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Identification of specific genes and pathways involved in NSAIDs-induced apoptosis of human colon cancer cells

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World Journal of Gastroenterology 2006年第40期12卷 6446-6452页

作者： Richard h huang Jianyuan Chai Andrzej S Tarnawski Department of Medicine Division of Gastroenterology University of California Irvine and VA Long Beach Healthcare System California United States Department of Medicine University of California Irvine and VA Long Beach Healthcare System California United States

AIM: To study whether indomethacin (IND), a nonselective cyclooxygenase (cox) inhibitor or NS-398 (NS), a cox-2-selective inhibitor, induces apoptosis in human colon cancer cells and which apoptosis-related genes and pathways are involved. METhODS: human colon cancer Caco-2 cells were treated with either: placebo, IND (0.05-0.5 mmol/L) or NS (0.01-0.2 mmol/L) for 1, 5 and 18 h. We then studied: (1) Cell death by the TUNEL method, (2) mRNA expression of 96 apoptosis-related genes using DNA microarray, (3) expression of selected apoptosis related proteins by Western blotting. RESULTS: Both IND and NS induced apoptosis in 30%-50% of Caco-2 cells in a dose dependent manner. IND (0.1 mmol/L for 1 h) significantly up-regulated pro-apoptotic genes in four families: (1) TNF receptor and ligand, (2) Caspase, (3) Bcl-2 and (4) Caspase recruiting domain. NS treatment up-regulated similar pro-apoptotic genes as IND. In addition, IND also down-regulated anti-apoptotic genes of the IAP family. CONCLUSION: (1) Both non-selective and cox-2-selective NSAIDs induce apoptosis in colon cancer cells in a dose dependent manner. (2) Both NSAIDs induce apoptosis by activating two main apoptotic pathways: the death receptor pathway (involving TNF-R) and the mitochondrial pathway. (3) IND induces apoptosis by up-regulating pro-apoptotic genes and down-regulating anti-apoptotic genes, while NS only up-regulates pro-apoptotic genes. (4) Induction of apoptosis in coloncancer cells by NSAIDs may explain in part, their inhibitory action on colon cancer growth.

关键词： Nonsteroidal anti-inflammatory drugs Colon cancer Apoptosis Cyclooxygenase cDNA microarray

Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection

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World Journal of Gastroenterology 2014年第40期20卷 14841-14854页

作者： Astrit R hamza Avdyl S Krasniqi Pramod Kadaba Srinivasan Mamdouh Afify Christian Bleilevens Uwe Klinge René h Tolba Institute for Laboratory Animal Science and Experimental Surgery University Hospital Rheinisch-Westf?lische Technische Hochschule Aachen 52074 Aachen Germany Department of AbdominalSurgery University Clinical Center of Kosova Prishtina 10000Kosovo Department of Anesthesiology University Hospital Rheinisch-Westf?lische Technische Hochschule Aachen 52074 Aachen Germany Department of Surgery University Hospital Rheinisch-Westf?lische Technische Hochschule Aachen 52074 Aachen Germany

AIM: To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection.

关键词： Liver cirrhosis Liver resection Gut-liver axis Meloxicam Cyclooxigenase-2 Microcirculation

用PCR-RFLP方法分析流感病毒h_3N_2亚型毒株

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中华疾病控制杂志 1997年第3期9卷 176-178页

作者：黄平 C.A.Bender 沈桂章周惠琼 N.J.cox 广东省流行病防治研究所广州510300 美国疾病控制与预防中心(CDC) atlanta30333

采用PCR－RFLP方法，将1996年流感病毒h3N2亚型分成阿拉斯加变异株系和武汉变异株系；分析发现，全球流感病毒h3N2亚型以武汉变异株系为优势毒株。来自中国的28份流感病毒h3N2亚型均为武汉变异株系；美国主要流行武汉变异株系（41／50... 详细信息

采用PCR－RFLP方法，将1996年流感病毒h3N2亚型分成阿拉斯加变异株系和武汉变异株系；分析发现，全球流感病毒h3N2亚型以武汉变异株系为优势毒株。来自中国的28份流感病毒h3N2亚型均为武汉变异株系；美国主要流行武汉变异株系（41／50），其次为阿拉斯加变异株系；世界其它地区以武汉变异株系为主。作者认为，PCR－RFLP方法作为一种分子流行病学筛选实验，在流感变异研究中具有重要作用。

关键词：流感病毒血凝素 RFLP 变异

Evaluation of the hepatoprotective and antioxidant effects of Tegillarca granosa flesh body extract against potassium bromide toxicity via targeting the histomorphometry,chromosomal and expressions of TGF-β1,VEGF and cox-2 genes in rats

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BIOCELL 2022年第1期46卷 219-234页

作者： ALI h.ABU ALMAATY BASMA M.hENDAM FAYEZ ALThOBAITI EMAN FAYAD YASMIN M.ABD EL-AZIZ Department of Zoology Faculty of SciencePort Said UniversityPort Said42526Egypt Department of husbandry and Development of Animal Wealth Faculty of Veterinary MedicineMansoura UniversityMansoura35516Egypt Department of Biotechnology Faculty of ScienceTaif UniversityTaif21944Saudi Arabia

The hepatotoxic effect of potassium bromide(KBr)on rat liver tissues were determined,as well as the potential protective effect of Tegillaraca granosa(***)flesh body *** adult male albino rats were equally distributed into four groups;Group(I)treated with physiological saline(control group),Group(II)was orally gavaged by 200 mg/kg of *** body extract day after day,Group(III)was intoxicated by KBr(150 mg/kg bwt day after day orally)and finally,Group(IV)was given a combination of *** flesh body extract plus KBr with similar doses in the second and third *** the end of one month,blood,liver tissue and bone marrow samples were collected to be used for the required laboratory *** response to KBr toxicity,there was a significant increase in serum antioxidant biomarkers,which was accompanied by a significant change in hepatocyte ultrastructure and a significant change in carbohydrate and protein levels within the liver *** addition,KBr intoxication resulted in a substantial increase in the incidence of chromosomal aberrations such as holes,splits,deletions,fragments,ploidy,and ring chromosomes,as well as significant upregulation of TGF-1,VEGF,and cox-2 gene *** hepatotoxic effect of KBr was counteracted by treatment with *** flesh body *** flesh body extract has a curative antioxidant and numerous protective effects against KBr hepatotoxicity.

关键词： Potassium bromide Tegillarca granosa hepatic toxicity Antioxidant biomarker histomorphometry Chromosomal aberrations Gene expression

婴儿先天性心脏病术后拔管失败的发生率、原因和危险因素

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中华儿科杂志 2002年第9期40卷 529-529页

作者： A Marc harrison Amy C cox Steve Davis 唐浩勋樊寻梅

大多数先天性心脏病患儿术后需机械通气。拔管失败将导致生理状态不稳定 ,推迟停止机械通气的时间。目的研究导致小婴儿先天性心脏病术后拔管失败的发生率、病因和危险因素。对象　 1998年 1月～ 1999年 7月克利夫兰儿童医院危重症监护... 详细信息

大多数先天性心脏病患儿术后需机械通气。拔管失败将导致生理状态不稳定 ,推迟停止机械通气的时间。目的研究导致小婴儿先天性心脏病术后拔管失败的发生率、病因和危险因素。对象　 1998年 1月～ 1999年 7月克利夫兰儿童医院危重症监护病房年满 3岁的先天性心脏病患儿。测量与统计方法　采用回顾分析表法。拔管后 2 4h内复插视为拔管失败。收集研究对象术前、术中和术后的相应指标。对每个研究对象的多个非独立资料采取Logistic回归法评价拔管失败的危险因素 ,P h成功拔管。 2 2例首次拔管失败者 ,平均拔管时间为术后 6 7 8h (2 4～ 335 5h) ,其中 5例第 2次拔管亦失败 ,平均拔管时间 189 5h (115 8～ 6 0 2 5h)。拔管失败的早期原因为心功能障碍 (n =6 )、肺疾病 (n =6 )、气道水肿 (n =3)。拔管失败的危险因素为肺高压 (EOR =38 7,95

关键词：婴儿先天性心脏病术后拔管失败发生率危险因素

Spontaneous bacterial peritonitis prevalence in pretransplant patients and its effect on survival and graft loss post-transplant

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World Journal of hepatology 2016年第36期8卷 1617-1622页

作者： Neeral L Shah Nicolas M Intagliata Zachary h henry Curtis K Argo Patrick G Northup Division of Gastroenterology and hepatology Department of Medicine University of Virginia

AIM To investigate the incidence of spontaneous bacterial peritonitis(SBP) in pre-transplant patients and its effect on post transplant mortality and graft failure. METhODS We conducted a retrospective cohort study of patient records from the organ procurement and transplant network data set. Patients were identified by the presence of SBP pre-transplant. Univariate post-transplant survival models were constructed using the Kaplan-Meier technique and multivariate models were constructed using the cox proportional hazards model. Variables that affected post-transplant graft survival were identified in the SBP population. RESULTS Forty-seven thousand eight hundred and eighty patient records were included in the analysis for both groups, and 1966(4.11%) patients were identified in the data set as having pre-transplant SBP. Patients that had pre-transplant SBP had higher rates of graft loss from recurrent hepatitis C virus(hCV)(3.6% vs 2.0%, P hronic rejection(1.1% vs 0.7%, P = 0.04). Kaplan-Meier survival analysis showed a statistically significant difference in all-cause survival in patients with a history of SBP vs those without(P history of SBP was independently predictiveof mortality due to recurrent hCV(hR = 1.11, 95%CI: 1.02-1.21, P hCV patients prior to the advent of directing acting anti-viral agents had a higher incidence of pre-transplant SBP than other patients on the liver transplant wait list. SBP history pre-transplant resulted in a higher rate of graft loss due to recurrent hCV infection and chronic rejection.

关键词： Spontaneous bacterial peritonitis Liver transplant Graft failure hepatitis C

cox-2 polymorphisms-765G→C and-1195A→G and colorectal cancer risk

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World Journal of Gastroenterology 2009年第36期15卷 4561-4565页

作者： Juliёt h hoff Rene hM te Morsche hennie MJ Roelofs Elise MJ van der Logt Fokko M Nagengast Wilbert hM Peters Department of Gastroenterology Radboud University Nijmegen Medical Center6500 HB NijmegenThe Netherlands

AIM： TO determine the possible modulating effect of the cox-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer （CRC） in a Dutch population. METhODS： This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the cox-2 polymorphisms -7dEG→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. cox-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS： The -765GG genotype was associated with an increased risk of developing CRC （OR, 1.45; 95% CI, 1.03-2.04）. No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls （OR 0.44; 95% CI, 0.22-0.85）. When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls （OR（AG/AC） 0.78; 95% CI, 0.57-1.06）. CONCLUSION： The -765GG genotype is associated with an increased risk of developing CRC and the G6/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the cox-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.

关键词： Colorectal carcinoma Cyclooxygenase-2 Genetic polymorphism

The impact of chemotherapy-naïve open radical cystectomy delay and perioperative transfusion on the recurrence-free survival: A perioperative parameters-based nomogram

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Asian Journal of Urology 2024年第2期11卷 294-303页

作者： Ahmed M.harraz Ahmed Elkarta Mohamed h.Zahran Ahmed Mosbah Atallah A.Shaaban hassan Abol-Enein Urology and Nephrology Center Mansoura UniversityEgypt

Objective: To develop and internally validate a nomogram to predict recurrence-free survival (RFS) including the time to radical cystectomy (RC) and perioperative blood transfusion (PBT) as potential ***: Patients who underwent open RC and ileal conduit between January 1996 to December 2016 were split into developing (n=948) and validating (n=237) cohorts. The time to radical cystectomy (TTC) was defined as the interval between the onset of symptoms and RC. The regression coefficients of the independent predictors obtained by cox regression were used to construct the nomogram. Discrimination, validation, and clinical usefulness in the validation cohort were assessed by the area under the curve, the calibration plot, and decision curve ***: In the developing dataset, the 1-, 5-, and 10-year RFS were 83.0%, 47.2%, and 44.4%, respectively. On multivariate analysis, independent predictors were TTC (hazards ratio [hR] 1.07, 95% confidence interval [CI] 1.05-1.08, phR 1.40, 95% CI 1.03-1.90, p=0.03;two or more units: hR 1.72, 95% CI 1.29-2.29, phydronephrosis (hR 1.54, 95% CI 1.21-1.97, phR 0.60, 95% CI 0.45-0.81, p=0.001), pT3-T4 (hR 1.77, 95% CI 1.41-2.22, ph node status (hR 1.53, 95% CI 1.21-1.95, phovascular invasion (hR 1.28, 95% CI 1.01-1.62, p=0.044). The areas under the curve in the validation dataset were 79.3%, 69.6%, and 76.2%, for 1-, 5-, and 10-year RFS, respectively. Calibration plots showed considerable correspondence between predicted and actual survival probabilities. The decision curve analysis revealed a better net benefit of the ***: A nomogram with good discrimination, validation, and clinical utility was constructed utilizing TTC and PBT in addition to standard pathological criteria.

关键词： Radicalcystectomy Blood transfusion Time to radical cystectomy Survival Nomogram

Implantable cardiac defibrillators in octogenarians

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Journal of Geriatric Cardiology 2023年第1期20卷 23-31页

作者： Maarten Pauwelyn Sebastian Ingelaere Ruben hoffmann Johan Vijgen Georges h.Mairesse Ivan Blankoff Yves Vandekerckhove Jean-Benoit le Polain de Waroux Bert Vandenberk Rik Willems University hospitals Leuven CardiologyLeuvenBelgium KU Leuven Department of Cardiovascular SciencesLeuvenBelgium UZA Department of CardiologyAntwerpBelgium Jessa Ziekenhuis Department of CardiologyHasseltBelgium Cliniques du Sud Luxembourg Department of CardiologyArlonBelgium ChU Charleroi Department of CardiologyCharleroiBelgium AZ Sint-Jan Department of CardiologyBruggeBelgium University of Calgary Libin Cardiovascular InstituteCalgaryCanada

OBJECTIVE Implantable cardiac defibrillators(ICD)implantation in the very elderly remains *** aimed to describe the experience and outcome of patients over 80 years old implanted with an ICD in *** Data were extracted from the national QERMID-ICD *** implantations performed in octogenarians between February 2010 and March 2019 were *** on baseline patient characteristics,type of prevention,device configuration and all-cause mortality were *** determine predictors of mortality,multivariable cox proportional hazard regression modelling was *** Nationwide,704 primo ICD implantations were performed in octogenarians(median age 82,IQR 81-83 years;83% male and 45% secondary prevention).During a mean follow-up of 3.1±2.3 years,249(35%)patients died,of which 76(11%)within the first year after *** multivariable cox regression analysis age(hR=1.15,P=0.004),oncological history(hR=2.43,P=0.027)and secondary prevention(hR=2.23,P=0.001)were independently associated with 1-year mortality.A better preserved left ventricular ejection fraction(LVEF)was associated with a better outcome(hR=0.97,P=0.002).Regarding overall mortality multivariable analysis withheld age,history of atrial fibrillation,centre volume and oncological history as significant *** LVEF was again protective(hR=0.99,P=0.008).CONCLUSIONS Primary ICD implantation in octogenarians is not often performed in *** this population,11%died within the first year after ICD *** age,oncological history,secondary prevention and a lower LVEF were associated with an increased one-year ***,low LVEF,atrial fibrillation,centre volume and oncological history were indicative of higher overall mortality.

关键词： prevention implantation protective