Chen D

References (62)

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 : OsLDDT1, encoding a transmembrane structural DUF726 family protein, is essential for tapetum degradation and pollen formation in rice - Sun_2023_Plant.Sci__111596
Author(s) : Sun Z , Liu K , Chen C , Chen D , Peng Z , Zhou R , Liu L , He D , Duan W , Chen H , Huang C , Ruan Z , Zhang Y , Cao L , Zhan X , Cheng S , Sun L
Ref : Plant Sci , :111596 , 2023
Abstract : Formation of the pollen wall, which is mainly composed of lipid substances secreted by tapetal cells, is important to ensure pollen development in rice. Although several regulatory factors related to lipid biosynthesis during pollen wall formation have been identified in rice, the molecular mechanisms controlling lipid biosynthesis are unclear. We isolated the male-sterile rice mutant oslddt1 (leaked and delayed degraded tapetum 1). oslddt1 plants show complete pollen abortion resulting from delayed degradation of the tapetum and blocked formation of Ubisch bodies and pollen walls. OsLDDT1 (LOC_Os03g02170) encodes a DUF726 containing protein of unknown functionwith highly conserved transmembrane and alpha/beta Hydrolase domains. OsLDDT1 localizes to the endoplasmic reticulum and the gene is highly expressed in rice panicles. Genes involved in regulating fatty acid synthesis and formation of sporopollenin and pollen exine during anther developmentshowed significantly different expression patterns in oslddt1 plants. Interestingly, the wax and cutin contents in mature oslddt1-1 anthers were decreased by 74.07% and 72.22% compared to WT, indicating that OsLDDT1 is involved in fatty acid synthesis and affects formation of the anther epidermis. Our results provide as deeper understanding of the role of OsLDDT1 in regulating male sterility and also provide materials for hybrid rice breeding.
ESTHER : Sun_2023_Plant.Sci__111596
PubMedSearch : Sun_2023_Plant.Sci__111596
PubMedID: 36657664
Gene_locus related to this paper: orysj-q10ss2

Title : DAGLbeta is the principal synthesizing enzyme of 2-AG and promotes aggressive intrahepatic cholangiocarcinoma via AP-1\/DAGLbeta\/miR4516 feedforward circuitry - Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Ma M , Zeng G , Tan B , Zhao G , Su Q , Zhang W , Song Y , Liang J , Xu B , Wang Z , Chen J , Hou M , Yang C , Yun J , Huang Y , Lin Y , Chen D , Han Y , DeMorrow S , Liang L , Lai J , Huang L
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2023
Abstract : The endocannabinoid system (ECS) is dysregulated in various liver diseases. Previously we had shown that the major endocannabinoid 2-arachidonoyl glycerol (2-AG) promoted tumorigenesis of intrahepatic cholangiocarcinoma (ICC). However, biosynthesis regulation and clinical significance of 2-AG remain elusive. In present study we quantified 2-AG by gas chromatography/mass spectrometry (GC/MS) and showed that 2-AG was enriched in ICC patients' samples as well as in thioacetamide-induced orthotopic rat ICC model. Moreover, we found that diacylglycerol lipase beta (DAGLbeta) was the principal synthesizing enzyme of 2-AG which significantly upregulated in ICC. DAGLbeta promoted tumorigenesis and metastasis of ICC in vitro and in vivo, and positively correlated with clinical stage and poor survival in ICC patients. Functional studies showed that AP-1 (heterodimers of c-Jun and FRA1) directly binded to the promoter and regulated transcription of DAGLbeta, which can be enhanced by lipopolysaccharide (LPS). miR-4516 was identified as the tumor-suppressing miRNA of ICC which can be significantly suppressed by LPS, 2-AG or ectopic DAGLbeta overexpression. FRA1 and STAT3 were targets of miR-4516 and overexpression of miRNA-4516 significantly suppressed expression of FRA1, SATA3 and DAGLbeta. Expression of miRNA-4516 was negatively correlated with FRA1, SATA3 and DAGLbeta in ICC patients' samples. Our findings identify DAGLbeta as the principal synthesizing enzyme of 2-AG in ICC. DAGLbeta promotes oncogenesis and metastasis of ICC and is transcriptionally regulated by a novel AP-1/DAGLbeta/miR4516 feedforward circuitry.
ESTHER : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 37366545
Gene_locus related to this paper: human-DAGLB

Title : Transcriptional landscape of pathogen-responsive lncRNAs in tomato unveils the role of hydrolase encoding genes in response to Botrytis cinerea invasion - Chen_2023_Plant.Cell.Environ__
Author(s) : Chen D , Zhang Z , Chen Y , Li B , Chen T , Tian S
Ref : Plant Cell Environ , : , 2023
Abstract : LncRNAs have gained increasing attention owing to their important regulatory roles on growth and stress responses of plants. However, the mechanisms underlying the functions of lncRNAs in fruit-pathogen interaction are still largely unknown. In this study, a total of 273 lncRNAs responding to Botrytis cinerea infection were identified in tomato fruit, among which a higher percentage of antisense lncRNAs were targeted to the genes enriched in hydrolase activity. To ascertain the roles of these lncRNAs, seven hydrolase-related transcripts were transiently knocked-down by virus-induced gene silencing. Silencing of lncRNACXE20 reduced the expression level of a carboxylesterase gene, further enhancing the resistance of tomato to B. cinerea. In contrast, silencing of lncRNACHI, lncRNAMMP, lncRNASBT1.9 and lncRNAPME1.9 impaired the resistance to B. cinerea, respectively. Further RT-qPCR assay and enzymatic activity detection displayed that the attenuated resistance of lncRNAMMP and lncRNASBT1.9-silenced plants was associated with the inhibition on the expression of JA-related genes, while the decreased resistance of lncRNACHI-silenced plants resulted in reduced chitinase activity. Collectively, these results may provide references for deciphering the mechanisms underlying specific lncRNAs to interfere with B. cinerea infection by regulating the expression of defence-related genes or affecting hydrolase activity.
ESTHER : Chen_2023_Plant.Cell.Environ__
PubMedSearch : Chen_2023_Plant.Cell.Environ__
PubMedID: 37899711

Title : 4-Methylbenzylidene camphor triggers estrogenic effects via the brain-liver-gonad axis in zebrafish larvae - Xian_2023_Environ.Pollut__122260
Author(s) : Xian H , Li Z , Ye R , Dai M , Feng Y , Bai R , Guo J , Yan X , Yang X , Chen D , Huang Z
Ref : Environ Pollut , :122260 , 2023
Abstract : 4-Methylbenzylidene camphor (4-MBC), an emerging contaminant, is a widely-used ultraviolet (UV) filter incorporated into cosmetics because it protects the skin from UV rays and counters photo-oxidation. Despite the well-established estrogenic activity of 4-MBC, the link between this activity and its effects on neurobehavior and the liver remains unknown. Thus, we exposed zebrafish larvae to environmentally relevant concentrations of 4-MBC with 1.39, 4.17, 12.5 and 15.4 microg/mL from 3 to 5 days postfertilization. We found that 4-MBC produced an estrogenic effect by intensifying fluorescence in the transgenic zebrafish, which was counteracted by co-exposure with estrogen receptor antagonist. 4-MBC-upregulated estrogen receptor alpha (eralpha) mRNA, and an interaction between 4-MBC and ERalpha suggested ERalpha's involvement in the 4-MBC-induced estrogenic activity. RNA sequencing unearthed 4-MBC-triggered responses in estrogen stimulus and lipid metabolism. Additionally, 4-MBC-induced hypoactivity and behavioral phenotypes were dependent on the estrogen receptor (ER) pathway. This may have been associated with the disruption of acetylcholinesterase and acetylcholine activities. As a result, 4-MBC increased vitellogenin expression and caused lipid accumulation in the liver of zebrafish larvae. Collectively, this is the first study to report 4-MBC-caused estrogenic effects through the brain-liver-gonad axis. It provides novel insight into how 4-MBC perturbs the brain and liver development.
ESTHER : Xian_2023_Environ.Pollut__122260
PubMedSearch : Xian_2023_Environ.Pollut__122260
PubMedID: 37506809

Title : OsGELP77, a QTL for broad-spectrum disease resistance and yield in rice, encodes a GDSL-type lipase - Zhang_2023_Plant.Biotechnol.J__
Author(s) : Zhang M , Chen D , Tian J , Cao J , Xie K , He Y , Yuan M
Ref : Plant Biotechnol J , : , 2023
Abstract : Lipids and lipid metabolites have essential roles in plant-pathogen interactions. GDSL-type lipases are involved in lipid metabolism modulating lipid homeostasis. Some plant GDSLs modulate lipid metabolism altering hormone signal transduction to regulate host-defence immunity. Here, we functionally characterized a rice lipase, OsGELP77, promoting both immunity and yield. OsGELP77 expression was induced by pathogen infection and jasmonic acid (JA) treatment. Overexpression of OsGELP77 enhanced rice resistance to both bacterial and fungal pathogens, while loss-of-function of osgelp77 showed susceptibility. OsGELP77 localizes to endoplasmic reticulum and is a functional lipase hydrolysing universal lipid substrates. Lipidomics analyses demonstrate that OsGELP77 is crucial for lipid metabolism and lipid-derived JA homeostasis. Genetic analyses confirm that OsGELP77-modulated resistance depends on JA signal transduction. Moreover, population genetic analyses indicate that OsGELP77 expression level is positively correlated with rice resistance against pathogens. Three haplotypes were classified based on nucleotide polymorphisms in the OsGELP77 promoter where OsGELP77(Hap3) is an elite haplotype. Three OsGELP77 haplotypes are differentially distributed in wild and cultivated rice, while OsGELP77(Hap3) has been broadly pyramided for hybrid rice development. Furthermore, quantitative trait locus (QTL) mapping and resistance evaluation of the constructed near-isogenic line validated OsGELP77, a QTL for broad-spectrum disease resistance. In addition, OsGELP77-modulated lipid metabolism promotes JA accumulation facilitating grain yield. Notably, the hub defence regulator OsWRKY45 acts upstream of OsGELP77 by initiating the JA-dependent signalling to trigger immunity. Together, OsGELP77, a QTL contributing to immunity and yield, is a candidate for breeding broad-spectrum resistant and high-yielding rice.
ESTHER : Zhang_2023_Plant.Biotechnol.J__
PubMedSearch : Zhang_2023_Plant.Biotechnol.J__
PubMedID: 38100249

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 : Sertoli cell survival and barrier function are regulated by miR-181c\/d-Pafah1b1 axis during mammalian spermatogenesis - Feng_2022_Cell.Mol.Life.Sci_79_498
Author(s) : Feng Y , Chen D , Wang T , Zhou J , Xu W , Xiong H , Bai R , Wu S , Li J , Li F
Ref : Cell Mol Life Sciences , 79 :498 , 2022
Abstract : Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.
ESTHER : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedSearch : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedID: 36008729

Title : Fluorescence-activated droplet sorting of PET degrading microorganisms - Qiao_2022_J.Hazard.Mater_424_127417
Author(s) : Qiao Y , Hu R , Chen D , Wang L , Wang Z , Yu H , Fu Y , Li C , Dong Z , Weng YX , Du W
Ref : J Hazard Mater , 424 :127417 , 2022
Abstract : Enzymes that can decompose synthetic plastics such as polyethylene terephthalate (PET) are urgently needed. Still, a bottleneck remains due to a lack of techniques for detecting and sorting environmental microorganisms with vast diversity and abundance. Here, we developed a fluorescence-activated droplet sorting (FADS) pipeline for high-throughput screening of PET-degrading microorganisms or enzymes (PETases). The pipeline comprises three steps: generation and incubation of droplets encapsulating single cells, picoinjection of fluorescein dibenzoate (FDBz) as the fluorogenic probe, and screening of droplets to obtain PET-degrading cells. We characterized critical factors associated with this method, including specificity and sensitivity for discriminating PETase from other enzymes. We then optimized its performance and compatibility with environmental samples. The system was used to screen a wastewater sample from a PET textile mill. We successfully obtained PET-degrading species from nine different genera. Moreover, two putative PETases from isolates Kineococcus endophyticus Un-5 and Staphylococcus epidermidis Un-C2-8 were genetically derived, heterologously expressed, and preliminarily validated for PET-degrading activities. We speculate that the FADS pipeline can be widely adopted to discover new plastic-degrading microorganisms and enzymes in various environments and may be utilized in the directed evolution of degrading enzymes using synthetic biology.
ESTHER : Qiao_2022_J.Hazard.Mater_424_127417
PubMedSearch : Qiao_2022_J.Hazard.Mater_424_127417
PubMedID: 34673397

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

Title : Risk Factors and a Nomogram Model Establishment for Postoperative Delirium in Elderly Patients Undergoing Arthroplasty Surgery: A Single-Center Retrospective Study - Chen_2021_Biomed.Res.Int_2021_6607386
Author(s) : Chen D , Li Y , Li Q , Gao W , Li J , Wang S , Cao J
Ref : Biomed Res Int , 2021 :6607386 , 2021
Abstract : OBJECTIVE: To explore the related risk factors of postoperative delirium (POD) after hip or knee arthroplasty in elderly orthopedic patients and the predictive value of related risk factors. Material and Methods. In total, 309 patients (<=60 years) who received knee and hip arthroplasty between January 2017 and May 2020 were consecutively selected into the POD and nonpostoperative delirium (NPOD) groups. Group bias was eliminated through propensity score matching. Univariate and multivariable logistic analysis was used to determine the risk factors for POD. The nomogram was made by R. RESULTS: 58 patients were included in each group after propensity score matching; multivariable analysis demonstrated that LDH (OR = 4.364, P = 0.017), CHE (OR = 4.640, P = 0.004), Cystatin C (OR = 5.283, P = 0.006), arrhythmia (OR = 5.253, P = 0.002), and operation duration (OR = 1.017, P = 0.050) were independent risk factors of POD. LDH, CHE, Cystatin C, and arrhythmia were used to construct a nomogram to predict the POD. The nomogram was well calibrated and had moderate discriminative ability (AUC = 0.821, 95% CI: 0.760~0.883). Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: Our study revealed that arrhythmia, operation duration, the increase of lactate dehydrogenase and Cystatin C, and the decrease of cholinesterase were reliable factors for predicting postoperative delirium after elderly hip and knee arthroplasty. Meanwhile, the nomogram we developed can assist the clinician to filtrate potential patients with postoperative delirium.
ESTHER : Chen_2021_Biomed.Res.Int_2021_6607386
PubMedSearch : Chen_2021_Biomed.Res.Int_2021_6607386
PubMedID: 34901277

Title : Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy - Wang_2021_J.Nanobiotechnology_19_31
Author(s) : Wang K , Shang F , Chen D , Cao T , Wang X , Jiao J , He S , Liang X
Ref : J Nanobiotechnology , 19 :31 , 2021
Abstract : BACKGROUND: Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. RESULTS: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. CONCLUSIONS: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.
ESTHER : Wang_2021_J.Nanobiotechnology_19_31
PubMedSearch : Wang_2021_J.Nanobiotechnology_19_31
PubMedID: 33482834

Title : Soluble ligands as drug targets for treatment of inflammatory bowel disease - Tong_2021_Pharmacol.Ther__107859
Author(s) : Tong X , Zheng Y , Li Y , Xiong Y , Chen D
Ref : Pharmacol Ther , :107859 , 2021
Abstract : Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is characterized by persistent inflammation in a hereditarily susceptible host. In addition to gastrointestinal symptoms, patients with IBD frequently suffer from extra-intestinal complications such as fibrosis, stenosis or cancer. Mounting evidence supports the targeting of cytokines for effective treatment of IBD. Cytokines can be included in a newly proposed classification "soluble ligands" that has become the third major target of human protein therapeutic drugs after enzymes and receptors. Soluble ligands have potential significance for research and development of anti-IBD drugs. Compared with traditional drug targets for IBD treatment, such as receptors, at least three factors contribute to the increasing importance of soluble ligands as drug targets. Firstly, cytokines are the main soluble ligands and targeting of them has demonstrated efficacy in patients with IBD. Secondly, soluble ligands are more accessible than receptors, which are embedded in the cell membrane and have complex tertiary membrane structures. Lastly, certain potential target proteins that are present in membrane-bound forms can become soluble following cleavage, providing further opportunities for intervention in the treatment of IBD. In this review, 49 drugs targeting 25 distinct ligands have been evaluated, including consideration of the characteristics of the ligands and drugs in respect of IBD treatment. In addition to approved drugs targeting soluble ligands, we have also assessed drugs that are in preclinical research and drugs inhibiting ligand-receptor binding. Some new types of targetable soluble ligands/proteins, such as epoxide hydrolase and p-selectin glycoprotein ligand-1, are also introduced. Targeting soluble ligands not only opens a new field of anti-IBD drug development, but the circulating soluble ligands also provide diagnostic insights for early prediction of treatment response. In conclusion, soluble ligands serve as the third-largest protein target class in medicine, with much potential for the drugs targeting them.
ESTHER : Tong_2021_Pharmacol.Ther__107859
PubMedSearch : Tong_2021_Pharmacol.Ther__107859
PubMedID: 33895184

Title : Susceptibility of Four Species of Aphids in Wheat to Seven Insecticides and Its Relationship to Detoxifying Enzymes - Gong_2020_Front.Physiol_11_623612
Author(s) : Gong P , Chen D , Wang C , Li M , Li X , Zhang Y , Zhu X
Ref : Front Physiol , 11 :623612 , 2020
Abstract : Sitobion avenae (Fabricius), Rhopalosiphum padi (Linnaeus), Schizaphis graminum (Rondani), and Metopolophium dirhodum (Walker) (Hemiptera: Aphididae) are important pests of wheat and other cereals worldwide. In this study, the susceptibilities of four wheat aphid species to seven insecticides were assessed. Furthermore, the activities of carboxylesterase (CarE), glutathione S-transferase (GSTs), and cytochrome P450 monooxygenase (P450s) were determined in imidacloprid treated and untreated aphids. The results showed that the susceptibilities of four wheat aphid species to tested insecticides are different and M. dirhodum has shown higher tolerance to most insecticides. Relatively higher CarE and GST activities were observed in M. dirhodum, and P450s activities increased significantly in response to imidacloprid treatment. Moreover, susceptibility to imidacloprid were increased by the oxidase inhibitor piperonyl butoxide in M. dirhodum (20-fold). The results we have obtained imply that P450s may play an important role in imidacloprid metabolic process in M. dirhodum. We suggest that a highly species-specific approach is essential for managing M. dirhodum.
ESTHER : Gong_2020_Front.Physiol_11_623612
PubMedSearch : Gong_2020_Front.Physiol_11_623612
PubMedID: 33536942

Title : Correlation between CYP1A1 polymorphisms and susceptibility to glyphosate-induced reduction of serum cholinesterase: A case-control study of a Chinese population - Cai_2020_Pestic.Biochem.Physiol_162_23
Author(s) : Cai W , Zhang F , Zhong L , Chen D , Guo H , Zhang H , Zhu B , Liu X
Ref : Pestic Biochem Physiol , 162 :23 , 2020
Abstract : Glyphosate (GLP) is one of the most common herbicides worldwide. The serum cholinesterase (ChE) may be affected when exposed to glyphosate. Reduction of serum ChE by herbicides is probably related to cytochrome P450 (CYP450) family polymorphisms. We suspect that the abnormal ChE caused by GLP could be correlated with the CYP family members. To determine whether CYP1B1 (rs1056827 and rs1056836) and CYP1A1 (rs1048943) gene polymorphisms and individual susceptibility to GLP-induced ChE abnormalities were interrelated in the Chinese Han population, we performed this genetic association study on a total of 230 workers previously exposed to GLP, including 115 cases with reduced serum ChE and 115 controls with normal serum ChE. Two even groups of cases and controls were enrolled. The CYP1A1 and CYP1B1 polymorphisms in both groups were genotyped using TaqMan. Subjects with the CYP1A1 rs619586 genotypes showed an increased risk of GLP-induced reduction of serum ChE, which was more evident in the following subgroups: female, > 35years old, history of GLP exposure time <10years and >10years, nonsmoker and nondrinker. The results show that CYP1A1 rs619586 was significantly associated with the GLP-induced reduction in serum ChE and could be a biomarker of susceptibility for Chinese GLP exposed workers. Because of a large number of people exposed to glyphosate, this study has a significance in protecting their health.
ESTHER : Cai_2020_Pestic.Biochem.Physiol_162_23
PubMedSearch : Cai_2020_Pestic.Biochem.Physiol_162_23
PubMedID: 31836050

Title : Potential of esterase DmtH in transforming plastic additive dimethyl terephthalate to less toxic mono-methyl terephthalate - Cheng_2020_Ecotoxicol.Environ.Saf_187_109848
Author(s) : Cheng X , Dong S , Chen D , Rui Q , Guo J , Dayong W , Jiang J
Ref : Ecotoxicology & Environmental Safety , 187 :109848 , 2020
Abstract : Dimethyl terephthalate (DMT) is a primary ingredient widely used in the manufacture of polyesters and industrial plastics; its environmental fate is of concern due to its global use. Microorganisms play key roles in the dissipation of DMT from the environment; however, the enzymes responsible for the initial transformation of DMT and the possible altered toxicity due to this biotransformation have not been extensively studied. To reduce DMT toxicity, we identified the esterase gene dmtH involved in the initial transformation of DMT from the AOPP herbicide-transforming strain Sphingobium sp. C3. DmtH shows 24-41% identity with alpha/beta-hydrolases and belongs to subfamily V of bacterial esterases. The purified recombinant DmtH was capable of transforming DMT to mono-methyl terephthalate (MMT) and potentially transforming other p-phthalic acid esters, including diallyl terephthalate (DAT) and diethyl terephthalate (DET). Using C. elegans as an assay model, we observed the severe toxicity of DMT in inducing reactive oxygen species (ROS) production, decreasing locomotion behavior, reducing lifespan, altering molecular basis for oxidative stress, and inducing mitochondrial stress. In contrast, exposure to MMT did not cause obvious toxicity, induce oxidative stress, and activate mitochondrial stress in nematodes. Our study highlights the usefulness of Sphingobium sp. C3 and its esterase DmtH in transforming p-phthalic acid esters and reducing the toxicity of DMT to organisms.
ESTHER : Cheng_2020_Ecotoxicol.Environ.Saf_187_109848
PubMedSearch : Cheng_2020_Ecotoxicol.Environ.Saf_187_109848
PubMedID: 31670182
Gene_locus related to this paper: 9sphn-a0a3s8nd90

Title : Copper exposure enhances Spodoptera litura larval tolerance to beta-cypermethrin - Lu_2019_Pestic.Biochem.Physiol_160_127
Author(s) : Lu K , Li W , Cheng Y , Ni H , Chen X , Li Y , Tang B , Sun X , Liu T , Qin N , Chen D , Zeng R , Song Y
Ref : Pestic Biochem Physiol , 160 :127 , 2019
Abstract : Environmental xenobiotics can influence the tolerance of insects to chemical insecticides. Heavy metals are widespread distributed, can be easily bio-accumulated in plants and subsequently within phytophagous insects via the food chains. However, less attention has been paid to the effect of heavy metal exposure on their insecticide tolerance. In this study, pre-exposure of copper (Cu, 25-100mgkg(-1)) significantly enhanced the subsequent tolerance of Spodoptera litura to beta-cypermethrin, a widely used pyrethroid insecticide in crop field. Cytochrome P450 monooxygenases (CYPs) activities were cross-induced in larvae exposed to Cu and beta-cypermethrin, while the activities of glutathione S-transferase (GST) and carboxylesterase (CarE) were not affected. Application of piperonyl butoxide (PBO), a P450 synergist, effectively impaired the tolerance to beta-cypermethrin in Cu-exposed S. litura larvae with a synergistic ratio of 1.72, indicating that P450s contribute to larval tolerance to beta-cypermethrin induced by Cu exposure. Among the four CYP6AB family genes examined, only larval midgut-specific CYP6AB12 was found to be cross-induced by Cu and beta-cypermethrin. RNA interference (RNAi)-mediated silencing of CYP6AB12 effectively decreased the mRNA levels of the target gene, and significantly reduced the larval tolerance to beta-cypermethrin following exposure to Cu. These results showed that pre-exposure of heavy metal Cu enhanced larval tolerance to beta-cypermethrin in S. litura, possibly through the cross-induction of P450s. Our findings provide new insights on the relationship between heavy metals and chemical insecticides that may benefit both the risk evaluation of heavy metal contamination and development of pest management strategies.
ESTHER : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedSearch : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedID: 31519247

Title : Tracing and attribution of V-type nerve agents in human exposure by strategy of assessing the phosphonylated and disulfide adducts on ceruloplasmin - Fu_2019_Toxicology_430_152346
Author(s) : Fu F , Chen J , Zhao P , Lu X , Gao R , Chen D , Liu H , Wang H , Pei C
Ref : Toxicology , 430 :152346 , 2019
Abstract : V-type agents are highly toxic organophosphorus nerve agents that inhibit acetylcholinesterase in the nervous system, causing a series of poison symptoms. Trace analytical methods are essential for the specific verification of exposure to these agents, especially for human exposure. This paper investigates the phosphonylated and disulfide adducts between human ceruloplasmin and O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2-(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). After being digested by trypsin, the mixture of peptides was separated by a nano-liquid chromatography (nano-LC) and analyzed using quadrupole-orbitrap mass spectrometry (Q-Orbitrap-MS). The sensitive LC-MS/MS-assisted proteomics approach was developed to achieve the identification of human exposure to V-type agents based on these modified sites; results revealed that potential biomarkers could be derived from adducts based on the sulfur- and phosphorus-containing groups of V-type agents. This work offered a novel insight into the mechanism of disulfide-containing adducts resulting from the replacement of disulfide bridges by the thiolate groups from the V-type agents. Moreover, four disulfide adducts on human ceruloplasmin were also discovered during this research, specifically confirming exposure to the V-type agents. Furthermore, molecular simulation testified to the reactivity of the modified sites. Collectively, our findings suggest that the eleven binding sites on human ceruloplasmin have the potential use as a selective marker for prediction the V-type agent exposure in humans.
ESTHER : Fu_2019_Toxicology_430_152346
PubMedSearch : Fu_2019_Toxicology_430_152346
PubMedID: 31857189

Title : Enhancing the atypical esterase promiscuity of the gamma-lactamase Sspg from Sulfolobus solfataricus by substrate screening - Wang_2019_Appl.Microbiol.Biotechnol_103_4077
Author(s) : Wang J , Zhao H , Zhao G , Chen D , Tao Y , Wu S
Ref : Applied Microbiology & Biotechnology , 103 :4077 , 2019
Abstract : Promiscuous enzymes can be modified by protein engineering, which enables the catalysis of non-native substrates. gamma-lactamase Sspg from Sulfolobus solfataricus is an enzyme with high activity, high stability, and pronounced tolerance of high concentrations of the gamma-lactam substrate. These characteristics suggest Sspg as a robust enzymatic catalyst for the preparation of optically pure gamma-lactam. This study investigated the modification of this enzyme to expand its application toward resolving chiral esters. gamma-Lactamase-esterase conversion was performed by employing a three-step method: initial sequence alignment, followed by substrate screening, and protein engineering based on the obtained substrate-enzyme docking results. This process of fine-tuning of chemical groups on substrates has been termed "substrate screening." Steric hindrance and chemical reactivity of the substrate are major concerns during this step, since both are determining factors for the enzyme-substrate interaction. By employing this three-step method, gamma-lactamase Sspg was successfully converted into an esterase with high enantioselectivity towards phenylglycidate substrates (E value > 300). However, since both wild-type Sspg and Sspg mutants did not hydrolyze para-nitrophenyl substrates (pNPs), this esterase activity was termed "atypical esterase activity." The gamma-lactamase activity and stability of the Sspg mutants were not severely compromised. The proposed method can be applied to find novel multi-functional enzyme catalysts within existing enzyme pools.
ESTHER : Wang_2019_Appl.Microbiol.Biotechnol_103_4077
PubMedSearch : Wang_2019_Appl.Microbiol.Biotechnol_103_4077
PubMedID: 30955078

Title : Characterization of a Novel Thermo-Stable Lipasefrom Endophyte Pseudomonas putida in Pistacia chinensis Bunge - Song_2017_Appl.Biochem.Microbiol_53_524
Author(s) : Song C , Liu Z , Xie Q , Wang H , Huang Y , Ruan Y , Chen D
Ref : Applied Biochemistry and Microbiology , 53 :524 , 2017
Abstract : A novel lipolytic enzyme-producing endophytic strain PC2 was successfully isolated from the seeds of an ideal bioenergy plant Pistacia chinensis Bunge. Based on the analysis of morphology and 16S rRNA sequence, bacterial strain PC2 was identified as a subspecies of Pseudomonas putida, therefore named as P. putida PC2. Whole-genome sequencing showed PC2 contained a 1224-nucleotide lipase gene (named lip-PC2) predicted to encode a 407-amino-acid protein. Purified lipases from both the original PC2 strain and heterologously expressed Escherichia coli were nearly 50 kD with specific activity of 9.48 U/mL. LIP-PC2 displayed the maximal activity at 50C or pH 8.0, and maintained above 80% relative activity in the range of from 40 to 60degC or pH in the range of from 6.0 to 8.0, indicating thermostable and alkaline properties. Enzyme activity was enhanced by Mg2+, Na+ and Mn2+, but strongly inhibited by Cu2+, Zn2+ Co2+, EDTA as well as organic solvents and surfactants. Additionally, the analysis of amino acid sequence and structure indicated that LIP-PC2 was a novel member belonging to family I.3 of bacterial lipolytic enzymes and its catalytic triad was consisted of Ser-200, Asp-342 and His-374
ESTHER : Song_2017_Appl.Biochem.Microbiol_53_524
PubMedSearch : Song_2017_Appl.Biochem.Microbiol_53_524
Gene_locus related to this paper: psepu-a0a160gpc6

Title : Neuroprotective effect of Amorphallus campanulatus in STZ induced Alzheimer rat model - Chen_2016_Afr.J.Tradit.Complement.Altern.Med_13_47
Author(s) : Chen D
Ref : Afr J Tradit Complement Altern Med , 13 :47 , 2016
Abstract : BACKGROUND: The present investigation deals with the assessment of neuroprotective effect Amorphophallus campanulatus (AC) tuber in alzheimer diseased (AD) rat and also postulates its possible mechanism of action. MATERIAL AND
METHODS: AD was induced by administering streptozotocin i.e. STZ (3 mg/kg, ICV) day one and 3rd day after surgery. Surgery was performed on anesthetized rats by the help of stereotaxic apparatus. STZ induced AD rats were treated with petroleum ether extract of AC (100, 200 and 500 mg/kg, p.o.) for 14 days. Effect of AC tuber in AD rats were assessed by estimating the alteration in the behavior (Y maze apparatus and single trail passive avoidance), biochemical parameter in the brain tissue {Oxidative stress parameters (SOD, CAT and LPO), amyloid beta peptide (Abeta) and acetylcholinesterase (AchE)} and histopathological study of brain tissue. RESULT: Treatment with AC shows significant (p<0.01) increased in the % of alteration in the behavior and step through latency in Y maze task and single trial passive avoidance test compared to AD rats. AC significantly (p<0.01) decreases the Abeta1-40, Abeta1-42 peptides and AchE in the brain tissue compared to AD rats. Whereas, treatment with AC significantly reduces the oxidative stress level in AD rats. Histopathological study reveals that treatment with AC extract reduces the amyloid plaque formation in the brain tissue of AD rat. CONCLUSION: The present study concludes the neuroprotective effect of AC extract in AD rats by reducing oxidative stress, Abeta and AchE in the brain tissue.
ESTHER : Chen_2016_Afr.J.Tradit.Complement.Altern.Med_13_47
PubMedSearch : Chen_2016_Afr.J.Tradit.Complement.Altern.Med_13_47
PubMedID: 28480351

Title : Orf Virus 002 Protein Targets Ovine Protein S100A4 and Inhibits NF-B Signaling - Chen_2016_Front.Microbiol_7_1389
Author(s) : Chen D , Zheng Z , Xiao B , Li W , Long M , Chen H , Li M , Rock DL , Hao W , Luo S
Ref : Front Microbiol , 7 :1389 , 2016
Abstract : Orf virus (ORFV), a member of Parapoxvirus, has evolved various strategies to modulate the immune responses of host cells. The ORFV-encoded protein ORFV002, a regulator factor, has been found to inhibit the acetylation of NF-kappaB-p65 by blocking phosphorylation of NF-kappaB-p65 at Ser(276) and also to disrupt the binding of NF-kappaB-p65 and p300. To explore the mechanism by which ORFV002 regulates NF-kappaB signaling, the understanding of ORFV002 potential binding partners in host cells is critical. In this study, ovine S100 calcium binding protein A4 (S100A4), prolyl endopeptidase-like (PREPL) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8) were found to interact with ORFV002 based on the yeast two-hybrid (Y2H) assay using a cDNA library derived from primary ovine fetal turbinate cells (OFTu). GST pull-down and bidirectional co-immunoprecipitation assay results demonstrate that ORFV002 interacts with S100A4 directly. Following the pEGFP-ORFV002 (p002GFP) transfection, we found that cytoplasmic S100A4 translocates into the nucleus and co-localizes with ORFV002. Furthermore, the inhibitory effect of ORFV002 on NF-kappaB signaling was significantly restored by S100A4 knock-down phenotype, suggesting that ovine S100A4 participates in the ORFV002-mediated NF-kappaB signaling. These data demonstrate that ORFV002 inhibits the NF-kappaB activation through its interaction with S100A4 along with its nucleus translocation.
ESTHER : Chen_2016_Front.Microbiol_7_1389
PubMedSearch : Chen_2016_Front.Microbiol_7_1389
PubMedID: 27679610

Title : Fumonisins: oxidative stress-mediated toxicity and metabolism in vivo and in vitro - Wang_2016_Arch.Toxicol_90_81
Author(s) : Wang X , Wu Q , Wan D , Liu Q , Chen D , Liu Z , Martinez-Larranaga MR , Martinez MA , Anadon A , Yuan Z
Ref : Archives of Toxicology , 90 :81 , 2016
Abstract : Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn contaminants. FBs could cause a variety of diseases in animals and humans, such as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals. To date, almost no review has addressed the toxicity of FBs in relation to oxidative stress and their metabolism. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for FB-induced toxicity as well as the metabolism. The present review showed that studies have been carried out over the last three decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of FBs treatment and have correlated them with various types of FBs toxicity, indicating that oxidative stress plays critical roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis, acylation and transamination. Ceramide synthase, carboxylesterase FumD and aminotransferase FumI could degrade FB1 and FB2. The cecal microbiota of pigs and alkaline processing such as nixtamalization can also transform FB1 into metabolites. Most of the metabolites of FB1 were less toxic than FB1, except its partial (pHFB1) metabolites. Further understanding of the role of oxidative stress in FB-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of metabolism and the metabolizing enzymes of FBs. The present review might contribute to reveal the toxicity of FBs and help to protect against their oxidative damage.
ESTHER : Wang_2016_Arch.Toxicol_90_81
PubMedSearch : Wang_2016_Arch.Toxicol_90_81
PubMedID: 26419546

Title : The Association Between Epoxide Hydrolase Genetic Variant and Effectiveness of Nicotine Replacement Therapy in a Han Chinese Population -
Author(s) : Wang F , Liu Y , Guo S , Chen D , Sun H
Ref : Neurosci Bull , 32 :545 , 2016
PubMedID: 27783326

Title : An alpha\/beta-hydrolase fold protein in the biosynthesis of thiostrepton exhibits a dual activity for endopeptidyl hydrolysis and epoxide ring opening\/macrocyclization - Zheng_2016_Proc.Natl.Acad.Sci.U.S.A_113_14318
Author(s) : Zheng Q , Wang S , Duan P , Liao R , Chen D , Liu W
Ref : Proc Natl Acad Sci U S A , 113 :14318 , 2016
Abstract : Thiostrepton (TSR), an archetypal bimacrocyclic thiopeptide antibiotic that arises from complex posttranslational modifications of a genetically encoded precursor peptide, possesses a quinaldic acid (QA) moiety within the side-ring system of a thiopeptide-characteristic framework. Focusing on selective engineering of the QA moiety, i.e., by fluorination or methylation, we have recently designed and biosynthesized biologically more active TSR analogs. Using these analogs as chemical probes, we uncovered an unusual indirect mechanism of TSR-type thiopeptides, which are able to act against intracellular pathogens through host autophagy induction in addition to direct targeting of bacterial ribosome. Herein, we report the accumulation of 6'-fluoro-7', 8'-epoxy-TSR, a key intermediate in the preparation of the analog 6'-fluoro-TSR. This unexpected finding led to unveiling of the TSR maturation process, which involves an unusual dual activity of TsrI, an alpha/beta-hydrolase fold protein, for cascade C-N bond cleavage and formation during side-ring system construction. These two functions of TsrI rely on the same catalytic triad, Ser72-His200-Asp191, which first mediates endopeptidyl hydrolysis that occurs selectively between the residues Met-1 and Ile1 for removal of the leader peptide and then triggers epoxide ring opening for closure of the QA-containing side-ring system in a regio- and stereo-specific manner. The former reaction likely requires the formation of an acyl-Ser72 enzyme intermediate; in contrast, the latter is independent of Ser72. Consequently, C-6' fluorination of QA lowers the reactivity of the epoxide intermediate and, thereby, allows the dissection of the TsrI-associated enzymatic process that proceeds rapidly and typically is difficult to be realized during TSR biosynthesis.
ESTHER : Zheng_2016_Proc.Natl.Acad.Sci.U.S.A_113_14318
PubMedSearch : Zheng_2016_Proc.Natl.Acad.Sci.U.S.A_113_14318
PubMedID: 27911800
Gene_locus related to this paper: strlu-c0l0l7

Title : Acetylcholinesterase biosensor based on multi-walled carbon nanotubes-SnO2-chitosan nanocomposite - Chen_2015_Bioprocess.Biosyst.Eng_38_315
Author(s) : Chen D , Sun X , Guo Y , Qiao L , Wang X
Ref : Bioprocess Biosyst Eng , 38 :315 , 2015
Abstract : A sensitive amperometric acetylcholinesterase (AChE) biosensor was developed based on the nanocomposite of multi-walled carbon nanotubes (MWCNTs), tin oxide (SnO2) nanoparticles and chitosan (CHIT). Acetylcholinesterase (AChE) and Nafion were immobilized onto the nanocomposite film to prepare AChE biosensor for pesticide residues detection. The morphologies and electrochemistry properties of the surface modification were investigated using cyclic voltammetry, differential pulse voltammetry, and scanning electron microscopy, respectively. Compared with individual MWCNTs-CHIT, SnO2-CHIT and bare gold electrode, this nanocomposite showed the most obvious electrochemical signal in the presence of [Fe(CN)6](3-/4-) as a redox couple. Incorporating MWCNTs and SnO2 into 0.2 % CHIT solution can promote electron transfer, enhance the electrochemical response, and improve the microarchitecture of the electrode surface. All variables involved in the preparation process and analytical performance of the biosensor were optimized. Under optimized conditions, the AChE biosensor exhibited a wide linear range from 0.05 to 1.0 x 10(5 )mug/L and with a detection limit for chlorpyrifos was 0.05 mug/L. Based on the inhibition of pesticides on the AChE activity, using chlorpyrifos as model pesticide, the proposed biosensor exhibited a wide range, low detection limit, good reproducibility, and high stability. Using cabbages, lettuces, leeks, and pakchois as model samples, acceptable recovery of 98.7-105.2 % was obtained. The proposed method was proven to be a feasible quantitative method for chlorpyrifos analysis, which may open a new door ultrasensitive detection of chlorpyrifos residues in vegetables and fruits.
ESTHER : Chen_2015_Bioprocess.Biosyst.Eng_38_315
PubMedSearch : Chen_2015_Bioprocess.Biosyst.Eng_38_315
PubMedID: 25147124

Title : Rapid modulation of synaptogenesis and spinogenesis by 17beta-estradiol in primary cortical neurons - Sellers_2015_Front.Cell.Neurosci_9_137
Author(s) : Sellers KJ , Erli F , Raval P , Watson IA , Chen D , Srivastava DP
Ref : Front Cell Neurosci , 9 :137 , 2015
Abstract : In the mammalian forebrain, the majority of excitatory synapses occur on dendritic spines. Changes in the number of these structures is important for brain development, plasticity and the refinement of neuronal circuits. The formation of excitatory synapses involves the coordinated formation of dendritic spines and targeting of multi-protein complexes to nascent connections. Recent studies have demonstrated that the estrogen 17beta-estradiol (E2) can rapidly increase the number of dendritic spines, an effect consistent with the ability of E2 to rapidly influence cognitive function. However, the molecular composition of E2-induced spines and whether these protrusions form synaptic connections has not been fully elucidated. Moreover, which estrogen receptor(s) (ER) mediate these spine-morphogenic responses are not clear. Here, we report that acute E2 treatment results in the recruitment of postsynaptic density protein 95 (PSD-95) to novel dendritic spines. In addition neuroligin 1 (Nlg-1) and the NMDA receptor subunit GluN1 are recruited to nascent synapses in cortical neurons. The presence of these synaptic proteins at nascent synapses suggests that the machinery to allow pre- and post-synapses to form connections are present in E2-induced spines. We further demonstrate that E2 treatment results in the rapid and transient activation of extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the mammalian target of rapamycin (mTOR) signaling pathways. However, only ERK1/2 and Akt are required for E2-mediated spinogenesis. Using synthetic receptor modulators, we further demonstrate that activation of the estrogen receptor beta (ERbeta) but not alpha (ERalpha) mimics rapid E2-induced spinogenesis and synaptogenesis. Taken together these findings suggest that in primary cortical neurons, E2 signaling via ERbeta, but not through ERalpha, is capable of remodeling neuronal circuits by increasing the number of excitatory synapses.
ESTHER : Sellers_2015_Front.Cell.Neurosci_9_137
PubMedSearch : Sellers_2015_Front.Cell.Neurosci_9_137
PubMedID: 25926772

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 : Drosophila neuroligin3 regulates neuromuscular junction development and synaptic differentiation - Xing_2014_J.Biol.Chem_289_31867
Author(s) : Xing G , Gan G , Chen D , Sun M , Yi J , Lv H , Han J , Xie W
Ref : Journal of Biological Chemistry , 289 :31867 , 2014
Abstract : Neuroligins (Nlgs) are a family of cell adhesion molecules thought to be important for synapse maturation and function. Mammalian studies have shown that different Nlgs have different roles in synaptic maturation and function. In Drosophila melanogaster, the roles of Drosophila neuroligin1 (DNlg1), neuroligin2, and neuroligin4 have been examined. However, the roles of neuroligin3 (dnlg3) in synaptic development and function have not been determined. In this study, we used the Drosophila neuromuscular junctions (NMJs) as a model system to investigate the in vivo role of dnlg3. We showed that DNlg3 was expressed in both the CNS and NMJs where it was largely restricted to the postsynaptic site. We generated dnlg3 mutants and showed that these mutants exhibited an increased bouton number and reduced bouton size compared with the wild-type (WT) controls. Consistent with alterations in bouton properties, pre- and postsynaptic differentiations were affected in dnlg3 mutants. This included abnormal synaptic vesicle endocytosis, increased postsynaptic density length, and reduced GluRIIA recruitment. In addition to impaired synaptic development and differentiation, we found that synaptic transmission was reduced in dnlg3 mutants. Altogether, our data showed that DNlg3 was required for NMJ development, synaptic differentiation, and function.
ESTHER : Xing_2014_J.Biol.Chem_289_31867
PubMedSearch : Xing_2014_J.Biol.Chem_289_31867
PubMedID: 25228693
Gene_locus related to this paper: drome-nlg3

Title : Identification and characterization of a new erythromycin biosynthetic gene cluster in Actinopolyspora erythraea YIM90600, a novel erythronolide-producing halophilic actinomycete isolated from salt field - Chen_2014_PLoS.One_9_e108129
Author(s) : Chen D , Feng J , Huang L , Zhang Q , Wu J , Zhu X , Duan Y , Xu Z
Ref : PLoS ONE , 9 :e108129 , 2014
Abstract : Erythromycins (Ers) are clinically potent macrolide antibiotics in treating pathogenic bacterial infections. Microorganisms capable of producing Ers, represented by Saccharopolyspora erythraea, are mainly soil-dwelling actinomycetes. So far, Actinopolyspora erythraea YIM90600, a halophilic actinomycete isolated from Baicheng salt field, is the only known Er-producing extremophile. In this study, we have reported the draft genome sequence of Ac. erythraea YIM90600, genome mining of which has revealed a new Er biosynthetic gene cluster encoding several novel Er metabolites. This Er gene cluster shares high identity and similarity with the one of Sa. erythraea NRRL2338, except for two absent genes, eryBI and eryG. By correlating genotype and chemotype, the biosynthetic pathways of 3'-demethyl-erythromycin C, erythronolide H (EH) and erythronolide I have been proposed. The formation of EH is supposed to be sequentially biosynthesized via C-6/C-18 epoxidation and C-14 hydroxylation from 6-deoxyerythronolide B. Although an in vitro enzymatic activity assay has provided limited evidence for the involvement of the cytochrome P450 oxidase EryFAc (derived from Ac. erythraea YIM90600) in the catalysis of a two-step oxidation, resulting in an epoxy moiety, the attempt to construct an EH-producing Sa. erythraea mutant via gene complementation was not successful. Characterization of EryKAc (derived from Ac. erythraea YIM90600) in vitro has confirmed its unique role as a C-12 hydroxylase, rather than a C-14 hydroxylase of the erythronolide. Genomic characterization of the halophile Ac. erythraea YIM90600 will assist us to explore the great potential of extremophiles, and promote the understanding of EH formation, which will shed new insights into the biosynthesis of Er metabolites.
ESTHER : Chen_2014_PLoS.One_9_e108129
PubMedSearch : Chen_2014_PLoS.One_9_e108129
PubMedID: 25250723
Gene_locus related to this paper: 9acto-a0a099d7w4 , 9actn-a0a099d934

Title : Comparative genomic analysis shows that Streptococcus suis meningitis isolate SC070731 contains a unique 105K genomic island - Wu_2014_Gene_535_156
Author(s) : Wu Z , Wang W , Tang M , Shao J , Dai C , Zhang W , Fan H , Yao H , Zong J , Chen D , Wang J , Lu C
Ref : Gene , 535 :156 , 2014
Abstract : Streptococcus suis (SS) is an important swine pathogen worldwide that occasionally causes serious infections in humans. SS infection may result in meningitis in pigs and humans. The pathogenic mechanisms of SS are poorly understood. Here, we provide the complete genome sequence of S. suis serotype 2 (SS2) strain SC070731 isolated from a pig with meningitis. The chromosome is 2,138,568bp in length. There are 1933 predicted protein coding sequences and 96.7% (57/59) of the known virulence-associated genes are present in the genome. Strain SC070731 showed similar virulence with SS2 virulent strains HA9801 and ZY05719, but was more virulent than SS2 virulent strain P1/7 in the zebrafish infection model. Comparative genomic analysis revealed a unique 105K genomic island in strain SC070731 that is absent in seven other sequenced SS2 strains. Further analysis of the 105K genomic island indicated that it contained a complete nisin locus similar to the nisin U locus in S. uberis strain 42, a prophage similar to S. oralis phage PH10 and several antibiotic resistance genes. Several proteins in the 105K genomic island, including nisin and RelBE toxin-antitoxin system, contribute to the bacterial fitness and virulence in other pathogenic bacteria. Further investigation of newly identified gene products, including four putative new virulence-associated surface proteins, will improve our understanding of SS pathogenesis.
ESTHER : Wu_2014_Gene_535_156
PubMedSearch : Wu_2014_Gene_535_156
PubMedID: 24316490
Gene_locus related to this paper: strej-e8uk64

Title : Study on the interaction of catalase with pesticides by flow injection chemiluminescence and molecular docking - Tan_2014_Chemosphere_108_26
Author(s) : Tan X , Wang Z , Chen D , Luo K , Xiong X , Song Z
Ref : Chemosphere , 108 :26 , 2014
Abstract : The interaction mechanisms of catalase (CAT) with pesticides (including organophosphates: disulfoton, isofenphos-methyl, malathion, isocarbophos, dimethoate, dipterex, methamidophos and acephate; carbamates: carbaryl and methomyl; pyrethroids: fenvalerate and deltamethrin) were first investigated by flow injection (FI) chemiluminescence (CL) analysis and molecular docking. By homemade FI-CL model of lg[(I0-I)/I]=lgK+nlg[D], it was found that the binding processes of pesticides to CAT were spontaneous with the apparent binding constants K of 10(3)-10(5) L mol(-1) and the numbers of binding sites about 1.0. The binding abilities of pesticides to CAT followed the order: fenvalerate>deltamethrin>disulfoton>isofenphos-methyl>carbaryl>malathion>isocarbo phos>dimethoate>dipterex>acephate>methomyl>methamidophos, which was generally similar to the order of determination sensitivity of pesticides. The thermodynamic parameters revealed that CAT bound with hydrophobic pesticides by hydrophobic interaction force, and with hydrophilic pesticides by hydrogen bond and van der Waals force. The pesticides to CAT molecular docking study showed that pesticides could enter into the cavity locating among the four subdomains of CAT, giving the specific amino acid residues and hydrogen bonds involved in CAT-pesticides interaction. It was also found that the lgK values of pesticides to CAT increased regularly with increasing lgP, Mr, MR and MV, suggesting that the hydrophobicity and steric property of pesticide played essential roles in its binding to CAT.
ESTHER : Tan_2014_Chemosphere_108_26
PubMedSearch : Tan_2014_Chemosphere_108_26
PubMedID: 24875908

Title : Quantum dots-based fluorescent probes for turn-on and turn-off sensing of butyrylcholinesterase - Chen_2013_Biosens.Bioelectron_44C_204
Author(s) : Chen Z , Ren X , Meng X , Tan L , Chen D , Tang F
Ref : Biosensors & Bioelectronics , 44C :204 , 2013
Abstract : A novel turn-on and turn-off sensor based on the fluorescence change of quantum dots (QDs) has been developed to detect the activity of butyrylcholinesterase (BChE). In the turn-on sensing system, we realized the detection of BChE with just one enzyme. A linear calibration plot of the activity of BChE was obtained in the wide amounts range from 10 to 1000U/L and the detection limit was 10U/L. In the turn-off sensing system, we realized the sensing of BChE with a wide linear relationship of 10-2000U/L which was much wider than many other detection methods. We also studied the application in serum sample detection. The BChE sensor shows great performances. Furthermore, the turn-on and turn-off sensing mechanisms were studied extensively. These results showed that our strategy would most probably be applicable in assembling diagnostic micro-device for realizing the rapid clinical analysis of BChE.
ESTHER : Chen_2013_Biosens.Bioelectron_44C_204
PubMedSearch : Chen_2013_Biosens.Bioelectron_44C_204
PubMedID: 23428734

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 : Highly sensitive detection of organophosphorus pesticides by acetylcholinesterase-coated thin film bulk acoustic resonator mass-loading sensor - Chen_2013_Biosens.Bioelectron_41_163
Author(s) : Chen D , Wang J , Xu Y , Li D , Zhang L , Li Z
Ref : Biosensors & Bioelectronics , 41 :163 , 2013
Abstract : An acetylcholinesterase-coated thin film bulk acoustic resonator has been developed for the detection of organophosphorus pesticides. The thin film bulk acoustic resonator acts as a robust mass-sensitive transducer for bio-sensing. This device works in thickness shear mode with a resonance at 1.97GHz. The detection is based on the inhibitory effects of organophosphorus compounds on the enzymatic activity of the acetylcholinesterase immobilized on one of the faces of the acoustic resonator. The enzyme reaction in the substrate solution and the inhibitory effect is observed are real time by measuring the frequency shift. The presence of organophosphorus pesticides can be detected from the diminution of the frequency shift compared with the levels found in their absence. The device exhibits linear responses, good reproducibility, simple operation, portability and a low detection limit of 5.3x10(-11)M for paraoxon. The detection results of organophosphorus pesticide residues in practical samples show that the proposed sensor has the feasibility and sensing accuracy comparable to gas chromatography.
ESTHER : Chen_2013_Biosens.Bioelectron_41_163
PubMedSearch : Chen_2013_Biosens.Bioelectron_41_163
PubMedID: 23017678

Title : Assessment of activities and conformation of lipases treated with sub- and supercritical carbon dioxide - Chen_2013_Appl.Biochem.Biotechnol_169_2189
Author(s) : Chen D , Peng C , Zhang H , Yan Y
Ref : Appl Biochem Biotechnol , 169 :2189 , 2013
Abstract : In order to illustrate the underlining mechanism of the effect of high pressure on lipases from different resources, the influence of compressed carbon dioxide treatment on the esterification activities and conformation of the three lipases Candida rugosa lipase (CRL), Pseudomonas fluorescens lipase, and Rhizopus oryzae lipase was investigated in the present work. The results showed that the lipases activities were significantly enhanced in most of high-pressure treatments, except the pressure had a negative effect on CRL activity in supercritical condition. Mild depressurization rate could remain the lipase's activity by protecting its rigid structure under supercritical fluid. Conformational analysis by Fourier transform-infrared spectrometry and fluorescence emission spectra revealed that the variances of lipase activity after high-pressure treatment were correlated with the changes of its alpha-helix content and fluorescence intensity. Additionally, transesterification catalyzed by three lipases in supercritical carbon dioxide were conducted, and 87.2 % biodiesel conversion was obtained by CRL after 3 h, resulting in a great reduction of reaction time.
ESTHER : Chen_2013_Appl.Biochem.Biotechnol_169_2189
PubMedSearch : Chen_2013_Appl.Biochem.Biotechnol_169_2189
PubMedID: 23417391

Title : A thin film electro-acoustic enzyme biosensor allowing the detection of trace organophosphorus pesticides - Chen_2012_Anal.Biochem_429_42
Author(s) : Chen D , Wang J , Xu Y , Zhang L
Ref : Analytical Biochemistry , 429 :42 , 2012
Abstract : We report an analytical method using a thin film electro-acoustic resonator for the detection of organophosphorus pesticides The acetylcholinesterase AChE enzyme was immobilized on the surface of the resonator In the presence of organophosphorus compounds the degree of inhibitory effect of organophosphorus compounds on the AChE activity and the concentration of pesticides were detected in real time by measuring the frequency shift of the resonator The proposed device has a remarkably low detection limit of 1.8x10(-11)M and obvious advantages such as small size simple operation and integrated circuit compatibility providing a promising tool for pesticide analysis.
ESTHER : Chen_2012_Anal.Biochem_429_42
PubMedSearch : Chen_2012_Anal.Biochem_429_42
PubMedID: 22796536

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 : Type II thioesterase gene (ECO-orf27) from Amycolatopsis orientalis influences production of the polyketide antibiotic, ECO-0501 (LW01) - Shen_2012_Biotechnol.Lett_34_2087
Author(s) : Shen Y , Huang H , Zhu L , Luo M , Chen D
Ref : Biotechnol Lett , 34 :2087 , 2012
Abstract : ECO-orf27 associated with the cluster of ECO-0501 (LW01) from Amycolatopsis orientalis is deduced to encode a type II thioesterase. Disruption of ECO-orf27 reduced LW01 production by 95 %. Complementation of the disrupted mutant with intact ECO-orf27 restored the production of LW01 suggesting that ECO-orf27 is crucial for LW01 biosynthesis. ECO-TE I, the gene encoding type I thioesterase from LW01 polyketide synthases, cannot complement ECO-orf27 deficient mutant distinguishing ECO-orf27 from type I thioesterase gene. Type II thioesterase gene pikAV from Streptomyces venezuelae could complement ECO-orf27 in A. orientalis indicating that the two genes are equivalent in their function. Overexpression of ECO-orf27 resulted in a 20 % increase in LW01 production providing an alternative approach for yield improvement.
ESTHER : Shen_2012_Biotechnol.Lett_34_2087
PubMedSearch : Shen_2012_Biotechnol.Lett_34_2087
PubMedID: 22850790

Title : Pharmacokinetics and pharmacodynamics of AR9281, an inhibitor of soluble epoxide hydrolase, in single- and multiple-dose studies in healthy human subjects - Chen_2012_J.Clin.Pharmacol_52_319
Author(s) : Chen D , Whitcomb R , MacIntyre E , Tran V , Do ZN , Sabry J , Patel DV , Anandan SK , Gless R , Webb HK
Ref : Journal of Clinical Pharmacology , 52 :319 , 2012
Abstract : AR9281, a potent and selective inhibitor of soluble epoxide hydrolase (s-EH), is in clinical development targeting hypertension and type 2 diabetes. The safety, pharmacokinetics, and pharmacodynamics of AR9281 were evaluated in double-blind, randomized, placebo-controlled, ascending, single oral dose (10-1000 mg) and multiple dose (100-400 mg every 8 hours for 7 days) studies in healthy subjects. AR9281 was well tolerated, and no dose-related adverse events were observed during either study. The drug was rapidly absorbed with a mean terminal half-life ranging from 3 to 5 hours. The area under the plasma concentration-time curve increased in an approximately dose-proportional manner up to the 500-mg dose and exhibited a greater than dose linearity at higher doses. AR9281 directly and dose-dependently inhibited blood s-EH activity with 90% inhibition or greater over an 8-hour period at the 250-mg dose and over a 12-hour period at the 500-mg dose. Multiple doses of AR9281 ranging from 100 to 400 mg every 8 hours resulted in a sustained inhibition of s-EH activity at 90% or greater during the trough. The current studies provide proof of safety and target inhibition of AR9281 in healthy subjects. AR9281 pharmacokinetic and pharmacodynamic characteristics support a twice-daily or thrice-daily dosing regimen in patients.
ESTHER : Chen_2012_J.Clin.Pharmacol_52_319
PubMedSearch : Chen_2012_J.Clin.Pharmacol_52_319
PubMedID: 21422238

Title : [Construction of Aspergillus niger lipase mutants with oil-water interface independence] - Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
Author(s) : Chen D , Shu Z , Xue L , Lin R , Wu J , Jiang Y , Li X , Lin Y , Huang J
Ref : Sheng Wu Gong Cheng Xue Bao , 27 :860 , 2011
Abstract : Based on previous bioinformational analysis results, two Aspergillus niger lipase (ANL) mutants, ANL-Ser84Gly and ANL-Asp99Pro were constructed to screen ANL mutants with oil-water interface independence. ANL-Ser84Gly still displayed a pronounced interfacial activation, while ANL-Asp99Pro displayed no interfacial activation. The specific activity of ANL-Ser84Gly towards p-nitrophenyl palmitate (-myristate, -laurate and -decanoate) decreased by 29.8% (53.1, 60.1 and 77.1, respectively) than that of ANL, while the specific activity of ANL-Asp99Pro towards p-nitrophenyl palmitate increased by 2.2-fold. The mutation in the hinge region at both sides of the lid domain also destabilized various secondary structure factors of ANL-S84G and ANL-D99P, which resulted in a substantial decrease in thermostability. The achievement to construct oil-water interface-independent ANL mutants would help to further understand lipase interfacial activation mechanism.
ESTHER : Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
PubMedSearch : Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
PubMedID: 22034814

Title : Biodiesel synthesis and conformation of lipase from Burkholderia cepacia in room temperature ionic liquids and organic solvents - Liu_2011_Bioresour.Technol_102_10414
Author(s) : Liu Y , Chen D , Yan Y , Peng C , Xu L
Ref : Bioresour Technol , 102 :10414 , 2011
Abstract : Biodiesel synthesis and conformation of Burkholderia cepacia lipase (BCL) were studied in 19 different room temperature ionic liquids (RTLLs) with a range of cation and anion structures. Overall, anion selection had a greater influence on biodiesel conversion than cation choice. RTILs containing Tf2N- and PF6- anions were suitable reaction media, while RTIL of [OmPy][BF4] was the best reaction medium with a biodiesel yield of 82.2+/-1.2%. RTILs with strong water miscible properties showed very low biodiesel yields. Conformational analysis by FT-IR revealed that higher biodiesel conversion in RTILs was correlated with a low tendency in alpha-helix content of BCL. An ultrasound-assisted biocatalysis process in RTILs was used to improve mass transfer rate, leading to 83% reduction of the reaction time for biodiesel production.
ESTHER : Liu_2011_Bioresour.Technol_102_10414
PubMedSearch : Liu_2011_Bioresour.Technol_102_10414
PubMedID: 21955878

Title : Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors - Shen_2011_Bioorg.Med.Chem.Lett_21_1299
Author(s) : Shen HC , Ding FX , Zhou C , Xiong Y , Verras A , Chabin RM , Xu S , Tong X , Xie D , Lassman ME , Bhatt UR , Garcia-Calvo MM , Geissler W , Shen Z , Chen D , SinhaRoy R , Hale JJ , Tata JR , Pinto S , Shen DM , Colletti SL
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :1299 , 2011
Abstract : A series of benzimidazole pyrrolidinyl amides containing a piperidinyl group were discovered as novel prolylcarboxypeptidase (PrCP) inhibitors. Low-nanomolar IC(50)'s were achieved for several analogs, of which compound 9b displayed modest ex vivo target engagement in eDIO mouse plasma. Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed.
ESTHER : Shen_2011_Bioorg.Med.Chem.Lett_21_1299
PubMedSearch : Shen_2011_Bioorg.Med.Chem.Lett_21_1299
PubMedID: 21315588
Gene_locus related to this paper: human-PRCP

Title : Inhibition of soluble epoxide hydrolase attenuates endothelial dysfunction in animal models of diabetes, obesity and hypertension - Zhang_2011_Eur.J.Pharmacol_654_68
Author(s) : Zhang LN , Vincelette J , Chen D , Gless RD , Anandan SK , Rubanyi GM , Webb HK , MacIntyre DE , Wang YX
Ref : European Journal of Pharmacology , 654 :68 , 2011
Abstract : Endothelial dysfunction is a hallmark of, and plays a pivotal role in the pathogenesis of cardiometabolic diseases, including type II diabetes, obesity, and hypertension. It has been well established that epoxyeicosatrienoic acids (EETs) act as an endothelial derived hyperpolarization factor (EDHF). Soluble epoxide hydrolase (s-EH) rapidly hydrolyses certain epoxylipids (e.g. EETs) to less bioactive diols (DHETs), thereby attenuating the evoked vasodilator effects. The aim of the present study was to examine if inhibition of s-EH can restore impaired endothelial function in three animal models of cardiometabolic diseases. Isolated vessel rings of the aorta and/or mesenteric artery from mice or rats were pre-contracted using phenylephrine or U46619. Endothelium-dependent and independent vasorelaxation to acetylcholine and sodium nitroprusside (SNP) were measured using wire myography in vessels isolated from db/db or diet-induced obesity (DIO) mice, and angiotensin II-induced hypertensive rats treated chronically with s-EH inhibitors AR9281 or AR9276 or with vehicle. Vasorelaxation to acetylcholine, but not to SNP was severely impaired in all three animal models. Oral administration of AR9281 or AR9276 abolished whole blood s-EH activity, elevated epoxy/diol lipid ratio, and abrogated endothelial dysfunction in all three models. Incubating the mesenteric artery of db/db mice with L-NAME and indomethacin to block nitric oxide (NO) and prostacyclin formation did not affect AR9821-induced improvement of endothelial function. These data indicate that inhibition of s-EH ameliorates endothelial dysfunction and that effects in the db/db model are independent of the presence of NO and cyclooxygenase derived prostanoids. Thus, preserving vasodilator EETs by inhibition of s-EH may be of therapeutic benefit by improving endothelial function in cardiometabolic diseases.
ESTHER : Zhang_2011_Eur.J.Pharmacol_654_68
PubMedSearch : Zhang_2011_Eur.J.Pharmacol_654_68
PubMedID: 21187082

Title : 1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia - Anandan_2011_Bioorg.Med.Chem.Lett_21_983
Author(s) : Anandan SK , Webb HK , Chen D , Wang YX , Aavula BR , Cases S , Cheng Y , Do ZN , Mehra U , Tran V , Vincelette J , Waszczuk J , White K , Wong KR , Zhang LN , Jones PD , Hammock BD , Patel DV , Whitcomb R , MacIntyre DE , Sabry J , Gless R
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :983 , 2011
Abstract : 1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea 14a (AR9281), a potent and selective soluble epoxide hydrolase inhibitor, was recently tested in a phase 2a clinical setting for its effectiveness in reducing blood pressure and improving insulin resistance in pre-diabetic patients. In a mouse model of diet induced obesity, AR9281 attenuated the enhanced glucose excursion following an intraperitoneal glucose tolerance test. AR9281 also attenuated the increase in blood pressure in angiotensin-II-induced hypertension in rats. These effects were dose-dependent and well correlated with inhibition of the sEH activity in whole blood, consistent with a role of sEH in the observed pharmacology in rodents.
ESTHER : Anandan_2011_Bioorg.Med.Chem.Lett_21_983
PubMedSearch : Anandan_2011_Bioorg.Med.Chem.Lett_21_983
PubMedID: 21211973

Title : Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications - Liao_2009_Chem.Biol_16_141
Author(s) : Liao R , Duan L , Lei C , Pan H , Ding Y , Zhang Q , Chen D , Shen B , Yu Y , Liu W
Ref : Chemical Biology , 16 :141 , 2009
Abstract : Thiopeptides, with potent activity against various drug-resistant pathogens, contain a characteristic macrocyclic core consisting of multiple thiazoles, dehydroamino acids, and a 6-membered nitrogen heterocycle. Their biosynthetic pathways remain elusive, in spite of great efforts by in vivo feeding experiments. Here, cloning, sequencing, and characterization of the thiostrepton and siomycin A gene clusters unveiled a biosynthetic paradigm for the thiopeptide specific core formation, featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. The paradigm generality for thiopeptide biosynthesis was supported by genome mining and ultimate confirmation of the thiocillin I production in Bacillus cereus ATCC 14579, a strain that was previously unknown as a thiopeptide producer. These findings set the stage to accelerate the discovery of thiopeptides by prediction at the genetic level and to generate structural diversity by applying combinatorial biosynthesis methods.
ESTHER : Liao_2009_Chem.Biol_16_141
PubMedSearch : Liao_2009_Chem.Biol_16_141
PubMedID: 19246004
Gene_locus related to this paper: 9acto-c0jrv0 , 9acto-c0jrv6 , strlu-c0jry1 , 9actn-c0jrw3 , strlu-c0l0l7

Title : Association of the lipoprotein lipase gene T+495G polymorphism with central obesity and serum lipids in a twin study - Li_2008_Ann.Epidemiol_18_760
Author(s) : Li J , Huang A , Hu Y , Chen D
Ref : Ann Epidemiol , 18 :760 , 2008
Abstract : PURPOSE: The lipoprotein lipase (LPL) gene polymorphism is possibly involved in the pathophysiology of central obesity and dyslipidemia. The aim of this study was to investigate the association of LPL gene T+495G polymorphism with central obesity and serum lipids. METHODS: A total of 961 adult twin pairs were enrolled from the program of Chinese Twin Registry, between 2001 and 2002. We used 90 cm of waist circumference in male and 80 cm in female as cut-off values of central obesity. The LPL gene T+495G polymorphism was analyzed with the use of genomic polymerase chain reaction and HindIII-restriction fragment length polymorphism. Two statistical methods were performed to test the effect of T+495G polymorphism of LPL gene on the relation between central obesity and lipid levels: one was the generalized estimating equation model for all twin pairs and the other was co-twin matched case-control analysis in 82 central obesity discordant monozygotic twin pairs. RESULTS: In male twins, central obesity was significantly associated with serum lipids except for high-density lipoprotein (HDL). In female twins, obesity twins had significantly higher levels of triglyceride (TG) and TG/HDL than nonobesity twins. There was no significant association between T+495G polymorphism and lipid levels for all twins, although +495G allele carrier was related with 6.7% decrease of TG was observed only in female twins. The interactions of T+495G polymorphism and central obesity were not found for TG, HDL, and TG/HDL. In central obesity discordant monozygotic twin pairs, central obesity was significantly related with 24.2%, 26.1%, and 4.1% increase of TG ,TG/HDL, and TC, respectively, in +495T/T genotype. CONCLUSIONS: These results suggest no association and interaction of T+495G polymorphism with central obesity and serum lipids for all twin pairs. Meanwhile, a modest genetic-environmental effect of T+495G polymorphism and central obesity was found in discordant monozygotic twin pairs. Therefore, the +495T/T genotype may be an independent risk factor associated with central obesity and lipids level. However, the role of LPL gene T+195G polymorphism in central obesity and dyslipidemia is complex and remains controversial. This hypothesis needs further investigation.
ESTHER : Li_2008_Ann.Epidemiol_18_760
PubMedSearch : Li_2008_Ann.Epidemiol_18_760
PubMedID: 18693040

Title : Controlled release of huperzine A from biodegradable microspheres: In vitro and in vivo studies - Gao_2007_Int.J.Pharm_330_1
Author(s) : Gao P , Xu H , Ding P , Gao Q , Sun J , Chen D
Ref : Int J Pharm , 330 :1 , 2007
Abstract : The objective of the present work was to further study the in vitro characteristics, in vivo pharmacokinetics and pharmacodynamics of huperzine A (HupA) loaded biodegradable microspheres designed for sustained release of HupA over several weeks. A conventional o/w emulsion-solvent evaporation method was used to incorporate HupA, which is of interest in the palliative treatment of Alzheimer's disease (AD), into end-group uncapped poly(D,L-lactide-co-glycolide) (PLG-H). A prolonged in vitro drug release profile was observed, with a complete release of the incorporated drug within 5-6 weeks. The in vivo pharmacokinetics study of HupA loaded microspheres showed sustained plasma HupA concentration-time profile after subcutaneous injection into rats. The pharmacodynamics evaluated by determination of the activity of acetylcholinesterase in the rat cortex also showed a prolonged pharmacological response. Both the in vitro release and in vivo pharmacological responses correlated well with the in vivo pharmacokinetics profile. The results suggest the potential use of HupA-loaded biodegradable microspheres for treatment of AD over long periods.
ESTHER : Gao_2007_Int.J.Pharm_330_1
PubMedSearch : Gao_2007_Int.J.Pharm_330_1
PubMedID: 16987624

Title : The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice - Lahiri_2007_J.Pharmacol.Exp.Ther_320_386
Author(s) : Lahiri DK , Chen D , Maloney B , Holloway HW , Yu QS , Utsuki T , Giordano T , Sambamurti K , Greig NH
Ref : Journal of Pharmacology & Experimental Therapeutics , 320 :386 , 2007
Abstract : Major characteristics of Alzheimer's disease (AD) are synaptic loss, cholinergic dysfunction, and abnormal protein depositions in the brain. The amyloid beta-peptide (Abeta), a proteolytic fragment of amyloid beta precursor protein (APP), aggregates to form neuritic plaques and has a causative role in AD. A present focus of AD research is to develop safe Abeta-lowering drugs. A selective acetylcholinesterase inhibitor, phenserine, in current human trials lowers both APP and Abeta. Phenserine is dose-limited in animals by its cholinergic actions; its cholinergically inactive enantiomer, posiphen (+)-[phenserine], was assessed. In cultured human neuroblastoma cells, posiphen, like phenserine, dose- and time-dependently lowered APP and Abeta levels by reducing the APP synthesis rate. This action translated to an in vivo system. Posiphen administration to mice (7.5-75 mg/kg daily, 21 consecutive days) significantly decreased levels of total APP (tissue mass-adjusted) in a dose-dependent manner. Abeta40 and Abeta42 levels were significantly lowered by posiphen (> or =15 mg/kg) compared with controls. The activities of alpha-, beta-, and gamma-secretases were assessed in the same brain samples, and beta-secretase activity was significantly reduced. Posiphen, like phenserine, can lower Abeta via multiple mechanisms and represents an interesting drug candidate for AD treatment.
ESTHER : Lahiri_2007_J.Pharmacol.Exp.Ther_320_386
PubMedSearch : Lahiri_2007_J.Pharmacol.Exp.Ther_320_386
PubMedID: 17003227

Title : Differential effects of two hexahydropyrroloindole carbamate-based anticholinesterase drugs on the amyloid beta protein pathway involved in Alzheimer's disease - Lahiri_2007_Neuromolecular.Med_9_157
Author(s) : Lahiri DK , Alley GM , Tweedie D , Chen D , Greig NH
Ref : Neuromolecular Med , 9 :157 , 2007
Abstract : One of the main hallmarks of Alzheimer's disease (AD) is the brain deposition of senile plaques made up of toxic amyloid beta-peptide (Abeta), which is derived from a larger protein called the beta-amyloid precursor protein (APP). Both APP processing and cholinesterase activity are affected in the AD brain, but, yet, cholinesterase inhibitors (ChEI) remain the primary Food and Drug Administration approved drugs for AD within the United States. Herein, we evaluated the effects of two clinically relevant drugs on the APP pathway, which is presumably involved in AD pathogenesis. Specifically, we compared the actions of the classical ChEI physostigmine (PHY) and its analog phenserine (PHE) on neuronal cell viability, on IC50 and on levels of different amyloid proteins. Interestingly, these drugs share the same chemical backbone, inhibit acetylcholinesterase with similar potency, but differentially affect APP processing. PHE treatment decreased levels of APP in the human neuroblastoma cells (p=0.009) whereas PHY showed a similar but less-pronounced trend, which did not attain statistical significance. PHE treatment significantly decreased levels of Abeta in human neuroblastoma cells (p=0.02) whereas PHY showed no significant change under the same conditions. The divergent actions of these two structurally related drugs on the amyloid pathway indicate that the mechanisms underpinning the cholinergic and the amyloid-lowering properties for this class of drugs are independent of each other.
ESTHER : Lahiri_2007_Neuromolecular.Med_9_157
PubMedSearch : Lahiri_2007_Neuromolecular.Med_9_157
PubMedID: 17627035

Title : Study of biochemical pathways and enzymes involved in pyrene degradation by Mycobacterium sp. strain KMS - Liang_2006_Appl.Environ.Microbiol_72_7821
Author(s) : Liang Y , Gardner DR , Miller CD , Chen D , Anderson AJ , Weimer BC , Sims RC
Ref : Applied Environmental Microbiology , 72 :7821 , 2006
Abstract : Pyrene degradation is known in bacteria. In this study, Mycobacterium sp. strain KMS was used to study the metabolites produced during, and enzymes involved in, pyrene degradation. Several key metabolites, including pyrene-4,5-dione, cis-4,5-pyrene-dihydrodiol, phenanthrene-4,5-dicarboxylic acid, and 4-phenanthroic acid, were identified during pyrene degradation. Pyrene-4,5-dione, which accumulates as an end product in some gram-negative bacterial cultures, was further utilized and degraded by Mycobacterium sp. strain KMS. Enzymes involved in pyrene degradation by Mycobacterium sp. strain KMS were studied, using 2-D gel electrophoresis. The first protein in the catabolic pathway, aromatic-ring-hydroxylating dioxygenase, which oxidizes pyrene to cis-4,5-pyrene-dihydrodiol, was induced with the addition of pyrene and pyrene-4,5-dione to the cultures. The subcomponents of dioxygenase, including the alpha and beta subunits, 4Fe-4S ferredoxin, and the Rieske (2Fe-2S) region, were all induced. Other proteins responsible for further pyrene degradation, such as dihydrodiol dehydrogenase, oxidoreductase, and epoxide hydrolase, were also found to be significantly induced by the presence of pyrene and pyrene-4,5-dione. Several nonpathway-related proteins, including sterol-binding protein and cytochrome P450, were induced. A pyrene degradation pathway for Mycobacterium sp. strain KMS was proposed and confirmed by proteomic study by identifying almost all the enzymes required during the initial steps of pyrene degradation.
ESTHER : Liang_2006_Appl.Environ.Microbiol_72_7821
PubMedSearch : Liang_2006_Appl.Environ.Microbiol_72_7821
PubMedID: 17041157

Title : High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression - Sokol_2006_J.Child.Neurol_21_444
Author(s) : Sokol DK , Chen D , Farlow MR , Dunn DW , Maloney B , Zimmer JA , Lahiri DK
Ref : Journal of Child Neurology , 21 :444 , 2006
Abstract : Autism is characterized by restricted, repetitive behaviors and impairment in socialization and communication. Although no neuropathologic substrate underlying autism has been found, the findings of brain overgrowth via neuroimaging studies and increased levels of brain-derived neurotrophic factor (BDNF) in neuropathologic and blood studies favor an anabolic state. We examined acetylcholinesterase, plasma neuronal proteins, secreted beta-amyloid precursor protein (APP), and amyloid-beta 40 and amyloid-beta 42 peptides in children with and without autism. Children with severe autism and aggression expressed secreted beta-amyloid precursor protein at two or more times the levels of children without autism and up to four times more than children with mild autism. There was a trend for children with autism to show higher levels of secreted beta-amyloid precursor protein and nonamyloidogenic secreted beta-amyloid precursor protein and lower levels of amyloid-beta 40 compared with controls. This favors an increased alpha-secretase pathway in autism (anabolic), opposite to what is seen in Alzheimer disease. Additionally, a complex relationship between age, acetylcholinesterase, and plasma neuronal markers was found.
ESTHER : Sokol_2006_J.Child.Neurol_21_444
PubMedSearch : Sokol_2006_J.Child.Neurol_21_444
PubMedID: 16948926

Title : In vitro and in vivo characterization of huperzine a loaded microspheres made from end-group uncapped poly(d,l-lactide acid) and poly(d,l-lactide-co-glycolide acid) - Gao_2006_Chem.Pharm.Bull.(Tokyo)_54_89
Author(s) : Gao P , Ding P , Xu H , Yuan Z , Chen D , Wei J
Ref : Chem Pharm Bull (Tokyo) , 54 :89 , 2006
Abstract : The purpose of this work was to develop biodegradable microspheres for long term delivery of a potent acetyl cholinesterase inhibitor, huperzine A (Hup-A), which is of interest in the palliative treatment of Alzheimer's disease. Microspheres were successfully prepared with specifically end-group uncapped poly(d,l-lactide acid) and poly(d,l-lactide-co-glycolide acid) using a simple o/w solvent evaporation method. The morphology, particle size and size distribution, drug loading capacity, drug entrapment efficiency (EE) and in vitro drug release were studied in detail. It was found that the terminal group and the inherent viscosity (IV) of the polymers played key role in the drug encapsulation: higher EE was achieved with end-group uncapped and low IV polymers. In vitro drug release from microspheres made from the selected three kinds of polymers revealed sustained release of Hup-A without significant burst release. Preliminary pharmacokinetic study following subcutaneous injection of Hup-A loaded microspheres illustrated the sustained release of the drug over 6-8 weeks at clinically relevant doses in vivo. The studies demonstrated the feasibility of long term delivery of Hup-A using biodegradable microspheres.
ESTHER : Gao_2006_Chem.Pharm.Bull.(Tokyo)_54_89
PubMedSearch : Gao_2006_Chem.Pharm.Bull.(Tokyo)_54_89
PubMedID: 16394556

Title : Identification of novel small molecule inhibitors of amyloid precursor protein synthesis as a route to lower Alzheimer's disease amyloid-beta peptide - Utsuki_2006_J.Pharmacol.Exp.Ther_318_855
Author(s) : Utsuki T , Yu QS , Davidson D , Chen D , Holloway HW , Brossi A , Sambamurti K , Lahiri DK , Greig NH , Giordano T
Ref : Journal of Pharmacology & Experimental Therapeutics , 318 :855 , 2006
Abstract : A wealth of independent research with transgenic mice, antibodies, and vaccines has pointed to a causative role of the amyloid-beta peptide (A beta) in Alzheimer's disease (AD). Based on these and earlier associative studies, A beta represents a promising target for development of therapeutics focused on AD disease progression. Interestingly, a cholinesterase inhibitor currently in clinical trials, phenserine, has been shown to inhibit production of both amyloid precursor protein (APP) and A beta. We have shown that this inhibition occurs at the post-transcriptional level with a specific blocking of the synthesis of APP relative to total protein synthesis (Shaw et al., 2001). However, the dose of phenserine necessary to block APP production is far higher than that needed to elicit its anticholinesterase activity, and it is these latter actions that are dose limiting in vivo. The focus of this study was to screen 144 analogs of phenserine to identify additional small molecules that inhibit APP protein synthesis, and thereby A beta production, without possessing potent acetylcholinesterase (AChE) inhibitory activity. An enzyme-linked immunosorbent assay was used to identify analogs capable of suppressing APP production following treatment of human neuroblastoma cells with 20 muM of compound. Eight analogs were capable of dose dependently reducing APP and A beta production without causing cell toxicity in further studies. Several of these analogs had little to no AChE activities. Translation of APP and A beta actions to mice was demonstrated with one agent. They thus represent interesting lead molecules for assessment in animal models, to define their tolerance and utility as potential AD therapeutics.
ESTHER : Utsuki_2006_J.Pharmacol.Exp.Ther_318_855
PubMedSearch : Utsuki_2006_J.Pharmacol.Exp.Ther_318_855
PubMedID: 16690718

Title : Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent - Greig_2005_Proc.Natl.Acad.Sci.U.S.A_102_17213
Author(s) : Greig NH , Utsuki T , Ingram DK , Wang Y , Pepeu G , Scali C , Yu QS , Mamczarz J , Holloway HW , Giordano T , Chen D , Furukawa K , Sambamurti K , Brossi A , Lahiri DK
Ref : Proc Natl Acad Sci U S A , 102 :17213 , 2005
Abstract : Like acetylcholinesterase, butyrylcholinesterase (BChE) inactivates the neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in Alzheimer's disease, which is characterized by a cholinergic deficit. Potent, reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed based on binding domain structures to help elucidate the role of this enzyme in the central nervous system. In rats, cymserine analogs caused long-term inhibition of brain BChE and elevated extracellular ACh levels, without inhibitory effects on acetylcholinesterase. In rat brain slices, selective BChE inhibition augmented long-term potentiation. These compounds also improved the cognitive performance (maze navigation) of aged rats. In cultured human SK-N-SH neuroblastoma cells, intra- and extracellular beta-amyloid precursor protein, and secreted beta-amyloid peptide levels were reduced without affecting cell viability. Treatment of transgenic mice that overexpressed human mutant amyloid precursor protein also resulted in lower beta-amyloid peptide brain levels than controls. Selective, reversible inhibition of brain BChE may represent a treatment for Alzheimer's disease, improving cognition and modulating neuropathological markers of the disease.
ESTHER : Greig_2005_Proc.Natl.Acad.Sci.U.S.A_102_17213
PubMedSearch : Greig_2005_Proc.Natl.Acad.Sci.U.S.A_102_17213
PubMedID: 16275899

Title : Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus - Nierman_2005_Nature_438_1151
Author(s) : Nierman WC , Pain A , Anderson MJ , Wortman JR , Kim HS , Arroyo J , Berriman M , Abe K , Archer DB , Bermejo C , Bennett J , Bowyer P , Chen D , Collins M , Coulsen R , Davies R , Dyer PS , Farman M , Fedorova N , Feldblyum TV , Fischer R , Fosker N , Fraser A , Garcia JL , Garcia MJ , Goble A , Goldman GH , Gomi K , Griffith-Jones S , Gwilliam R , Haas B , Haas H , Harris D , Horiuchi H , Huang J , Humphray S , Jimenez J , Keller N , Khouri H , Kitamoto K , Kobayashi T , Konzack S , Kulkarni R , Kumagai T , Lafon A , Latge JP , Li W , Lord A , Lu C , Majoros WH , May GS , Miller BL , Mohamoud Y , Molina M , Monod M , Mouyna I , Mulligan S , Murphy L , O'Neil S , Paulsen I , Penalva MA , Pertea M , Price C , Pritchard BL , Quail MA , Rabbinowitsch E , Rawlins N , Rajandream MA , Reichard U , Renauld H , Robson GD , Rodriguez de Cordoba S , Rodriguez-Pena JM , Ronning CM , Rutter S , Salzberg SL , Sanchez M , Sanchez-Ferrero JC , Saunders D , Seeger K , Squares R , Squares S , Takeuchi M , Tekaia F , Turner G , Vazquez de Aldana CR , Weidman J , White O , Woodward J , Yu JH , Fraser C , Galagan JE , Asai K , Machida M , Hall N , Barrell B , Denning DW
Ref : Nature , 438 :1151 , 2005
Abstract : Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.
ESTHER : Nierman_2005_Nature_438_1151
PubMedSearch : Nierman_2005_Nature_438_1151
PubMedID: 16372009
Gene_locus related to this paper: aspfc-b0xp50 , aspfc-b0xu40 , aspfc-b0xzj6 , aspfc-dpp5 , aspfu-apth1 , aspfu-axe1 , aspfu-CBPYA , aspfu-faec , aspfu-kex1 , aspfu-ppme1 , aspfu-q4wa39 , aspfu-q4wa78 , aspfu-q4wf56 , aspfu-q4wg73 , aspfu-q4wk44 , aspfu-q4wkh6 , aspfu-q4wnx3 , aspfu-q4wpb9 , aspfu-q4wqv2 , aspfu-q4wub2 , aspfu-q4wxr1 , aspfu-q4x0n6 , aspfu-q4x1n0 , aspfu-q5vjg7 , neofi-a1cwa6 , neofi-a1dfr9 , aspfm-a0a084bf80 , aspfu-fmac

Title : An unbiased cDNA library prepared from isolated Aplysia sensory neuron processes is enriched for cytoskeletal and translational mRNAs - Moccia_2003_J.Neurosci_23_9409
Author(s) : Moccia R , Chen D , Lyles V , Kapuya E , E Y , Kalachikov S , Spahn CM , Frank J , Kandel ER , Barad M , Martin KC
Ref : Journal of Neuroscience , 23 :9409 , 2003
Abstract : Local protein synthesis is required for long-lasting synapse-specific plasticity in cultured Aplysia sensorimotor synapses. To identify synaptically localized mRNAs, we prepared a cDNA library from isolated sensory neurites. By sequence analysis, we estimate that the library contains 263 distinct mRNAs, with 98 of these mRNAs constituting 70% of all clones. The localized transcripts are enriched for mRNAs encoding cytoskeletal elements and components of the translational machinery. In situ hybridization confirms that the mRNAs for at least eight of these transcripts are present in distal neurites. Immunocytochemistry reveals that serotonin regulates the translation of one of the localized mRNAs, that encoding alpha1-tubulin. Our identification of mRNAs encoding cytoskeletal elements suggests that local protein synthesis is required for the growth of new synaptic connections associated with persistent synaptic strengthening. Our finding of mRNAs encoding components of the translational machinery suggests that local protein synthesis serves to increase the translational capacity of synapses.
ESTHER : Moccia_2003_J.Neurosci_23_9409
PubMedSearch : Moccia_2003_J.Neurosci_23_9409
PubMedID: 14561869

Title : Nicotine reduces the secretion of Alzheimer's beta-amyloid precursor protein containing beta-amyloid peptide in the rat without altering synaptic proteins - Lahiri_2002_Ann.N.Y.Acad.Sci_965_364
Author(s) : Lahiri DK , Utsuki T , Chen D , Farlow MR , Shoaib M , Ingram DK , Greig NH
Ref : Annals of the New York Academy of Sciences , 965 :364 , 2002
Abstract : Alzheimer's disease (AD) is characterized by cerebrovascular deposition of the amyloid beta-peptide (A beta), which is derived from a larger beta-amyloid precursor protein (beta APP). Altered metabolism of beta APP, resulting in increased A beta production, appears central in the neuropathology of AD. The processing of the holoprotein beta APP by different "secretase" enzymes results in three major carboxyl-truncated species. One species, which results from the cleavage of beta APP by gamma-secretase, is secreted into the cerebrospinal fluid (CSF) and is called sAPP gamma as it contains an intact A beta domain. Moreover, AD is characterized by cholinergic dysfunction and the loss of synaptic proteins. Reports of an inverse relation between nicotine intake, due to cigarette smoking, and the incidence of AD prompted us to investigate the effects of nicotine on beta APP processing and synaptic proteins in rats and in cell culture. Nicotine, 1 and 8 mg/kg/day, doses commensurate with cigarette smoking, and a higher but well tolerated dose, respectively, was administered over 14 days to rats. Levels of sAPP in the CSF sample were evaluated by Western blot analysis. The higher dose significantly increased levels of total sAPP; however, both doses significantly reduced sAPP gamma, which contains the amyloidogenic portion of A beta. These actions were blocked by nicotinic receptor antagonism. Nicotinic antagonists alone had no effect on either total sAPP or sAPP gamma levels in CSF. Nicotine did not significantly change the intracellular levels of total beta APP in rat brain extracts, which is consistent with neuronal cell culture data. Similarly, levels of vesicular protein, such as synaptophysin, and presynaptic terminal protein SNAP-25 were unaffected by nicotine treatment both in vivo and in cell culture experiments. Taken together, these results suggest that nicotine modifies beta APP processing away from the formation of potentially amyloidogenic products, without altering the levels of synaptic proteins, and that this can potentially offer therapeutic potential for Alzheimer's disease.
ESTHER : Lahiri_2002_Ann.N.Y.Acad.Sci_965_364
PubMedSearch : Lahiri_2002_Ann.N.Y.Acad.Sci_965_364
PubMedID: 12105112

Title : Distributions of nicotinic acetylcholine receptor alpha7 and beta2 subunits on cultured hippocampal neurons - Zarei_1999_Neurosci_88_755
Author(s) : Zarei MM , Radcliffe KA , Chen D , Patrick JW , Dani JA
Ref : Neuroscience , 88 :755 , 1999
Abstract : The hippocampus receives cholinergic afferents and expresses neuronal nicotinic acetylcholine receptors. In particular, the alpha7 and beta2 nicotinic subunits are highly expressed in the hippocampus. There has been controversy about the location, distribution and roles of neuronal nicotinic acetylcholine receptors [Role L. W. and Berg D. K. (1996) Neuron 16, 1077-1085; Wonnacott S. (1997) Trends Neurosci. 20, 92-98]. Using immunocytochemistry and patch-clamp techniques, we examined the density and distribution of nicotinic receptors on rat hippocampal neurons in primary tissue culture. The density and distribution of alpha7 subunits change with days in culture. Before 10 days in culture, alpha7 expression, monitored immunocytochemically, is low and nicotinic currents are small or absent. In older cultures, about two-thirds of the neurons express nicotinic currents, and alpha7 appears in small patches on the soma and out along the neuronal processes. These patches of alpha7 subunits on the surface of the neuronal processes often co-localize with the presynaptic marker, synaptotagmin. The other most common nicotinic subunit, beta2, stays confined mainly to the soma and proximal processes, and beta2 is distributed more uniformly and is not specifically localized at presynaptic areas. The two subunits, alpha7 and beta2, have different expression patterns on the surface of the cultured hippocampal neurons. Taken together with previous physiological studies, the results indicate that alpha7 subunits can be found at presynaptic terminals, and at these locations, these calcium-permeable channels may influence transmitter release.
ESTHER : Zarei_1999_Neurosci_88_755
PubMedSearch : Zarei_1999_Neurosci_88_755
PubMedID: 10363815

Title : Contributions of N-linked glycosylation to the expression of a functional alpha7-nicotinic receptor in Xenopus oocytes - Chen_1998_J.Neurochem_70_349
Author(s) : Chen D , Dang H , Patrick JW
Ref : Journal of Neurochemistry , 70 :349 , 1998
Abstract : The alpha7 subunit of the neuronal nicotinic acetylcholine receptor, when expressed in Xenopus oocytes, forms homooligomeric ligand-gated ion channels that are blocked by a snake toxin, alpha-bungarotoxin. The amino-terminal extracellular domain of the alpha7 sequence has three consensus sites for asparagine-linked glycosylation (N46DS, N90MS, and N133AS). In this study, we show that alpha7 expressed either in vivo or in vitro is a glycoprotein of 57 kDa. In addition, we demonstrate by site-directed mutagenesis that all three consensus sites are used for glycosylation. To elucidate the role(s) of asparagine-linked glycosylation in the formation and function of the alpha7 receptor, wild-type and glycosylation-deficient alpha7 subunits were expressed in COS cells and oocytes. We examined biochemical and physiological properties of expressed receptors and found that alpha7 glycosylation mutations do not affect homooligomerization and surface protein expression of the alpha7 receptor but do affect surface expression of alpha-bungarotoxin binding sites and the function of the receptor. Our data indicate that asparagine-linked glycosylation is required for the expression of a functional alpha7 receptor in oocytes.
ESTHER : Chen_1998_J.Neurochem_70_349
PubMedSearch : Chen_1998_J.Neurochem_70_349
PubMedID: 9422381

Title : The alpha-bungarotoxin-binding nicotinic acetylcholine receptor from rat brain contains only the alpha7 subunit - Chen_1997_J.Biol.Chem_272_24024
Author(s) : Chen D , Patrick JW
Ref : Journal of Biological Chemistry , 272 :24024 , 1997
Abstract : When expressed in Xenopus oocytes, the rat alpha7 subunit forms homo-oligomeric nicotinic acetylcholine receptors, which are blocked by alpha-bungarotoxin. Since the pharmacological and physiological properties of the alpha7 receptor expressed in oocytes are similar to those of the alpha-bungarotoxin-sensitive nicotinic currents recorded from neuronal preparations and the distribution patterns of alpha7 mRNA and alpha-bungarotoxin-binding sites in the rat brain are very similar, alpha7 is thought to be the main component of the alpha-bungarotoxin-binding nicotinic receptor in the mammalian brain. However, while alpha7 is found in purified alpha-bungarotoxin-binding complexes from rat brain or PC12 cells, other proteins copurify with it. Therefore, the question whether alpha7 forms a homo-oligomeric alpha-bungarotoxin-binding nicotinic receptor in the mammalian brain remains. We have developed and characterized affinity-purified polyclonal antibodies and used these antibodies in Western blot analyses of alpha-bungarotoxin-binding proteins purified from rat brains. We report here that our experimental data support the current working hypothesis that the alpha-bungarotoxin-binding nicotinic receptor is a homo-oligomer of alpha7 subunits in the rat brain.
ESTHER : Chen_1997_J.Biol.Chem_272_24024
PubMedSearch : Chen_1997_J.Biol.Chem_272_24024
PubMedID: 9295355

Title : Antinociceptive activity of calcitonin and central cholinergic system: behavioural and neurochemical analyses - Chen_1995_Biochem.Pharmacol_49_1623
Author(s) : Chen D , Lee KH
Ref : Biochemical Pharmacology , 49 :1623 , 1995
Abstract : Behavioural and neurochemical analyses were carried out to investigate the relationship between the antinociceptive activity of porcine calcitonin (pCT) and central cholinergic system in mice and rats. Behavioural studies revealed that the antinociceptive activity of pCT encapsulated in sulphatide-containing liposomes injected intravenously into mice was significantly inhibited by atropine sulphate, but not by atropine methylnitrate, and potentiated by physostigmine, but not by neostigmine. Neurochemical studies using rat brain synaptosomes showed that pCT stimulated synaptosomal sodium-dependent high-affinity choline uptake, which was found to be closely associated with acetylcholine (ACh) synthesis (50-60%). This effect was concentration-dependent. In addition, pCT elicited a biphasic effect on ACh release from synaptosomes with an initial brief period of stimulation and subsequent prolonged inhibition. This stimulation was not affected by atropine sulphate, but markedly reduced by incubation in the presence of diltiazem or in a calcium-free medium, indicating that the modulation of ACh release by the peptide may be mediated by calcium fluxes across the synaptosomal membrane independent of cholinergic receptor activation. However, pCT does not affect the activity of synaptosomal acetylcholinesterase. Therefore, the behavioural study in vivo with the neurochemical analysis in vitro suggests that the central cholinergic system may be involved in the antinociceptive activity of calcitonin.
ESTHER : Chen_1995_Biochem.Pharmacol_49_1623
PubMedSearch : Chen_1995_Biochem.Pharmacol_49_1623
PubMedID: 7786303