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| 1 | Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner显示文摘AIM:To investigate the role of osteopontin(OPN) and its splice variants in the proliferation of hepatocellular carcinoma(HCC).METHODS:The expression of OPN variants in HCC cell lines as well as HCC tissue samples and nontumour tissue was studied using polymerase chain reaction.OPN variant cDNAs were cloned into a mammalian expression vector allowing both transient expression and the production of stable OPN expressing cell lines.OPN expression was studied in these cells using Western blotting,immunofluoresnce and enzyme linked immunosorbent assay.A CD44 blocking antibody and siRNA targeting of CD44 were used to examine the role of this receptor in the OPN stimulated cell growth observed in culture.Huh-7 cells stably expressing either OPN-A,-B or-C were injected subcutaneously into the flanks of nude mice to observe in vivo tumour growth.Expression of OPN mRNA and protein in these tumours was examined using reverse transcriptionpolymerase chain reaction and immunohistochemistry.RESULTS:OPN is expressed in HCC in 3 forms,the full length OPN-A and 2 splice variants OPN-B and-C.OPN variant expression was noted in HCC tissue as well as cognate surrounding cirrhotic liver tissue.Expression of these OPN variants in the HCC derived cell line Huh-7 resulted in secretion of OPN into the culture medium.Transfer of OPN conditioned media to na ve Huh-7 and HepG2 cells resulted in significant cell growth suggesting that all OPN variants can modulate cell proliferation in a paracrine manner.Furthermore the OPN mediated increase in cellular proliferation was dependent on CD44 as only CD44 positive cell lines responded to OPN conditioned media while siRNA knockdown of CD44 blocked the proliferative effect.OPN expression also increased the proliferation of Huh-7 cells in a subcutaneous nude mouse tumour model,with Huh-7 cells expressing OPN-A showing the greatest proliferative effect.CONCLUSION:This study demonstrates that OPN plays a significant role in the proliferation of HCC through interaction with the cell surface receptor CD44.Modulation of this interaction could represent a novel strategy for the control of HCC. | Renee J Phillips Karla J Helbig Kylie H Van der Hoek Devanshi Seth Michael R Beard | 2012 | World Journal of Gastroenterology2012，18，26： | 12 |
| 2 | Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno-or squamous cell carcinoma显示文摘AIM:To determine whether-1195 A→G and/or-765 G→C polymorphisms in Cyclooxygenase-2(COX-2 ) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population.METHODS:Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area.DNA was isolated from whole blood and used for genotyping.PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis.Odds ratios(OR) and 95% confldence intervals(CI) were estimated.RESULTS:The distribution of the-1195 A→G polymorphism was signif icantly different in esophageal cancer patients compared to controls.The-1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma(OR = 3.85, 95% CI:1.45-10.3) compared with the-1195 AA genotype as a reference.The-765 G→C genotype distribution was not different between the two groups.The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls(OR = 3.45, 95% CI:1.24-9.58;with AG/AG as a reference).The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical signif icance.CONCLUSION:Presence of the COX-2-1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma. | Jón O Kristinsson Paul van Westerveld Rene HM te Morsche Hennie MJ Roelofs T Wobbes Ben JM Witteman Adriaan CITL Tan Martijn GH van Oijen Jan BMJ Jansen Wilbert HM Peters | 2009 | World Journal of Gastroenterology2009，15，28： | 11 |
| 3 | 钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。 | Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无 郭鹤鸣(译) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 4 | Inhibition of nitric oxide synthesis improves the vasoconstrictive effect of noradrenalline in sepsis显示文摘 | Landin L Lorente J A Renes E | 1994 | Chest1994，106，1： | 2 |
| 5 | Anti-Hu antibodies in patients with small-cell lung cancer:association with complete response to therapy and improved survival显示文摘 | Dalmou J Rene R | 1997 | J Clin Oncol1997，15，8： | 1 |
| 6 | Acomparison of accelerated life testing designs within A singleBayesian inferential framework显示文摘 | J Rene Van Dorp Thomas A Mazzuchi Jorge E Garciduenas | 2006 | Newport Beach UnitedStates2006，，： | 1 |
| 7 | Dynamic properties of chemically stabilized sulfate rich clay显示文摘 | Laureano Rene Hoyos Anand J Puppala Phonlawut Chainuwat | 2004 | Journal of Geotechnical and Geoenvironmental Engineering2004，130，2： | 1 |
| 8 | Unilateral pulmonary arteryagenesis presentingwith hemoptysis:treatment by embolization of systemic collaterals显示文摘 | Rene M Sans J Dominguez J | 1995 | Cardiovasc Intervent Radio1995，18，4： | 1 |
| 9 | Excitation-emission matrix fluorescence based determination of carbamate pesticides and polycyclic aromatic hydrocarbons显示文摘 | Renee D J Gary A C Karl S B | 1999 | Analytica Chimica Acta1999，，397： | 1 |
| 10 | Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis显示文摘 | Maarten Boers Arco C Verhoeven Harry M Markusse Mart AFJ van de Laar Rene Westhovens J Christiaan van Denderen Derkjen van Zeben Ben AC Dijkmans Andre J Peeters Piet Jacobs Hans R van den Brink Hubert JA Schouten Désirée MFM van der Heijde Annelies Boonen | 1997 | The Lancet1997，，9074： | 1 |
| 11 | 基于G-蛋白偶联受体激酶2抑制剂治疗心力衰竭的合理药物设计(英文)显示文摘G protein-coupled receptors(GPCRs)convert extracellular stimuli in the form of hormones,odorants and light into profound changes in cell homeostasis.Their timely desensitization is critical for cells to rapidly respond to changes in their environment and to avoid damage from sustained signaling.Seven GPCR kinases(GRKs)phosphorylate and regulate the activity of most of the^800 GPCRs in the human genome.Although GRKs normally play an adaptive role,in conditions such as chronic heart failure they are overexpressed and linked to disease progression.GRK2 and GRK5 have thus become important targets for the treatment of heart failure and pathological cardiac hypertrophy,respectively.Our lab has determined atomic structures representing all three vertebrate GRK subfamilies,and is now in the midst of a campaign to develop selective inhibitors of these enzymes using structure-based rational design.We have identified the FDA approved drug paroxetine as a selective GRK2 inhibitor,determined the crystal structure of the GRK2·paroxetine complex and,in collaboration with the Koch lab,showed that the drug improves contractility in myocytes and,most impressively,recovery in postmyocardial infarcted mice.Since then,we have identified additional chemical scaffolds that exhibit even higher potency and/or selectivity for GRK5.Using a'hybrid'inhibitor design approach we have generated GRK selective chemical probes that exhibit improved potency and stability and are able to increase inotropy and dampen the hypertrophic response in cardiomyocytes and small animal models.Structural analysis has revealed the molecular basis for selectivity and potency in many of these compounds,allowing for the design of future generations of GRK chemical probes. | John J TESMER Helen V WALDSCHMIDT Marie C CATO Renee BOULEY Osvaldo CRUZ-RODRIGUEZ Scott D LARSEN | 2017 | 中国药理学与毒理学杂志2017，31，10： | 1 |
| 12 | Higher rates of autism and attention deficit/hyperactivity disorder in American children:Are food quality issues impacting epigenetic inheritance?显示文摘In the United States,schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals.Pediatricians may play a key role in helping children access special education services.The number of children ages 6-21 in the United States receiving special education services increased 10.4%from 2006 to 2021.Children receiving special education services under the autism category increased 242%during the same period.The demand for special education services for children under the developmental delay and other health impaired categories increased by 184%and 83%respectively.Although student enrollment in American schools has remained stable since 2006,the percentage distribution of children receiving special education services nearly tripled for the autism category and quadrupled for the developmental delay category by 2021.Allowable heavy metal residues remain persistent in the American food supply due to food ingredient manufacturing processes.Numerous clinical trial data indicate heavy metal exposures and poor diet are the primary epigenetic factors responsible for the autism and attention deficit hyperactivity disorder epidemics.Dietary heavy metal exposures,especially inorganic mercury and lead may impact gene behavior across generations.In 2021,the United States Congress found heavy metal residues problematic in the American food supply but took no legislative action.Mandatory health warning labels on select foods may be the only way to reduce dietary heavy metal exposures and improve child learning across generations. | Renee J Dufault Raquel A Crider Richard C Deth Roseanne Schnoll Steven G Gilbert Walter J Lukiw Amanda L Hitt | 2023 | World Journal of Clinical Pediatrics2023，12，2： | 1 |
| 13 | Analisys of mixed-mode fracture in concrete显示文摘 | Rots J G Rene de Borst | 1987 | Journal of Structural Engineering1987，3，11： | 1 |
| 14 | The Relationship Between Molecular Structure and Ion Adsorption on Variable Charge Minerals显示文摘 | Rene P J J Rietra Tjisse Hiemstra Willem H | 1999 | Geochimica et Cosmochimica Acta1999，63，1920： | 1 |
| 15 | Equiangular tight frames from Paley tournaments显示文摘 | Renes J M | 2007 | Linear Alg Appl2007，426，： | 1 |
| 16 | A plasma homocysteine concentrationbut not MTHFR Genotype is associated with variation in carotid plaquearea显示文摘 | DAVID SPENSE J RENE MALINOW M BARNETT PETE | 1999 | Stroke1999，30，： | 1 |
| 17 | Measuring the environmental load of household consumption using some methods based on input output energy analysis: A comparison of methods and a discussion of results 显示文摘 | Kok R Rene M J B Henri C M | 2006 | Energy Policy2006，34，17： | 1 |
| 18 | Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database显示文摘 | COHEN D P A RENES J BOUWMAN F G | | 0，，： | 1 |
| 19 | Critical National Infrastructure Reliability Modeling and Analysis显示文摘 | Stephen H Conrad Rene J LeClaire Gerard P O'Reilly | 2006 | Bell Labs Technical Journal2006，，： | 1 |
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