application of enzymes. SYNOPSIS: This research can promote the development of better PET hydrolase and its applications in PET pollution treatment via bacteria surface-display.
ESTHER : Han_2024_J.Hazard.Mater_461_132632
PubMedSearch : Han_2024_J.Hazard.Mater_461_132632
PubMedID: 37804764

Title : Metal-organic framework-based multienzyme cascade bioreactor for sensitive detection of methyl parathion - Chen_2024_Food.Chem_442_138389
Author(s) : Chen D , Wang L , Wei J , Jiao T , Chen Q , Oyama M , Chen X
Ref : Food Chem , 442 :138389 , 2024
Abstract : In this study, a cascade nanobioreactor was developed for the highly sensitive detection of methyl parathion (MP) in food samples. The simultaneous encapsulation of acetylcholinesterase (AChE) and choline oxidase (CHO) in a zeolitic imidazole ester backbone (ZIF-8) effectively improved the stability and cascade catalytic efficiency of the enzymes. In addition, glutathione-stabilized gold nanoclusters (GSH-AuNCs) were encapsulated in ZIF-8 by ligand self-assembly, conferring excellent fluorescence properties. Acetylcholine (ATCh) is catalyzed by a cascade of AChE/CHO@ZIF-8 as well as Fe(II) to generate hydroxyl radicals (.OH) with strong oxidizing properties. The .OH radicals then oxidize Au(0) in GSH-AuNCs@ZIF-8 to Au(I), resulting in fluorescence quenching. MP, as an inhibitor of AChE, hinders the cascade reaction and thus restores the fluorescence emission, enabling its quantitative detection. The limit of detection of the constructed nanobioreactor for MP was 0.23 microg/L. This MOF-based cascade nanobioreactor has great potential for the detection of trace hazards.
ESTHER : Chen_2024_Food.Chem_442_138389
PubMedSearch : Chen_2024_Food.Chem_442_138389
PubMedID: 38219569

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 : Effects of age and tissue of Juniperus sabina L. on its phytochemical characteristics, anti-cholinesterase, antidiabetes, and anti-drug resistant bacteria activities - Xu_2023_Front.Plant.Sci_14_1174922
Author(s) : Xu S , Chen Q , Luo N , Yang J , Li D
Ref : Front Plant Sci , 14 :1174922 , 2023
Abstract : Juniperus sabina L. is used in the traditional Chinese medicine (TCM) system to prevent or treat various diseases. However, only the leaves and branches are used as medicinal parts. The aim of this study was to compare the chemical characteristics of different tissues (leaves, branches, stems, and roots) of J. sabina at different ages by HPLC-MS and to evaluate the biological activity (enzyme inhibition, anti-drug-resistant bacteria). Total phenol (TPC) and total lignan (TLC) contents in J. sabina were determined by Folin-Ciocalteu method and UV spectrophotometry, respectively. High levels of total phenols (87.16 mg GAE/g dry weight) and total lignans (491.24 mg PPT/g dry weight) were detected in fifteen annual J. sabina roots and current year leaves, respectively. Eleven compounds, of which six were phenolic compounds and five were lignans, were identified and quantified by HPLC/HPLC-MS. Statistical analysis showed that the distribution and content of the detected compounds showed considerable variation among ages and tissues, and that the current year leaves of fifteen annual J. sabina could be used as a potential application site for the source of podophyllotoxin. Acetylcholinesterase (AChE) inhibitory activity was found to be the highest on the extracts of fifteen annual J. sabina current year leaves (47.37 microg/mL), while the highest inhibition towards butyrylcholinesterase (BChE) was observed for the extracts of seven annual J. sabina previous year leaves (136.3 microg/mL). And the second annual J. sabina current year stem's extracts showed the best antidiabetic activity (anti-alpha-glucosidase, 62.59 microg/mL). In addition, the extracts of fifteen annual J. sabina roots (47.37 microg/mL) showed the highest anti-MRSA activity (31.25 microg/mL). Redundancy analysis (RDA) was conducted to clarify the factors affecting the biological activity of J. sabina, and its results showed that epicatechin and matairesinol showed positive promotion. This study provides a new perspective for understanding the chemical differences and comprehensive utilization of different tissues of J. sabina.
ESTHER : Xu_2023_Front.Plant.Sci_14_1174922
PubMedSearch : Xu_2023_Front.Plant.Sci_14_1174922
PubMedID: 37731973

Title : CDP-choline modulates cholinergic signaling and gut microbiota to alleviate DSS-induced inflammatory bowel disease - Guo_2023_Biochem.Pharmacol_217_115845
Author(s) : Guo L , Chen Q , Gao Y , Jiang H , Zhou F , Zhang F , Xu M
Ref : Biochemical Pharmacology , 217 :115845 , 2023
Abstract : Inflammatory bowel diseases (IBD) represent chronic gastrointestinal inflammatory disorders characterized by a complex and underexplored pathogenic mechanism. Previous research has revealed that IBD patients often have a deficiency of choline and its metabolites, including acetylcholine (ACh) and phosphatidylcholine (PC), within the colon. However, a comprehensive study linking these three substances and their mechanistic implications in IBD remains lacking. This study aimed to investigate the efficacy and underlying mechanism of cytidine diphosphate (CDP)-choline (citicoline), an intermediate product of choline metabolism, in a mouse model of IBD induced by dextran sulfate sodium salt (DSS). The results demonstrated that CDP-choline effectively alleviated colonic inflammation and deficiencies in choline, ACh, and PC by increasing the raw material. Further detection showed that CDP-choline also increased the ACh content by altering the expression of high-affinity choline transporter (ChT1) and acetylcholinesterase (AChE) in DSS-induced mice colon. Moreover, CDP-choline increased the expression of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) and activated the cholinergic anti-inflammatory pathway (CAP), leading to reduced colon macrophage activation and proinflammatory M1 polarization in IBD mice, thus reducing the levels of TNF-alpha and IL-6. In addition, CDP-choline reduced intestinal ecological imbalance and increased the content of hexanoic acid in short-chain fatty acids (SCFAs) in mice. In conclusion, this study elucidates the ability of CDP-choline to mitigate DSS-induced colon inflammation by addressing choline and its metabolites deficiencies, activating the CAP, and regulating the composition of the intestinal microbiome and SCFAs content, providing a potential prophylactic and therapeutic approach for IBD.
ESTHER : Guo_2023_Biochem.Pharmacol_217_115845
PubMedSearch : Guo_2023_Biochem.Pharmacol_217_115845
PubMedID: 37827341

Title : Effects and mechanism of extracts rich in phenylpropanoids-polyacetylenes and polysaccharides from Codonopsis Radix on improving scopolamine-induced memory impairment of mice - Xie_2023_J.Ethnopharmacol__117106
Author(s) : Xie Q , Hu X , Zhao X , Xiang Z , Chen Q , Xie Z , Wang H , Zhao Y , Cheng X , Wang C
Ref : J Ethnopharmacol , :117106 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive developmental neurodegenerative disease that primarily develops in old age. Memory impairment is an important manifestation of AD. It has been demonstrated that inflammation and oxidative stress are important mediators in the development and progression of AD. Codonopsis Radix (CR) has a long history of consumption, exhibiting lots of beneficial health effects, including anti-ageing, antioxidant, and anti-inflammatory properties. However, studies on the effects of CR on scopolamine-induced amnesia have rarely been reported. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of macromolecular portion (polysaccharides, POL) and small molecule portion (fine extract rich in phenylpropanoids-polyacetylenes, EPP) from CR on improving scopolamine-induced memory impairment and to elucidate the potential mechanism of action. MATERIALS AND METHODS: C57BL/6 mice were pretreated with EPP (0.2, 0.4, and 0.6 g/kg), POL (0.3, 0.6, and 0.9 g/kg), and donepezil (5 mg/kg) by gavage for 7 days, followed by intraperitoneal injection of scopolamine (1 mg/kg) to induce memory impairment. The 16S rRNA gene sequencing, histopathological, western blotting, and biochemical analysis (various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation) were performed to further elucidate the mechanism of action. Moreover, the acetylcholinesterase (AChE) inhibitory activities of POL, EPP, and its main compounds tangshenoside I, lobetyol, lobetyolin, and lobetyolinin were evaluated. RESULTS: Experiments have confirmed that both POL and EPP from CR could improve scopolamine-induced spatial learning memory deficits. Both of them could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities. They also could enhance antioxidant defense via increasing the activities of superoxide dismutase and glutathione peroxidase, and anti-inflammatory function through suppressing inflammatory factors (nitric oxide, TNF-alpha, and IL-6) and regulating gut flora. Besides, in vitro experiments demonstrated that four monomeric compounds and EPP, except POL, exhibited inhibition of AChE activity. CONCLUSION: EPP and POL from CR exert a beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. CR may be a promising medicine for preventing and improving learning memory.
ESTHER : Xie_2023_J.Ethnopharmacol__117106
PubMedSearch : Xie_2023_J.Ethnopharmacol__117106
PubMedID: 37652198

Title : Progesterone induces meiosis through two obligate co-receptors with PLA2 activity - Nader_2023_bioRxiv__
Author(s) : Nader N , Zarif L , Halama A , Yadav S , Dib M , Attarwala N , Chen Q , Suhre K , Gross SS , Machaca K
Ref : Biorxiv , : , 2023
Abstract : The steroid hormone progesterone (P4) regulates multiple aspects of reproductive and metabolic physiology. Classical P4 signaling operates through nuclear receptors that regulate transcription. In addition, P4 signals through membrane P4 receptors (mPRs) in a rapid nongenomic modality. Despite the established physiological importance of P4 nongenomic signaling, its detailed signal transduction remains elusive. Here, using Xenopus oocyte maturation as a well-established physiological readout of nongenomic P4 signaling, we identify the lipid hydrolase ABHD2 (alpha/beta hydrolase domain-containing protein 2) as an essential mPRbeta co-receptor to trigger meiosis. We show using functional assays coupled to unbiased and targeted cell-based lipidomics that ABHD2 possesses a phospholipase A2 (PLA2) activity that requires both P4 and mPRbeta. This PLA2 activity bifurcates P4 signaling by inducing mPRbeta clathrin-dependent endocytosis and producing lipid messengers that are G-protein coupled receptors agonists. Therefore, P4 drives meiosis by inducing the ABHD2 PLA2 activity that requires both mPRbeta and ABHD2 as obligate co-receptors. SIGNIFICANCE STATEMENT: Nongenomic progesterone signaling is important for many physiological functions yet the details of its signaling remain elusive. Here we define the early signaling steps downstream of membrane progesterone receptor beta (mPRbeta) during Xenopus oocyte meiosis. We show that progesterone requires two cell membrane receptors to work in unison to signal. The co-receptor complex possesses lipase activity that produces lipid messenger and induces receptor endocytosis to trigger meiosis progression. Our findings have broad physiological implications because nongenomic progesterone signaling operates in many tissues and regulates reproduction and metabolism.
ESTHER : Nader_2023_bioRxiv__
PubMedSearch : Nader_2023_bioRxiv__
PubMedID: 37905030
Gene_locus related to this paper: human-ABHD2

Title : Sublethal Effects of Neonicotinoid Insecticides on the Development, Body Weight and Economic Characteristics of Silkworm - Chen_2023_Toxics_11_
Author(s) : Chen Q , Sun S , Yang X , Yan H , Wang K , Ba X , Wang H
Ref : Toxics , 11 : , 2023
Abstract : Silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae) is a critical insect for silk producers, but the inappropriate application of insecticides negatively affects the physiology and behavior of silkworms. This study found that the effects of neonicotinoid insecticides applied using two spraying methods on the growth and development of silkworms were different: the median lethal concentration (LC(50)) values of two pesticides applied using the leaf-dipping method were 0.33 and 0.83 mg L(-1) and those of two pesticides applied using the quantitative spraying method were 0.91 and 1.23 mg kg(-1). The concentration of pesticides on the mulberry leaves did not decrease after their application using the quantitative spraying method, and a uniform spraying density was observed after the mulberry leaves were air-dried (no liquid) under realistic conditions. We then treated silkworms with the quantitative spraying method and leaf-dipping method. The treatment of silkworm larvae with imidacloprid and thiamethoxam at sublethal concentrations significantly prolonged the development time and significantly decreased the weight and pupation rate, as well as economic indicators of enamel layers and sputum production. Thiamethoxam treatment significantly increased the activities of carboxylesterase (CarE) and glutathione-S-transferase (GST). The activity of CarE and GST increased, decreased, and then increased, and the highest activity was detected on the 10th and 12th days. Thiamethoxam exposure significantly elevated the transcription levels of CarE-11, GSTe3 and GSTz2 and induced DNA damage in hemocytes. This study confirmed that the quantitative spray method is more stable than the leaf-dipping method. Moreover, imidacloprid and thiamethoxam treatment affected the economy and indexes of silkworms and induced changes in detoxification enzymes and DNA damage in silkworms. These results provide a basis for understanding the mechanism of the sublethal effects of insecticides on silkworms.
ESTHER : Chen_2023_Toxics_11_
PubMedSearch : Chen_2023_Toxics_11_
PubMedID: 37235217

Title : Antidementia Medication Use in Nursing Home Residents - Ott_2023_J.Geriatr.Psychiatry.Neurol__8919887231202948
Author(s) : Ott BR , Hollins C , Tjia J , Baek J , Chen Q , Lapane KL , Alcusky M
Ref : J Geriatr Psychiatry Neurol , :8919887231202948 , 2023
Abstract : BACKGROUND: Antidementia medication can provide symptomatic improvements in patients with Alzheimer's disease, but there is a lack of consensus guidance on when to start and stop treatment in the nursing home setting. METHODS: We describe utilization patterns of cholinesterase inhibitors (ChEI) and memantine for 3,50,197 newly admitted NH residents with dementia between 2011 and 2018. RESULTS: Overall, pre-admission use of antidementia medications declined from 2011 to 2018 (ChEIs: 44.5% to 36.9%; memantine: 27.4% to 23.2%). Older age, use of a feeding tube, and greater functional dependency were associated with lower odds of ChEI initiation. Coronary artery disease, parenteral nutrition, severe aggressive behaviors, severe cognitive impairment, and high functional dependency were associated with discontinuation of ChEIs. Comparison of clinical factors related to anti-dementia drug treatment changes from pre to post NH admission in 2011 and 2018 revealed a change toward lower likelihood of initiation of treatment among residents with more functional dependency and those with indicators of more complex illness as well as a change toward higher likelihood of discontinuation in residents having 2 or more hospital stays. CONCLUSIONS: These prescribing trends highlight the need for additional research on the effects of initiating and discontinuing antidementia medications in the NH to provide clear guidance for clinicians when making treatment decisions for individual residents.
ESTHER : Ott_2023_J.Geriatr.Psychiatry.Neurol__8919887231202948
PubMedSearch : Ott_2023_J.Geriatr.Psychiatry.Neurol__8919887231202948
PubMedID: 37715795

Title : Exogenous methyl jasmonate induced cassava defense response and enhanced resistance to Tetranychus urticae - Zhang_2023_Exp.Appl.Acarol__
Author(s) : Zhang Y , Liu Y , Liang X , Wu C , Liu X , Wu M , Yao X , Qiao Y , Zhan X , Chen Q
Ref : Exp Appl Acarol , : , 2023
Abstract : Exogenous application of methyl jasmonate (MeJA) could activate plant defense response against the two-spotted spider mite (TSSM), Tetranychus urticae Koch,sin different plants. However, whether MeJA can also serve as an elicitor in cassava (Manihot esculenta Crantz) remains unknown. In this study, induced defense responses were investigated in TSSM-resistant cassava variety C1115 and TSSM-susceptible cassava variety KU50 when applied with MeJA. The performance of TSSM feeding on cassava plants that werespre-treated with various concentrations of MeJA was first evaluated. Subsequently, the activities of antioxidative enzymes (superoxide dismutase and catalase), detoxification enzymes (glutathione S-transferase, cytochrome P450 and carboxylesterase) and digestive enzymes (protease, amylase and invertase) in TSSM were analyzed at days 1, 2, 4 and 8 post-feeding. The results showed that MeJA treatment can induce cassava defense responses to TSSM in terms of reducing egg production and adult longevity as well as slowing development and prolonging thesegg stage. Noticeably, C1115 exhibited stronger inhibition of TSSM development and reproduction than KU50. In addition, the activities of all the tested enzymes were induced in both C1115 and KU50, the most in C1115. We conclude that exogenous methyl jasmonate can induce cassava defense responses and enhance resistance to TSSM.
ESTHER : Zhang_2023_Exp.Appl.Acarol__
PubMedSearch : Zhang_2023_Exp.Appl.Acarol__
PubMedID: 36635606

Title : Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe - Chen_2023_Anal.Chem__
Author(s) : Chen Q , Liu J , Liu S , Zhang J , He L , Liu R , Jiang H , Han X , Zhang K
Ref : Analytical Chemistry , : , 2023
Abstract : Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 microM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 microM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents.
ESTHER : Chen_2023_Anal.Chem__
PubMedSearch : Chen_2023_Anal.Chem__
PubMedID: 36802493

Title : Co-exposure to sodium hypochlorite and cadmium induced locomotor behavior disorder by influencing neurotransmitter secretion and cardiac function in larval zebrafish - Ma_2023_Environ.Pollut_342_123070
Author(s) : Ma L , Yang H , Xiao X , Chen Q , Lv W , Xu T , Jin Y , Wang W , Xiao Y
Ref : Environ Pollut , 342 :123070 , 2023
Abstract : Sodium hypochlorite (NaClO) and cadmium (Cd) are widely co-occurring in natural aquatic environment; however, no study has been conducted on effects of their combined exposure on aquatic organisms. To assess effects of exposure to NaClO and Cd in zebrafish larvae, we designed six treatment groups, as follows: control group, NaClO group (300 microg/L), 1/100 Cd group (48 microg/L), 1/30 Cd group (160 microg/L), NaClO+1/100 Cd group, and NaClO+1/30 Cd group analyzed behavior, neurological function and cardiac function. Results revealed that exposure to 1/30 Cd and NaClO+1/30 Cd caused abnormal embryonic development in larvae by altering body morphology and physiological indicators. Combined exposure to NaClO and 1/30 Cd affected the free-swimming activity and behavior of larvae in response to light-dark transition stimuli. Moreover, exposure to 1/30 Cd or NaClO+1/30 Cd resulted in a significant increase in tyrosine hydroxylase and acetylcholinesterase activities, as well as significant changes of various neurotransmitters. Lastly, exposure to 1/30 Cd or NaClO+1/30 Cd influenced the transcription of cardiac myosin-related genes and disturbed the myocardial contractile function. Altogether, our results suggested that combined exposure to NaClO and Cd induced oxidative damage in larvae, resulting in detrimental effects on nervous system and cardiac function, thus altering their swimming behavior.
ESTHER : Ma_2023_Environ.Pollut_342_123070
PubMedSearch : Ma_2023_Environ.Pollut_342_123070
PubMedID: 38056588

Title : Application of Marine Natural Products against Alzheimer's Disease: Past, Present and Future - Hu_2023_Mar.Drugs_21_
Author(s) : Hu D , Jin Y , Hou X , Zhu Y , Chen D , Tai J , Chen Q , Shi C , Ye J , Wu M , Zhang H , Lu Y
Ref : Mar Drugs , 21 : , 2023
Abstract : Alzheimer's disease (AD), a neurodegenerative disease, is one of the most intractable illnesses which affects the elderly. Clinically manifested as various impairments in memory, language, cognition, visuospatial skills, executive function, etc., the symptoms gradually aggravated over time. The drugs currently used clinically can slow down the deterioration of AD and relieve symptoms but cannot completely cure them. The drugs are mainly acetylcholinesterase inhibitors (AChEI) and non-competitive N-methyl-D-aspartate receptor (NDMAR) antagonists. The pathogenesis of AD is inconclusive, but it is often associated with the expression of beta-amyloid. Abnormal deposition of amyloid and hyperphosphorylation of tau protein in the brain have been key targets for past, current, and future drug development for the disease. At present, researchers are paying more and more attention to excavate natural compounds which can be effective against Alzheimer's disease and other neurodegenerative pathologies. Marine natural products have been demonstrated to be the most prospective candidates of these compounds, and some have presented significant neuroprotection functions. Consequently, we intend to describe the potential effect of bioactive compounds derived from marine organisms, including polysaccharides, carotenoids, polyphenols, sterols and alkaloids as drug candidates, to further discover novel and efficacious drug compounds which are effective against AD.
ESTHER : Hu_2023_Mar.Drugs_21_
PubMedSearch : Hu_2023_Mar.Drugs_21_
PubMedID: 36662216

Title : LncRNA ABHD11-AS1 promotes tumor progression in papillary thyroid carcinoma by regulating EPS15L1\/EGFR signaling pathway - Lu_2022_Clin.Transl.Oncol_24_1124
Author(s) : Lu H , Zhu C , Chen Y , Ruan Y , Fan L , Chen Q , Wei Q
Ref : Clin Transl Oncol , 24 :1124 , 2022
Abstract : OBJECTIVES: lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11-AS1 could be helpful in therapeutic targeting for PTC treatment. METHODS: Differentially expressed lncRNAs were selected from TCGA database. qRT-PCR analysis was applied to examine the expression of ABHD11-AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by Kaplan-Meier analysis. Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo. RESULTS: High expression of ABHD11-AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated. CONCLUSION: ABHD11-AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.
ESTHER : Lu_2022_Clin.Transl.Oncol_24_1124
PubMedSearch : Lu_2022_Clin.Transl.Oncol_24_1124
PubMedID: 35098448
Gene_locus related to this paper: human-ABHD11

Title : Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites - Meier-Stephenson_2022_Alzheimers.Dement.(N.Y)_8_e12283
Author(s) : Meier-Stephenson FS , Meier-Stephenson VC , Carter MD , Meek AR , Wang Y , Pan L , Chen Q , Jacobo S , Wu F , Lu E , Simms GA , Fisher L , McGrath AJ , Fermo V , Barden CJ , Clair HDS , Galloway TN , Yadav A , Campagna-Slater V , Hadden M , Reed M , Taylor M , Kelly B , Diez-Cecilia E , Kolaj I , Santos C , Liyanage I , Sweeting B , Stafford P , Boudreau R , Reid GA , Noyce RS , Stevens L , Staniszewski A , Zhang H , Murty M , Lemaire P , Chardonnet S , Richardson CD , Gabelica V , DePauw E , Brown R , Darvesh S , Arancio O , Weaver DF
Ref : Alzheimers Dement (N Y) , 8 :e12283 , 2022
Abstract : INTRODUCTION: Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Abeta) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses. METHODS: We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Abeta-mediated neurotoxicities in AD. Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD. RESULTS: In response to various stimuli (e.g., infection, trauma, ischemia, air pollution, depression), Abeta is released as an early responder immunopeptide triggering an innate immunity cascade in which Abeta exhibits both immunomodulatory and antimicrobial properties (whether bacteria are present, or not), resulting in a misdirected attack upon "self" neurons, arising from analogous electronegative surface topologies between neurons and bacteria, and rendering them similarly susceptible to membrane-penetrating attack by antimicrobial peptides (AMPs) such as Abeta. After this self-attack, the resulting necrotic (but not apoptotic) neuronal breakdown products diffuse to adjacent neurons eliciting further release of Abeta, leading to a chronic self-perpetuating autoimmune cycle. AD thus emerges as a brain-centric autoimmune disorder of innate immunity. Based upon the hypothesis that autoimmune processes are susceptible to endogenous regulatory processes, a subsequent comprehensive screening program of 1137 small molecules normally present in human brain identified tryptophan metabolism as a regulator of brain innate immunity and a source of potential endogenous anti-AD molecules capable of chemical modification into multi-site therapeutic modulators targeting AD's complex immunopathic-proteopathic pathogenesis. DISCUSSION: Conceptualizing AD as an autoimmune disease, identifying endogenous regulators of this autoimmunity, and designing small molecule drug-like analogues of these endogenous regulators represents a novel therapeutic approach for AD.
ESTHER : Meier-Stephenson_2022_Alzheimers.Dement.(N.Y)_8_e12283
PubMedSearch : Meier-Stephenson_2022_Alzheimers.Dement.(N.Y)_8_e12283
PubMedID: 35415204

Title : Methyl Jasmonate-Treated Pepper (Capsicum annuum L.) Depresses Performance and Alters Activities of Protective, Detoxification and Digestive Enzymes of Green Peach Aphid [Myzus persicae (Sulzer) (Hemiptera: Aphididae)] - Zhan_2022_J.Insect.Sci_22_
Author(s) : Zhan X , Liu Y , Liang X , Wu C , Liu X , Shui J , Zhang Y , Wang Y , Chen Q
Ref : J Insect Sci , 22 : , 2022
Abstract : Methyl jasmonate (MeJA) is a phytohormone that has been used to artificially induce plant resistance against multiple arthropod herbivores. However, it is still uncertain whether MeJA can trigger pepper plant resistance against Myzus persicae (Sulzer) (Hemiptera: Aphididae) (green peach aphid, GPA). In this study, we assessed the effects of different concentrations (0, 0.008, 0.04, 0.2, 1.0, and 5.0 mM) of MeJA-treated pepper on the development and reproduction performance of GPA to identify an appropriate concentration for vigorous resistance enhancement. MeJA dose was applied on the pepper to investigate the changes in activities of protective enzyme (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD and polyphenol oxidase, PPO), detoxification enzymes (acetylcholinesterase, AchE; glutathione S-transferase, GSTs; cytocrome P450, CYP450, and carboxylesterase, CarE), and digestive enzymes (protease, PRO and amylase, AMY) in GPA. The results showed that all concentrations of MeJA-treated pepper significantly suppressed GPA performance, wherein 0.2 mM was the optimal concentration, as it presented the lowest intrinsic rate of increase (rm), finite rate of increase (lambda), and the highest population doubling time (Dt) values. Furthermore, the protective enzymes (SOD and CAT), detoxification enzymes (GSTs, CYP450, and CarE), and AMY activities increased significantly in MeJA-treated groups than the control group, while the POD and PPO activities were remarkly inhibited under 0.2 mM treatment. These findings indicate that exogenous spraying of 0.2 mM of MeJA significantly enhanced pepper resistance against GPA. The result of this study suggests MeJA application can be used as a promising strategy in integrative management of this insect pest.
ESTHER : Zhan_2022_J.Insect.Sci_22_
PubMedSearch : Zhan_2022_J.Insect.Sci_22_
PubMedID: 36545895

Title : PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma - Li_2022_Med.Oncol_39_250
Author(s) : Li H , Wu Z , Zhong R , Zhang Q , Chen Q , Shen Y
Ref : Med Oncol , 39 :250 , 2022
Abstract : Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC.
ESTHER : Li_2022_Med.Oncol_39_250
PubMedSearch : Li_2022_Med.Oncol_39_250
PubMedID: 36209344

Title : Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment - Ye_2022_Nanomedicine__102581
Author(s) : Ye Z , Gao L , Cai J , Wang Y , Li Y , Tong S , Yan T , Sun Q , Qi Y , Xu Y , Jiang H , Zhang S , Zhao L , Chen Q
Ref : Nanomedicine , :102581 , 2022
Abstract : Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.
ESTHER : Ye_2022_Nanomedicine__102581
PubMedSearch : Ye_2022_Nanomedicine__102581
PubMedID: 35811067

Title : Longitudinal atrophy in prodromal dementia with Lewy bodies points to cholinergic degeneration - Kantarci_2022_Brain.Commun_4_fcac013
Author(s) : Kantarci K , Nedelska Z , Chen Q , Senjem ML , Schwarz CG , Gunter JL , Przybelski SA , Lesnick TG , Kremers WK , Fields JA , Graff-Radford J , Savica R , Jones D , Botha H , Knopman DS , Lowe V , Graff-Radford NR , Murray MM , Dickson DW , Reichard RR , Jack CR, Jr. , Petersen RC , Ferman TJ , Boeve BF
Ref : Brain Commun , 4 :fcac013 , 2022
Abstract : Mild cognitive impairment with the core clinical features of dementia with Lewy bodies is recognized as a prodromal stage of dementia with Lewy bodies. Although grey matter atrophy has been demonstrated in prodromal dementia with Lewy bodies, longitudinal rates of atrophy during progression to probable dementia with Lewy bodies are unknown. We investigated the regional patterns of cross-sectional and longitudinal rates of grey matter atrophy in prodromal dementia with Lewy bodies, including those who progressed to probable dementia with Lewy bodies. Patients with mild cognitive impairment with at least one core clinical feature of dementia with Lewy bodies (mean age = 70.5; 95% male), who were enrolled in the Mayo Clinic Alzheimer's Disease Research Center and followed for at least two clinical evaluations and MRI examinations, were included (n = 56). A cognitively unimpaired control group (n = 112) was matched 2:1 to the patients with mild cognitive impairment by age and sex. Patients either remained stable (n = 28) or progressed to probable dementia with Lewy bodies (n = 28) during a similar follow-up period and pathologic confirmation was available in a subset of cases (n = 18). Cross-sectional and longitudinal rates of grey matter atrophy were assessed using voxel-based and atlas-based region of interest analyses. At baseline, prodromal dementia with Lewy bodies was characterized by atrophy in the nucleus basalis of Meynert both in those who remained stable and those who progressed to probable dementia with Lewy bodies (P < 0.05 false discovery rate corrected). Increase in longitudinal grey matter atrophy rates were widespread, with greatest rates of atrophy observed in the enthorhinal and parahippocampal cortices, temporoparietal association cortices, thalamus and the basal ganglia, in mild cognitive impairment patients who progressed to probable dementia with Lewy bodies at follow-up (P < 0.05 false discovery rate corrected). Rates of inferior temporal atrophy were associated with greater rates of worsening on the clinical dementia rating-sum of boxes. Seventeen of the 18 (94%) autopsied cases had Lewy body disease. Results show that atrophy in the nucleus basalis of Meynert is a feature of prodromal dementia with Lewy bodies regardless of proximity to progression to probable dementia with Lewy bodies. Longitudinally, grey matter atrophy progresses in regions with significant cholinergic innervation, in alignment with clinical disease progression, with widespread and accelerated rates of atrophy in patients who progress to probable dementia with Lewy bodies. Given the prominent neurodegeneration in the cholinergic system, patients with prodromal dementia with Lewy bodies may be candidates for cholinesterase inhibitor treatment.
ESTHER : Kantarci_2022_Brain.Commun_4_fcac013
PubMedSearch : Kantarci_2022_Brain.Commun_4_fcac013
PubMedID: 35415608

Title : Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects - Wang_2022_Front.Neurol_13_933217
Author(s) : Wang R , Gao H , Xie H , Jia Z , Chen Q
Ref : Front Neurol , 13 :933217 , 2022
Abstract : Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with (18)F-flortaucipir and (11)C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the (11)C-DOPA and (11)C-CFT in PET and the (123)I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the (11)C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the (11)C-DAA1106 and (11)C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. (18)F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types.
ESTHER : Wang_2022_Front.Neurol_13_933217
PubMedSearch : Wang_2022_Front.Neurol_13_933217
PubMedID: 36051222

Title : Comparative transcriptome analysis of Chinese grass shrimp (Palaemonetes sinensis) hepatopancreas under ectoparasitic isopod (Tachaea chinensis) infection - Yu_2021_Fish.Shellfish.Immunol__
Author(s) : Yu C , Xu W , Li X , Jin J , Zhao X , Wang S , Zhang Z , Wei Y , Chen Q , Li Y
Ref : Fish Shellfish Immunol , : , 2021
Abstract : Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species. To better understand the interaction between shrimp immunity and isopod infection, we performed a transcriptome analysis of the hepatopancreas of Palaemonetes sinensis challenged with T. chinensis. After assembly and annotation, 75,980 high-quality unigenes were obtained using RNA-seq data. Dierential gene expression analysis revealed 896 signicantly dierently expressed genes (DEGs) after infection, with 452 and 444 upregulated and downregulated genes, respectively. Specifically, expression levels of genes involved in detoxification, such as the interferon regulatory factor, venom carboxylesterase-6, serine proteinase inhibitor, and cytochrome P450, were upregulated. Furthermore, expression levels of genes corresponding to retinol dehydrogenase, triosephosphate isomerase, variant ionotropic glutamate receptor, and phosphoenolpyruvate carboxykinase were significantly upregulated after isopod parasitization, indicating that the shrimp's visual system was influenced by isopod parasitization. Moreover, quantitative real-time PCR of 10 DEGs helped validate the RNA-seq findings. These results provide a valuable basis for future studies on the elucidation of immune responses of P. sinensis to T. chinensis infection.
ESTHER : Yu_2021_Fish.Shellfish.Immunol__
PubMedSearch : Yu_2021_Fish.Shellfish.Immunol__
PubMedID: 34303835

Title : [Computation-aided design of the flexible region of zearalenone hydrolase improves its thermal stability] - Chen_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_4415
Author(s) : Chen Q , Lu C , Xu F
Ref : Sheng Wu Gong Cheng Xue Bao , 37 :4415 , 2021
Abstract : The zearalenone hydrolase (ZHD101) derived from Clonostachys rosea can effectively degrade the mycotoxin zearalenone (ZEN) present in grain by-products and feed. However, the low thermal stability of ZHD101 hampers its applications. High throughput screening of variants using spectrophotometer is challenging because the reaction of hydrolyzing ZEN does not change absorbance. In this study, we used ZHD101 as a model enzyme to perform computation-aided design followed by experimental verification. By comparing the molecular dynamics simulation trajectories of ZHD101 at different temperatures, 32 flexible sites were selected. 608 saturated mutations were introduced into the 32 flexible sites virtually, from which 12 virtual mutants were screened according to the position specific score and enzyme conformation free energy calculation. Three of the mutants N156F, S194T and T259F showed an increase in thermal melting temperature (deltaTm>4 degreesC), and their enzyme activities were similar to or even higher than that of the wild type (relative enzyme activity 95.8%, 131.6% and 169.0%, respectively). Molecular dynamics simulation analysis showed that the possible mechanisms leading to the improved thermal stability were NH-Pi force, salt bridge rearrangement, and hole filling on the molecular surface. The three mutants were combined iteratively, and the combination of N156F/S194T showed the highest thermal stability (deltaTm=6.7 degreesC). This work demonstrated the feasibility of engineering the flexible region to improve enzyme performance by combining virtual computational mutations with experimental verification.
ESTHER : Chen_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_4415
PubMedSearch : Chen_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_4415
PubMedID: 34984886

Title : Atomically dispersed Fe\/Bi dual active sites single-atom nanozymes for cascade catalysis and peroxymonosulfate activation to degrade dyes - Chen_2021_J.Hazard.Mater_422_126929
Author(s) : Chen Q , Liu Y , Lu Y , Hou Y , Zhang X , Shi W , Huang Y
Ref : J Hazard Mater , 422 :126929 , 2021
Abstract : Constructing single-atom nanozymes (SAzymes) with densely exposed and dispersed double metal-N(x) catalytic sites for pollution remediation remains rare and challenging. Herein, we report a novel Fe-Bi bimetallic MOF-derived carbon supported Fe-N(4) and Bi-N(4) dual-site FeBi-NC SAzyme for cascade catalysis and peroxymonosulfate activation to degrade dye pollutants, which is synthesized from the Fe-doped Bi-MOF as a precursor. The formation of both Fe-N(4) and Bi-N(4) sites is demonstrated by XANES and EXAFS. The FeBi-NC SAzyme has high single atoms loadings of Fe (2.61 wt%) and Bi (8.01 wt%), and displays 5.9- and 9.8-fold oxidase mimicking activity enhancement relative to the Fe-NC and Bi-NC SAzymes, respectively. When integrated acetylcholinesterase (AChE) and FeBi-NC SAzyme, a cascade enzyme-nanozyme system is developed for selective and sensitive screening of AChE activity with a low detection limit of 1 x 10(-4) mU mL(-1). Both Fe-N(4) and Bi-N(4) in FeBi-NC display a strong binding energy and electron donating capability to promote peroxymonosulfate activation to generate highly active intermediates for rhodamine B degradation. 100% rhodamine B removal occurs within 5 min via FeBi-NC mediated activation of peroxymonosulfate. The DFT calculations reveal that high activity of FeBi-NC is due to the isolated Fe-N(4) and Bi-N(4) sites and their synergy.
ESTHER : Chen_2021_J.Hazard.Mater_422_126929
PubMedSearch : Chen_2021_J.Hazard.Mater_422_126929
PubMedID: 34523499

Title : Pig Liver Esterases Hydrolyze Endocannabinoids and Promote Inflammatory Response - Zhou_2021_Front.Immunol_12_670427
Author(s) : Zhou Q , Yan B , Sun W , Chen Q , Xiao Q , Xiao Y , Wang X , Shi D
Ref : Front Immunol , 12 :670427 , 2021
Abstract : Endocannabinoids are endogenous ligands of cannabinoid receptors and activation of these receptors has strong physiological and pathological significance. Structurally, endocannabinoids are esters (e.g., 2-arachidonoylglycerol, 2-AG) or amides (e.g., N-arachidonoylethanolamine, AEA). Hydrolysis of these compounds yields arachidonic acid (AA), a major precursor of proinflammatory mediators such as prostaglandin E(2). Carboxylesterases are known to hydrolyze esters and amides with high efficiency. CES1, a human carboxylesterase, has been shown to hydrolyze 2-AG, and shares a high sequence identity with pig carboxylesterases: PLE1 and PLE6 (pig liver esterase). The present study was designed to test the hypothesis that PLE1 and PLE6 hydrolyze endocannabinoids and promote inflammatory response. Consistent with the hypothesis, purified PLE1 and PLE6 efficaciously hydrolyzed 2-AG and AEA. PLE6 was 40-fold and 3-fold as active as PLE1 towards 2-AG and AEA, respectively. In addition, both PLE1 and PLE6 were highly sensitive to bis(4-nitrophenyl) phosphate (BNPP), an aryl phosphodiester known to predominately inhibit carboxylesterases. Based on the study with BNPP, PLEs contributed to the hydrolysis of 2-AG by 53.4 to 88.4% among various organs and cells. Critically, exogenous addition or transfection of PLE6 increased the expression and secretion of proinflammatory cytokines in response to the immunostimulant lipopolysaccharide (LPS). This increase was recapitulated in cocultured alveolar macrophages and PLE6 transfected cells in transwells. Finally, BNPP reduced inflammation trigged by LPS accompanied by reduced formation of AA and proinflammatory mediators. These findings define an innovative connection: PLE-endocannabinoid-inflammation. This mechanistic connection signifies critical roles of carboxylesterases in pathophysiological processes related to the metabolism of endocannabinoids.
ESTHER : Zhou_2021_Front.Immunol_12_670427
PubMedSearch : Zhou_2021_Front.Immunol_12_670427
PubMedID: 34079552
Gene_locus related to this paper: pig-PLE1 , pig-a0a1s6l967

Title : Inhibition of soluble epoxide hydrolase (sEH) protects hippocampal neurons and reduces cognitive decline in type 2 diabetic mice - Wu_2021_Eur.J.Neurosci__
Author(s) : Wu J , Fan Z , Zhao Y , Chen Q , Xiao Q
Ref : European Journal of Neuroscience , : , 2021
Abstract : Diabetes mellitus is a metabolic disorder that can lead to cognitive dysfunction. The hippocampus plays an important role in the cognitive function. Research has identified correlations between hippocampal impairment and diabetes, yet their intermediate remains unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects by suppressing inflammation, apoptosis and oxidative stress. In this study, under diabetic conditions both hippocampal injury, and cognitive decline are accompanied by upregulation of sEH. Moreover, the sEH inhibitor trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) prevents cognitive dysfunction and decreased ROS accumulation and apoptosis in the diabetic hippocampus. t-AUCB treatment restored neuronal synaptic plasticity by restoring the expression of the postsynaptic proteins Postsynaptic density protein-95 (PSD95) and N-methyl-d-aspartate receptor subunit 2B (NR2B), the levels of which were positively correlated with Proline-rich tyrosine kinase 2 (Pyk2) levels under diabetic conditions. Thus, we suggest that hippocampal protection via sEH inhibition might be a potential therapeutic approach to attenuate the progression of cognitive decline in diabetes.
ESTHER : Wu_2021_Eur.J.Neurosci__
PubMedSearch : Wu_2021_Eur.J.Neurosci__
PubMedID: 33595911

Title : Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK\/HO-1 pathway - Wu_2020_Biochem.Biophys.Res.Commun__
Author(s) : Wu J , Zhao Y , Fan Z , Chen Q , Chen J , Sun Y , Jiang X , Xiao Q
Ref : Biochemical & Biophysical Research Communications , : , 2020
Abstract : Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation.
ESTHER : Wu_2020_Biochem.Biophys.Res.Commun__
PubMedSearch : Wu_2020_Biochem.Biophys.Res.Commun__
PubMedID: 32001002

Title : PEI-crosslinked lipase on the surface of magnetic microspheres and its characteristics - Cao_2020_Colloids.Surf.B.Biointerfaces_189_110874
Author(s) : Cao YP , Xia YP , Gu XF , Han L , Chen Q , Zhi GY , Zhang DH
Ref : Colloids Surf B Biointerfaces , 189 :110874 , 2020
Abstract : Here, PEI@PMMA microspheres were prepared by grafting polyethyleneimine (PEI) on poly(methyl methacrylate) (PMMA) magnetic microspheres and successfully used to immobilize lipase. The results showed that PEI@PMMA microspheres had strongly adsorbed lipase (49.1mg/g microsphere) via electrostatic attraction. To prevent lipase shedding, the adsorbed lipase was further crosslinked with PEI on microspheres using glutaraldehyde as crosslinker. Consequently, PEI-crosslinked lipase (2.14 U/mg) exhibited 2.6 times and 1.4 times higher activity respectively than the directly covalent lipase (0.82 U/mg) and the crosslinked lipase aggregates (1.57 U/mg), which was close to the activity of adsorbed lipase (2.20 U/mg). Conformational analysis from FTIR spectroscopy showed that PEI-crosslinked lipase retained its natural structure well. And the alpha-helix structure seemed to play a key role in enhancing lipase activity. Furthermore, the effects of various parameters on crosslinking reaction were investigated. Also, PEI-crosslinked lipase revealed higher pH and thermal stability. The Michaelis constant (Km) was increased and the optimum temperature of lipase was widened observably after crosslinking with PEI on PEI@PMMA magnetic microspheres.
ESTHER : Cao_2020_Colloids.Surf.B.Biointerfaces_189_110874
PubMedSearch : Cao_2020_Colloids.Surf.B.Biointerfaces_189_110874
PubMedID: 32087531

Title : Chemical Composition, Antibacterial, Anti-Inflammatory, and Enzyme Inhibitory Activities of Essential Oil from Rhynchanthus beesianus Rhizome - Zhao_2020_Molecules_26_
Author(s) : Zhao X , Chen Q , Lu T , Wei F , Yang Y , Xie D , Wang H , Tian M
Ref : Molecules , 26 : , 2020
Abstract : Rhynchanthus beesianus W. W. Smith, an edible, medicinal, and ornamental plant, is mainly cultivated in China and Myanmar. The essential oil (EO) from R. beesianus rhizome has been used as an aromatic stomachic in China. The chemical composition and biological activities of EO from R. beesianus rhizome were reported for the first time. Based on gas chromatography with flame ionization or mass selective detection (GC-FID/MS) results, the major constituents of EO were 1,8-cineole (47.6%), borneol (15.0%), methyleugenol (11.2%), and bornyl formate (7.6%). For bioactivities, EO showed a significant antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris with the diameter of the inhibition zone (DIZ) (8.66-10.56 mm), minimal inhibitory concentration (MIC) (3.13-6.25 mg/mL), and minimal bactericidal concentration (MBC) (6.25-12.5 mg/mL). Moreover, EO (128 microg/mL) significantly inhibited the production of proinflammatory mediators nitric oxide (NO) (92.73 +/- 1.50%) and cytokines tumor necrosis factor-alpha (TNF-alpha) (20.29 +/- 0.17%) and interleukin-6 (IL-6) (61.08 +/- 0.13%) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages without any cytotoxic effect. Moreover, EO exhibited significant acetylcholinesterase (AChE) inhibitory activity (the concentration of the sample that affords a 50% inhibition in the assay (IC(50)) = 1.03 +/- 0.18 mg/mL) and moderate alpha-glucosidase inhibition effect (IC(50) = 11.60 +/- 0.25 mg/mL). Thus, the EO could be regarded as a bioactive natural product and has a high exploitation potential in the cosmetics and pharmaceutical industries.
ESTHER : Zhao_2020_Molecules_26_
PubMedSearch : Zhao_2020_Molecules_26_
PubMedID: 33396533

Title : Computational redesign of a PETase for plastic biodegradation by the GRAPE strategy - Cui_2020_Biorxiv__
Author(s) : Cui YL , Chen YC , Liu XY , Dong SJ , Han J , Xiang H , Chen Q , Liu HY , Han X , Liu WD , Tang SY , Wu B
Ref : Biorxiv , : , 2020
Abstract : The excessive use of plastics has been accompanied by severe ecologically damaging effects. The recent discovery of a PETase from Ideonella sakaiensis that decomposes poly(ethylene terephthalate) (PET) under mild conditions provides an attractive avenue for the biodegradation of plastics. However, the inherent instability of the enzyme limits its practical utilization. Here, we devised a novel computational strategy (greedy accumulated strategy for protein engineering, GRAPE). A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the design of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31C and strikingly enhanced degradation performance toward semicrystalline PET films (23%) at mild temperatures (over two orders of magnitude improvement). The mechanism underlying the robust promotion of enzyme performance has been demonstrated via a crystal structure and molecular dynamics simulations. This work shows the capabilities of computational enzyme design to circumvent antagonistic epistatic effects and provides a valuable tool for further understanding and advancing polyester hydrolysis in the natural environment
ESTHER : Cui_2020_Biorxiv__
PubMedSearch : Cui_2020_Biorxiv__
Gene_locus related to this paper: idesa-peth

Title : Promoting Active Sites in MOF-Derived Homobimetallic Hollow Nanocages as a High-Performance Multifunctional Nanozyme Catalyst for Biosensing and Organic Pollutant Degradation - Li_2020_ACS.Appl.Mater.Interfaces_12_2581
Author(s) : Li S , Hou Y , Chen Q , Zhang X , Cao H , Huang Y
Ref : ACS Appl Mater Interfaces , 12 :2581 , 2020
Abstract : Nanozymes are one of the ideal alternatives to natural enzymes for various applications. The rational design of nanozymes with improved catalytic activity stimulates increasing attention to address the low activity of current nanozymes. Here, we reported a general strategy to fabricate the Co-based homobimetallic hollow nanocages (HNCs) (C-CoM-HNC, M = Ni, Mn, Cu, and Zn) by ion-assistant solvothermal reaction and subsequent low-temperature calcination from metal-organic frameworks. The C-CoM-HNCs are featured with HNCs composed of interlaced nanosheets with homogeneous bimetallic oxide dispersion. The hierarchical structure and secondary metallic doping endow the C-CoM-HNC highly active sites. In particular, the Cu-doped C-CoCu-HNCs nanostructures exhibit superior performances over the other C-CoM-HNC as both the oxidase mimicking and peroxymonosulfate (PMS) activator. A sensitive bioassay for acetylcholinesterase (AChE) was established based on the excellent oxidase-like activity of C-CoCu-HNC, offering a linear detection range from 0.0001 to 1 mU/mL with an ultralow detection limit of 0.1 mU/L. As the PMS activator, the C-CoCu-HNC was applied for targeted organic pollutant (rhodamine B, RhB) degradation. A highly efficient RhB degradation was realized, along with good adaptability in a wide pH range and good reusability during the eight-cycle run. The results suggest that C-CoCu-HNC holds a practical potential for clinical diagnostics and pollution removal. Further density functional theory calculation reveals that Cu doping leads to a tighter connection and more negative adsorption energy for O2/PMS, as well as an upshifted d-band center in the C-CoCu-HNCs nanostructures. These changes facilitated the adsorption of O2/PMS on the C-CoCu-HNC surface for dissociation. This work not only offers a promising multifunctional nanozyme catalyst for clinical diagnostics and pollution removal but also gives some clues for the further development of novel nanozymes with high catalytic activities.
ESTHER : Li_2020_ACS.Appl.Mater.Interfaces_12_2581
PubMedSearch : Li_2020_ACS.Appl.Mater.Interfaces_12_2581
PubMedID: 31854974

Title : A novel esterase LanE from Edaphocola flava HME-24 and the enantioselective degradation mechanism of herbicide lactofen - Hu_2020_Ecotoxicol.Environ.Saf_205_111141
Author(s) : Hu T , Xiang Y , Chen Q , Shang N , Xu M , Huang X
Ref : Ecotoxicology & Environmental Safety , 205 :111141 , 2020
Abstract : Lactofen is a chiral herbicide and widely used against broadleaf weeds in agriculture. As a pesticide, it is directly released to the environment, and easily caused contamination in soil and aquatic ecosystem. The enantioselective degradation of lactofen in the environment has been reported, but the molecular biological mechanism of this phenomenon is still unclear. In this study, strain Edaphocola flava HME-24 could degrade 96.7% of 50 mg L(-1) lactofen within 72 h. Lactofen was initially hydrolyzed to desethyl lactofen and subsequently acifluorfen by strain HME-24. A novel gene lanE, involved in lactofen transformation, was obtained from Edaphocola flava HME-24. Gene lanE encoded a protein of 471 amino acids that contained the conserved GXSXG esterase motif and clustered into esterase subfamily V. LanE shared the highest identity with esterase EstD (Q9WYH1) from Thermotoga maritima MSB8 (29.14%). This esterase was also able to transform p-nitrophenyl esters (C4-C8), and the activity decreased when the carbon chain length increased. LanE showed enantioselectivity during the degradation of lactofen, diclofop-methyl, and quizalofop-ethyl, with a higher degradation efficiency of (S)-enantiomers than (R)-enantiomers. The three-dimensional structure of LanE was simulated, and molecular docking revealed that when the (S)-enantiomers of lactofen occupied the active sites, the distance between the ligand molecule and the coordination atom was shorter than that when the (R)-enantiomers occupied the active sites, which facilitated the formation of the transition state complex. The results in this study enhanced our understanding of the preferential catabolism of the (S)-enantiomers of lactofen on the molecular level and could illustrate the reported enantioselective degradation of lactofen in the environment.
ESTHER : Hu_2020_Ecotoxicol.Environ.Saf_205_111141
PubMedSearch : Hu_2020_Ecotoxicol.Environ.Saf_205_111141
PubMedID: 32846294
Gene_locus related to this paper: 9bact-a0a7g9u6e3

Title : A tunable bifunctional hollow Co(3)O(4)\/MO(3) (M = Mo, W) mixed-metal oxide nanozyme for sensing H(2)O(2) and screening acetylcholinesterase activity and its inhibitor - Zhang_2020_J.Mater.Chem.B_8_6459
Author(s) : Zhang X , Lu Y , Chen Q , Huang Y
Ref : J Mater Chem B , 8 :6459 , 2020
Abstract : A self-templated strategy was adopted to design hollow Co3O4/MO3 (M = Mo, W) mixed-metal oxides via the Mo or W doping of ZIF-67, and subsequent pyrolysis under an atmosphere of air at a low temperature of 450 degreesC. The hollow Co3O4/MO3 (M = Mo, W) mixed-metal oxides displayed tunable oxidase-like and peroxidase-like activities able to efficiently catalyze the oxidation of TMB to generate a deep blue color in the absence or presence of H2O2. Relative to that of the un-doped Co3O4, the oxidase mimic activity of the Mo-doped Co3O4 increased to 1.3 to 2.1-fold, while its peroxidase mimic activity increased to 7.1 to 19.9-fold, depending on different Mo doping amounts. The oxidase mimic activity of the W-doped Co3O4 increased to 2.1 to 2.3-fold, while its peroxidase mimic activity increased to 4.8 to 5.9-fold, depending on the different W doping amounts. The Mo- and W-doped Co3O4 nanohybrid exhibited both higher O2 and H2O2 activating capability, and their H2O2 activating capacity was superior to the O2 activating capability. Furthermore, the Mo- and W-doped Co3O4 nanohybrids exhibited similar O2 activating abilities, while the Mo-doped one displayed a higher H2O2 activating capability than the W-doped one. The discrepant peroxidase-like nature of Mo- and W-doped Co3O4 nanohybrids is likely attributed to their different catalytic mechanisms. The peroxidase-like activity of Mo-doped Co3O4 is highly related to the OH free radical, while that of W-doped Co3O4 is likely ascribed to the electron transfer between TMB and H2O2. The Km values of Co3O4/MoO3 for TMB and H2O2 were 0.0352 mM and 0.134 mM, which were 3.2- and 1.9-fold lower than that of pure Co3O4, respectively. A Co3O4/MoO3-based colorimetric platform was developed for the determination of H2O2 in the 0.1-200 microM range, with a limit of detection of 0.08 microM (3sigma). Based on the thiocholine (TCh) inhibition of the excellent peroxidase-like activity of Co3O4/MoO3 and the TCh generation via acetylcholinesterase (AChE) catalyzed hydrolysis of acetylthiocholine chloride (ATCh), the colorimetric platform was extended to screen AChE activity and its inhibitor.
ESTHER : Zhang_2020_J.Mater.Chem.B_8_6459
PubMedSearch : Zhang_2020_J.Mater.Chem.B_8_6459
PubMedID: 32597916

Title : Inhibition of acetylcholinesterase attenuated retinal inflammation via suppressing NF-kappaB activation - Li_2020_Exp.Eye.Res__108003
Author(s) : Li J , Chen Y , Zhang X , Ye S , Yi J , Chen Q , Liu Q
Ref : Experimental Eye Research , :108003 , 2020
Abstract : Elevated inflammatory cytokines contribute to the pathogenesis of various retinal diseases such as diabetic retinopathy, retinal vasculitis and retinitis. However, the underlying mechanism of retinal inflammation remains largely unknown. Recent studies demonstrated that acetylcholinesterase (ACHE) is an inflammatory indicator in central neural system. This study was aimed to dissect the role of ACHE in retinal inflammation, and its mechanism of action. Retinal inflammation was induced by intravitreal injection of tumor necrosis factor-alpha (TNF-alpha) in heterozygous ACHE knockout mice (ACHE(+/-)) and wild type mice (ACHE(+/+)). Donepezil, a well-known ACHE inhibitor, was administrated by daily gavage. Expression of ACHE and intercellular adherent molecule-1 (ICAM-1), infiltration of CD11b(+) inflammatory cells, retinal leukostasis and vascular leakage was determined in both ACHE (+/-) and ACHE(+/+) mice. ARPE-19cells, a human retinal pigment epithelial cell line, were cultured for in vitro assay. Knockdown of ACHE was achieved by lipofectamine-mediated siRNA transfection and pharmaceutical suppression of ACHE was manipulated by donepezil. Cellular expression and distribution of ACHE, ICAM-1, and phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta were detected by western-blot analysis or immunocytochemistry. Retinal expression of ACHE was dramatically upregulated, in parallel with increased ICAM-1 expression, enhanced leukostasis and augmented CD11b(+) inflammatory cells infiltration as well as vascular hyperpermeability in ACHE(+/+) mice injected with TNF-alpha. However, TNF-alpha-injected ACHE (+/-) mice showed lower level of ICAM-1, less leukostasis and fewer infiltrated CD11b(+) cells. Moreover, TNF-alpha-induced retinal vascular leakage was significantly reduced in ACHE (+/-) mice. Similarly, TNF-alpha-induced retinal inflammatory response were also attenuated by donepezil intervention. In addition, TNF-alpha treatment resulted in significant induction of ACHE, upregulation of ICAM-1 and nuclear translocation of NF-kappaB in cultured-ARPE-19cells. Genetic and pharmaceutical suppression of ACHE markedly attenuated TNF-alpha-induced ICAM-1 expression. Meanwhile, inhibition of ACHE reduced TNF-alpha-induced phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta in ARPE-19cells. The present study reveals a pivotal role of ACHE in retinal inflammation. Inhibition of ACHE attenuates retinal inflammation and retinal leakage likely through suppressing NF-kappaB signaling activation.
ESTHER : Li_2020_Exp.Eye.Res__108003
PubMedSearch : Li_2020_Exp.Eye.Res__108003
PubMedID: 32184102

Title : Applanaic acids A-C, three new highly oxygenated lanostane triterpenoids from the fruiting bodies of Ganoderma applanatum - Chen_2020_Nat.Prod.Res__1
Author(s) : Chen Y , Gao J , Chen Q , Liu W , Qi Y , Aisa HA , Yuan T
Ref : Nat Prod Res , :1 , 2020
Abstract : Three new highly oxygenated lanostane triterpenoids, applanaic acids A-C (1-3), were isolated from the fruiting bodies of the basidiomycete Ganoderma applanatum. Among them, applanaic acid B (2) possessed the Delta(17(20))-double bond connection between the side chain and the tetracyclic skeleton, which was not common in the natural lanostane triterpenoids. Their structures were determined by 1D, 2D NMR and HRESIMS spectroscopic analysis. Compound 3 showed a weak acetylcholinesterase (AchE) inhibitory activity with 33.5% inhibition rate at 50 muM.
ESTHER : Chen_2020_Nat.Prod.Res__1
PubMedSearch : Chen_2020_Nat.Prod.Res__1
PubMedID: 32252566

Title : ABAD\/17beta-HSD10 reduction contributes to the protective mechanism of huperzine a on the cerebral mitochondrial function in APP\/PS1 mice - Xiao_2019_Neurobiol.Aging_81_77
Author(s) : Xiao X , Chen Q , Zhu X , Wang Y
Ref : Neurobiology of Aging , 81 :77 , 2019
Abstract : Huperzine A (HupA) is a kind of Lycopodium alkaloid with potential disease-modifying qualities that has been reported to protect against beta-amyloid (Abeta)-mediated mitochondrial damage in Alzheimer's disease. However, the fundamental molecular mechanism underlying the protective action of HupA against Abeta-mediated mitochondrial malfunction is not completely understood. Recently, the mitochondrial enzyme amyloid-binding alcohol dehydrogenase (ABAD) protein has been reported to facilitate Abeta-induced mitochondrial damage, resulting in mitochondrial malfunction and cell death. Our study found that HupA, but not the acetylcholinesterase inhibitor tacrine, reduced the deposition of Abeta and the ABAD level, and further reduced Abeta-ABAD complexes, thereby improving cerebral mitochondrial function in APP/PS1 mice. This was accompanied by attenuated reactive oxygen species overload, as well as increases adenosine triphosphate levels. Moreover, HupA decreased the release of cytochrome-c from mitochondria and the level of cleaved caspase-3, thereby increasing dissociated brain cell viability in APP/PS1 mice. Thus, our study demonstrated that a reduction in ABAD was involved in the protective mechanism of HupA on the cerebral mitochondrial function in APP/PS1 mice.
ESTHER : Xiao_2019_Neurobiol.Aging_81_77
PubMedSearch : Xiao_2019_Neurobiol.Aging_81_77
PubMedID: 31252207

Title : Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats - Wang_2019_Front.Pharmacol_10_1003
Author(s) : Wang K , Chen Q , Wu N , Li Y , Zhang R , Wang J , Gong D , Zou X , Liu C , Chen J
Ref : Front Pharmacol , 10 :1003 , 2019
Abstract : Background: Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairment via the cholinergic anti-inflammatory and insulin signaling pathways. Methods: Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit and beta-Amyloid (Abeta) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression. Results: We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Abeta formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine. Discussion: In conclusion, berberine clears Abeta deposit and consequently ameliorates spatial learning memory impairment via the activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats.
ESTHER : Wang_2019_Front.Pharmacol_10_1003
PubMedSearch : Wang_2019_Front.Pharmacol_10_1003
PubMedID: 31551793

Title : Single and joint oxidative stress-related toxicity of sediment-associated cadmium and lead on Bellamya aeruginosa - Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
Author(s) : Liu X , Chen Q , Ali N , Zhang J , Wang M , Wang Z
Ref : Environ Sci Pollut Res Int , 26 :24695 , 2019
Abstract : The biotoxicity of heavy metals in sediments toward benthic organisms has evoked great concern for the health of freshwater ecosystems. This study applied a sediment toxicity testing protocol to investigate the single and joint toxicity of cadmium (Cd) and lead (Pb) on Bellamya aeruginosa. B. aeruginosa were exposed to different concentrations of Cd (5, 25, and 100 mg/kg), Pb (20, 100, and 400 mg/kg), and their different concentration combinations. A suite of biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), metallothionein (MT), malondialdehyde (MDA), and acetylcholinesterase (AChE), were measured after 7, 14, 21, and 28 days of exposure to evaluate their oxidative stress status. Cell apoptosis of soft tissue was also determined after exposure. Results revealed that these endpoints represented sensitive biomarkers for the characterization of the oxidative stress response induced by these metals. Specifically, a decrease of SOD and GPx and an increase of MDA were indicative of the potential failure of the antioxidant defense system in neutralizing the reactive oxygen species (ROS) generated in the exposure of the Pb-treated group. The integrated biomarker response (IBR) index revealed the most significant sub-lethal toxicity for Pb-spiked sediments, leading to the highest rate of cell apoptosis (70.8%). Exposure to Cd resulted in a time- and dose-dependent effect on MT levels, which suggested active detoxification of this metal. Exposure to the mixture resulted in amelioration of Pb toxicity, likely due to the competitive binding of Cd to active enzyme, with the result of an observed antagonistic interaction. This study indicated that B. aeruginosa represents a good biomonitor for assessing Cd and Pb contamination of sediments, and laid the foundation for their potential risk assessments in freshwater ecosystems.
ESTHER : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedSearch : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedID: 31240645

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

Title : Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model - Shen_2019_Brain.Behav.Immun_81_535
Author(s) : Shen Y , Peng W , Chen Q , Hammock BD , Liu J , Li D , Yang J , Ding J , Wang X
Ref : Brain Behavior & Immunity , 81 :535 , 2019
Abstract : PURPOSE: This study aimed to investigate whether 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor with anti-inflammatory effects, could alleviate spontaneous recurrent seizures (SRS) and epilepsy-associated depressive behaviours in the lithium chloride (LiCl)-pilocarpine-induced post-status epilepticus (SE) rat model. METHODS: The rats were intraperitoneally (IP) injected with LiCl (127mg/kg) and pilocarpine (40mg/kg) to induce SE. A video surveillance system was used to monitor SRS in the post-SE model for 6weeks (from the onset of the 2nd week to the end of the 7th week after SE induction). TPPU (0.1mg/kg/d) was intragastrically given for 4weeks from the 21st day after SE induction in the SRS+0.1 TPPU group. The SRS+PEG 400 group was given the vehicle (40% polyethylene glycol 400) instead, and the control group was given LiCl and PEG 400 but not pilocarpine. The sucrose preference test (SPT) and forced swim test (FST) were conducted to evaluate the depression-like behaviours of rats. Immunofluorescent staining, enzyme-linked immunosorbent assay, and western blot analysis were performed to measure astrocytic and microglial gliosis, neuronal loss, and levels of soluble epoxide hydrolase (sEH), cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6], and cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB). RESULTS: The frequency of SRS was significantly decreased at 6weeks and 7weeks after SE induction in the 0.1TPP U group compared with the SRS+PEG 400 group. The immobility time (IMT) evaluated by FST was significantly decreased, whereas the climbing time (CMT) was increased, and the sucrose preference rate (SPR) evaluated by SPT was in an increasing trend. The levels of sEH, TNF-alpha, IL-1beta, and IL-6 in the hippocampus (Hip) and prefrontal cortex (PFC) were all significantly increased in the SRS+PEG 400 group compared with the control group; neuronal loss, astrogliosis, and microglial activation were also observed. The astrocytic and microglial activation and levels of the pro-inflammatory cytokines in the Hip and PFC were significantly attenuated in the TPPU group compared with the SRS+PEG 400 group; moreover, neuronal loss and the decreased CREB expression were significantly alleviated as well. CONCLUSION: TPPU treatment after SE attenuates SRS and epilepsy-associated depressive behaviours in the LiCl-pilocarpine induced post-SE rat model, and it also exerts anti-inflammatory effects in the brain. Our findings suggest a new therapeutic approach for epilepsy and its comorbidities, especially depression.
ESTHER : Shen_2019_Brain.Behav.Immun_81_535
PubMedSearch : Shen_2019_Brain.Behav.Immun_81_535
PubMedID: 31306773

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

Title : Novel Method of Preparation and Activity Research on Arctigenin from Fructus Arctii - Cai_2018_Pharmacogn.Mag_14_87
Author(s) : Cai E , Han J , Yang L , Zhang W , Zhao Y , Chen Q , Guo M , He X
Ref : Pharmacogn Mag , 14 :87 , 2018
Abstract : Background: Arctigenin has many pharmacological activities with clinical significance and is derived from Arctium lappa L. However, the present extraction method is inefficient and does not have meaningful industrial production. Objective: A new method to directly prepare arctigenin was established by combining enzyme-assisted extraction and central composite design. Arctigenin's further pharmacological activity was also surveyed in vitro. Materials and Methods: beta-D-Glucosidase, a food-grade enzyme, was added directly to the fruits of A. lappa L. to hydrolyze the arctiin to arctigenin, and the obtained samples were subsequently subjected to ethanol (30%, v/v) extraction. The pharmacological activity of the extraction and arctigenin was determined by inhibiting acetylcholinesterase (AChE) and scavenging nitrite. Results: The factors investigated include the enzyme concentration (0.5%-2.5%), ultrasound time (10 min(-3) 0 min), and extraction temperature (30 degrees C-50 degrees C). From the analysis of the results by Design-Expert (V8.0.6), the optimal extraction conditions were obtained: enzyme concentration (1.4%), ultrasound time (25 min), and extraction temperature (45 degrees C). The highest yield of arctigenin, obtained under the optimal conditions was 6.39%, representing an increase of 28.15% compared to the reference extraction without enzyme processing. The IC50 values of the extraction and arctigenin, respectively, for inhibiting AChE were 0.572 mg/ml and 0.462 mg/ml, and those for nitrite-scavenging were 34.571 mg/ml and 17.49 mg/ml. Conclusions: The results demonstrate that using an enzyme directly in the production is an effective means for extracting arctigenin from Fructus arctii. The extraction has the activities of inhibiting AChE and scavenging nitrite, probably because there has arctigenin in it. It is implied that the extraction and arctigenin could contribute to human health in clinical applications. SUMMARY: The new method of adding enzyme directly to the preparation of arctigenin was carried out instead of preparing arctigenin by two-step methodThree factors affecting the efficiency of preparation were analyzed and discussed include the enzyme concentration, ultrasound time, and extraction temperature by central composite designThis new method of preparing arctigenin improved the yield significantly than other methodsArctigenin has remarkable pharmacological activities of inhibiting acetylcholinesterase and scavenging nitrite. Abbreviations used: AChE: Acetylcholinesterase, CCD: Central composite design, TCM: Traditional Chinese medicines, AD.
ESTHER : Cai_2018_Pharmacogn.Mag_14_87
PubMedSearch : Cai_2018_Pharmacogn.Mag_14_87
PubMedID: 29576707

Title : Structural investigation of the enantioselectivity and thermostability mechanisms of esterase RhEst1 - Chen_2018_J.Mol.Graph.Model_85_182
Author(s) : Chen Q , Yu HL , Cheng X , Xu JH
Ref : J Mol Graph Model , 85 :182 , 2018
Abstract : The esterase RhEst1 can catalyze the asymmetric hydrolysis of ethyl (+/-)-2,2-dimethylcyclopropane carboxylate (DmCpCe), yielding a pharmaceutically relevant (S)-carboxylic acid. A triple mutant RhEst1A147I/V148F/G254A showed a 5-fold increase in the catalytic activity but a significant decrease in the enantioselectivity. Further optimization studies led to a new enzyme with an additional A143T mutation, which showed both increased catalytic activity and recovered enantioselectivity as well as improved thermostability. To reveal the detailed structural mechanisms for these improved properties, we performed all-atom molecular dynamics simulations on the wild type and two mutants A147I/V148F/G254A and A143T/A147I/V148F/G254A RhEst1, in complex with R-DmCpCe and S-DmCpCe substrates, respectively. The structural stability of the enzyme variants was investigated with the residue interaction network analysis. In RhEst1M2, S-DmCpCe was observed to adopt a more "activated" conformation than R-DmCpCe, with the active site residues better prearranged for the reaction, leading to the improved enantioselectivity towards S-DmCpCe. The mutations in the two mutants, especially A143T, could lead to different motion patterns in the cap domain, thus affecting the structure of the substrate entrance tunnel. The residue interaction networks analysis showed an increased number of interactions in RhEst1M1 and RhEst1M2 as compared to the wild type enzyme, especially the pi-pi stacking interactions between Phe148 and the nearby residues, providing an explanation for the increased thermostability of the two mutant enzymes observed experimentally. Our work provides essential molecular insights into the substrate binding, enantioselectivity and structural stability of esterase RhEst1, which will facilitate the development of more efficient RhEst1 variants for pharmaceutical applications.
ESTHER : Chen_2018_J.Mol.Graph.Model_85_182
PubMedSearch : Chen_2018_J.Mol.Graph.Model_85_182
PubMedID: 30227363
Gene_locus related to this paper: rhosp-AHY95170

Title : Protein termini relocation plus random mutation: A new strategy for finding key sites in esterase evolution - Qi_2018_Mol.Catal_460_94
Author(s) : Qi Y-K , Li F-L , Chen Q , Zhang Z-J , Luan Z-J , Xu J-H , Yu H-L
Ref : Molecular Catalysis , 460 :94 , 2018
Abstract : A pharmaceutically relevant esterase, RhEst1, could catalyze the hydrolysis of (R,S)-ethyl-2,2-dimethyl cyclopropane carboxylate [(R,S)-DmCpCe] with excellent enantioselectivity, producing (S)-(+)-2,2-dimethyl cyclopropane carboxylic acid [(S)-DmCpCa], which is a key chiral building block for the synthesis of Cilastatin. In our previous work, a mutant RhEst1-M2 was identified with 6.4-fold higher activity than the wild-type. Additionally, the termini of RhEst1 protein were altered by circular permutation (CP), resulting in a mutant CP-176 which still maintains the catalytic activity of esterase. In this work, to improve the catalytic properties of RhEst1, the mutant CP-176 was taken as the parent of directed evolution. Consequently, a new mutant designated as CP-M1 (=CP-176G282S) was identified, indicating 3.2-fold catalytic efficiency enhancement and nearly 7 degC improvement in melting temperature (Tm) as compared with CP-176. Furthermore, the beneficial mutation ""G282S"" of CP-M1 was reversely introduced into RhEst1-M2, generating the best mutant M3 (=RhEst1-M2G167S), with 1.8-fold catalytic efficiency improvement and nearly 10 degC improvement of Tm, as compared with RhEst1-M2. This is the first report that the circular permutation and random mutagenesis were combined to reshape a protein, affording distinctly improved activity and thermostability.
ESTHER : Qi_2018_Mol.Catal_460_94
PubMedSearch : Qi_2018_Mol.Catal_460_94

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

Title : Nature-based molecules combined with rivastigmine: A symbiotic approach for the synthesis of new agents against Alzheimer's disease - Nesi_2017_Eur.J.Med.Chem_141_232
Author(s) : Nesi G , Chen Q , Sestito S , Digiacomo M , Yang X , Wang S , Pi R , Rapposelli S
Ref : Eur Journal of Medicinal Chemistry , 141 :232 , 2017
Abstract : Starting from nature as original source, new potential agents with pleiotropic activities have been synthesized and evaluated as neuroprotective agents. In this work, novel nature-based hybrids, combining antioxidant motifs with rivastigmine, have been designed and synthesized. The biological results revealed that the new compounds inhibit both AChE and BuChE. In particular, lipoic acid hybrids LA1, LA2, LA3 resulted to be the most potent inhibitors of BuChE showing IC(50) values ranging from 340 to 378 nM. Analogously, all the compounds were able to inhibit the self beta-amyloid(1-42) aggregation. The gallic acid hybrid GA2 as well as the 2-chromonecarboxylic acid hybrids CA1 and CA2 prevented the self-mediated Abeta aggregation with percentages of inhibition ranging from 53% to 59%. Finally, some of them also show potent neuroprotective effects against glutamate-induced cell death and low toxicity in HT22 cells.
ESTHER : Nesi_2017_Eur.J.Med.Chem_141_232
PubMedSearch : Nesi_2017_Eur.J.Med.Chem_141_232
PubMedID: 29031070

Title : 2D-SAR and 3D-QSAR analyses for acetylcholinesterase inhibitors - Niu_2017_Mol.Divers_21_413
Author(s) : Niu B , Zhao M , Su Q , Zhang M , Lv W , Chen Q , Chen F , Chu D , Du D , Zhang Y
Ref : Mol Divers , 21 :413 , 2017
Abstract : Alzheimer's disease (AD) accounts for almost three quarters of dementia patients and interferes people's normal life. Great progress has been made recently in the study of Acetylcholinesterase (AChE), known as one of AD's biomarkers. In this study, acetylcholinesterase inhibitors (AChEI) were collected to build a two-dimensional structure-activity relationship (2D-SAR) model and three-dimensional quantitative structure-activity relationship (3D-QSAR) model based on feature selection method combined with random forest. After calculation, the prediction accuracy of the 2D-SAR model was 89.63% by using the tenfold cross-validation test and 87.27% for the independent test set. Three cutting ways were employed to build 3D-QSAR models. A model with the highest [Formula: see text] (cross-validated correlation coefficient) and [Formula: see text](non-cross-validated correlation coefficient) was obtained to predict AChEI activity. The mean absolute error (MAE) of the training set and the test set was 0.0689 and 0.5273, respectively. In addition, molecular docking was also employed to reveal that the ionization state of the compounds had an impact upon their interaction with AChE. Molecular docking results indicate that Ser124 might be one of the active site residues.
ESTHER : Niu_2017_Mol.Divers_21_413
PubMedSearch : Niu_2017_Mol.Divers_21_413
PubMedID: 28275924

Title : Quantitative investigation of the mechanisms of microplastics and nanoplastics toward zebrafish larvae locomotor activity - Chen_2017_Sci.Total.Environ_584-585_1022
Author(s) : Chen Q , Gundlach M , Yang S , Jiang J , Velki M , Yin D , Hollert H
Ref : Sci Total Environ , 584-585 :1022 , 2017
Abstract : This study investigated the direct and indirect toxic effects of microplastics and nanoplastics toward zebrafish (Danio rerio) larvae locomotor activity. Results showed that microplastics alone exhibited no significant effects except for the upregulated zfrho visual gene expression; whereas nanoplastics inhibited the larval locomotion by 22% during the last darkness period, and significantly reduced larvae body length by 6%, inhibited the acetylcholinesterase activity by 40%, and upregulated gfap, alpha1-tubulin, zfrho and zfblue gene expression significantly. When co-exposed with 2mug/L 17 alpha-ethynylestradiol (EE2), microplastics led to alleviation on EE2's inhibition effect on locomotion, which was probably due to the decreased freely dissolved EE2 concentration. However, though nanoplastics showed stronger adsorption ability for EE2, the hypoactivity phenomenon still existed in the nanoplastics co-exposure group. Moreover, when co-exposed with a higher concentration of EE2 (20mug/L), both plastics showed an enhanced effect on the hypoactivity. Principal component analysis was performed to reduce data dimensions and four principal components were reconstituted in terms of oxidative stress, body length, nervous and visual system related genes explaining 84% of total variance. Furthermore, oxidative damage and body length reduction were evaluated to be main reasons for the hypoactivity. Therefore, nanoplastics alone suppressed zebrafish larvae locomotor activity and both plastic particles can change the larvae swimming behavior when co-exposed with EE2. This study provides new insights into plastic particles' effects on zebrafish larvae, improving the understanding of their environmental risks to the aquatic environment.
ESTHER : Chen_2017_Sci.Total.Environ_584-585_1022
PubMedSearch : Chen_2017_Sci.Total.Environ_584-585_1022
PubMedID: 28185727

Title : Research Advances and Detection Methodologies for Microbe-Derived Acetylcholinesterase Inhibitors: A Systemic Review - Su_2017_Molecules_22_
Author(s) : Su J , Liu H , Guo K , Chen L , Yang M , Chen Q
Ref : Molecules , 22 : , 2017
Abstract : Acetylcholinesterase inhibitors (AChEIs) are an attractive research subject owing to their potential applications in the treatment of neurodegenerative diseases. Fungi and bacteria are major producers of AChEIs. Their active ingredients of fermentation products include alkaloids, terpenoids, phenylpropanoids, and steroids. A variety of in vitro acetylcholinesterase inhibitor assays have been developed and used to measure the activity of acetylcholinesterases, including modified Ellman's method, thin layer chromatography bioautography, and the combined liquid chromatography-mass spectrometry/modified Ellman's method. In this review, we provide an overview of the different detection methodologies, the microbe-derived AChEIs, and their producing strains.
ESTHER : Su_2017_Molecules_22_
PubMedSearch : Su_2017_Molecules_22_
PubMedID: 28125001

Title : Enhanced uptake of BPA in the presence of nanoplastics can lead to neurotoxic effects in adult zebrafish - Chen_2017_Sci.Total.Environ_609_1312
Author(s) : Chen Q , Yin D , Jia Y , Schiwy S , Legradi J , Yang S , Hollert H
Ref : Sci Total Environ , 609 :1312 , 2017
Abstract : Plastic particles have been proven to be abundant in the aquatic environment, raising concerns about their potential toxic effects. In the present study, we determined the bioaccumulation potential of bisphenol A (BPA) in adult zebrafish (Danio rerio) in the absence and presence of nano-sized plastic particles (nanoplastics, NPPs). Results show that BPA can accumulate in the viscera, gill, head and muscle of zebrafish with 85, 43, 20, and 3mug/g ww after 1d exposure. NPPs were also found to accumulate in different tissues of the fish. Relative equilibrium was reached after 1d exposure in different tissues with 39 to 636mg/kg ww. Co-exposure of NPPs and BPA led to a 2.2 and 2.6-fold significant increment of BPA uptake in the head and viscera, if compared with BPA alone treatment after 3d exposure. As such, we further investigated several neurotoxic biomarker alterations in the fish head. It was found that either BPA or NPPs can cause myelin basic protein (MBP)/gene up-regulation in the central nervous system (CNS); meanwhile, both contaminants exhibited significant inhibition of acetylcholinesterase (AChE) activity, which is a well-known representative biomarker for neurotoxicity. Moreover, for the co-exposure treatment, biomarkers of myeline and tubulin protein/gene expressions, dopamine content, and the mRNA expression of mesencephalic astrocyte derived neurotrophic factor (MANF) were all significantly up-regulated, suggesting that an enhanced neurotoxic effects in both CNS and dopaminergic system occurred. However, AChE activity was no more inhibited in the co-exposure treatment, which implies that solely AChE measurement may not be sufficient to identify neurotoxic effects in the cholinergic system. Overall, the present study demonstrates that the presence of NPPs can increase BPA bioavailability and cause neurotoxicity in adult zebrafish.
ESTHER : Chen_2017_Sci.Total.Environ_609_1312
PubMedSearch : Chen_2017_Sci.Total.Environ_609_1312
PubMedID: 28793400

Title : miR27a promotes proliferation, migration, and invasion of colorectal cancer by targeting FAM172A and acts as a diagnostic and prognostic biomarker - Liu_2017_Oncol.Rep_37_3554
Author(s) : Liu W , Qian K , Wei X , Deng H , Zhao B , Chen Q , Zhang J , Liu H
Ref : Oncol Rep , 37 :3554 , 2017
Abstract : Accumulating evidence shows that mircroRNAs (miRNAs) play a crucial role in the development of colorectal cancer. In our previous study, FAM172A was demonstrated to be a novel tumor suppressor gene in CRC. Therefore, the aim of the present study was to identify whether the miR27a could be a diagnostic and prognostic marker and the regulatory relationships between miR27a and FAM172A. We demonstrated high levels of miR27a expression in tissues of patients with CRC as well as in CRC cell lines. There was a positive correlation between the levels of miR27a and the poor overall survival of patients with CRC. Furthermore, elevated levels of miR27a expression were associated with TNM stage and distant metastasis. Increased expression or inhibition of miR27a promoted or inhibited the metastasis of CRC cell lines, respectively. Moreover, we showed that miR27a directly targets the 3'-untranslated region of FAM172A mRNA by using a dual-luciferase assay. Increased or decreased expression of FAM172A expression was observed when miR27a expression was inhibited or elevated in the CRC cells, respectively. In summary, our study showed that miR27a expression is a diagnostic and prognostic marker and correlates with overall survival of patients with CRC. Therefore, it may be a therapeutic approach for preventing metastasis of CRC to inhibit expression of miR27a or increase expression of FAM172A.
ESTHER : Liu_2017_Oncol.Rep_37_3554
PubMedSearch : Liu_2017_Oncol.Rep_37_3554
PubMedID: 28440497
Gene_locus related to this paper: human-f172a

Title : Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease - Chen_2017_Eur.J.Med.Chem_125_784
Author(s) : Chen Z , Digiacomo M , Tu Y , Gu Q , Wang S , Yang X , Chu J , Chen Q , Han Y , Chen J , Nesi G , Sestito S , Macchia M , Rapposelli S , Pi R
Ref : Eur Journal of Medicinal Chemistry , 125 :784 , 2017
Abstract : A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Abeta) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Abeta self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD.
ESTHER : Chen_2017_Eur.J.Med.Chem_125_784
PubMedSearch : Chen_2017_Eur.J.Med.Chem_125_784
PubMedID: 27736684

Title : Production of Diacylglycerol-enriched Oil by Glycerolysis of Soybean Oil using a Bubble Column Reactor in a Solvent-free System - Zhang_2016_J.Oleo.Sci_65_207
Author(s) : Zhang N , Yang X , Fu J , Chen Q , Song Z , Wang Y
Ref : J Oleo Sci , 65 :207 , 2016
Abstract : In this study, diacylglycerol-enriched soybean oil (DESO) was synthesized through Lipozyme 435-catalyzed glycerolysis of soybean oil (SO) in a solvent-free system using a modified bubble column reactor. The effects of enzyme load, mole ratio of glycerol to soybean oil, reaction temperature, gas flow and reaction time on DAG production were investigated. The selected conditions were established as being enzyme load of 4 wt% (mass of substrates), glycerol/soybean oil mole ratio of 20:1, reaction temperature of 80 degC, gas flow of 10.6 cm/min, and a reaction time of 2.5 h, obtaining the DAG content of 49.4+/-0.5 wt%. The reusability of Lipozyme 435 was evaluated by monitoring the contents of DAG, monoacylglycerol (MAG) and triacylglycerol (TAG) in 10 consecutive runs. After purified by one-step molecular distillation, the DAG content of 63.5+/-0.3 wt% was achieved in DESO. The mole ratio of 1, 3-DAG to 1, 2-DAG was 2:1 and the fatty acid composition had no significant difference from that of soybean oil. However, the thermal properties of DESO and SO had considerable differences. Polymorphic form of DESO were mainly the beta form and minor amounts of the beta' form. Granular aggregation and round-shaped crystals were detected in DESO.
ESTHER : Zhang_2016_J.Oleo.Sci_65_207
PubMedSearch : Zhang_2016_J.Oleo.Sci_65_207
PubMedID: 26876674

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 : Rational selection of circular permutation sites in characteristic regions of the alpha\/beta-hydrolase fold enzyme RhEst1 - Li_2016_J.Mol.Catal.B.Enzym_125_75
Author(s) : Li FL , Luan ZJ , Chen Q , Xu JH , Yu HL
Ref : J Mol Catal B Enzym , 125 :75 , 2016
Abstract : Circular permutation (CP) involves the cleavage of polypeptide to obtain new termini, which can result in different protein structures and functions. It has been demonstrated to be an effective strategy for the evolution of proteins, but the lack of principle for selecting CP site to construct functional variants is still a challenge for CP. In this study we performed the CP analysis of the typical esterase RhEst1 to explore the CP site-selection strategy of the alpha/beta-hydrolase fold family. A CP library of 97 mutants was generated to identify the effect of CP on three characteristic regions of RhEstl including the flexible cap domain (Region 1), the region around the entrance to substrate binding pocket (Region 2) and the surface exposed sectors in catalytic domain (Region 3). We found the protein folding, stability and bioactivity of CP variants were altered significantly and the CP sites of active variants were mainly located in the flexible loops. These studies reveal the importance of site-selection for CP and provide more information for CP of other alpha/beta-hydrolases. (C) 2016 Elsevier B.V. All rights reserved.
ESTHER : Li_2016_J.Mol.Catal.B.Enzym_125_75
PubMedSearch : Li_2016_J.Mol.Catal.B.Enzym_125_75
Gene_locus related to this paper: rhosp-AHY95170

Title : Dramatically Improved Performance of an Esterase for Cilastatin Synthesis by Cap Domain Engineering - Luan_2016_Ind.Eng.Chem.Res_55_12167
Author(s) : Luan ZJ , Yu HL , Ma BD , Qi YK , Chen Q , Xu JH
Ref : Ind. Eng. Chem. Res , 55 :12167 , 2016
Abstract : Whole-protein random mutation and substrate tunnel evolution have recently been applied to the pharmaceutically relevant esterase RhEst1 for the synthesis of a cilastatin precursor. The mutant RhEst1 M1(=RhEst1 A147I/V148F/G254A) was identified from a large library consisting of 1.5 10 4 variants. Though the activity of this mutant was improved 5-fold, the enantioselectivity for biohydrolysis decreased at the same time. Herein a smart library (3.0 10 3) focused on the cap doman of Rh Est1 was constructed to improve its catalytic performance comprehensively. As a result, a variant designated as Rh Est1 M2 (=RhEst1M1 A143T), showed a 6-fold increase in specific activity compared with the wild type. Meanwhile, the decreased enantioselectivity for enzymatic resolution was recovered to the native enzyme level. The melting temperature of Rh Est1 M2was nearly 11C higher than that of the wild type. This work provides detailed insight into the vitalrole of alpha/beta hydrolase cap domains in influencing all aspects of enzyme characteristics. Furthermore, the commercial resin ESR-1 with free amino groups was used for enzyme immobilization to enhance the operational performance of Rh Est1 M2. No obvious activity loss was observed when the immobilized enzyme was incubated at 30C for 200 h. The immobilized enzyme could be repeatedly used for up to 20 batches, and the total turnover number (TTN) reached up to 8.0 10 5
ESTHER : Luan_2016_Ind.Eng.Chem.Res_55_12167
PubMedSearch : Luan_2016_Ind.Eng.Chem.Res_55_12167
Gene_locus related to this paper: rhosp-AHY95170

Title : FAM172A modulates apoptosis and proliferation of colon cancer cells via STAT1 binding to its promoter - Qian_2016_Oncol.Rep_35_1273
Author(s) : Qian K , Zhang J , Lu J , Liu W , Yao X , Chen Q , Lu S , Xiang G , Liu H
Ref : Oncol Rep , 35 :1273 , 2016
Abstract : In our previous study, low expression of FAM172A protein was found in colon cancer tissues. This research was planned to explore the functions of FAM172A gene and examine the mechanisms of its transcriptional regulation. Firstly, flow cytometry showed that FAM172A inhibited proliferation and promoted apoptosis and differentiation of colon cancer cells. Then through continuous truncation, we identified the minimal functional promoter region of FAM172A. Subsequently, we found that STAT1, as a transcription factor, could bind to the minimal FAM172A promoter, as evaluated using Chromatin immunoprecipitation (ChIP) and Electrophoreticmobility shift assay (EMSA). The results of Western blot analysis and qRT-PCR indicated that STAT1 was able to upregulate the expression of FAM172A. Our results showed that FAM172A could suppress proliferation of colon cancer cells, and STAT1 could bind to the minimum promoter region of FAM172A and upregulated the expression of FAM172A. These results may provide advanced insights into the functions of FAM172A and its regulatory mechanisms.
ESTHER : Qian_2016_Oncol.Rep_35_1273
PubMedSearch : Qian_2016_Oncol.Rep_35_1273
PubMedID: 26676844
Gene_locus related to this paper: human-f172a

Title : Alzheimer's Disease therapeutics: current and future therapies - Gao_2016_Minerva.Med_107_108
Author(s) : Gao LB , Yu XF , Chen Q , Zhou D
Ref : Minerva Med , 107 :108 , 2016
Abstract : Pathologically, Alzheimer's Disease is characterized by amyloidal protein plaques that lead to dementia in the elderly population. While advances have been made in therapeutics over the course of the last 20 years, the drugs generally target the symptoms rather than the underlying pathology. Unfortunately, despite the advances, the mechanisms behind Alzheimer's Disease have still not been clearly identified. Some of these current treatments include acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor agonists. Recently, the pathophysiology behind this disease is becoming more clearly understood and this has led to some novel therapeutic targets that may be able to break the barrier and target the underlying disease. In this review, we will discuss Alzheimer's Disease pathology and the pharmacological therapy that has been in use for a long time as well as novel therapies.
ESTHER : Gao_2016_Minerva.Med_107_108
PubMedSearch : Gao_2016_Minerva.Med_107_108
PubMedID: 26933835

Title : Rational design of a carboxylic esterase RhEst1 based on computational analysis of substrate binding - Chen_2015_J.Mol.Graph.Model_62_319
Author(s) : Chen Q , Luan ZJ , Yu HL , Cheng X , Xu JH
Ref : J Mol Graph Model , 62 :319 , 2015
Abstract : A new carboxylic esterase RhEst1 which catalyzes the hydrolysis of (S)-(+)-2,2-dimethylcyclopropanecarboxylate (S-DmCpCe), the key chiral building block of cilastatin, was identified and subsequently crystallized in our previous work. Mutant RhEst1A147I/V148F/G254A was found to show a 5-fold increase in the catalytic activity. In this work, molecular dynamic simulations were performed to elucidate the molecular determinant of the enzyme activity. Our simulations show that the substrate binds much more strongly in the A147I/V148F/G254A mutant than in wild type, with more hydrogen bonds formed between the substrate and the catalytic triad and the oxyanion hole. The OH group of the catalytic residue Ser101 in the mutant is better positioned to initiate the nucleophilic attack on S-DmCpCe. Interestingly, the "170-179" loop which is involved in shaping the catalytic sites and facilitating the product release shows remarkable dynamic differences in the two systems. Based on the simulation results, six residues were identified as potential "hot-spots" for further experimental testing. Consequently, the G126S and R133L mutants show higher catalytic efficiency as compared with the wild type. This work provides molecular-level insights into the substrate binding mechanism of carboxylic esterase RhEst1, facilitating future experimental efforts toward developing more efficient RhEst1 variants for industrial applications.
ESTHER : Chen_2015_J.Mol.Graph.Model_62_319
PubMedSearch : Chen_2015_J.Mol.Graph.Model_62_319
PubMedID: 26556053

Title : Effects of supplementation of rumen-protected choline on growth performance, meat quality and gene expression in longissimus dorsi muscle of lambs - Li_2015_Arch.Anim.Nutr_69_340
Author(s) : Li H , Wang H , Yu L , Wang M , Liu S , Sun L , Chen Q
Ref : Arch Anim Nutr , 69 :340 , 2015
Abstract : This study determined the effects of rumen-protected choline (RPC) on growth performance, blood lipids, meat quality and expression of genes involved in fatty-acid metabolism in young lambs. A total of 24 Dorper x Hu lambs (about 20 kg body weight) were kept in individual pens and fed diets with 0%, 0.25%, 0.50% and 0.75% RPC for 60 d. Supplementation of 0.25% RPC increased average daily gain of lambs, whereas treatments had no significant effect on feed intake. The pH values of meat were increased at 0.25% RPC and both, dripping loss and shear force of meat, were significantly decreased in RPC-supplemented lambs. No significant changes were observed for dressing percentage and intramuscular fat. RPC supplementations had no significant effect on the concentrations of triglycerides and cholesterols in serum, but the concentration of high-density lipoprotein was decreased at 0.50% RPC and that of low-density lipoprotein was increased at 0.75% RPC. In m. longissimus dorsi, the expressions of cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FASN) genes were increased at 0.25% RPC. Supplementation of 0.75% RPC increased the expressions of lipoprotein lipase (LPL) and FASN genes, decreased the expression of ACC gene and had no effect on CD36 gene. The results of this study showed that supplementation of 0.25% RPC could promote growth performance of lambs and improve meat quality. This may be mediated by effects on blood lipid profiles and the metabolism of fatty acids in skeleton muscles. However, the beneficial effects of 0.25% RPC supplementation need to be validated with a larger number of animals. Higher doses, particularly 0.75% RPC, showed adverse effects on live weight gain and ACC expression.
ESTHER : Li_2015_Arch.Anim.Nutr_69_340
PubMedSearch : Li_2015_Arch.Anim.Nutr_69_340
PubMedID: 26305383

Title : Single and Multiple Dose Pharmacokinetics, Pharmacodynamics and Safety of the Novel Lipoprotein-Associated Phospholipase A2 Enzyme Inhibitor Darapladib in Healthy Chinese Subjects: An Open Label Phase-1 Clinical Trial - Hu_2015_PLoS.One_10_e0139862
Author(s) : Hu C , Tompson D , Magee M , Chen Q , Liu YM , Zhu W , Zhao H , Gross AS , Liu Y
Ref : PLoS ONE , 10 :e0139862 , 2015
Abstract : BACKGROUND AND OBJECTIVES: Darapladib is a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. This study evaluated the pharmacokinetics, pharmacodynamics and safety of darapladib in healthy Chinese subjects.
METHODS: Twenty-four subjects received darapladib 160 mg orally, approximately 1 hour after a standard breakfast, as a single dose and once daily for 28 days. Non-compartmental methods were used to determine the single and multiple dose pharmacokinetics of darapladib and its metabolite SB-553253. Repeat dose Lp-PLA2 activity and safety were evaluated.
RESULTS: Systemic exposure (AUC(0-T), Cmax geometric mean (CVb%)) of darapladib was higher after multiple-dosing (519 ng.h/mL (33.3%), 34.4 ng/mL (49.9%)) compared to single-dose administration (153 ng.h/mL (69.0%), 17.9 ng/mL (55.2%). The steady-state accumulation ratio was less than unity (Rs = 0.80), indicating time-dependent pharmacokinetics of darapladib. Darapladib steady-state was reached by Day 14 of once daily dosing. Systemic exposure to SB-553253 was lower than darapladib with median (SB-553253: darapladib) ratios for AUC(0-tau) of 0.0786 for single dose and 0.0532 for multiple dose administration. On Day 28, pre-dose and maximum inhibition of Lp-PLA2 activity was approximately 70% and 75% relative to the baseline value, respectively and was dependent of darapladib concentration. The most common adverse events (>/= 21% subjects) were abnormal faeces, abnormal urine odour, diarrhoea and nasopharyngitis. CONCLUSION: Darapladib 160 mg single and repeat doses were profiled in healthy Chinese subjects. Single dose systemic exposure to darapladib in healthy Chinese subjects was consistent with that observed previously in Western subjects whereas steady-state systemic exposure was approximately 65% higher in Chinese than Western subjects. The Lp-PLA2 activity and adverse event profile were similar in healthy Chinese and previous reports in Western subjects. Ethnic-specific dose adjustment of darapladib is not considered necessary for the Chinese population. TRIAL REGISTRATION: NCT02000804.
ESTHER : Hu_2015_PLoS.One_10_e0139862
PubMedSearch : Hu_2015_PLoS.One_10_e0139862
PubMedID: 26465780

Title : The chronic effects of lignin-derived bisphenol and bisphenol A in Japanese medaka Oryzias latipes - Li_2015_Aquat.Toxicol_170_199
Author(s) : Li D , Chen Q , Cao J , Chen H , Li L , Cedergreen N , Xie H , Xie L
Ref : Aquat Toxicol , 170 :199 , 2015
Abstract : One of the ultimate goals of green chemistry is to produce greener and more environmentally friendly chemicals to replace the existing toxic chemicals. In this study, Japanese medaka were exposed to 1.5mg/L of bisphenol A or lignin-derived bisphenol for 60 days, and the expressions of various biochemical markers, effects on reproduction, and histopathology were evaluated. The results showed that concentrations of liver vitellogenin of LD-BP exposed males were approximately 125% higher compared to the control males. Total number of eggs from the BPA and LD-BP exposed fish was approximately 47% (p<0.001) and 25% (p<0.05) less than the control fish, respectively. Total number of brood was lower from the BPA (46%, p<0.05) and LD-BP (17%, p<0.05) exposed fish than that of the control fish. Relative to the control fish, catalase and glutathione-S-transferase were significantly affected by the two chemicals in all tested tissues. BPA and LD-BP caused lipid peroxidation in all the tested tissues. Furthermore, acetylcholinesterase and alpha-glucosidase activity were significantly inhibited. Histopathological analysis showed that both the testis and ovary were mildly damaged by both chemicals. LD-BP affected medaka slightly more severe than BPA except on the reproduction, which was most likely due to different uptake, translocation, binding to targets and metabolism. Our results demonstrated that chronic exposure to both chemicals caused several adverse effects to medaka. Further research on the toxicity of LD-BP to other aquatic organisms is needed before substitution of traditional BPA with LD-BP can be recommended.
ESTHER : Li_2015_Aquat.Toxicol_170_199
PubMedSearch : Li_2015_Aquat.Toxicol_170_199
PubMedID: 26674368

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

Title : Molecular dynamics investigation of the substrate binding mechanism in carboxylesterase - Chen_2015_Biochemistry_54_1841
Author(s) : Chen Q , Luan ZJ , Cheng X , Xu JH
Ref : Biochemistry , 54 :1841 , 2015
Abstract : A recombinant carboxylesterase, cloned from Pseudomonas putida and designated as rPPE, is capable of catalyzing the bioresolution of racemic 2-acetoxy-2-(2'-chlorophenyl)acetate (rac-AcO-CPA) with excellent (S)-enantioselectivity. Semirational design of the enzyme showed that the W187H variant could increase the activity by approximately 100-fold compared to the wild type (WT) enzyme. In this study, we performed all-atom molecular dynamics (MD) simulations of both apo-rPPE and rPPE in complex with (S)-AcO-CPA to gain insights into the origin of the increased catalysis in the W187H mutant. Our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of the substrate with the two active site residues Ser159 and His286. The replacement of Trp187 by His leads to considerable structural rearrangement in the active site of W187H. Unlike in the WT rPPE, the cap domain in the W187 mutant shows an open conformation in the simulations of both apo and substrate-bound enzymes. This open conformation exposes the catalytic triad to the solvent through a water accessible channel, which may facilitate the entry of the substrate and/or the exit of the product. Binding free energy calculations confirmed that the substrate binds more strongly in W187H than in WT. On the basis of these computational results, we further predicted that the mutations W187Y and D287G might also be able to increase the substrate binding and thus improve the enzyme's catalytic efficiency. Experimental binding and kinetic assays on W187Y and D287G show improved catalytic efficiency over WT, but not W187H. Contrary to our prediction, W187Y shows slightly decreased substrate binding coupled with a 100-fold increase in turnover rate, while in D287G the substrate binding is 8 times stronger but with a slightly reduced turnover rate. Our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase rPPEs, which will help guide future development of more efficient rPPE variants.
ESTHER : Chen_2015_Biochemistry_54_1841
PubMedSearch : Chen_2015_Biochemistry_54_1841
PubMedID: 25711934

Title : Cloning and Characterization of the Acetylcholinesterase1 Gene of Tetranychus cinnabarinus (Acari: Tetranychidae) - Bu_2015_J.Econ.Entomol_108_769
Author(s) : Bu CY , Feng XJ , Wang XQ , Cao Y , Wang YN , Chen Q , Gao P , Peng B , Li JL , Han JY , Shi GL
Ref : J Econ Entomol , 108 :769 , 2015
Abstract : The carmine spider mite, Tetranychus cinnabarinus (Boisduval), is a major agriculture pest. It can be found worldwide, has an extensive host plant range, and has shown resistance to pesticides. Organophosphate and carbamate insecticides account for more than one-third of all insecticide sales. Insecticide resistance and the toxicity of organophosphate and carbamate insecticides to mammals have become a growing concern. Acetylcholinesterase (AChE) is the major targeted enzyme of organophosphate and carbamate insecticides. In this study, we fully cloned, sequenced and characterized the ace1 gene of T. cinnabarinus, and identified the differences between T. cinnabarinus AChE1, Tetranychus urticae Koch AChE1, and human AChE1. Resistance-associated target-site mutations were displayed by comparing the AChE amino acid sequences and their AChE three-dimensional (3D) structures of the insecticide-susceptible strains of T. cinnabarinus and T. urticae to that of a T. urticae-resistant strain. We identified variation in the active-site gorge and the sites interacting with gorge residues by comparing AChE1 3D structures of T. cinnabarinus, T. urticae, and humans, though their 3D structures were similar. Furthermore, the expression profile of T. cinnabarinus AChE, at the different developmental stages, was determined by quantitative real-time polymerase chain reaction; the transcript levels of AChE were higher in the larvae stage than in other stages. The changes in AChE expression between different developmental stages may be related to their growth habits and metabolism characteristics. This study may offer new insights into the problems of insecticide resistance and insecticide toxicity of nontarget species.
ESTHER : Bu_2015_J.Econ.Entomol_108_769
PubMedSearch : Bu_2015_J.Econ.Entomol_108_769
PubMedID: 26470189
Gene_locus related to this paper: 9acar-m9t420

Title : Novel and selective acetylcholinesterase inhibitors for Tetranychus cinnabarinus (Acari: Tetranychidae) - Bu_2015_Insect.Biochem.Mol.Biol_66_129
Author(s) : Bu C , Peng B , Cao Y , Wang X , Chen Q , Li J , Shi G
Ref : Insect Biochemistry & Molecular Biology , 66 :129 , 2015
Abstract : The carmine spider mite, Tetranychus cinnabarinus (Acari: Tetranychidae), is an economically important and extremely polyphagous herbivorous pest, with the title of "resistance champion" among arthropods. Anticholinesterase insecticides such as organophosphate and carbamate account for more than one-third of global insecticide sales. The non-target toxicity and resistance problem of organophosphate and carbamate have become of growing concern, which may be due to the fact that they target the ubiquitous catalytic serine residue of acetylcholinesterase (AChE) in mammals, birds, and beneficial insects. In this study, the structural differences between T. cinnabarinus AChE and human AChE, at or near the catalytic pocket, were illustrated. From the SPECS chemical lead-compound database, 55 AChE inhibitor candidates were screened for high affinity for T. cinnabarinus AChE, but low affinity for human AChE, using the DOCK 6 and AutoDock Vina software. Three of the fifty-five candidates had inhibitory activity greater than that of the reversible AChE inhibitor eserine, with no observed inhibitory activities against human AChE. Two of the three had toxicity to T. cinnabarinus comparable to that of natural insecticidal pyrethrins. However, their potency is low compared with that of etoxazole, and further work is needed to optimize their potency. The selectivity of the three compounds over human and mite AChE may be due to their interaction with the mite-specific residues, as analyzed by Cyscore. The three compounds are potential lead compounds for development of novel acaricides against T. cinnabarinus with reduced toxicity to non-target species and a low propensity for resistance.
ESTHER : Bu_2015_Insect.Biochem.Mol.Biol_66_129
PubMedSearch : Bu_2015_Insect.Biochem.Mol.Biol_66_129
PubMedID: 26520174

Title : Structural insights into the specific recognition of N-heterocycle biodenitrogenation-derived substrates by microbial amide hydrolases - Wu_2014_Mol.Microbiol_91_1009
Author(s) : Wu G , Chen D , Tang H , Ren Y , Chen Q , Lv Y , Zhang Z , Zhao YL , Yao Y , Xu P
Ref : Molecular Microbiology , 91 :1009 , 2014
Abstract : N-heterocyclic compounds from industrial wastes, including nicotine, are environmental pollutants or toxicants responsible for a variety of health problems. Microbial biodegradation is an attractive strategy for the removal of N-heterocyclic pollutants, during which carbon-nitrogen bonds in N-heterocycles are converted to amide bonds and subsequently severed by amide hydrolases. Previous studies have failed to clarify the molecular mechanism through which amide hydrolases selectively recognize diverse amide substrates and complete the biodenitrogenation process. In this study, structural, computational and enzymatic analyses showed how the N-formylmaleamate deformylase Nfo and the maleamate amidase Ami, two pivotal amide hydrolases in the nicotine catabolic pathway of Pseudomonas putida S16, specifically recognize their respective substrates. In addition, comparison of the alpha-beta-alpha groups of amidases, which include Ami, pinpointed several subgroup-characteristic residues differentiating the two classes of amide substrates as containing either carboxylate groups or aromatic rings. Furthermore, this study reveals the molecular mechanism through which the specially tailored active sites of deformylases and amidases selectively recognize their unique substrates. Our work thus provides a thorough elucidation of the molecular mechanism through which amide hydrolases accomplish substrate-specific recognition in the microbial N-heterocycles biodenitrogenation pathway.
ESTHER : Wu_2014_Mol.Microbiol_91_1009
PubMedSearch : Wu_2014_Mol.Microbiol_91_1009
PubMedID: 24397579
Gene_locus related to this paper: psep6-f8g0m2

Title : A novel angular dioxygenase gene cluster encoding 3-phenoxybenzoate 1',2'-dioxygenase in Sphingobium wenxiniae JZ-1 - Wang_2014_Appl.Environ.Microbiol_80_3811
Author(s) : Wang C , Chen Q , Wang R , Shi C , Yan X , He J , Hong Q , Li S
Ref : Applied Environmental Microbiology , 80 :3811 , 2014
Abstract : Sphingobium wenxiniae JZ-1 utilizes a wide range of pyrethroids and their metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was obtained by successive streaking on LB agar. Comparison of the draft genomes of strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1. PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding alpha and beta subunits and the ferredoxin component of dioxin dioxygenase from Sphingomonas wittichii RW1, respectively. Complementation of pbaA1A2B in strain MJZ-1 resulted in the active 3-phenoxybenzoate 1',2'-dioxygenase, but the enzyme activity in Escherichia coli was achieved only through the coexpression of pbaA1A2B and a glutathione reductase (GR)-type reductase gene, pbaC, indicating that the 3-phenoxybenzoate 1',2'-dioxygenase belongs to a type IV Rieske non-heme iron aromatic ring-hydroxylating oxygenase system consisting of a hetero-oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. The pbaC gene is not located in the immediate vicinity of pbaA1A2B. 3-Phenoxybenzoate 1',2'-dioxygenase catalyzes the hydroxylation in the 1' and 2' positions of the benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol. Transcription of pbaA1A2B and pbaC was induced by 3-phenoxybenzoate, but the transcriptional level of pbaC was far less than that of pbaA1A2B, implying the possibility that PbaC may not be the only reductase that can physiologically transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that PbaA1A2B has a low specificity for reductase.
ESTHER : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedSearch : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedID: 24747891
Gene_locus related to this paper: 9sphn-q0kjt3 , sphwj-a0a059u2z8

Title : Complete Genome Sequence of the p-Nitrophenol-Degrading Bacterium Pseudomonas putida DLL-E4 - Hu_2014_Genome.Announc_2_e00596
Author(s) : Hu X , Wang J , Wang F , Chen Q , Huang Y , Cui Z
Ref : Genome Announc , 2 : , 2014
Abstract : The first complete genome sequence of a p-nitrophenol (PNP)-degrading bacterium is reported here. Pseudomonas putida DLL-E4, a Gram-negative bacterium isolated from methyl-parathion-polluted soil, can utilize PNP as the sole carbon and nitrogen source. P. putida DLL-E4 has a 6,484,062 bp circular chromosome that contains 5,894 genes, with a G+C content of 62.46%.
ESTHER : Hu_2014_Genome.Announc_2_e00596
PubMedSearch : Hu_2014_Genome.Announc_2_e00596
PubMedID: 24948765
Gene_locus related to this paper: psepu-q9wwz4 , psepu-a0a059uyg1

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

Title : Crystal structure of tannase from lactobacillusplantarum - Ren_2013_J.Mol.Biol_425_2737
Author(s) : Ren B , Wu M , Wang Q , Peng X , Wen H , McKinstry WJ , Chen Q
Ref : Journal of Molecular Biology , 425 :2737 , 2013
Abstract : Tannins are water-soluble polyphenolic compounds in plants. Hydrolyzable tannins are derivatives of gallic acid (3,4,5-trihydroxybenzoic acid) or its meta-depsidic forms that are esterified to polyol, catechin, or triterpenoid units. Tannases are a family of esterases that catalyze the hydrolysis of the galloyl ester bond in hydrolyzable tannins to release gallic acid. The enzymes have found wide applications in food, feed, beverage, pharmaceutical, and chemical industries since their discovery more than a century ago, although little is known about them at the molecular level, including the details of the catalytic and substrate binding sites. Here, we report the first three-dimensional structure of a tannase from Lactobacillus plantarum. The enzyme displays an alpha/beta structure, featured by a large cap domain inserted into the classical serine hydrolase fold. A catalytic triad was identified in the structure, which is composed of Ser163, His451, and Asp419. During the binding of gallic acid, the carboxyl group of the molecule forges hydrogen-bonding interactions with the catalytic triad of the enzyme while the three hydroxyl groups make contacts with Asp421, Lys343, and Glu357 to form another hydrogen-bonding network. Mutagenesis studies demonstrated that these residues are indispensable for the activity of the enzyme. Structural studies of the enzyme in complex with a number of substrates indicated that the interactions at the galloyl binding site are the determinant force for the binding of substrates. The single galloyl binding site is responsible for the esterase and depsidase activities of the enzyme.
ESTHER : Ren_2013_J.Mol.Biol_425_2737
PubMedSearch : Ren_2013_J.Mol.Biol_425_2737
PubMedID: 23648840
Gene_locus related to this paper: lacpl-tanL

Title : Expression, purification, crystallization and preliminary X-ray analysis of tannase from Lactobacillus plantarum. - Wu_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_456
Author(s) : Wu M , Peng X , Wen H , Wang Q , Chen Q , McKinstry WJ , Ren B
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 69 :456 , 2013
Abstract : Tannase catalyses the hydrolysis of the galloyl ester bond of tannins to release gallic acid. It belongs to the serine esterases and has wide applications in the food, feed, beverage, pharmaceutical and chemical industries. The tannase from Lactobacillus plantarum was cloned, expressed and purified. The protein was crystallized by the sitting-drop vapour-diffusion method with microseeding. The crystals belonged to space group P1, with unit-cell paramters a = 46.5, b = 62.8, c = 83.8 A, alpha = 70.4, beta = 86.0, gamma = 79.4degre. Although the enzyme exists mainly as a monomer in solution, it forms a dimer in the asymmetric unit of the crystal. The crystals diffracted to beyond 1.60A resolution using synchrotron radiation and a complete data set was collected to 1.65A resolution.
ESTHER : Wu_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_456
PubMedSearch : Wu_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_456
PubMedID: 23545659
Gene_locus related to this paper: lacpl-tanL

Title : Discovery and optimization of orally active cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors - Debenham_2013_Bioorg.Med.Chem.Lett_23_6228
Author(s) : Debenham JS , Graham TH , Verras A , Zhang Y , Clements MJ , Kuethe JT , Madsen-Duggan C , Liu W , Bhatt UR , Chen D , Chen Q , Garcia-Calvo M , Geissler WM , He H , Li X , Lisnock J , Shen Z , Tong X , Tung EC , Wiltsie J , Xu S , Hale JJ , Pinto S , Shen DM
Ref : Bioorganic & Medicinal Chemistry Lett , 23 :6228 , 2013
Abstract : The synthesis, SAR, binding affinities and pharmacokinetic profiles are described for a series of cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors discovered by high throughput screening. Compounds show high levels of ex vivo target engagement in mouse plasma 20 h post oral dose.
ESTHER : Debenham_2013_Bioorg.Med.Chem.Lett_23_6228
PubMedSearch : Debenham_2013_Bioorg.Med.Chem.Lett_23_6228
PubMedID: 24157366

Title : Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers - Xing_2013_Environ.Mol.Mutagen_54_397
Author(s) : Xing C , Chen Q , Li G , Zhang L , Zheng M , Zou Z , Hou L , Wang QF , Liu X , Guo X
Ref : Environmental & Molecular Mutagenesis , 54 :397 , 2013
Abstract : Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated with benzene-induced alterations in DNA methylation and hematotoxicity, we genotyped four commonly studied SNPs in three metabolic enzymes genes CYP1A1, EPHX1 and NQO1; and analyzed promoter DNA methylation status in 11 genes which have been reported to be associated with benzene-induced hematotoxicity (BLM, CYP1A1, EPHX1, ERCC3, NQO1, NUDT1, p15, p16, RAD51, TP53 and WRAP53) in 77 benzene-exposed workers and 25 unexposed controls in China. ERCC3, a DNA repair gene, showed a small but statistically significant increase of promoter DNA methylation in the exposed group compared with the unexposed group (mean +/- SD: 4.73 +/- 3.46% vs. 3.63 +/- 1.96%, P = 0.048). We also observed that an increased number of C allele for rs1051740 in EPHX1 was associated with decreased ERCC3 methylation levels in benzene-exposed workers (P(trend) = 0.001), but not in unexposed controls (P(trend) = 0.379). Interestingly, another EPHX1 SNP (rs2234922) was associated with lower white blood cell (WBC) counts (P(trend) = 0.044) in benzene-exposed workers. These associations remained the same when ERCC3 promoter methylation and WBCs were dichotomized according to the 90th percentile (>/=6%) of methylation levels in controls and a leucopenia cutoff (<4 x 10(9) /L), respectively. Our findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene-exposed workers.
ESTHER : Xing_2013_Environ.Mol.Mutagen_54_397
PubMedSearch : Xing_2013_Environ.Mol.Mutagen_54_397
PubMedID: 23797950

Title : Design, synthesis, and bioevaluation of benzamides: novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, Abeta aggregation, and beta-secretase - Peng_2012_Bioorg.Med.Chem_20_6739
Author(s) : Peng DY , Sun Q , Zhu XL , Lin HY , Chen Q , Yu NX , Yang WC , Yang GF
Ref : Bioorganic & Medicinal Chemistry , 20 :6739 , 2012
Abstract : Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. In this study, we conducted a structure-based design and successfully produced a series of new multi-site AChE inhibitors with a novel framework. Compound 2e, characterized by a central benzamide moiety linked to an isoquinoline at one side and acetophenone at the other, was the most potent candidate with K(i) of 6.47nM against human AChE. Particularly, it showed simultaneous inhibitory effects against BChE, Abeta aggregation, and beta-secretase. We therefore conclude that compound 2e is a very promising multi-function lead for the treatment of AD.
ESTHER : Peng_2012_Bioorg.Med.Chem_20_6739
PubMedSearch : Peng_2012_Bioorg.Med.Chem_20_6739
PubMedID: 23041347

Title : The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors - Graham_2012_Bioorg.Med.Chem.Lett_22_658
Author(s) : Graham TH , Shen HC , Liu W , Xiong Y , Verras A , Bleasby K , Bhatt UR , Chabin RM , Chen D , Chen Q , Garcia-Calvo M , Geissler WM , He H , Lassman ME , Shen Z , Tong X , Tung EC , Xie D , Xu S , Colletti SL , Tata JR , Hale JJ , Pinto S , Shen DM
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :658 , 2012
Abstract : Novel prolylcarboxypeptidase (PrCP) inhibitors with nanomolar IC(50) values were prepared by replacing the previously described dichlorobenzimidazole-substituted pyrrolidine amides with a variety of substituted benzylamine amides. In contrast to prior series, the compounds demonstrated minimal inhibition shift in whole serum and minimal recognition by P-glycoprotein (P-gp) efflux transporters. The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied.
ESTHER : Graham_2012_Bioorg.Med.Chem.Lett_22_658
PubMedSearch : Graham_2012_Bioorg.Med.Chem.Lett_22_658
PubMedID: 22079761
Gene_locus related to this paper: human-PRCP

Title : Genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from a patient before and after treatment with tigecycline - Hua_2012_J.Bacteriol_194_6979
Author(s) : Hua X , Zhou H , Jiang Y , Feng Y , Chen Q , Ruan Z , Yu Y
Ref : Journal of Bacteriology , 194 :6979 , 2012
Abstract : Acinetobacter baumannii is a Gram-negative bacterium which emerged as a significant nosocomial pathogen worldwide. To investigate the molecular basis of the tigecycline-resistant mechanism, we determined the genome sequences of two multidrug-resistant A. baumannii strains isolated from a patient before and after treatment with tigecycline.
ESTHER : Hua_2012_J.Bacteriol_194_6979
PubMedSearch : Hua_2012_J.Bacteriol_194_6979
PubMedID: 23209232
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : Amperometric acetylcholine biosensor based on self-assembly of gold nanoparticles and acetylcholinesterase on the sol-gel\/multi-walled carbon nanotubes\/choline oxidase composite-modified platinum electrode - Hou_2012_Biosens.Bioelectron_33_44
Author(s) : Hou S , Ou Z , Chen Q , Wu B
Ref : Biosensors & Bioelectronics , 33 :44 , 2012
Abstract : A novel acetylcholinesterase (AChE)/choline oxidase (ChOx) bienzyme amperometric acetylcholine biosensor based on gold nanoparticles (AuNPs) and multi-walled carbon nanotubes (MWCNTs) has been successfully developed by self-assembly process in combination of sol-gel technique. A thiolated aqueous silica sol containing MWCNTs and ChOx was first dropped on the surface of a cleaned Pt electrode, and then AuNPs were assembled with the thiolated sol-gel network. Finally, the alternate deposition of poly (diallyldimethylammonium chloride) (PDDA) and AChE was repeated to assemble different layers of PDDA-AChE on the electrode for optimizing AChE loading. Among the resulting biosensors, the biosensor based on two layers of PDDA-AChE multilayer films showed the best performance. It exhibited a wide linear range, high sensitivity and fast amperometric response, which were 0.005-0.4mM, 3.395 muA/mM, and within 15s, respectively. The biosensor showed long-term stability and acceptable reproducibility. More importantly, this study could provide a simple and effective multienzyme immobilization platform for meeting the demand of the effective immobilization enzyme on the electrode surface.
ESTHER : Hou_2012_Biosens.Bioelectron_33_44
PubMedSearch : Hou_2012_Biosens.Bioelectron_33_44
PubMedID: 22230694

Title : Cholinesterase inhibition in chlorpyrifos workers: Characterization of biomarkers of exposure and response in relation to urinary TCPy - Garabrant_2009_J.Expo.Sci.Environ.Epidemiol_19_634
Author(s) : Garabrant DH , Aylward LL , Berent S , Chen Q , Timchalk C , Burns CJ , Hays SM , Albers JW
Ref : J Expo Sci Environ Epidemiol , 19 :634 , 2009
Abstract : The objective of this study was to evaluate the quantitative relation between measured red blood cell acetylcholinesterase (RBC AChE) and plasma butyrylcholinesterase (BuChE) activities with exposure to chlorpyrifos (CPF) as assessed by measurement of urinary 3,5,6-trichloro-2-pyridinol (TCPy) in a study group of workers occupationally exposed in the manufacture of CPF and a referent group of chemical manufacturing workers. Measures of plasma BuChE and RBC AChE activity and urinary TCPy concentration collected over a year-long study (1999-2000) in CPF-exposed workers (n=53) and referents (n=60) were analyzed using linear mixed models to characterize exposure-response relationships. Intraindividual variability in cholinesterase measures was compared between CPF-exposed workers and referents. Urinary TCPy concentrations in CPF workers were substantially elevated compared to referents, with median and 95th percentile concentrations during typical employment conditions 10-fold and more than 30-fold higher, respectively, than corresponding measures in the referents. Intraindividual variability in cholinesterase activities was substantial, with 17% of unexposed referents experiencing one or more plasma BuChE measures more than 20% below baseline over a year of repeated, periodic measurements. RBC AChE activity, an early biomarker of effect, was unrelated to urinary TCPy concentration over the entire range of exposure, up to 1000 microg TCPy/g creatinine (Cr). Plasma BuChE activity, a non-adverse biomarker of exposure, was negatively related to urinary TCPy concentrations above approximately 110 microg TCPy/g Cr. No-effect levels for inhibition of plasma BuChE and RBC AChE corresponding to absorbed doses of CPF of approximately 5 and greater than 50 microg/kg/day, respectively, were identified. These findings are consistent with previous no-effect level determinations for ChE inhibition in humans and suggest that general population CPF exposure levels are substantially below the identified no-effect levels. The dose-response relationships observed in this study are consistent with predictions from the previously published physiologically based pharmacokinetic/pharmacodynamic model for CPF. Intraindividual variability in measured cholinesterase activities in referents was substantial, suggesting that ongoing monitoring programs may have a substantial rate of false positives.
ESTHER : Garabrant_2009_J.Expo.Sci.Environ.Epidemiol_19_634
PubMedSearch : Garabrant_2009_J.Expo.Sci.Environ.Epidemiol_19_634
PubMedID: 18716607

Title : New cholesterol-based gelators with maleimide unit and the relevant Michael adducts: chemoresponsive organogels - Chen_2009_Langmuir_25_11436
Author(s) : Chen Q , Zhang D , Zhang G , Zhu D
Ref : Langmuir , 25 :11436 , 2009
Abstract : Compound 1 containing cholesteryl and maleimide units can gel a few organic solvents such as cyclohexane. It is interesting to note that the gel-sol transition can be triggered by addition of trace amounts of thiol and triethylamine. In this regard, we successfully demonstrate the proof of principle for designing chemoresponsive gels by incorporating the reactive groups into the gelators. Additionally, the Michael adducts 2 and 3 were prepared. Compounds 2 and 3 can also gel several organic solvents. The results also show that slight molecular structural variation has a large effect on the gelation ability of the compound. These organogels were characterized with SEM, AFM, CD, and XRD. Interestingly, gelation-induced CD spectra were observed for gels of 1, 2, and 3.
ESTHER : Chen_2009_Langmuir_25_11436
PubMedSearch : Chen_2009_Langmuir_25_11436
PubMedID: 19507817

Title : Genome sequences of three agrobacterium biovars help elucidate the evolution of multichromosome genomes in bacteria - Slater_2009_J.Bacteriol_191_2501
Author(s) : Slater SC , Goldman BS , Goodner B , Setubal JC , Farrand SK , Nester EW , Burr TJ , Banta L , Dickerman AW , Paulsen I , Otten L , Suen G , Welch R , Almeida NF , Arnold F , Burton OT , Du Z , Ewing A , Godsy E , Heisel S , Houmiel KL , Jhaveri J , Lu J , Miller NM , Norton S , Chen Q , Phoolcharoen W , Ohlin V , Ondrusek D , Pride N , Stricklin SL , Sun J , Wheeler C , Wilson L , Zhu H , Wood DW
Ref : J. Bacteriol , 191 :2501 , 2009
Abstract : The family Rhizobiaceae contains plant-associated bacteria with critical roles in ecology and agriculture. Within this family, many Rhizobium and Sinorhizobium strains are nitrogen-fixing plant mutualists, while many strains designated as Agrobacterium are plant pathogens. These contrasting lifestyles are primarily dependent on the transmissible plasmids each strain harbors. Members of the Rhizobiaceae also have diverse genome architectures that include single chromosomes, multiple chromosomes, and plasmids of various sizes. Agrobacterium strains have been divided into three biovars, based on physiological and biochemical properties. The genome of a biovar I strain, A. tumefaciens C58, has been previously sequenced. In this study, the genomes of the biovar II strain A. radiobacter K84, a commercially available biological control strain that inhibits certain pathogenic agrobacteria, and the biovar III strain A. vitis S4, a narrow-host-range strain that infects grapes and invokes a hypersensitive response on nonhost plants, were fully sequenced and annotated. Comparison with other sequenced members of the Alphaproteobacteria provides new data on the evolution of multipartite bacterial genomes. Primary chromosomes show extensive conservation of both gene content and order. In contrast, secondary chromosomes share smaller percentages of genes, and conserved gene order is restricted to short blocks. We propose that secondary chromosomes originated from an ancestral plasmid to which genes have been transferred from a progenitor primary chromosome. Similar patterns are observed in select Beta- and Gammaproteobacteria species. Together, these results define the evolution of chromosome architecture and gene content among the Rhizobiaceae and support a generalized mechanism for second-chromosome formation among bacteria.
ESTHER : Slater_2009_J.Bacteriol_191_2501
PubMedSearch : Slater_2009_J.Bacteriol_191_2501
PubMedID: 19251847
Gene_locus related to this paper: agrrk-b9j7k2 , agrrk-b9j8e4 , agrrk-b9j8g5 , agrrk-b9j9n4 , agrrk-b9j9p4 , agrrk-b9ja88 , agrrk-b9jbs5 , agrrk-b9jd67 , agrrk-b9jd85 , agrrk-b9jfh5 , agrrk-b9jfj6 , agrrk-b9jfu6 , agrrk-b9jfy6 , agrrk-b9jh78 , agrrk-b9ji04 , agrrk-b9jih5 , agrrk-b9jih7 , agrrk-b9jj14 , agrrk-b9jjt5 , agrrk-b9jjt6 , agrrk-b9jk42 , agrrk-b9jki6 , agrrk-b9jkt4 , agrrk-b9jla0 , agrrk-b9jlc3 , agrrk-b9jlj1 , agrrk-b9jlj2 , agrrk-b9jlr1 , agrrk-b9jmj9 , agrrk-b9jml0 , agrrk-b9jmn1 , agrrk-b9jnw6 , agrrk-b9jq01 , agrrk-b9jq11 , agrrk-b9jq35 , agrtu-DHAA , agrvs-b9jqv2 , agrvs-b9jr09 , agrvs-b9js24 , agrvs-b9js61 , agrvs-b9ju03 , agrvs-b9jw40 , agrvs-b9jx20 , agrvs-b9jy84 , agrvs-b9k1h8 , agrvs-b9k2m9 , agrvs-b9k3r6 , agrvs-b9k5p9 , agrvs-b9k093 , agrvs-b9k188 , agrvs-b9k312 , agrrk-b9jls9 , agrrk-b9jca1 , agrvs-b9jur1 , agrrk-rutd

Title : Water-soluble derivative of propolis mitigates scopolamine-induced learning and memory impairment in mice - Chen_2008_Pharmacol.Biochem.Behav_90_441
Author(s) : Chen J , Long Y , Han M , Wang T , Chen Q , Wang R
Ref : Pharmacol Biochem Behav , 90 :441 , 2008
Abstract : The water-soluble derivative of propolis (WSDP) was prepared from fresh Chinese propolis. Its major constituents were identified by high performance liquid chromatography (HPLC) analysis. It has been reported that propolis possessed a broad spectrum of biological activities but including few studies on learning and memory by now. Thus, this study was aimed to investigate the effect of WSDP on scopolamine-induced learning and memory impairment in mice. WSDP (50 mg/kg, 100 mg/kg) was given by intragastric administration (i.g.) 40 min prior to the intraperitoneal (i.p.) injection of scopolamine (1 mg/kg). The effect on amnesia was investigated with both hidden-platform acquisition training and probe trial testing in Morris water maze test. The results from 100 mg/kg WSDP group showed significant mitigation scopolamine-induced amnesia in mice. Furthermore, WSDP's effect on the acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus was also assayed. As a result, WSDP (100 mg/kg) significantly inhibited AChE activity in the hippocampus of scopolamine-treated mice. These results indicated that WSDP may mitigate amnesia in vivo through inhibition of AChE activity in the hippocampus, which suggested propolis may have potential as a pharmaceutical of brain protection with elderly population for preventing Alzheimer's disease (AD) and other neurodegenerative diseases.
ESTHER : Chen_2008_Pharmacol.Biochem.Behav_90_441
PubMedSearch : Chen_2008_Pharmacol.Biochem.Behav_90_441
PubMedID: 18485465

Title : Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease - Chen_2008_Atherosclerosis_200_102
Author(s) : Chen Q , Razzaghi H , Demirci FY , Kamboh MI
Ref : Atherosclerosis , 200 :102 , 2008
Abstract : Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism by hydrolyzing triglyceride (TG)-rich lipoprotein particles. Abnormalities in normal LPL function are associated with the risk of coronary artery disease (CAD). A number of genetic variants have been identified in the LPL gene that affects different functions of the LPL protein. A common HindIII polymorphism in intron 8 (T/G) of the LPL gene has been found to be associated with altered plasma TG and HDL-cholesterol, and CAD risk in several studies, but its functional significance is unknown. It has been shown that certain intronic sequence contain regulatory elements that are important for transcription and translational regulation of a gene. In this study we tested the hypothesis that this polymorphism affects the binding site of a transcription factor that regulates the transcription of LPL gene. Electrophoretic mobility shift assays (EMSAs) revealed that the HindIII site binds to a transcription factor and that the mutant allele has lower binding affinity than the wild type allele. Transcription assays containing the entire intron 8 sequence along with full-length human LPL promoter were carried out in COS-1 and human vascular smooth muscle cells. The mutant allele was associated with significantly decreased luciferase expression level compared to the wild type allele in both the muscle (3.394+/-0.022 vs. 4.184+/-0.028; P=4.7 x 10(-6)) and COS-1 (11.603+/-0.409 vs. 14.373+/-1.096; P<0.0001) cells. In conclusion, this study demonstrates for the first time that the polymorphic HindIII site in the LPL gene is functional because it affects the binding of a transcription factor and it also has an impact on LPL expression.
ESTHER : Chen_2008_Atherosclerosis_200_102
PubMedSearch : Chen_2008_Atherosclerosis_200_102
PubMedID: 18242618

Title : Two gene determinants are differentially involved in the biogenesis of Fap1 precursors in Streptococcus parasanguis - Wu_2007_J.Bacteriol_189_1390
Author(s) : Wu H , Bu S , Newell P , Chen Q , Fives-Taylor P
Ref : Journal of Bacteriology , 189 :1390 , 2007
Abstract : Mature Fap1, a 200-kDa fimbria-associated adhesin, is required for fimbrial biogenesis and biofilm formation in Streptococcus parasanguis. Fap1-like proteins are found in the genomes of many streptococcal and staphylococcal species. Fap1 is a serine-rich glycoprotein modified by O-linked glycan moieties. In this study, we identified a seven-gene cluster including secY2, orf1, orf2, orf3, secA2, gtf1, and gtf2 that is localized immediately downstream of fap1. The lower G+C contents and the presence of a putative transposase element suggest that this gene cluster was horizontally transferred from other bacteria and represents a genomic island. At least two genes in this island mediated Fap1 biogenesis. Mutation of a glucosyltransferase (Gtf1) gene led to accumulation of a Fap1 precursor, which had no detectable glycan moieties. Inactivation of a gene coding for an accessory Sec protein (SecY2) resulted in expression of a distinct Fap1 precursor, which reacted with one glycan-specific Fap1 antibody but not with another glycan-specific antibody. Furthermore, partially glycosylated Fap1 was detected on the cell surface and in the culture supernatant. These data suggest that SecY2 has a role in complete glycosylation of Fap1 and imply that SecY2 is not the only translocation channel for the Fap1 precursor and that alternative secretion machinery exists. Together, Gtf1 and SecY2 are involved in biogenesis of two distinct Fap1 precursors in S. parasanguis. Discovery of the effect of an accessory Sec protein on Fap1 glycosylation suggests that Fap1 secretion and glycosylation are coupled during Fap1 biogenesis.
ESTHER : Wu_2007_J.Bacteriol_189_1390
PubMedSearch : Wu_2007_J.Bacteriol_189_1390
PubMedID: 16997950

Title : Complete sequence of virulence plasmid pJM1 from the marine fish pathogen Vibrio anguillarum strain 775 - Di Lorenzo_2003_J.Bacteriol_185_5822
Author(s) : Di Lorenzo M , Stork M , Tolmasky ME , Actis LA , Farrell D , Welch TJ , Crosa LM , Wertheimer AM , Chen Q , Salinas P , Waldbeser L , Crosa JH
Ref : Journal of Bacteriology , 185 :5822 , 2003
Abstract : The virulence plasmid pJM1 enables the fish pathogen Vibrio anguillarum, a gram-negative polarly flagellated comma-shaped rod bacterium, to cause a highly fatal hemorrhagic septicemic disease in salmonids and other fishes, leading to epizootics throughout the world. The pJM1 plasmid 65,009-nucleotide sequence, with an overall G+C content of 42.6%, revealed genes and open reading frames (ORFs) encoding iron transporters, nonribosomal peptide enzymes, and other proteins essential for the biosynthesis of the siderophore anguibactin. Of the 59 ORFs, approximately 32% were related to iron metabolic functions. The plasmid pJM1 confers on V. anguillarum the ability to take up ferric iron as a complex with anguibactin from a medium in which iron is chelated by transferrin, ethylenediamine-di(o-hydroxyphenyl-acetic acid), or other iron-chelating compounds. The fatDCBA-angRT operon as well as other downstream biosynthetic genes is bracketed by the homologous ISV-A1 and ISV-A2 insertion sequences. Other clusters on the plasmid also show an insertion element-flanked organization, including ORFs homologous to genes involved in the biosynthesis of 2,3-dihydroxybenzoic acid. Homologues of replication and partition genes are also identified on pJM1 adjacent to this region. ORFs with no known function represent approximately 30% of the pJM1 sequence. The insertion sequence elements in the composite transposon-like structures, corroborated by the G+C content of the pJM1 sequence, suggest a modular composition of plasmid pJM1, biased towards acquisition of modules containing genes related to iron metabolic functions. We also show that there is considerable microheterogeneity in pJM1-like plasmids from virulent strains of V. anguillarum isolated from different geographical sources.
ESTHER : Di Lorenzo_2003_J.Bacteriol_185_5822
PubMedSearch : Di Lorenzo_2003_J.Bacteriol_185_5822
PubMedID: 13129954
Gene_locus related to this paper: viban-sast

Title : A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome - Mural_2002_Science_296_1661
Author(s) : Mural RJ , Adams MD , Myers EW , Smith HO , Miklos GL , Wides R , Halpern A , Li PW , Sutton GG , Nadeau J , Salzberg SL , Holt RA , Kodira CD , Lu F , Chen L , Deng Z , Evangelista CC , Gan W , Heiman TJ , Li J , Li Z , Merkulov GV , Milshina NV , Naik AK , Qi R , Shue BC , Wang A , Wang J , Wang X , Yan X , Ye J , Yooseph S , Zhao Q , Zheng L , Zhu SC , Biddick K , Bolanos R , Delcher AL , Dew IM , Fasulo D , Flanigan MJ , Huson DH , Kravitz SA , Miller JR , Mobarry CM , Reinert K , Remington KA , Zhang Q , Zheng XH , Nusskern DR , Lai Z , Lei Y , Zhong W , Yao A , Guan P , Ji RR , Gu Z , Wang ZY , Zhong F , Xiao C , Chiang CC , Yandell M , Wortman JR , Amanatides PG , Hladun SL , Pratts EC , Johnson JE , Dodson KL , Woodford KJ , Evans CA , Gropman B , Rusch DB , Venter E , Wang M , Smith TJ , Houck JT , Tompkins DE , Haynes C , Jacob D , Chin SH , Allen DR , Dahlke CE , Sanders R , Li K , Liu X , Levitsky AA , Majoros WH , Chen Q , Xia AC , Lopez JR , Donnelly MT , Newman MH , Glodek A , Kraft CL , Nodell M , Ali F , An HJ , Baldwin-Pitts D , Beeson KY , Cai S , Carnes M , Carver A , Caulk PM , Center A , Chen YH , Cheng ML , Coyne MD , Crowder M , Danaher S , Davenport LB , Desilets R , Dietz SM , Doup L , Dullaghan P , Ferriera S , Fosler CR , Gire HC , Gluecksmann A , Gocayne JD , Gray J , Hart B , Haynes J , Hoover J , Howland T , Ibegwam C , Jalali M , Johns D , Kline L , Ma DS , MacCawley S , Magoon A , Mann F , May D , McIntosh TC , Mehta S , Moy L , Moy MC , Murphy BJ , Murphy SD , Nelson KA , Nuri Z , Parker KA , Prudhomme AC , Puri VN , Qureshi H , Raley JC , Reardon MS , Regier MA , Rogers YH , Romblad DL , Schutz J , Scott JL , Scott R , Sitter CD , Smallwood M , Sprague AC , Stewart E , Strong RV , Suh E , Sylvester K , Thomas R , Tint NN , Tsonis C , Wang G , Williams MS , Williams SM , Windsor SM , Wolfe K , Wu MM , Zaveri J , Chaturvedi K , Gabrielian AE , Ke Z , Sun J , Subramanian G , Venter JC , Pfannkoch CM , Barnstead M , Stephenson LD
Ref : Science , 296 :1661 , 2002
Abstract : The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
ESTHER : Mural_2002_Science_296_1661
PubMedSearch : Mural_2002_Science_296_1661
PubMedID: 12040188
Gene_locus related to this paper: mouse-ABH15 , mouse-Ces3b , mouse-Ces4a , mouse-dpp4 , mouse-FAP , mouse-Lipg , mouse-Q8C1A9 , mouse-rbbp9 , mouse-SERHL , mouse-SPG21 , mouse-w4vsp6

Title : A case-control study of microsomal epoxide hydrolase, smoking, meat consumption, glutathione S-transferase M3, and risk of colorectal adenomas - Cortessis_2001_Cancer.Res_61_2381
Author(s) : Cortessis V , Siegmund K , Chen Q , Zhou N , Diep A , Frankl H , Lee E , Zhu QS , Haile R , Levy D
Ref : Cancer Research , 61 :2381 , 2001
Abstract : We estimated associations between polymorphisms in the gene encoding microsomal epoxide hydrolase (mEH) among 464 cases diagnosed with first occurrence of colorectal adenoma and 510 matched controls. In an analysis controlling only for the matching variables, we found little or no association between adenoma and mEH genotypes defined by polymorphisms at either codon 113 and 139 or mEH activity predicted by both polymorphisms. However, in subsequent analyses, high predicted mEH activity was significantly associated with adenoma among certain subgroups defined by smoking history [odds ratio (OR), 4.27; 95% confidence interval (CI), 1.68-10.81 among current smokers; interaction, P = 0.11], meat consumption (OR, 2.47; CI, 0.99-6.19 among individuals who regularly eat well-done meat; interaction, P = 0.03), and genotypes for the *A/*B polymorphism in the gene encoding glutatione S-transferase M3 (OR, 2.60; CI, 1.28-5.28 among individuals with *A*A genotype; interaction, P = 0.03). These findings are consistent with causal roles for environmental polycyclic aromatic hydrocarbons and genetically encoded variants in enzymes whose actions lead to the production of activated polycyclic aromatic hydrocarbon metabolites.
ESTHER : Cortessis_2001_Cancer.Res_61_2381
PubMedSearch : Cortessis_2001_Cancer.Res_61_2381
PubMedID: 11289100

Title : [Effect of acupuncture on enzymology of motor neuron of anterior horn of experimental spinal cord injury in rats] - Wu_1999_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_19_740
Author(s) : Wu Y , Liu C , Chen Q
Ref : Zhongguo Zhong Xi Yi Jie He Za Zhi , 19 :740 , 1999
Abstract : OBJECTIVE To study the effect of acupuncture on enzymology of the motor neuron of anterior horn of injured spinal cord in rats METHODS Chemical staining method was used to quantitatively analyze the acetylcholinesterase ACHE succinate dehydrogenase SDH acid phosphatase ACP changes in motor neuron of anterior horn of spinal cord simultaneously and auto-analysis photogram apparatus was used to quantitatively analyze RESULTS After spinal cord was injured the AchE and SDH reduced ACP raised in the acupuncture group ACHE and SDH were increased and ACP was lowered after acupuncture P 0.05 P 0.01 CONCLUSION Acupuncture could regulate enzymology of the motor neuron of anterior horn of injured spinal cord Acupuncture could inhibit or delay the deterioration of neuron and also could promote the recovery
ESTHER : Wu_1999_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_19_740
PubMedSearch : Wu_1999_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_19_740
PubMedID: 11783148

Title : Characterization of the angR gene of Vibrio anguillarum: essential role in virulence - Wertheimer_1999_Infect.Immun_67_6496
Author(s) : Wertheimer AM , Verweij W , Chen Q , Crosa LM , Nagasawa M , Tolmasky ME , Actis LA , Crosa JH
Ref : Infect Immun , 67 :6496 , 1999
Abstract : The ability to utilize the iron bound by high-affinity iron-binding proteins in the vertebrate host is an important virulence factor for the marine fish pathogen Vibrio anguillarum. Virulence in septicemic infections is due to the presence of a highly efficient plasmid-encoded iron transport system. AngR, a 110-kDa protein component of this system, appears to play a role in both regulation of the expression of the iron transport genes fatDCBA and the production of the siderophore anguibactin. Therefore, study of the expression of the angR gene and the properties of its product, the AngR protein, may contribute to the understanding of the mechanisms of virulence of this pathogen. In this work, we present genetic and molecular evidence from transposition mutagenesis experiments and RNA analysis that angR, which maps immediately downstream of the fatA gene, is part of a polycistronic transcript that also includes the iron transport genes fatDCBA and angT, a gene located downstream of angR which showed domain homology to certain thioesterases involved in nonribosomal peptide synthesis of siderophores and antibiotics. In order to dissect the specific domains of AngR associated with regulation of iron transport gene expression, anguibactin production, and virulence, we also generated a panel of site-directed angR mutants, as well as deletion derivatives. Both virulence and anguibactin production were dramatically affected by each one of the angR modifications. In contrast to the need for an intact AngR molecule for anguibactin production and virulence, the regulation of iron transport gene expression does not require the entire AngR molecule, since truncation of the carboxy terminus carrying the nonribosomal peptide synthetase cores, as well as the site-directed mutations, resulted in derivatives that retained their ability to regulate gene expression which was only abolished after truncation of amino-terminal sequences containing helix-turn-helix and leucine zipper motifs and a specialized heterocyclization and condensation domain found in certain nonribosomal peptide synthetases. The evidence, while not rigorously eliminating the possibility that a separate regulatory polypeptide exists and is encoded somewhere within the 5'-end region of the angR gene, strongly supports the idea that AngR is a bifunctional protein and that it plays an essential role in the virulence mechanisms of V. anguillarum. We also show in this study that the angT gene, found downstream of angR, intervenes in the mechanism of anguibactin production but is not essential for virulence or iron transport gene expression.
ESTHER : Wertheimer_1999_Infect.Immun_67_6496
PubMedSearch : Wertheimer_1999_Infect.Immun_67_6496
PubMedID: 10569768
Gene_locus related to this paper: viban-sast

Title : Digestion of triacylglycerols containing long-chain polyenoic fatty acids in vitro by colipase-dependent pancreatic lipase and human milk bile salt-stimulated lipase - Chen_1994_Biochim.Biophys.Acta_1210_239
Author(s) : Chen Q , Blackberg L , Nilsson A , Sternby B , Hernell O
Ref : Biochimica & Biophysica Acta , 1210 :239 , 1994
Abstract : To assess the role of human milk bile salt-stimulated lipase (BSSL) in the digestion of polyunsaturated ester bonds of triacylglycerols, hydrolysis of docosahexaenoic acid (22:6(n-3)) ester bonds was compared to that of oleic acid (18:1(n-9)) or arachidonic acid (20:4(n-6)) esters. As model substrates, we used rat chylomicrons obtained after feeding human milk fat globules and radiolabeled fatty acids. Radiolabeled chylomicrons were incubated with colipase-dependent pancreatic lipase, with BSSL, or with both enzymes in combination. Both enzymes hydrolyzed 18:1 more efficiently than 22:6 esters. With colipase-dependent lipase there was a large accumulation of 22:6 in diacylglycerol whereas with BSSL it accumulated mainly in monoacylglycerol. Esters containing 20:4 were hydrolyzed by BSSL as efficiently as 18:1 but this fatty acid also accumulated as diacylglycerol with colipase-dependent lipase. At low bile salt concentrations, as found in duodenal contents of newborns, colipase-dependent lipase was virtually unable to hydrolyze esters of 20:4 and 22:6 whereas BSSL hydrolyzed these esters at appreciable rates. Combining the two enzymes gave the most efficient hydrolysis of all fatty acids tested regardless of bile salt concentrations. BSSL may thus have a physiological role in completing duodenal hydrolysis of milk triacylglycerols containing 22:6- or 20:4-esters to free fatty acids and monoacylglycerol.
ESTHER : Chen_1994_Biochim.Biophys.Acta_1210_239
PubMedSearch : Chen_1994_Biochim.Biophys.Acta_1210_239
PubMedID: 8280776

Title : Does the bile salt-stimulated lipase of human milk have a role in the use of the milk long-chain polyunsaturated fatty acids? - Hernell_1993_J.Pediatr.Gastroenterol.Nutr_16_426
Author(s) : Hernell O , Blackberg L , Chen Q , Sternby B , Nilsson A
Ref : J Pediatr Gastroenterol Nutr , 16 :426 , 1993
Abstract : Long-chain polyunsaturated (LCP) fatty acids derived from linoleic (18:2 n-6) and alpha-linolenic (18:3 n-3) acids are considered essential nutrients in preterm infants. The efficiency by which such fatty acids are released as absorbable products from triacylglycerol was explored in vitro using rat chylomicron triacylglycerol as substrate. When incubated with purified human pancreatic colipase-dependent lipase and colipase, arachidonic acid (20:4 n-6) was released less efficiently than linoleic acid from such triacylglycerol. This difference was not seen when purified human milk bile salt-stimulated lipase (BSSL) was incubated with the triacylglycerol substrate, and it was almost abolished when colipase-dependent lipase (with colipase) and BSSL acted simultaneously, as they do in breast-fed infants. There was no difference in arachidonic acid and eicosapentaenoic acid (20:5 n-3) release rates with either colipase-dependent lipase or BSSL, albeit the release was more rapid with the milk enzyme than with colipase-dependent lipase. Again, the most efficient release as absorbable free fatty acids was achieved when the two lipases operated together. The relative resistance to hydrolysis of arachidonic acid and eicosapentaenoic acid by colipase-dependent lipase was best explained by the localization of the first double bond to the delta-5 position of the respective fatty acid. The results obtained suggest that BSSL is of importance for the efficient use of human milk LCP fatty acids.
ESTHER : Hernell_1993_J.Pediatr.Gastroenterol.Nutr_16_426
PubMedSearch : Hernell_1993_J.Pediatr.Gastroenterol.Nutr_16_426
PubMedID: 8315552

Title : Induction of dystrophin localization in cultured Xenopus muscle cells by latex beads - Peng_1992_J.Cell.Sci_103 ( Pt 2)_551
Author(s) : Peng HB , Chen Q
Ref : Journal of Cell Science , 103 ( Pt 2) :551 , 1992
Abstract : The distribution of dystrophin in Xenopus myotomal muscle cells was examined in conventional and confocal immunofluorescence microscopy. By labeling dissociated single muscle fibers with a monoclonal or a polyclonal antibody against dystrophin, we found that dystrophin is ten times more concentrated at the myotendinous junction (MTJ) than at the extrajunctional sarcolemma. At the MTJ, dystrophin lines the membrane invaginations where myofibrils attach to the membrane. It is colocalized with talin, but is not related to the distribution of acetylcholine receptors (AChRs) which are clustered at the postsynaptic membrane in the vicinity of the MTJ in these fibers. We found that the localization of dystrophin can be induced in cultured Xenopus myotomal muscle cells by treating them with polystyrene latex beads. Dystrophin is discretely localized at the bead-muscle contacts. With electron microscopy, a sarcolemma specialization with all the salient features of the MTJ, including basal lamina-lined membrane invaginations along which myofibrils make attachment. Although these beads also induce clustering of AChRs, the patterns of dystrophin and AChR localization are distinct. The appearance of dystrophin at the bead-contacted sarcolemma is coincident with the development of the membrane invaginations. This, together with its concentration along membrane invaginations at the MTJ in vivo, suggests a role for dystrophin in the formation of this junctional specialization. Since the signal for MTJ development can be presented to cultured muscle cells in a temporally and spatially controlled manner by beads, this system offers a simple model for analyzing the mechanism of this sarcolemma specialization.
ESTHER : Peng_1992_J.Cell.Sci_103 ( Pt 2)_551
PubMedSearch : Peng_1992_J.Cell.Sci_103 ( Pt 2)_551
PubMedID: 1478954

Title : Induction of acetylcholine receptor clustering by native polystyrene beads. Implication of an endogenous muscle-derived signalling system - Baker_1992_J.Cell.Sci_102 ( Pt 3)_543
Author(s) : Baker LP , Chen Q , Peng HB
Ref : Journal of Cell Science , 102 ( Pt 3) :543 , 1992
Abstract : Aneural muscle cells in culture often form acetylcholine receptor (AChR) clusters, termed hot spots, which are similar to those found at the postsynaptic membrane both in structure and in molecular composition. Although hot spots form on both dorsal and ventral surfaces of the cell, the ventral ones are better characterized because of their association with sites of cell-substratum contact. To understand the stimuli and mechanisms involved in ventral hot spot formation, native, uncoated polystyrene beads were applied to cultured Xenopus myotomal muscle cells to create local membrane-substratum contacts. These beads were able to induce a postsynaptic-type development as evidenced by the clustering of AChRs and the development of a set of ultrastructural specializations, including membrane infoldings and a basement membrane. Whereas these native beads were effective in inducing clustering, beads coated with bovine serum albumin or treated with serum-containing medium were ineffective. Native beads were also capable of inducing clusters in serum-free medium, indicating that their effect was mediated by endogenous molecules that were locally presented by the beads, rather than by bead adsorption of components in the medium. Heparan sulfate proteoglycan (HSPG) is a major component of the muscle extracellular matrix and our previous study has shown that basic fibroblast growth factor (bFGF), a member of the heparin-binding growth factor (HBGF) family, and its receptor are present in Xenopus myotomal muscle during the period of synaptogenesis. Therefore, we tested the involvement of HBGF in bead induction. The results of this study show the following: (1) preincubation of cultures in heparin, which solubilizes matrix-bound HBGFs, suppressed the bead-induced AChR clustering. (2) Suramin, which interferes with the interaction between several growth factors and their receptors, also inhibited bead-induced clustering. (3) Tyrphostin, which blocks tyrosine kinase activity associated with a number of growth factor receptors, was also inhibitory to the bead effect. (4) The percentage of bead-induced AChR clusters was significantly enhanced by pretreating the cultures with bFGF prior to bead application. This exogenously applied bFGF could be largely removed by treatment of cultures with heparin, suggesting its association with HSPG at the cell surface. (5) An anti-bFGF neutralizing antiserum significantly reduced the efficacy of the bead stimulation. These data suggest that uncoated beads, which adhere to the cell surface and can mimic the cell-substratum interaction, effect a local presentation of HBGFs, such as bFGF, residing with the HSPG to their membrane receptors, thereby locally activating receptor-associated tyrosine kinases.
ESTHER : Baker_1992_J.Cell.Sci_102 ( Pt 3)_543
PubMedSearch : Baker_1992_J.Cell.Sci_102 ( Pt 3)_543
PubMedID: 1380514

Title : Induction of synaptic development in cultured muscle cells by basic fibroblast growth factor - Peng_1991_Neuron_6_237
Author(s) : Peng HB , Baker LP , Chen Q
Ref : Neuron , 6 :237 , 1991
Abstract : The role of basic fibroblast growth factor (bFGF) in signaling the development of the neuromuscular junction was examined. Beads coated with bFGF induced the formation of acetylcholine receptor (AChR) clusters in cultured Xenopus myotomal muscle cells. Tyrphostin, a tyrosine kinase inhibitor, abolished AChR clustering induced by bFGF beads, suggesting a role of tyrosine kinase activation in AChR clustering. Using specific antibodies, we demonstrated the presence of both bFGF and its receptor in the myotomal muscle in vivo during the period of neuromuscular connection. However, similar tissue from older animals with mature neuromuscular junctions showed an apparently truncated form of the bFGF receptor. These data suggest that bFGF may play a role in signaling synaptogenesis in skeletal muscle.
ESTHER : Peng_1991_Neuron_6_237
PubMedSearch : Peng_1991_Neuron_6_237
PubMedID: 1847064

Title : Tissue culture of Xenopus neurons and muscle cells as a model for studying synaptic induction -
Author(s) : Peng HB , Baker LP , Chen Q
Ref : Methods Cell Biol , 36 :511 , 1991
PubMedID: 1811149

Title : Effects of human pancreatic lipase-colipase and carboxyl ester lipase on eicosapentaenoic and arachidonic acid ester bonds of triacylglycerols rich in fish oil fatty acids - Chen_1990_Biochim.Biophys.Acta_1044_111
Author(s) : Chen Q , Sternby B , Akesson B , Nilsson A
Ref : Biochimica & Biophysica Acta , 1044 :111 , 1990
Abstract : Fish oil chylomicrons, obtained from mesenteric duct chyle of rats fed [3H]20:5 and [14C]20:4 or [3H]20:5 and [14C]18:2 in a fish oil emulsion, were incubated with human pancreatic lipase-colipase, human carboxyl ester lipase (CEL) and human duodenal contents. With duodenal contents, the triacylglycerols labelled with [3H]20:5 and [14C]20:4 were rapidly converted to free fatty acids (FFA) and monoacylglycerols. Also during incubation with lipase-colipase the [3H]- and [14C]triacylglycerols disappeared completely and at equal rates, but in this case much [3H]20:5 and [14C]20:4 accumulated in diacylglycerols. When CEL was also added, the rate of disappearance of [3H]- and [14C]triacylglycerols increased and the radioactivity of diacylglycerols decreased markedly. During incubation of chylomicrons labelled with [3H]20:5 and [14C]18:2 with lipase-colipase, the rates of hydrolysis of [3H]- and [14C]triacylglycerols were similar, but more [3H]20:5 than [14C]18:2 accumulated in diacylglycerols. The accumulation of [3H]diacylglycerol was reduced by adding CEL. Also when fatty acids were analyzed by gas chromatography, 20:5 was enriched in remaining triacylglycerol and in diacylglycerol after incubation with lipase-colipase alone. The data thus indicate that both lipase-colipase and CEL participate in the hydrolysis of 20:5 and 20:4 ester bonds of dietary triacylglycerol.
ESTHER : Chen_1990_Biochim.Biophys.Acta_1044_111
PubMedSearch : Chen_1990_Biochim.Biophys.Acta_1044_111
PubMedID: 2340300

Title : A protein homologous to the Torpedo postsynaptic 58K protein is present at the myotendinous junction - Chen_1990_J.Cell.Biol_110_2061
Author(s) : Chen Q , Sealock R , Peng HB
Ref : Journal of Cell Biology , 110 :2061 , 1990
Abstract : The 58K protein is a peripheral membrane protein enriched in the acetylcholine receptor (AChR)-rich postsynaptic membrane of Torpedo electric organ. Because of its coexistence with AChRs in the postsynaptic membrane in both electrocytes and skeletal muscle, it is thought to be involved in the formation and maintenance of AChR clusters. Using an mAb against the 58K protein of Torpedo electric organ, we have identified a single protein band in SDS-PAGE analysis of Xenopus myotomal muscle with an apparent molecular mass of 48 kD. With this antibody, the distribution of this protein was examined in the myotomal muscle fibers with immunofluorescence techniques. We found that the 48K protein is concentrated at the myotendinous junctions (MTJs) of these muscle fibers. The MTJ is also enriched in talin and vinculin. By double labeling muscle fibers with antibodies against talin and the 48K protein, these two proteins were found to colocalize at the membrane invaginations of the MTJ. In cultured myotomal muscle cells, the 48K protein and talin are also colocalized at sites of membrane-myofibril interaction. The 48K protein is, however, not found at focal adhesion sites in nonmuscle cells, which are enriched in talin. These data suggest that the 48K protein is specifically involved in the interaction of myofibrillar actin filaments with the plasma membrane at the MTJ. In addition to the MTJ localization, 48K protein is also present at AChR clusters both in vivo and in vitro. Thus, this protein is shared by both the MTJ and the neuromuscular junction.
ESTHER : Chen_1990_J.Cell.Biol_110_2061
PubMedSearch : Chen_1990_J.Cell.Biol_110_2061
PubMedID: 2112550

Title : Hydrolysis of triacylglycerol arachidonic and linoleic acid ester bonds by human pancreatic lipase and carboxyl ester lipase - Chen_1989_Biochim.Biophys.Acta_1004_372
Author(s) : Chen Q , Sternby B , Nilsson A
Ref : Biochimica & Biophysica Acta , 1004 :372 , 1989
Abstract : The hydrolysis of polyenoic fatty acid ester bonds with pure human colipase-dependent lipase, with carboxyl ester lipase (CEL) and with these enzymes in combination was studied, using [3H]arachidonic- and [14C]linoleic acid-labelled rat chylomicrons as a model substrate. During the hydrolysis with colipase-dependent lipase, the amount of 3H appearing in 1,2-X-diacylglycerol (DG) markedly exceeded that of 14C. When CEL was added in addition this [3H]DG was efficiently hydrolyzed. CEL alone hydrolyzed the triacylglycerol (TG) at a low rate. The hydrolysis pattern with human duodenal content was similar to that seen with colipase-dependent lipase and CEL in combination. Increasing the concentration of taurodeoxycholate (TDC) and taurocholate (TC) or of TDC alone stimulated the hydrolysis of [3H]- and [14C]TG, but increased the accumulation of labelled DG that could act as substrate for CEL. It is suggested that very-long-chain polyenoic fatty acids of DG formed during the action of the colipase-dependent lipase on TG containing these fatty acids may be a physiological substrate for CEL.
ESTHER : Chen_1989_Biochim.Biophys.Acta_1004_372
PubMedSearch : Chen_1989_Biochim.Biophys.Acta_1004_372
PubMedID: 2503032

Title : Localization of calcitonin gene-related peptide (CGRP) at a neuronal nicotinic synapse - Peng_1988_Neurosci.Lett_95_75
Author(s) : Peng HB , Chen Q
Ref : Neuroscience Letters , 95 :75 , 1988
Abstract : The localization of calcitonin gene-related peptide (CGRP) in the parasympathetic cardiac ganglion of the frog was investigated with an immunofluorescence method. By doubly staining the whole ganglion with antibodies against a synaptic-vesicle antigen and anti-CGRP antibodies, we found that all of the boutons at the nicotinic synapses on the postganglionic neurons contained immunoreactivity against this peptide. In contrast, neither the muscarinic nor the adrenergic terminals of the postganglionic fibers on the cardiac muscle contained CGRP immunoreactivity. This suggests that CGRP is involved in the functions of the neuronal nicotinic synapses.
ESTHER : Peng_1988_Neurosci.Lett_95_75
PubMedSearch : Peng_1988_Neurosci.Lett_95_75
PubMedID: 3265774