Chen P

References (27)

Title : COX-2\/sEH-mediated macrophage activation is a target for pulmonary protection in mouse models of chronic obstructive pulmonary disease - Duan_2023_Lab.Invest__100319
Author(s) : Duan JX , Guan XX , Cheng W , Deng DD , Chen P , Liu C , Zhou Y , Hammock BD , Yang HH
Ref : Lab Invest , :100319 , 2023
Abstract : Effective inhibition of macrophage activation is critical for resolving inflammation and restoring pulmonary function in patients with chronic obstructive pulmonary disease (COPD). Here, we identified the dual enhanced cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) as a novel regulator of macrophage activation in COPD. Both COX-2 and sEH were found to be increased in patients and mice with COPD, as well as in macrophages exposed to cigarette smoke extract (CSE). Pharmacological reduction of the COX-2 and sEH by PTUPB effectively prevented macrophage activation, down-regulated inflammation-related genes, and reduced lung injury, thereby improving respiratory function in a mouse model of COPD induced by cigarette smoke and lipopolysaccharide. Mechanistically, enhanced COX-2/sEH triggered the activation of the NLRP3 inflammasome, leading to the cleavage of pro-IL-1beta into its active form in macrophages and amplifying inflammatory responses. These findings demonstrate that targeting COX-2/sEH-mediated macrophage activation may be a promising therapeutic strategy for COPD. Importantly, our data support the potential use of the dual COX-2 and sEH inhibitor PTUPB as a therapeutic drug for the treatment of COPD.
ESTHER : Duan_2023_Lab.Invest__100319
PubMedSearch : Duan_2023_Lab.Invest__100319
PubMedID: 38158123

Title : Lipase-Catalyzed Phospha-Michael Addition Reactions under Mild Conditions - Xu_2022_Molecules_27_7798
Author(s) : Xu Y , Li F , Ma J , Li J , Xie H , Wang C , Chen P , Wang L
Ref : Molecules , 27 :7798 , 2022
Abstract : Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted beta-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis.
ESTHER : Xu_2022_Molecules_27_7798
PubMedSearch : Xu_2022_Molecules_27_7798
PubMedID: 36431898

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

Title : COX-2\/sEH Dual Inhibitor PTUPB Attenuates Epithelial-Mesenchymal Transformation of Alveolar Epithelial Cells via Nrf2-Mediated Inhibition of TGF-beta1\/Smad Signaling - Zhang_2022_Oxid.Med.Cell.Longev_2022_5759626
Author(s) : Zhang CY , Guan XX , Song ZH , Jiang HL , Liu YB , Chen P , Duan JX , Zhou Y
Ref : Oxid Med Cell Longev , 2022 :5759626 , 2022
Abstract : BACKGROUND: Arachidonic acid (ARA) metabolites are involved in the pathogenesis of epithelial-mesenchymal transformation (EMT). However, the role of ARA metabolism in the progression of EMT during pulmonary fibrosis (PF) has not been fully elucidated. The purpose of this study was to investigate the role of cytochrome P450 oxidase (CYP)/soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) metabolic disorders of ARA in EMT during PF. METHODS: A signal intratracheal injection of bleomycin (BLM) was given to induce PF in C57BL/6 J mice. A COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation to EMT in PF mice. In vitro experiments, murine alveolar epithelial cells (MLE12) and human alveolar epithelial cells (A549) were used to explore the roles and mechanisms of PTUPB on transforming growth factor (TGF)-beta1-induced EMT. RESULTS: PTUPB treatment reversed the increase of mesenchymal marker molecule alpha-smooth muscle actin (alpha-SMA) and the loss of epithelial marker molecule E-cadherin in lung tissue of PF mice. In vitro, COX-2 and sEH protein levels were increased in TGF-beta1-treated alveolar epithelial cells (AECs). PTUPB decreased the expression of alpha-SMA and restored the expression of E-cadherin in TGF-beta1-treated AECs, accompanied by reduced migration and collagen synthesis. Moreover, PTUPB attenuated TGF-beta1-Smad2/3 pathway activation in AECs via Nrf2 antioxidant cascade. CONCLUSION: PTUPB inhibits EMT in AECs via Nrf2-mediated inhibition of the TGF-beta1-Smad2/3 pathway, which holds great promise for the clinical treatment of PF.
ESTHER : Zhang_2022_Oxid.Med.Cell.Longev_2022_5759626
PubMedSearch : Zhang_2022_Oxid.Med.Cell.Longev_2022_5759626
PubMedID: 35509835

Title : Resistance of Bemisia tabaci Mediterranean (Q-biotype) to pymetrozine: resistance risk assessment, cross-resistance to six other insecticides and detoxification enzyme assay - Wang_2021_Pest.Manag.Sci_77_2114
Author(s) : Wang F , Liu J , Shuai S , Miao C , Chi B , Chen P , Wang K , Li H , Liu Y
Ref : Pest Manag Sci , 77 :2114 , 2021
Abstract : BACKGROUND: The whitefly Bemisia tabaci (Gennadius) is a severe pest that affects many field and glasshouse crops worldwide and has developed resistance to insecticides in most chemical classes. Pymetrozine, a neuroactive pyridine azomethine, is selective towards piercing-sucking pests in Hemiptera. The aim of this study was to assess the resistance of B. tabaci Mediterranean (MED) to pymetrozine in the laboratory. RESULTS: After successive selection of 18 generations of MED in the presence of using pymetrozine, there was an 11.28-fold increase in the median lethal concentration (LC(50) ). When the realized heritability (h(2) ) of B. tabaci to pymetrozine in the field was assumed to be the value estimated in the laboratory (h(2) = 0.1360) and the mortality was 70-90%, only 7.2-15.9 generations were estimated to be needed to obtain a ten-fold increase in resistance to pymetrozine. Compared with the susceptible populations (G(0) ), the Pyme-SEL strain (G(18) ) showed a low level of cross-resistance to neonicotinoids (nitenpyram, imidacloprid, acetamiprid, and thiamethoxam) and no cross-resistance to chlorpyrifos or abamectin. With the G(0) and the Pyme-SEL strains (G(11) and G(18) ) as test strains, the activity of multifunctional oxidase exhibited the greatest increase during selection, while the activities of carboxylesterase and glutathione-S-transferase did not change significantly. CONCLUSION: This study show that a potential risk of development of resistance to pymetrozine exists in B. tabaci after continuous application. During the application of pymetrozine to control B. tabaci in the field, the frequency of its use in combination with neonicotinoids should be used with caution. 2020 Society of Chemical Industry.
ESTHER : Wang_2021_Pest.Manag.Sci_77_2114
PubMedSearch : Wang_2021_Pest.Manag.Sci_77_2114
PubMedID: 33332688

Title : AChR myasthenia gravis switching to MuSK or double antibody positive myasthenia gravis in two children and literature review - Lu_2020_Neuromuscul.Disord__
Author(s) : Lu Y , Ran H , Yang W , Ma Q , Qiu L , Ou C , Chen P , Lin Z , Liu W
Ref : Neuromuscular Disorders , : , 2020
Abstract : Muscle-specific tyrosine kinase antibody (MuSK-Ab) and acetylcholine receptor antibody (AChR-Ab) coexistence in myasthenia gravis (MG) is very rare. In this report, two children with AChR-Ab switching to double antibody positive MG (DP-MG) or MuSK-Ab positive MG (MuSK-MG) are described. Six similar cases were found in the literature via online database search. Therefore, this study describes eight patients in total, six female and two male. The average age of onset was 7.25 +/- 5.95 years. Four AChR-MG patients switched to DP-MG with no known precipitating factor and four switched after thymectomy (two to MuSK-MG and two to DP-MG). After the serological switch, the patients transitioned to the phenotype of MuSK-MG and responded poorly to cholinesterase inhibitors and well to corticosteroids and plasma exchange.
ESTHER : Lu_2020_Neuromuscul.Disord__
PubMedSearch : Lu_2020_Neuromuscul.Disord__
PubMedID: 32387283

Title : Thiol inhibition of Hg cold vapor generation in SnCl2\/NaBH4 system: A homogeneous bioassay for H2O2\/glucose and butyrylcholinesterase\/pesticide sensing by atomic spectrometry - Chen_2020_Anal.Chim.Acta_1111_8
Author(s) : Chen P , Zheng C , Chen C , Huang K , Wang X , Hu P , Geng J
Ref : Anal Chim Acta , 1111 :8 , 2020
Abstract : Recently, the use of atomic spectrometry (AS) for biochemical analysis has attracted considerable attention due to its high sensitivity, selectivity and anti-interference ability. In this work, we conducted a detailed study on a phenomenon of thiol inhibition of mercury (Hg(2+)) cold vapor generation (CVG) and found L-cysteine (L-Cys), glutathione (GSH), dithiothreitol, N-Acetyl-L-cysteine, 3-mercaptopropionic acid, beta-mercaptoethanol, and NaI can inhibit the CVG of Hg(2+), while EDTA has no inhibitory effect. Furthermore, changing the content of -SH can effectively adjust the CVG atomic fluorescence spectrometer (CVG-AFS) signal of Hg(2+). As as a consequence, an AS-based homogeneous bioassay was constructed by adjusting the oxidation ratio and production quantity of -SH in the system. The quantitative analysis of the system was demonstrated by using AFS as a representative detector. Hydrogen peroxide (H2O2) and glucose were used as representative analytes for the validation of Hg(2+) atomic fluorescence signal turn-off strategy, and butyrylcholinesterase (BChE) as well as parathion (organophosphorus pesticides, OPs) as utilized as representative targets for the signal turn-on strategy. Under optimal experimental conditions, the homogeneous CVG-AFS sensor can be successfully used to detect 3 muM H2O2, 30 muM glucose, 0.25 U/L BChE, and 0.4 mug/mL parathion. In addition, the detection results of glucose and BChE in human serum samples agreed well with those obtained by using glucometer and kit, showing the promising potential of this method for practical applications. Therefore, this work provides a perspective for the construction of AS-based homogeneous bioassays and shows great potential for the detection of biomarkers.
ESTHER : Chen_2020_Anal.Chim.Acta_1111_8
PubMedSearch : Chen_2020_Anal.Chim.Acta_1111_8
PubMedID: 32312400

Title : A COX-2\/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation - Yang_2020_Theranostics_10_4749
Author(s) : Yang HH , Duan JX , Liu SK , Xiong JB , Guan XX , Zhong WJ , Sun CC , Zhang CY , Luo XQ , Zhang YF , Chen P , Hammock BD , Hwang SH , Jiang JX , Zhou Y , Guan CX
Ref : Theranostics , 10 :4749 , 2020
Abstract : Rationale: Dysregulation of arachidonic acid (ARA) metabolism results in inflammation; however, its role in acute lung injury (ALI) remains elusive. In this study, we addressed the role of dysregulated ARA metabolism in cytochromes P450 (CYPs) /cyclooxygenase-2 (COX-2) pathways in the pathogenesis of lipopolysaccharide (LPS)-induced ALI in mice. Methods: The metabolism of CYPs/COX-2-derived ARA in the lungs of LPS-induced ALI was investigated in C57BL/6 mice. The COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation in ALI. Primary murine macrophages were used to evaluate the underlying mechanism of PTUPB involved in the activation of NLRP3 inflammasome in vitro. Results: Dysregulation of CYPs/COX-2 metabolism of ARA occurred in the lungs and in primary macrophages under the LPS challenge. Decrease mRNA expression of Cyp2j9, Cyp2j6, and Cyp2j5 was observed, which metabolize ARA into epoxyeicosatrienoic acids (EETs). The expressions of COX-2 and soluble epoxide hydrolase (sEH), on the other hand, was significantly upregulated. Pre-treatment with the dual COX-2 and sEH inhibitor, PTUPB, attenuated the pathological injury of lung tissues and reduced the infiltration of inflammatory cells. Furthermore, PTUPB decreased the pro-inflammatory factors, oxidative stress, and activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in LPS-induced ALI mice. PTUPB pre-treatment remarkably reduced the activation of macrophages and NLRP3 inflammasome in vitro. Significantly, both preventive and therapeutic treatment with PTUPB improved the survival rate of mice receiving a lethal dose of LPS. Conclusion: The dysregulation of CYPs/COX-2 metabolized ARA contributes to the uncontrolled inflammatory response in ALI. The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation.
ESTHER : Yang_2020_Theranostics_10_4749
PubMedSearch : Yang_2020_Theranostics_10_4749
PubMedID: 32308747

Title : Bemisia tabaci (Hemiptera: Aleyrodidae) Insecticide Resistance in Shandong Province, China - Wang_2020_J.Econ.Entomol_113_911
Author(s) : Wang F , Liu J , Chen P , Li HY , Ma JJ , Liu YJ , Wang K
Ref : J Econ Entomol , 113 :911 , 2020
Abstract : The Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) complex comprises important pests and virus vectors in agricultural crops worldwide. In China, B. tabaci has spread to more than 20 provinces and caused severe losses of vegetables, fruits, and ornamental plants. However, B. tabaci has developed resistance to many insecticidal classes in Shandong Province, eastern China. In this study, we investigated the cryptic species, insecticide resistance and detoxifying enzymes of B. tabaci from six representative locations exhibiting severe damage in Shandong. At four of the six locations, B. tabaci Mediterranean (MED) comprised 100% of the samples collected. In a further two locations, species composition was predominantly (>94%) MED with B. tabaci Middle East-Asia Minor 1 (MEAM1), comprising a low proportion (<6%) of the samples collected. For all field populations, avermectin was the most effective insecticide against adult B. tabaci, pyriproxyfen had a significant effect on B. tabaci eggs and field populations were susceptible to pymetrozine. Six field populations of B. tabaci have developed low-to-moderate resistance to neonicotinoids. The detoxifying enzyme activity of carboxylesterase, glutathione S-transferase, and multifunctional oxidase were quantified. Multifunctional oxidase and glutathione S-transferase activity were positively correlated with insecticide resistance in several B. tabaci populations.
ESTHER : Wang_2020_J.Econ.Entomol_113_911
PubMedSearch : Wang_2020_J.Econ.Entomol_113_911
PubMedID: 31800055

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

Title : Carboxylesterase-Cleavable Biotinylated Nanoparticle for Tumor-Dual Targeted Imaging - Chen_2019_Theranostics_9_7359
Author(s) : Chen P , Kuang W , Zheng Z , Yang S , Liu Y , Su L , Zhao K , Liang G
Ref : Theranostics , 9 :7359 , 2019
Abstract : Near-infrared (NIR) nanoprobes with fluorescence "Turn-On" property are advantageous in cancer diagnosis but, to the best of our knowledge, "smart" nanoprobe that simultaneously targets both biotin receptor and carboxylesterase (CES) for HepG2 tumor-dual targeted imaging has not been reported. Methods: Using CBT-Cys click condensation reaction, we rationally designed a "smart" NIR fluorescence probe H2N-Cys(StBu)-Lys(Biotin)-Ser(Cy5.5)-CBT (NIR-CBT) and used it to facilely prepare the fluorescence-quenched nanoparticle NIR-CBT-NP. Results: In vitro results indicated that, after NIR-CBT-NP was incubated with CES for 6 h, its fluorescence was turned "On" by 69 folds. Cell experiments verified that NIR-CBT-NP was uptaken by HepG2 cells via biotin receptor-assisted endocytosis and its fluorescence was turned "On" by intracellular CES hydrolysis. Moreover, NIR-CBT-NP was successfully applied to image both biotin receptor- and CES-overexpressing HepG2 tumors. Conclusion: Fluorescence-quenched nanoparticle NIR-CBT-NP was facilely prepared to actively target biotin receptor-overexpressing HepG2 cancer cells and turn the fluorescence "On" by intracellular CES hydrolysis for tumor-dual targeted imaging. We anticipate that our fluorescence "Turn-On" nanoparticle could be applied for liver cancer diagnosis in clinic in the near future.
ESTHER : Chen_2019_Theranostics_9_7359
PubMedSearch : Chen_2019_Theranostics_9_7359
PubMedID: 31695773

Title : Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells - Tang_2018_Gene_667_95
Author(s) : Tang L , Wang G , Jiang L , Chen P , Wang W , Chen J , Wang L
Ref : Gene , 667 :95 , 2018
Abstract : OBJECTIVES: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Three recognized genes (LDLR, APOB and PCSK9) present in only 20-30% of patients with possible FH cases. Additional FH-causing genes need to be explored. The present study found an isolated gene change, sEH R287Q, in a core family of FH. In this study, we aimed to investigate the roles of R287Q on sEH expression and on LDLR expression, LDL binding to LDLR and LDL internalization. MATERIALS AND METHODS: 167 lipid-related genes of a core FH family were sequenced using a gene-capture chip. Through carrier dependent protein expression, the expression level (western blot), hydrolase activity (fluorescent chemistry) and intracellular localization (immunofluorescence and Confocal Laser Scanning Microscope) of recombinant sEH R287Q in cultured BEL-7402 cells were conducted. The effect of wild type and R287Q of sEH on LDLR expression, LDL binding to LDLR and LDL internalization were also conducted through Flow Cytometry. RESULTS: sEH R287Q was the only gene changes among 167 lipid-related genes in the FH core family. Both expression level and hydrolase activity of recombinant sEH R287Q in cultured cells were significantly declined compared with that of the wild type sEH. sEH R287Q also decreased the binding of LDL to LDLR and LDL internalization and had no effect on cell-surface LDLR protein level. CONCLUSION: Our results suggest that sEH R287Q may have a role in the elevation of blood LDL in FH. The exactly role of sEH R287Q on FH deserves further study.
ESTHER : Tang_2018_Gene_667_95
PubMedSearch : Tang_2018_Gene_667_95
PubMedID: 29665449
Gene_locus related to this paper: human-EPHX2

Title : Neuropsychiatric Symptoms and Caregiver Burden in Individuals With Alzheimer's Disease: The TEAM-AD VA Cooperative Study - Chen_2018_J.Geriatr.Psychiatry.Neurol__891988718783897
Author(s) : Chen P , Guarino PD , Dysken MW , Pallaki M , Asthana S , Llorente MD , Love S , Vertrees JE , Schellenberg GD , Sano M
Ref : J Geriatr Psychiatry Neurol , :891988718783897 , 2018
Abstract : OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms (NPS) in mild-to-moderate Alzheimer disease (AD) and their association with caregiver burden. METHODS: Secondary analyses of baseline data from the Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD) (N=613). Neuropsychiatric Inventory were used to measure severity of NPS and caregiver activity survey to measure caregiver burden. RESULTS: A total of 87% of patients displayed at least 1 NPS; 70% displayed clinically meaningful NPS. The most common symptoms were apathy (47%), irritability (44%), agitation (42%), and depression (40%). Those with moderate AD had more severe NPS than those with mild AD ( P = .03). Neuropsychiatric symptoms were significantly associated with caregiver time after adjusting for age, education, cognitive function, and comorbidity ( P-value < .0001) with every point increase in NPS associated with a 10-minute increase in caregiver time. CONCLUSION: Neuropsychiatric symptoms were prevalent in both mild and moderate AD, even in patients receiving treatment with an acetylcholinesterase inhibitors, and were more severe in moderate AD and associated with greater caregiver time.
ESTHER : Chen_2018_J.Geriatr.Psychiatry.Neurol__891988718783897
PubMedSearch : Chen_2018_J.Geriatr.Psychiatry.Neurol__891988718783897
PubMedID: 29966477

Title : Hydrolysis mechanism of carbendazim hydrolase from the strain Microbacterium sp. djl-6F - Lei_2017_J.Environ.Sci.(China)_54_171
Author(s) : Lei J , Wei S , Ren L , Hu S , Chen P
Ref : J Environ Sci (China) , 54 :171 , 2017
Abstract : The carbendazim (MBC) hydrolyzing enzyme gene was cloned and heterologously expressed in Escherichia coli BL21 (DE3) from a newly isolated MBC-degrading bacterium strain Microbacterium sp. strain djl-6F. High performance liquid chromatography-mass spectrometry (HPLC-MS) analysis revealed that purified MheI-6F protein catalyzes direct hydrolysis of MBC into 2-aminobenzimidazole (2-AB) with a high turnover rate and moderate affinity (K(m) of 6.69micromol/L and k(cat) of 160.88/min) without the need for any cofactors. The optimal catalytic condition of MheI-6F was identified as 45 degreesC, pH7.0. The enzymatic activity of MheI-6F was found to be diminished by metal ions, and strongly inhibited by sodium dodecyl sulfate (SDS). Through generating amino acid mutations in MheI-6F, Cys16 and Cys222 were identified as the catalytic groups that are essential for the hydrolysis of MBC. This is the first report on the biodegradation of MBC at the enzymatice level.
ESTHER : Lei_2017_J.Environ.Sci.(China)_54_171
PubMedSearch : Lei_2017_J.Environ.Sci.(China)_54_171
PubMedID: 28391926
Gene_locus related to this paper: 9acto-c8cp46

Title : Bicyclic [3.3.0]-Octahydrocyclopenta[c]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease - Cioffi_2015_J.Med.Chem_58_5863
Author(s) : Cioffi CL , Racz B , Freeman EE , Conlon MP , Chen P , Stafford DG , Schwarz DM , Zhu L , Kitchen DB , Barnes KD , Dobri N , Michelotti E , Cywin CL , Martin WH , Pearson PG , Johnson G , Petrukhin K
Ref : Journal of Medicinal Chemistry , 58 :5863 , 2015
Abstract : Antagonists of retinol-binding protein 4 (RBP4) impede ocular uptake of serum all-trans retinol (1) and have been shown to reduce cytotoxic bisretinoid formation in the retinal pigment epithelium (RPE), which is associated with the pathogenesis of both dry age-related macular degeneration (AMD) and Stargardt disease. Thus, these agents show promise as a potential pharmacotherapy by which to stem further neurodegeneration and concomitant vision loss associated with geographic atrophy of the macula. We previously disclosed the discovery of a novel series of nonretinoid RBP4 antagonists, represented by bicyclic [3.3.0]-octahydrocyclopenta[c]pyrrolo analogue 4. We describe herein the utilization of a pyrimidine-4-carboxylic acid fragment as a suitable isostere for the anthranilic acid appendage of 4, which led to the discovery of standout antagonist 33. Analogue 33 possesses exquisite in vitro RBP4 binding affinity and favorable drug-like characteristics and was found to reduce circulating plasma RBP4 levels in vivo in a robust manner (>90%).
ESTHER : Cioffi_2015_J.Med.Chem_58_5863
PubMedSearch : Cioffi_2015_J.Med.Chem_58_5863
PubMedID: 26181715

Title : Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial - Dysken_2014_JAMA_311_33
Author(s) : Dysken MW , Sano M , Asthana S , Vertrees JE , Pallaki M , Llorente M , Love S , Schellenberg GD , McCarten JR , Malphurs J , Prieto S , Chen P , Loreck DJ , Trapp G , Bakshi RS , Mintzer JE , Heidebrink JL , Vidal-Cardona A , Arroyo LM , Cruz AR , Zachariah S , Kowall NW , Chopra MP , Craft S , Thielke S , Turvey CL , Woodman C , Monnell KA , Gordon K , Tomaska J , Segal Y , Peduzzi PN , Guarino PD
Ref : Jama , 311 :33 , 2014
Abstract : IMPORTANCE: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures.
RESULTS: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00235716.
ESTHER : Dysken_2014_JAMA_311_33
PubMedSearch : Dysken_2014_JAMA_311_33
PubMedID: 24381967

Title : Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes - Biftu_2014_J.Med.Chem_57_3205
Author(s) : Biftu T , Sinha-Roy R , Chen P , Qian X , Feng D , Kuethe JT , Scapin G , Gao YD , Yan Y , Krueger D , Bak A , Eiermann G , He J , Cox J , Hicks J , Lyons K , He H , Salituro G , Tong S , Patel S , Doss G , Petrov A , Wu J , Xu SS , Sewall C , Zhang X , Zhang B , Thornberry NA , Weber AE
Ref : Journal of Medicinal Chemistry , 57 :3205 , 2014
Abstract : In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.
ESTHER : Biftu_2014_J.Med.Chem_57_3205
PubMedSearch : Biftu_2014_J.Med.Chem_57_3205
PubMedID: 24660890
Gene_locus related to this paper: human-DPP4

Title : Genome sequence of duck pathogen Mycoplasma anatis strain 1340 - Guo_2011_J.Bacteriol_193_5883
Author(s) : Guo Z , Chen P , Ren P , Kuang S , Zhou Z , Li Z , Liu M , Shi D , Xiao Y , Wang X , Zhou R , Jin H , Bi D
Ref : Journal of Bacteriology , 193 :5883 , 2011
Abstract : Mycoplasma anatis, a member of the class Mollicutes, is the causative agent of a contagious infectious disease of domestic ducklings, wild birds, and eggs. Increasing reports show that coinfection of M. anatis with Escherichia coli results in substantial economic impacts on the duck farms in China. Here, we announce the first genome sequence of M. anatis.
ESTHER : Guo_2011_J.Bacteriol_193_5883
PubMedSearch : Guo_2011_J.Bacteriol_193_5883
PubMedID: 21952548

Title : Poster: Deviance-based negativity in the conscious rat: Modulation by nicotinic agonists -
Author(s) : Digavalli S , Chen P , Lodge N
Ref : Biochemical Pharmacology , 82 :1039 , 2011
PubMedID:

Title : Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides - Chen_2009_Hum.Mutat_30_49
Author(s) : Chen P , Jou YS , Fann CS , Chen JW , Chung CM , Lin CY , Wu SY , Kang MJ , Chen YC , Jong YS , Lo HM , Kang CS , Chen CC , Chang HC , Huang NK , Wu YL , Pan WH
Ref : Hum Mutat , 30 :49 , 2009
Abstract : Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG.
ESTHER : Chen_2009_Hum.Mutat_30_49
PubMedSearch : Chen_2009_Hum.Mutat_30_49
PubMedID: 18649389

Title : Imidazopiperidine amides as dipeptidyl peptidase IV inhibitors for the treatment of diabetes - Chen_2007_Bioorg.Med.Chem.Lett_17_5853
Author(s) : Chen P , Caldwell CG , Mathvink RJ , Leiting B , Marsilio F , Patel RA , Wu JK , He H , Lyons KA , Thornberry NA , Weber AE
Ref : Bioorganic & Medicinal Chemistry Lett , 17 :5853 , 2007
Abstract : A series of substituted imidazopiperidine amides has been prepared and evaluated for inhibition of dipeptidyl peptidase IV (DPP-4). Substitution at the 1- and 3-positions produced increased selectivity for DPP-4 relative to DPP-8 and DPP-9. Compounds in this series had IC(50) values as low as 5.8 nM for inhibition of DPP-4.
ESTHER : Chen_2007_Bioorg.Med.Chem.Lett_17_5853
PubMedSearch : Chen_2007_Bioorg.Med.Chem.Lett_17_5853
PubMedID: 17869513

Title : Donepezil primarily attenuates scopolamine-induced deficits in psychomotor function, with moderate effects on simple conditioning and attention, and small effects on working memory and spatial mapping - Lindner_2006_Psychopharmacology.(Berl)_188_629
Author(s) : Lindner MD , Hogan JB , Hodges DB, Jr. , Orie AF , Chen P , Corsa JA , Leet JE , Gillman KW , Rose GM , Jones KM , Gribkoff VK
Ref : Psychopharmacology (Berl) , 188 :629 , 2006
Abstract : RATIONALE: Alzheimer's dementia (AD) patients have profound deficits in cognitive and social functions, mediated in part by a decline in cholinergic function. Acetylcholinesterase inhibitors (AChEI) are the most commonly prescribed treatment for the cognitive deficits in AD patients, but their therapeutic effects are small, and it is still not clear if they primarily affect attention, memory, or some other cognitive/behavioral functions. OBJECTIVES: The objective of the present experiments was to explore the effects of donepezil (Aricepttrade mark), an AChEI, on behavioral deficits related exclusively to cholinergic dysfunction. MATERIALS AND
METHODS: The effects of donepezil were assessed in Sprague-Dawley rats with scopolamine-induced deficits in a battery of cognitive/behavioral tests.
RESULTS: Scopolamine produced deficits in contextual and cued fear conditioning, the 5-choice serial reaction time test, delayed nonmatching to position, the radial arm maze, and the Morris water maze. Analyses of the pattern and size of the effects revealed that donepezil produced very large effects on scopolamine-induced deficits in psychomotor function (approximately 20-50% of the variance), moderate-sized effects on scopolamine-induced deficits in simple conditioning and attention (approximately 3-10% of the variance), but only small effects on scopolamine-induced deficits in higher cognitive functions of working memory and spatial mapping (approximately 1% of the variance).
CONCLUSIONS: These results are consistent with the limited efficacy of donepezil on higher cognitive function in AD patients, and suggest that preclinical behavioral models could be used not only to determine if novel treatments have some therapeutic potential, but also to predict more precisely what the pattern and size of the effects might be.
ESTHER : Lindner_2006_Psychopharmacology.(Berl)_188_629
PubMedSearch : Lindner_2006_Psychopharmacology.(Berl)_188_629
PubMedID: 17004085

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Characteristics of trapping various organophosphorus pesticides with a ferritin reactor of shark liver (Sphyrna zygaena) - Huang_2005_Anal.Chem_77_1920
Author(s) : Huang HQ , Xiao ZQ , Lin QM , Chen P
Ref : Analytical Chemistry , 77 :1920 , 2005
Abstract : A reactor is composed of liver ferritin of Sphyrna zygaena (SZLF) and an oscillating bag. A reactive procedure for trapping various organphosphorus pesticides (OPs) with the SZLF reactor in the flowing water is described in detail, showing the maximal trapping numbers of 28 +/-1.0 dichlorovos/SZLF, 42 +/- 1.0 dimethoate/SZLF, and 55 +/- 1.0 methamido-phos/SZLF determined by a improved spectrophotometric method in 12 h. In addition, it is found that the OP numbers trapped by the reactor increase along with the incubation time and its concentration increment in the flowing water (or seawater), respectively. This trapping capacity is considered to depend on the composition of amino acids on the surface of the ferritin shell interior rather than the available volume within the shell. A novel pathway for trapping various OPs with the ferritin is suggested in reference to unstable characteristics of the protein subunits. We claim that the ferritin reactor will be employed to monitor the contamination level of various OPs in the flowing water continuously.
ESTHER : Huang_2005_Anal.Chem_77_1920
PubMedSearch : Huang_2005_Anal.Chem_77_1920
PubMedID: 15762606

Title : Determination and analysis of single nucleotide polymorphisms and haplotype structure of the human carboxylesterase 2 gene - Wu_2004_Pharmacogenet_14_595
Author(s) : Wu MH , Chen P , Wu X , Liu W , Strom S , Das S , Cook EH, Jr. , Rosner GL , Dolan ME
Ref : Pharmacogenetics , 14 :595 , 2004
Abstract : Carboxylesterases are members of the serine esterase super family important in the metabolism of a wide variety of substrates, including xenobiotics and prodrugs. There are two known carboxylesterases expressed in human liver, small intestine and other tissues, carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2). The aim of this study was to identify polymorphisms in the CES2 gene and determine whether these polymorphisms affect expression levels of CES2 or rate of metabolism of irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin). Microsome samples prepared from liver tissues of 78 normal individuals were used to determine the rate of hydrolysis of irinotecan and procaine (an anaesthetic hydrolysed by CES2 but not CES1). The rate of hydrolysis of irinotecan is highly variable among individuals, ranging from 2.7-138 pmol/mg protein/h (mean +/- SD 26.0 +/- 22.9). Fifteen single nucleotide polymorphisms (SNPs) were identified, one is in an exon, 9 are in introns, three are in the 3'-untranslated region (UTR), and two are in the 5'-flanking region. Eight of the 15 SNP loci have rare allele frequencies greater than 5%, of which three were greater than 20%. Genotyping of samples from the SNP Consortium demonstrated different distributions among African-Americans, Asian-Americans and European-Americans. We also analysed the haplotype structure and estimated linkage disequilibrium (LD). A SNP located in the 5'-UTR (5'-UTR-363) was found in LD with loci in intron 1 (Intron1 + 947, Intron1 + 1361, Intron1 + 1643). Haplotypes with homozygous rare alleles on these loci exhibit lower mRNA levels as determined by real time polymerase chain reaction (P < 0.01) and the incorporation of rare alleles in haplotypes correlate with reduced mRNA (P = 0.03). The 5'-UTR-363 SNP is located in one of the three promoters of CES2. However, we did not observe significant differences in CES2 activities (irinotecan and procaine hydrolysis) among individuals with different haplotypes.
ESTHER : Wu_2004_Pharmacogenet_14_595
PubMedSearch : Wu_2004_Pharmacogenet_14_595
PubMedID: 15475733
Gene_locus related to this paper: human-CES2

Title : Characterization of multiple promoters in the human carboxylesterase 2 gene - Wu_2003_Pharmacogenet_13_425
Author(s) : Wu MH , Chen P , Remo BF , Cook EH, Jr. , Das S , Dolan ME
Ref : Pharmacogenetics , 13 :425 , 2003
Abstract : Carboxylesterases are a broad class of enzymes important in the detoxification of many ester- or amide-bond containing xenobiotics. They also activate analgesics, anticancer prodrugs, and other biologically active compounds, such as cocaine and heroin. The objective of this work was to identify the CES2 gene structure, complex 5' untranslated regions and three potential promoters for the initiation of transcription in different human tissues. Using bioinformatics and progressive reverse transcriptase-polymerase chain reaction, we found that the 5' untranslated region is more than 1100 bases longer than previously reported. Rapid amplification of cDNA ends showed three distinctive transcription start sites at -74, -629 and -1187. DNA fragments upstream of each of the three transcription start sites were found to be transcriptionally active in HepG2 cells. The distal promoter is active in both orientations, suggesting its potential role in the transcription of another gene, CGI-128, located immediately upstream to the distal promoter in the opposite direction with respect to CES2. Hybridization analyses showed that CES2 is highly expressed in the heart, skeletal muscle, colon, spleen, kidney and liver, but considerably less expressed in fetal tissues (e.g. fetal heart, kidney, spleen, and liver) and cancer cells. It is also evident that the distal promoter is responsible for low level expression of the gene in many tissues, whereas the other two promoters are tissue specific. These findings shed some light on CES2 gene regulation, a gene important in the metabolism of many drugs.
ESTHER : Wu_2003_Pharmacogenet_13_425
PubMedSearch : Wu_2003_Pharmacogenet_13_425
PubMedID: 12835618
Gene_locus related to this paper: human-CES2

Title : Structural characterization of the N-linked oligosaccharides in bile salt-stimulated lipase originated from human breast milk - Mechref_1999_Glycobiology_9_227
Author(s) : Mechref Y , Chen P , Novotny MV
Ref : Glycobiology , 9 :227 , 1999
Abstract : The detailed structures of N- glycans derived from bile salt-stimulated lipase (BSSL) found in human milk were determined by combining exoglycosidase digestion with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The N- glycan structures were conclusively determined in terms of complexity and degree of fucosylation. Ion-exchange chromatography with pulsed amperometric detection, together with mass-spectral analysis of the esterified N- glycans, indicated the presence of monosialylated structures. The molecular mass profile of esterified N- glycans present in BSSL further permitted the more detailed studies through collision-induced dissociation (CID) and sequential exoglycosidase cleavages. The N- glycan structures were elucidated to be complex/dibranched, fucosylated/complex/dibranched, monosialylated/complex/dibranched, and monosialylated/fucosylated/dibranched entities.
ESTHER : Mechref_1999_Glycobiology_9_227
PubMedSearch : Mechref_1999_Glycobiology_9_227
PubMedID: 10024660
Gene_locus related to this paper: human-CEL