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| 1 | Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease显示文摘Non-alcoholic fatty liver disease(NAFLD)has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations.Fatty liver disease encompasses a spectrum of hepatic pathology,ranging from simple steatosis to non-alcoholic steatohepatitis,cirrhosis,hepatocellular carcinoma and end-stage liver disease.Moreover,NAFLD is often associated with other metabolic conditions,such as diabetes mellitus type 2,dyslipidemia and visceral obesity.The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities.Diet and physical exercise are considered the first line of treatment for patients with NAFLD,but their results on therapeutic efficacy are often contrasting.Behavior therapy is necessary most of the time to achieve a sufficient result.Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and,often,little evidence supporting the real efficacy.Despite the abundance of clinical trials,NAFLD therapy remains a challenge for the scientific community,and there are no licensed therapies for NAFLD.Urgently,new pharmacological approaches are needed.Here,we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules. | Alessandro Federico Claudio Zulli Ilario de Sio Anna Del Prete Marcello Dallio Mario Masarone Carmela Loguercio | 2014 | World Journal of Gastroenterology2014，20，45： | 10 |
| 2 | 甲状腺激素类似物的临床研究进展显示文摘甲状腺激素类似物发挥拟甲状腺激素的调脂、减重作用,甚至能改善充血性心力衰竭的血液动力学异常和非酒精性脂肪肝的代谢异常,并对糖尿病、胰岛素抵抗等代谢性疾病有良好的治疗前景,同时无心脏、骨骼及肌肉等不良反应,是目前治疗代谢性疾病的合适选择。本文主要介绍靶向特异的甲状腺激素类似物的在临床中的研究进展及应用前景。 | 唐清丽 薛元明 | 2015 | 药品评价2015，12，9： | 1 |
| 3 | CRISPR/Cas9敲低环氧合酶2表达对黄曲霉毒素B1诱导肝细胞核DNA损伤与脂质蓄积的影响显示文摘为探讨黄曲霉毒素B1(AFB1)诱导的肝细胞核DNA损伤与脂质蓄积的关系,以慢病毒质粒为载体,采用CRISPR/Cas9技术构建含靶向环氧合酶2(COX-2)编码基因(PTGS2)小向导RNA(sgRNA)的重组质粒,经测序验证成功后,制备假病毒感染HepG2细胞,构建稳定敲低COX-2表达的细胞.通过实时荧光定量PCR(qRT-PCR)和蛋白免疫印迹(WB)检测mRNA和蛋白水平,结果显示与HepG2-Cas9-NC对照细胞相比,HepG2-Cas9-PTGS2敲低细胞中PTGS2 mRNA与COX-2蛋白表达水平分别减少至(49.1±1.8)%和(48.1±0.7)%.给予细胞AFB1处理,通过WB和免疫荧光(IF)法检测DNA损伤标志物γH2AX的表达水平,结果显示处理组敲低细胞中,γH2AX蛋白水平和荧光焦点形成数目显著低于对照细胞(p<0.05);进一步检测脂质合成相关指标,发现敲低细胞中PPARγ蛋白、总胆固醇(TC)、总甘油三脂(TG)水平以及油红O染色阳性脂滴的分布密度,均显著低于对照细胞中(p<0.05).在敲低细胞中回补COX-2后给予AFB1处理,γH2AX蛋白水平和脂质分布密度均显著升高(p<0.05).综上,成功构建了HepG2-Cas9-PTGS2敲低细胞,并发现敲低COX-2表达对AFB1诱导的肝细胞核DNA损伤和脂质蓄积有显著抑制作用,为进一步研究靶向干预COX-2在外源化学物诱导肝细胞毒性中的作用机制提供了细胞模型和依据. | 韩佩宇 车琳 陈圆圆 江珊 段军燕 孙宝芳 何承勇 林育纯 林忠宁 | 2018 | 厦门大学学报(自然科学版)2018，57，5： | 0 |
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