Formation of Acetylene Dicarboxylic Acid and Its Esters with 2-Butyne-1,4-diol from 2-Butyne-1,4-diol by Fusarium merismoides B11

Several kinds of compounds were formed by Fusarium merismoides Bll when the fungus was grown in the medium containing 2-butyne-1,4-diol as the sole source of carbon. Four of these compounds were isolated by thin-layer chromatography and identified as acetylene dicarboxylic acid, an ester of acetylene dicarboxylic acid with 2-butyne-1,4-diol, an acetylated derivative of the ester, and cis-aconitic acid.     

Nephroprotective potential of Quercus infectoria galls against experimentally induced diabetic nephropathy in rats through inhibition of renal oxidative stress and TGF-β

Diabetic nephropathy (DN) is the leading cause of death in diabetic patients and the current treatment options available have a limited significance. The insect galls of Quercus infectoria are traditionally important in the treatment of numerous diseases including diabetes. Hence, the present study was undertaken to evaluate the effect of Q. infectoria gall extract (QIGE) against experimental DN. Type 2 diabetes was induced by feeding rats with a high-fat diet (HFD) initially for 5 weeks, followed by a single intraperitoneal injection of streptozotocin (STZ, 35?mg/kg?bw/day). QIGE was administered to the rats orally at doses of 100 and 200?mg/kg?bw/day, respectively. At the end of the experimental period, various glycemic and renal function parameters were evaluated in the serum, urine and kidney tissues. The QIGE treatment significantly (p?p?via the inhibition of hyperglycemia-induced oxidative stress and renal TGF-β expression and is, therefore, a potential therapeutic agent in the treatment of diabetic complications, especially DN.     

中草药干预糖尿病肾病炎症的作用

随着糖尿病发病率逐年升高,糖尿病肾病成为导致慢性肾脏疾病和终末期肾脏疾病的主要原因。而目前控制血糖及抑制肾素-血管紧张素系统的药物治疗,并不能有效防止糖尿病肾病进展。近年来发现,慢性低水平炎症和免疫系统激活在糖尿病性肾病的发生及发展中起着至关重要的作用。明确糖尿病肾病进展中的炎症机制将有助于确定新的潜在靶点及研发抗炎治疗策略。越来越多的证据表明,中药治疗可以有效改善糖尿病性肾病的高血糖和蛋白尿,并能延缓其进展成为终末期肾病。糖尿病肾病动物实验和体外研究证实中药复方、中草药提取物和中药单体具有调节炎症介质的作用。本文旨在归纳总结文献中与糖尿病肾病肾损伤相关的炎症分子和途径,并探讨中草药靶向抗炎治疗糖尿病肾病的作用。     

丝胶对糖尿病肾病大鼠肾脏TGF-β_1/Smad3信号通路的作用

目的：观察彩色蚕茧提取物—丝胶对糖尿病肾病大鼠肾脏转化生长因子-β1（TGF-β1）和Smad3蛋白表达的影响。方法：60只雄性SD大鼠随机分为5组（n=12）：正常对照组、糖尿病肾病模型组、丝胶治疗组、二甲双胍组和丝胶预防组。模型组、丝胶治疗组、丝胶预防组和二甲双胍组大鼠均建立链脲佐菌素（STZ）致动物模型,以血糖≥16.7 mmol/L作为成模标准;待模型成功建立后,丝胶治疗组大鼠给予丝胶灌胃（2.4 g/（kg.d）,35 d）、二甲双胍组大鼠给予二甲双胍灌胃（55.33 mg/（kg.d）,35 d）,丝胶预防组大鼠于注射STZ前给予同等剂量丝胶灌胃35天。分别检测各组大鼠血糖和肾重/体重;免疫组化染色观察肾脏TGF-β1蛋白的表达;Western blot法观察肾脏Smad3蛋白的表达。结果：与正常对照组大鼠相比,模型组大鼠血糖、肾重/体重和肾脏TGF-β1、Smad3蛋白的表达均明显升高（P〈0.01）。丝胶治疗组、丝胶预防组和二甲双胍组大鼠的血糖和肾脏TGF-β1、Smad3蛋白的表达明显低于模型组（P〈0.01）,且丝胶治疗组、丝胶预防组与二甲双胍组比较无明显差别（P〉0.05）;丝胶治疗组、丝胶预防组和二甲双胍组大鼠的肾重/体重明显低于模型组（P〈0.01）,且丝胶治疗组、丝胶预防组大鼠的肾重/体重明显低于二甲双胍组（P〈0.05）。结论：丝胶可抑制糖尿病肾病大鼠肾脏TGF-β1/Smda3信号通路的激活,减轻肾小球硬化和肾间质纤维化,发挥对糖尿病肾病肾脏损伤的保护和预防保护作用,且作用与二甲双胍相当。     

糖、脂代谢及氧化应激与糖尿病肾病的相关性

糖尿病肾病是糖尿病的主要并发症之一。近年来,糖尿病肾病的发病率呈逐渐上升趋势。研究发现,糖、脂代谢与糖尿病肾病的发生密切相关,而氧化应激也在糖、脂代谢异常中起重要作用。本文综述了有关糖、脂代谢与糖尿病肾病相关性研究,以及硫氧还蛋白及硫氧还蛋白结合蛋白2在糖尿病肾病发生中的作用。     

Decoding telomere protein Rap1: Its telomeric and nontelomeric functions and potential implications in diabetic cardiomyopathy

Mammalian Rap1, the most conserved telomere-interacting protein, beyond its role within nucleus for the maintenance of telomeric functions, is also well known for its pleiotropic functions in various physiological and pathological conditions associated with metabolism, inflammation and oxidative stress. For all these, nowadays Rap1 is the subject of critical investigations aimed to unveil its molecular signaling pathways and to scrutinize the applicability of its modulation as a promising therapeutic strategy with clinical relevance. However, the underlying intimate mechanisms of Rap1 are not extensively studied, but any modulation of this protein level has been associated with pathologies like inflammation, oxidative stress and deregulated metabolism. This is considerably important in light of the recent discovery of Rap1 modulation in diseases like cancer and cardiac metabolic disorders. In this review, we focus on both the telomeric and nontelomeric functions of Rap1 and its modulation in various health risks, especially on the heart.     

mTOR信号通路在糖尿病肾病发病机制中的研究进展

糖尿病肾病（diabetic nephropathy,DN）是糖尿病最常见的并发症之一,因其具有高发病率且与晚期肾病、心血管疾病和过早死亡等风险相关,糖尿病肾病已成为全球性的公共健康问题,但目前其发病机制尚不清楚。雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）是一种丝氨酸/苏氨酸的蛋白酶,在延迟细胞凋亡以及促进细胞分裂、细胞存活、血管生成中发挥着重要作用。近年来有研究表明,mTOR存在于DN进展的关键步骤中,包括自噬、炎症及氧化应激等。因此,就mTOR介导的自噬、炎症及氧化应激信号通路在DN发病机制中的相关研究进展做一综述,以期为DN治疗及预防提供理论参考。     

Sex-specific associations of variants in regulatory regions of NADPH oxidase-2 (CYBB) and glutathione peroxidase 4 (GPX4) genes with kidney disease in type 1 diabetes

Abstract

Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2, encoded by the CYBB gene) and the antioxidant enzyme glutathione peroxidase 4 (GPX4) play opposing roles in the balance of cellular redox status. In the present study, we investigated associations of single nucleotide polymorphisms (SNPs) in the regulatory regions of CYBB and GPX4 with kidney disease in patients with type 1 diabetes. Two functional SNPs, rs6610650 (CYBB promoter region, chromosome X) and rs713041 (GPX4 3'untranslated region, chromosome 19), were genotyped in 451 patients with type 1 diabetes from a Brazilian cohort (diabetic nephropathy: 44.6%) and in 945 French/Belgian patients with type 1 diabetes from Genesis and GENEDIAB cohorts (diabetic nephropathy: 62.3%). The minor A-allele of CYBB rs6610650 was associated with lower estimated glomerular filtration rate (eGFR) in Brazilian women, and with the prevalence of established/advanced nephropathy in French/Belgian women (odds ratio 1.75, 95% CI 1.11–2.78, p = 0.016). The minor T-allele of GPX4 rs713041 was inversely associated with the prevalence of established/advanced nephropathy in Brazilian men (odds ratio 0.30, 95% CI 0.13–0.68, p = 0.004), and associated with higher eGFR in French/Belgian men. In conclusion, these heterogeneous results suggest that neither CYBB nor GPX4 are major genetic determinants of diabetic nephropathy, but nevertheless, they could modulate in a gender-specific manner the risk for renal disease in patients with type 1 diabetes.     

Metabolic memory: mechanisms and implications for diabetic vasculopathies

In the past decades, a persistent progression of diabetic vascular complications despite reversal of hyperglycemia has been observed in both experimental and clinical studies. This durable effect of prior hyperglycemia on the initiation and progression of diabetic vasculopathies was defined as “metabolic memory”. Subsequently, enhanced glycation of cellular proteins and lipids, sustained oxidative stress, and prolonged inflammation were demonstrated to mediate this phenomenon. Recently, emerging evidence strongly suggests that epigenetic modifications may account for the molecular and phenotypic changes associated with hyperglycemic memory. In this review, we presented an overview on the discovery of metabolic memory, the recent progress in its molecular mechanisms, and the future implications related to its fundamental research and clinical application.