IL - 22与糖尿病关系的研究进展

目的 本文总结了近年来白细胞介素22 (interleukin 22, IL - 22)与糖尿病(diabetes mellitus，DM)发病关系的研究，希望能为DM的防治及病情评估提供较为可行的策略靶点。方法 本文资料来源于中国知网、PubMed等数据库，以IL - 22、糖尿病、胰岛素、糖异生等关键词进行检索得到。结果 IL - 22可增加胰岛素分泌、促进胰岛素信号转导及维持葡萄糖稳态，参与DM发生、发展及病情演变。结论 IL - 22可通过多个环节参与DM的发病及病情演变，以IL - 22为靶点对于防治DM具有重要参考价值。     

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.     

异牡荆素对非小细胞性肺癌细胞自我更新和凋亡的影响

目的研究异牡荆素(ISO)对非小细胞性肺癌(NSCLC)细胞的影响和潜在的机制。方法将A549和H1650细胞分别分为空白组、低剂量实验组(4μmol·L^-1 ISO)和高剂量实验组(16μmol·L^-1 ISO)。用噻唑蓝法检测NSCLC细胞活性,用肿瘤球形成实验检测NSCLC细胞的细胞球形成率,用Western blot法检测NSCLC细胞凋亡、自我更新、无翅型MMTV整合位点家族/β-连环蛋白(Wnt/β-catenin)信号通路相关蛋白的表达水平。结果与空白组比较,低、高剂量实验组中A549和H1650细胞在24,48和72 h的细胞活性均显著降低。低、高剂量实验组和空白组中A549细胞的细胞球形成率分别为(4.18±0.45)%,(2.01±0.67)%和(6.02±0.57)%,切割的半胱氨酸蛋白酶-3相对表达量分别为0.24±0.08,1.25±0.13和0.06±0.07,SRY相关高迁移率族盒蛋白-2相对表达量分别为0.49±0.04,0.25±0.03和1.00±0.09,Kruppel样因子4相对表达量分别为0.68±0.04,0.44±0.03和1.01±0.06,Wnt1相对表达量分别为0.63±0.06,0.28±0.04和1.00±0.06,β-catenin相对表达量分别为0.41±0.05,0.22±0.03和1.01±0.09;与空白组比较,低、高剂量实验组中A549细胞的上述指标的差异均有统计学意义(P<0.05,P<0.01)。上述3组中H1650细胞的上述指标也呈现一致的现象。结论ISO可能通过抑制Wnt/β-catenin信号通路来抑制NSCLC细胞活性和自我更新,并促进其凋亡。     

靶向MLL1-WDR5蛋白-蛋白相互作用抑制剂的研究进展

Mixed lineage leukemia 1(MLL1)是组蛋白甲基转移酶SET家族的成员之一。MLL1与WDR5、RbBP5、Ash2L和DPY-30组成MLL1甲基转移酶复合物调控组蛋白H3的第4位赖氨酸的甲基化水平，对造血系统的发育和血细胞的更新至关重要。部分白血病患者体内存在因MLL1基因易位而产生的致癌蛋白——MLL1融合蛋白，MLL1融合蛋白在发挥其致癌作用时需要功能完整的MLL1酶复合物，故靶向MLL1-WDR5的蛋白-蛋白相互作用成为治疗MLL1融合型白血病的潜在策略。本文对MLL1-WDR5蛋白-蛋白相互作用的生物学机制、结构信息以及抑制剂进行了系统的总结，并结合已报道数据对该领域进行了展望，以期为后续研究提供参考。