Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats

Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus.     

端粒生物学与肿瘤治疗

端粒的生物学功能主要是保护染色体末端,避免核酸酶对染色体末端的降解,防止染色体之间发生融合和重排。大多数人类肿瘤细胞通常通过端粒酶活性的重新激活来延长端粒,从而稳定染色体端粒DNA的长度。端粒酶是由端粒酶逆转录酶和端粒酶RNA模板组成的具有特殊逆转录活性的核糖核蛋白复合物。抑制端粒酶阳性细胞中的端粒酶活性会导致细胞凋亡或衰老。目前有多种以端粒和端粒酶为靶点来进行肿瘤治疗的策略。     

Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat model of acute myocardial infarction

We used human angiopoietin-1 (hAng1)-modified mesenchymal stem cells (MSCs) to treat acute myocardial infarction (AMI) in rats. The hAng1 gene was transfected into cultured rat MSCs using an adenoviral vector. Five million hAng-transfected MSCs (MSC(Ang1)) or green fluorescent protein transfected MSCs (MSC(GFP)) or PBS only (PBS group) were injected intramyocardially into the inbred Lewis rat hearts immediately after myocardial infarction. MSC(Ang1) survived in the infarcted myocardium, and expressed hAng1 at both mRNA and protein levels. The vascular density was higher in the MSC(Ang1) and MSC(GFP) groups than in the PBS group. The measurements of infarcted ventricular wall thickness, infarction area, and left ventricular diameter indicated that heart remodeling was inhibited and heart function was improved in both the MSC(Ang1) and MSC(GFP) groups. However, in contrast to the MSC(GFP) group, the MSC(Ang1) group showed enhanced angiogenesis and arteriogenesis (by 11-35%), infarction area was reduced by 30% and the left ventricular wall was 46% thicker (P<0.05). The results indicated that hAng1-modified MSCs improved heart function, followed by angiogenic effects in salvaging ischemic myocardium and reduced cardiac remodeling.     

胰岛素样生长因子结合蛋白-1启动子的克隆与序列分析

用酚氯仿抽提法提取SD大鼠的肝脏基因组DNA,PCR扩增胰岛素样生长因子结合蛋白-1（IGFBP-1）启动子并克隆至pUC118载体。从含IGFBP-1启动子的质粒中酶切分离出IGFBP-1启动子并测序。PCR扩增出420bp的目的DNA片段,与文献报道的IGFBP-1启动子DNA大小一致。经正、反两方向序列分析显示,克隆的基因序列和GenBank数据库中的IGFBP-1启动子基因序列一致。以上结果表明克隆成功了IGFBP-1启动子基因,为构建具双向调节的胰岛素分泌调控基因质粒奠定了基础。     

微小RNA与肺癌耐药

肺癌细胞对化疗药物产生耐药性是目前肺癌化疗过程中遇到的主要问题。微小RNA（miRNA）是一类内源性非编码短链小分子RNA,它能调节细胞生长、凋亡和信号转导。miRNA的多态性与药物代谢和耐药形成密切相关,异常表达的miRNA对预测肺癌化疗药物敏感性有重要作用。调节特异miRNA的表达,将为克服肺癌耐药和选择个体化治疗开辟新的途径。     

随机、平行对照评价陶瓷膜室间隔缺损封堵器安全性和有效性

目的:随机、平行对照的临床试验验证先健科技(深圳)有限公司生产的TM陶瓷膜VSD封堵器治疗室间隔缺损的安全性及有效性。方法:根据试验的要求入选术前确诊为室间隔缺损的病人42例,随机分为实验组(A组)和对照组(B组),每组各21例,对A组病人植入CeraTM陶瓷膜VSD封堵器,对B组病人植入普通镍钛合金VSD封堵器,在超声心动图下或X线下观察室间隔缺损大小、位置、形态、类型,选择合适的封堵伞,经输送系统置入封堵器闭合VSD,分别于术前、术后24小时、术后30天、90天及术后180天进行随访,主要随访内容包括临床症状和体征、超声心动图、心电图、胸片、24小时动态心电图检查等。比较这两组患者的即刻手术成功率以及随访过程中终点事件发生率的不同。结果:试验组和对照组的成功率均为100%,残余分流率分别为0和4.8%,试验组的并发症发生率与对照组未见明显差异(P0.005)。结论:试验组与对照组安全性与疗效相当,应用国产陶瓷封堵器是安全、有效的。但由于该项技术是一项新技术,临床试验样本量较少,其安全性和疗效特别是中远期疗效仍需进一步观察。     

Selective gene therapy for human lung adenocarcinoma by tumor-specific expression of herpes simplex virus thymidine kinase gene

According to the fact that CEA gene expressed only in lung adenocarcinoma but not in normal lung cells, a retroviral expression vector (pCEATK) of the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by CEA promoter was constructed and introduced into CEA-producing human lung adenocarcinoma cells GL and non-CEA-producing HeLa cells. The expression of pCEATK and Ganciclovir (GCV) sensitivity of the transfected cells were tested in vitro and in vivo . pCEATK expressed only in CEA-producing GL cells but not in non-CEA-producing HeLa cells. The sensitivity to GCV of pCEATK-transfected GL was 992 times higher compared with that of the parental cell line and there was obvious "bystander effect" in vitro. HeLa cells transfected wtih pCEATK were still resistant to GCV. Injection of GCV resulted in significant regression of pCEATK-transfected GL tumors in nude mice. In addition, all mice with any fraction of GL cells expressing HSV-TK exhibited a significant reduction in tumor growth, including mice     

Short-term effects of wake- and bright light therapy on sleep in depressed youth

Chronotherapeutics are well established for the treatment of depression and associated sleeping problems in adults. However, effects are still understudied in adolescents. Two pilot studies highlighted the crucial role of sleep when it comes to the treatment of depression, by means of chronotherapeutics, in adolescents. The aim of the present study was to investigate the role of adjunctive wake therapy (WT) in addition to bright light therapy (BLT) with respect to sleep behaviors. In the present study, 62 depressed inpatients (aged 13–18 years; diagnosed with Beck Depression Inventory Revision) were randomly assigned to two groups: BLT only (BLT-group) and a combination of BLT and WT (COMB-group). After one night of WT adolescents in the COMB-group revealed longer sleep durations, time in bed, advanced sleep onset, less wakes during night and an improved sleep efficiency. However, one night of WT plus BLT had no additional effect on sleep parameters compared with BLT-group in the long run. Therefore, future studies should assess whether more nights of WT might lead to more sustainable effects.     

Methods for site-specific drug conjugation to antibodies

Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over traditional chemotherapy. Drugs and linkers have been the current focus of ADC development, in addition to antibody and target selection. Recently, however, the importance of conjugate homogeneity has been realized. The current methods for drug attachment lead to a heterogeneous mixture, and some populations of that mixture have poor in vivo performance. New methods for site-specific drug attachment lead to more homogeneous conjugates and allow control of the site of drug attachment. These subtle improvements can have profound effects on in vivo efficacy and therapeutic index. This review examines current methods for site-specific drug conjugation to antibodies, and compares in vivo results with their non-specifically conjugated counterparts. The apparent improvement in pharmacokinetics and the reduced off target toxicity warrant further development of this site-specific modification approach for future ADC development.