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Expression and reconstitution of the bioluminescent Ca2+reporter aequorin in human embryonic stem cells,and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes

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Science China(Life Sciences) 2016年第8期59卷 811-824页

作者： Harvey Y.S.chan Man Chun Cheung Yi Gao Andrew L.Miller Sarah E.Webb Division of Life Science&State Key Laboratory of Molecular Neuroscience HKUSTClear Water BayHong KongChina Stem Cell&Regenerative Medicine Consortium Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong KongChina Marine Biological Laboratory Woods Hole MA 02543USA

In order to develop a novel method of visualizing possible Ca2＋ signaling during the early differentiation of hESCs into cardi- omyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the biolumines- cent Ca2＋ reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation withf-coelenterazine. The temporal nature of the Ca2＋ signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca2＋ transients （generated by re- lease from intracellular stores） were detected in 1-12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KC1 or CaC12, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor （IP3R） agonist, small Ca2＋transients were generated from day 1 onward. That ATP was inducing Ca2＋ release from functional IP3Rs was demonstrated by treatment with 2-APB, a known IP3R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor （RyR） agonist, a minima/Ca2＋ response was observed at day 8 of differentiation only. Thus, our data indicate that unlike RyRs, IP3Rs are present and continually functional at these early stages of cardiomyocyte differentiation.

关键词： Ca2+ signaling apo-aequorin expression bioluminescence HES2 human embryonic stem cells hESC-derived cardiospheres IP3 and ryanodine receptors

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Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis

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World Journal of Gastroenterology 2019年第23期25卷 2961-2972页

作者： Hyo-Young Lee Hyunwoo Oh chan-Hyuk Park Yee-Hui Yeo Mindie H Nguyen Dae-Won Jun Department of Internal Medicine Hanyang University College of MedicineSeoul 04763South Korea Department of Internal Medicine Hanyang University Guri HospitalHanyang University College of MedicineGuri 11923South Korea Division of Gastroenterology and Hepatology Stanford University Medical CenterStanford UniversityStanford 94305CAUnited States

BACKGROUND Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir(TDF) and entecavir(ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and *** To investigate the effects of TDF and ETV on renal function, we performed systematic review and *** Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies(NRSs) using the keywords 'CHB', 'Tenofovir', and 'Entecavir', and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment,Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and24 *** NRSs comprising 2263 participants met the inclusion criteria. changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo[mean difference(MD) = 0.03 mg/dL;95%CI: 0.02-0.04;I2 = 0%], 12 mo(MD =0.05 mg/dL;95%CI: 0.02-0.08;I2 = 78%), and 24 mo(MD = 0.07 mg/dL;95%CI:0.01-0.13;I2 = 93%). The change in estimated glomerular filtration rate(eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo[standardized mean difference(SMD),-0.22;95%cl:-0.36--0.08;I2 = 0%], 12 mo(SMD =-0.24;95%cl:-0.43--0.05;I2 = 50%), and 24 mo(-0.35;95%cl:-0.61--0.09;I2= 67%).CONclUSION TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compa

关键词： Hepatitis B Chronic Tenofovir Entecavir Safety Review Systematic Meta-analysis

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Expression of CFTR in mouse oocytes and its involvement in oocyte maturation

Expression of CFTR in mouse oocytes and its involvement in o...

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2008北京国际生理科学学术大会

作者： chan Hsiao-chang Epithelial Cell Biology Research Centre Department of PhysiologyChinese University of Hong Kong

The cystic fibrosis transmembrane conductance regulator(CFTR),a cAMP dependent cl channel,is recognized to play an important role in reproduction;however,its exact role in various reproductive events remains *** previous study has shown that CFTR is expressed in mouse *** present study aimed to investigate the expression of CFTR in mouse oocytes and its involvement in oocyte *** expression of CFTR in oocytes was determined by immunofluorecscence study and the results showed that CFTR was localized to the membrane of the oocyte in *** involvement of CFTR in oocyte maturation was investigated by in vitro maturation(IVM).cl channel blocker NPPB(100μmol/L) significantly decreased the first polar body extrusion (PB) rate and germinal vesicle breakdown(GVBD) rate of the oocytes by 80.0%(Pclamide(100μmol/L) also decreased the PB rate by 24.4%(Pcluded that CFTR is expressed in mouse oocytes and plays an important role in oocyte maturation,especially in first polar body extrusion.

关键词： CFTR ovary oocyte maturation

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Critical Role of Cystic Fibrosis Transmembrane Conductance Regulation(CFTR)in Female Reproduction

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皖南医学院学报 2003年第Z1期22卷 4-5页

作者： Hsiao chang chan Epithelial Cell Biology Research Center Department of PhysiologyFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong

　　Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated cl- channel, mutations of which are responsible for defective cl- and/or HCO-3 secretions seen in cystic fibrosis (CF), a common lethal genetic disease affecting most exocrine glands/organs, including the lungs, intestine, pancreas and reproductive tracts of both sexes.　　……

关键词： cystic fibrosis genetic disease

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Prostate cancer antigen 3 test for prostate biopsy decision： a systematic review and meta analysis

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Chinese Medical Journal 2014年第9期127卷 1768-1774页

作者： Luo Yong Gou Xin Huang Peng Mou chan Department of Urology the First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China

Background The specificity for early interventions of prostate-specific antigen （PSA） in prostate cancer （PCa） is not *** is likely that prostate cancer antigen 3 （PCA3） can be used to predict biopsy outcomes more accurately than PSA for the early detection of *** systematically reviewed literatures and subsequently performed a *** A bibliographic search in the database of Embase,Medline,Web of Science,NCBI,PubMed,CNKI,and those of health technology assessment agencies published before April 2013 was *** key words used were ＂prostatic neoplasms＂,＂prostate＂,＂‘prostate,＇ ‘carcinoma＇ or ‘cancer＇ or ‘tumor＇,or ‘PCa,＇＂ and free terms of ＂upm3＂,＂pca3＂,＂dd3＂,＂aptimapca 3＂,and ＂prostate cancer antigen 3＂.All patients were *** intervention was detecting PCA3 in urine samples for PCa *** checked the quality based on the QUADAS criteria,collected data,and developed a meta-analysis to synthesize ***-four studies of diagnostic tests with moderate to high quality were *** The sensitivity was between 46.9％ and 82.3％; specificity was from 55％ to 92％; positive predictive value had a range of 39.0％-86.0％; and the negative predictive value was 61.0％-89.7％.The meta-analysis has heterogeneity between *** global sensitivity value was 0.82 （95％ cl 0.72-0.90）; specificity was 0.962 （95％ cl 0.73-0.99）; positive likelihood ratio was 2.39 （95％ cl 2.10-2.71）; negative likelihood ratio was 0.51 （95％ cl 0.46-0.86）; diagnostic odds ratio was 4.89 （95％ cl 3.94-6.06）; and AUC in SROC curve was 0.744 *** PCA3 can be used for early diagnosis of PCa and to avoid unnecessary biopsies.

关键词： prostate cancer antigen 3 prostate cancer, diagnosis early detection

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Tetramethylpyrazine stimulates cystic fibrosis transmembrane conductance regulator-mediated anion secretion in distal colon of rodents

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World Journal of Gastroenterology 2005年第27期11卷 4173-4179页

作者： Qiong He Jin-Xia Zhu Ying Xing Lai-Ling Tsang Ning Yang Dewi Kenneth Rowlands Yiu-Wa Chung Hsiao-chang chan Department of Physiology Medical School Zhengzhou University Zhengzhou 450052 Henan Province China Epithelial Cell Biology Research Center Department of PhysiologyFaculty of Medicine The Chinese University of Hong Kong ShatinHong Kong China

AIM： To investigate the effect of tetramethylpyrazine （TMP）, an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism ***： The short-circuit current （Isc） technique in conjunction with pharmacological agents and specific inhibitors were used in analyzing the electrolyte transport across the distal colon of rodents. The underlying cellular signaling mechanism was investigated by radioimmunoassay analysis （RIA） and a special mouse model of cystic ***： IMP stimulated a conoentration-dependent rise in IScl, which was dependent on both cl^- and HCO3^-, and inhibited by apical application of diphenylamine-2,2＇-dicarboxylic acid （DPC） and glibenclamide, but resistant to 4,4＇-diisothiocyanatostilbene-2,2＇-disulfonic acid disodium salt hydrate （DIDS）. Removal of Na^＋ from basolateral solution almost completely abolished the Isc response to TMP, but it was insensitive to apical Na^＋ replacement or apical Na^＋ channel blocker, amiloride. Pretreatment of colonic mucosa with BAPTA-AM, a membrane-permeable selective Ca2＋ chelator, did not significantly alter the TMP-induced Iso No additive effect of forskolin and 3-isobutyl-l-methylxanthine （[BMX） was observed on the TMP-induced Isc, but it was significantly reduced by a protein kinase A inhibitor, *** results showed that TMP （1 mmol/L） elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin （10μmol/L）. The TMP-elicited Isc as well as forskolin- or IBMX-induced Isc were abolished in mice with homozygous mutation of the cystic fibrosis transmembrane conductance regulator （CFTR） presenting defective CFTR functions and ***： TMP may stimulate cAMP-dependent and CFTR-mediated cl^- and HCO3^- secretion. This may have implications in the future development of alternative treatment for constipation.

关键词： Adrenergic beta-Agonists Animals Anions Colon Constipation Cystic Fibrosis Transmembrane Conductance Regulator Male Mice Mice, Inbred CFTR Pyrazines Rats Rats, Sprague-Dawley Research Support, Non-U.S. Gov't

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High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients

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World Journal of Gastroenterology 2013年第20期19卷 3083-3089页

作者： Tan To Cheung Sheung Tat Fan See Ching chan Kenneth SH Chok Ferdinand SK Chu Caroline R Jenkins Regina cl Lo James YY Fung Albert CY chan William W Sharr Simon HY Tsang Wing Chiu Dai Ronnie TP Poon Chung Mau Lo Department of Surgery the University of Hong Kong State Key Laboratory for Liver Research the University of Hong Kong Department of Diagnostic Radiology the University of Hong Kong Department of Anaesthesiology The University of Hong Kong Department of Pathology the University of Hong Kong Department of Medicine the University of Hong Kong

AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 ***-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before *** patients received HIFU ablation as a bridging *** five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for *** were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of ***:The HIFU group and TACE group showed no difference in terms of tumor size and tumor *** patient in the HIFU group and no patient in the TACE group had gross *** median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P clUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced *** may reduce the drop-out rate of liver transplant candidate.

关键词： Ablation Bridging therapy Cirrhosis Hepatocellular carcinoma High-intensity focused ultrasound Liver transplant New technology

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EVERESTTM Reversed-Phase Columns for Peptide Analysis

EVERESTTM Reversed-Phase Columns for Peptide Analysis

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8th Chinese International Peptide Symposium

作者： Reno NGUYEN Derek chan Grace Vydac 17434 Mojave Street Hesperia CA 92345 USA

Monomeric bonding is the most widely used method in preparation of silica-based reversed-phase(RP) packing materials. A major challenge with this bonding scheme is to achieve high carbon coverage. It is known that low carbon coverage often leads to poor peak shape, high secondary chromatographic effect and low column lifetime. There has been a great deal of effort devoted to increasing carbon coverage over the last several decades. At the present time, commercially available RP columns have carbon coverage typically in the range of 2.8 to 3.6 μmol/m2. Through using a combination of new technologies, Grace Vydac, has developed a new line of monomerically bonded 300 A RP

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Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer

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Asian Journal of Andrology 2015年第3期17卷 493-496页

作者： Jeremy YC Teoh Samson YS chan Peter KF Chiu Darren MC Poon Ho-Yuen Cheung Simon SM Hou Chi-Fai Ng Department of Surgery Division of Urology Prince of Wales Hospital The Chinese University of Hong Kong Shatin Hong Kong China Department of clinical Oncology Prince of Wales Hospital The Chinese University of Hong Kong Shatin Hong Kong China Department of Surgery Division of Urology North District Hospital Hong Kong China

We investigated the cardiovascular thrombotic risk after surgical castration （SC） versus genadotmpin-releasing hormone agonists （GnRHa） in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group （75.3 ~ 7.5 years） was significantly higher than the GnRHa group （71.8 ~ 8.3 years）（P 〈 0.001）. There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan-Meier analysis （P= 0.014）. Upon multivariate Cox regression analysis, age （hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04-1.11, P 〈 0.001）, hyperlipidemia （HR 2.455, 95% cl 1.53-3.93, P 〈 0.001）, and SC （HR 1.648, 95% CI 1.05-2.59, P = 0.031） were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.

关键词： androgen deprivation therapy Chinese population cardiovascular events myocardial infarction prostate cancer stroke

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Endoscopic and clinicopathologic characteristics of early gastric cancer with high microsatellite instability

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World Journal of Gastroenterology 2012年第27期18卷 3571-3577页

作者： Jaehoon Jahng Young Hoon Youn Kwang Hyun Kim Junghwan Yu Yong chan Lee Woo Jin Hyung Sung Hoon Noh Hyunki Kim Hoguen Kim Hyojin Park Sang In Lee Department of Internal Medicine Gangnam Severance HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Internal Medicine Institute of GastroenterologyYonsei University College of MedicineSeoul 100-753South Korea Department of Surgery Yonsei University College of MedicineSeoul 100-753South Korea Department of Pathology Yonsei University College of MedicineSeoul 100-753South Korea

AIM： To investigate endoscopic and clinicopathologic characteristics of early gastric cancer （EGC） according to microsatellite instability phenotype. METHODS： Data were retrospectively collected from a single tertiary referral center. Of 981 EGC patients surgically treated between December 2003 and October 2007, 73 consecutive EGC patients with two or more microsatellite instability （MSI） mutation [high MSI （MSI-H）] and 146 consecutive EGC patients with one or no MSI mutation （non-MSI-H） were selected. The endoscopic and clinicopathologic features were compared between the MSI-H and non-MSI-H EGC ***： In terms of endoscopic characteristics, MSI-H EGCs more frequently presented with elevated pattern （OR 4.38, 95% cl： 2.40-8.01, P 〈 0.001）, moderate- to-severe atrophy in the surrounding mucosa （OR 1.91, 95% CI： 1.05-3.47, P = 0.033）, antral location （OR 3.99, 95% CI： 2.12-7.52, P 〈 0.001） and synchronous le- sions, compared to non-MSI-H EGCs （OR 2.65, 95% CI： 1.16-6.07, P = 0.021）. Other significant clinicopatholog- ic characteristics of MSI-H EGC included predominance of female sex （OR 2.77, 95% CI： 1.53-4.99, P 〈 0.001）, older age （〉 70 years）（OR 3.30, 95% CI： 1.57-6.92, P = 0.002）, better histologic differentiation （OR 2.35, 95% cl： 1.27-4.34, P = 0.007）, intestinal type by Lau- ren classification （OR 2.34, 95% CI： 1.15-4.76, P = 0.019）, absence of a signet ring cell component （OR 2.44, 95% CI： 1.02-5.86, P = 0.046）, presence of mu- cinous component （OR 5.06, 95% cl： 1.27-20.17, P = 0.022）, moderate-to-severe lymphoid stromal reaction （OR 3.95, 95% CI： 1.59-9.80, P = 0.003）, and co-exist- ing underlying adenoma （OR 2.66, 95% CI： 1.43-4.95, P = 0.002）. CONclUSION： MSI-H EGC is associated with unique endoscopic and clinicopathologic characteristics includ- ing frequent presentation in protruded type, co-exist- ing underlying adenoma, and synchronous lesions.

关键词： Microsatellite instability Early gastric can-cer Endoscopic characteristic Advanced gastric cancer

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