微小核糖核酸对糖尿病足溃疡的作用机制研究及应用进展

糖尿病足溃疡是糖尿病最常见的并发症之一，目前缺乏有效的治疗手段。微小核糖核酸(miRNA)是调节创面愈合的核心因子，通过与靶基因相互作用，参与了糖尿病足溃疡愈合过程中关键细胞(内皮细胞、成纤维细胞、角质形成细胞)的病理反应。本文就这些与糖尿病足溃疡相关的miRNA对关键细胞的作用机制作一综述，并总结了目前通过人工合成特异性miRNA来促进创面愈合的相关实验研究，为临床治疗糖尿病足溃疡提供了新的思路和方法。     

Micro-ribonucleic acid modulation with oxidative stress and inflammation in patients with type 2 diabetes mellitus – a review article

In parallel with the rapid growth of obesity, there is also an increase in the prevalence of type 2 diabetes mellitus (T2D) worldwide. Due to its complications, cardiovascular diseases are the leading cause of death in those patients. In the last two decades, special attention has been given to oxidative stress and inflammation, as the underlying mechanisms related to T2D occurrence and progression. Moreover, micro-ribonucleic acids (miRNAs) as new genetic biomarkers take an important place in the investigation of different metabolic pathways of insulin signaling. In this review article, we discuss microRNA modulation with oxidative stress and inflammation in patients with T2D. Better insight into the novel potential therapeutic targets for treatment of diabetes and its complications is of utmost importance for public health.     

Molecular aspects of chronic hyperglycemia-induced tissue damage

The knowledge of the molecular basis of diabetes mellitus physiopathology will allow improvements in treatment or prevention of the disease. Diabetes mellitus is a complex disease in which hyperglycemia leads to complications in several organs. In this condition, there is increase in reactive oxygen species (ROS) as a result of glucose autooxidation; its metabolism produces accumulation of metabolites such as fructose, sorbitol, and triose phosphate. The latter generates a oxoaldehydes with high capacity to produce protein glycation and oxidative stress. Moreover, there is an increase in synthesis of diacylglycerol from triosephosphate, which activates protein kinase C. On the other hand, alteration of normal ratio between reduced and oxidized niacinamide nucleotides leads to low efficiency of antioxidative systems. Finally, this metabolic dysregulation causes altered signal transduction, abnormal gene expression, and tissue damage, resulting in development of diabetic complications.     

miRNAs as cornerstones in diabetic microvascular complications

Diabetes mellitus is usually accompanied by nephropathy, retinopathy, and neuropathy as microvascular complications. MicroRNAs (miRNAs) can affect the kidney, retina, and peripheral neurons through their implication in pathways involved in angiogenesis, inflammation, apoptosis, as well as fibrosis within these tissues and hence, play a crucial role in the pathogenesis of microvascular complications. In this review, the updated knowledge of the role of miRNAs in the pathogenesis of diabetic microvascular complications was summarized. PubMed Central was searched extensively to retrieve data from a wide range of reputable biomedical reports/articles published after the year 2000 to systematically collect and present a review of the key molecular pathways mediating the hyperglycemia-induced adverse effects on vascular tissues, particularly in persons with T2DM. In the present review, miR-126, miR-29b, and miR-125a are implicated in diabetes-induced microvascular complications, while miR-146a is found to be connected to all these complications. Also, vascular endothelial growth factors are noted to be the most impacted targets by miRNAs in all diabetic microvascular problems.     

妊娠合并糖尿病母婴预后分析

目的总结分析妊娠合并糖尿病对孕产妇及围产儿结局的影响.方法回顾性分析我院10年来产科住院分娩的19例妊娠合并糖尿病人及34例健康孕妇的母婴预后情况.结果糖尿病组病理妊娠、羊水过多、胎婴儿并发症、早产、围产儿死亡、畸形发生率分别为78.9%、15.8%、100%、57.9%、15.8%,高于对照组50%、0%、41.2%、0%、0%.结论糖尿病严重影响母婴健康.对于孕妇,主要是造成羊水过多;对于胎婴儿,主要是引起早产、围产儿死亡及畸形.以上各项均与母体孕期血糖控制情况相关,尤其是围产儿死亡,未治疗者围产儿死亡率很高.     

Non-coding RNA-based regulation of inflammation

Inflammation is a multifactorial process and various biological mechanisms and pathways participate in its development. The presence of inflammation is involved in pathogenesis of different diseases such as diabetes mellitus, cardiovascular diseases and even, cancer. Non-coding RNAs (ncRNAs) comprise large part of transcribed genome and their critical function in physiological and pathological conditions has been confirmed. The present review focuses on miRNAs, lncRNAs and circRNAs as ncRNAs and their potential functions in inflammation regulation and resolution. Pro-inflammatory and anti-inflammatory factors are regulated by miRNAs via binding to 3'-UTR or indirectly via affecting other pathways such as SIRT1 and NF-κB. LncRNAs display a similar function and they can also affect miRNAs via sponging in regulating levels of cytokines. CircRNAs mainly affect miRNAs and reduce their expression in regulating cytokine levels. Notably, exosomal ncRNAs have shown capacity in inflammation resolution. In addition to pre-clinical studies, clinical trials have examined role of ncRNAs in inflammation-mediated disease pathogenesis and cytokine regulation. The therapeutic targeting of ncRNAs using drugs and nucleic acids have been analyzed to reduce inflammation in disease therapy. Therefore, ncRNAs can serve as diagnostic, prognostic and therapeutic targets in inflammation-related diseases in pre-clinical and clinical backgrounds.     

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Diabetes mellitus is one of the most serious public health challenges of the twenty-first century. Allogenic islet transplantation is an efficient therapy for type 1 diabetes. However, immune rejection, side effects of immunosuppressive treatment as well as lack of sufficient donor organs limits its potential. In recent years, several promising approaches for generation of new pancreatic β cells have been developed. This review provides an overview of current status of pancreatic and extra-pancreatic stem cells differentiation into insulin-producing cells and the possible application of these cells for diabetes treatment. The PubMed database was searched for English language articles published between 2001 and 2012, using the keyword combinations: diabetes mellitus, differentiation, insulin-producing cells, stem cells.     

Markers of endocrine system and inflammation as prognostic risk factors of vascular complications of type 2 diabetes mellitus

The high risk of cardiovascular complications in patients with type 2 diabetes mellitus is a key problem in modern medicine. In this review, the basic risk factors of vascular complications in diabetes mellitus are described and their prognostic value analysed. Special attention is paid to the evaluation of the role of adipose tissue hormone adiponectin. The anti-inflammatory properties of adiponectin suggest its protective action against atherosclerosis and cardiovascular complications. In this article, we review a number of studies on the relationship between adiponectin and the main cardiovascular risk factors in patients with type 2 diabetes mellitus.     

糖尿病并发抑郁症的研究进展

抑郁症在糖尿病人群中的发病率显著高于非糖尿病人群,是糖尿病的重要并发症之一。抑郁与下丘脑-垂体-肾上腺素轴的活动相关,可导致升糖激素增多,胰岛素分泌水平降低。近年来,糖尿病并发抑郁症的潜在机制研究愈来愈受到医学界的重视。高血糖氧化应激状态下产生的过多自由基,以及与之伴随的高分子氧化损伤可能在糖尿病诱导抑郁的发生过程中起到重要作用。同时,炎症与线粒体的功能损伤可能也参与了抑郁在糖尿病患者的发生发展过程。糖尿病引发的神经系统的改变,包括神经递质的改变,重要区域的结构变化,神经细胞凋亡的发生等,都可能是其抑郁症高发的原因。本文主要阐述糖尿病并发抑郁症的研究进展。     

miRNAs at the heart of the matter

Cardiovascular disease is among the main causes of morbidity and mortality in developed countries. The pathological process of the heart is associated with altered expression profile of genes that are important for cardiac function. MicroRNAs (miRNAs) have emerged as one of the central players of gene expression regulation. The implications of miRNAs in the pathological process of cardiovascular system have recently been recognized, representing the most rapidly evolving research field. Here, we summarize and analyze the currently available data from our own laboratory and other groups, providing a comprehensive overview of miRNA function in the heart, including a brief introduction of miRNA biology, expression profile of miRNAs in cardiac tissue, role of miRNAs in cardiac hypertrophy and heart failure, the arrhythmogenic potential of miRNAs, the involvement of miRNAs in vascular angiogenesis, and regulation of cardiomyocyte apoptosis by miRNAs. The target genes and signaling pathways linking the miRNAs to cardiovascular disease are highlighted. The applications of miRNA interference technologies for manipulating miRNA expression, stability, and function as new strategies for molecular therapy of human disease are evaluated. Finally, some specific issues related to future directions of the research on miRNAs relevant to cardiovascular disease are pinpointed and speculated.     

滨海新区糖尿病并发症的发病情况及其影响因素分析

目的 探讨滨海新区糖尿病并发症发病情况及影响因素,为各级预防提供依据。方法 选取2015年1月1日~2017年12月30日在海滨新区七家医院就诊的糖尿病患者24697例,根据是否存在并发症分为伴有并发症组（6216例）和不伴有并发症组（18481例）,比较两组患者的性别、年龄、民族、职业、家庭住址等一般资料和临床资料,分析可能影响糖尿病并发症的危险因素。结果 ①两组患者性别、年龄、职业以及糖尿病诊断分型情况比较,差异有统计学意义（P＜0.05）;②多因素Logistics回归分析显示,年龄（OR=1.011,95%CI=1.000~1.020）、2型糖尿病（OR=2.650,95%CI=1.137~6.160）以及职业为国家机关、党群组织、企事业单位负责人（OR=1.769,95%CI=1.470~2.120）是糖尿病并发症的独立危险因素,而农、林、牧、渔、水利业生产人员（OR=0.647,95%CI=0.520~0.810）和生产、运输设备操作人员（OR=0.902,95%CI=0.833~0.968）,以及男性（OR=0.943,95%CI=0.887~1.016）是糖尿病并发症的保护因素。结论 疾控中心应重点关注高龄、女性、2型糖尿病患者,以及职业为国家机关、党群组织、企事业单位负责人的人群,为其提供积极干预措施,降低糖尿病并发症的发生风险。     

Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy

Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of diabetes mellitus. The pathogenesis of DSPN is not fully elucidated, but it is certainly multifactorial in nature and attributable to metabolic and microvessel disorders related to chronic hyperglycemia, diabetes duration, and several cardiovascular risk factors. Early diagnosis and appropriate management are extremely important, since up to 50% of DSPN cases may be asymptomatic, and patients are unaware of foot injury leading to foot ulcers and amputation. Simple, validated tests such as the Neuropathy Disability Score and/or Vibration Perception Threshold may be used to diagnose DSPN. Similarly, neurological dysfunction screening questionnaires should be used to assess the quality and severity of DSPN symptoms. Using both methods enables prediction of the prognosis of diabetic patients with DSPN. No causative treatment of DSPN is known, but the results of clinical trials indicate that several treatment options are highly effective in symptomatic treatment of painful DSPN. The appropriate treatment of DSPN may improve the outcome, preventing or delaying the development of numerous diabetic complications.     

MicroRNA single-nucleotide polymorphisms and diabetes mellitus: A comprehensive review

Diabetes mellitus (DM) has become the third major chronic non-communicable disease affecting global public health, following cancer and cardiovascular and cerebrovascular diseases. Although previous studies have found a correlation between microRNA (miRNA) and the development of DM, thus far, most reviews have focused on the studies describing the changes in miRNA expression profiles and the mechanisms by which miRNAs-induce DM. However, reviews summarizing the effect of miRNA single-nucleotide polymorphisms on the developmental stages of DM and its complications are still needed. Studies on the variation of miRNAs will not only help to further understand the role that genetic factors play in DM, but will also have important implications for treatment and disease prognosis.     

糖基化终产物(AGEs)的病理意义及其抑制性药物开发原理的研究进展

糖基化终产物(AGEs)是体内蛋白质与还原糖在无酶条件下发生反应后的产物。AGEs与糖尿病及其并发症、血管疾病、衰老以及肾脏疾病等密切相关。本文从AGEs的产生过程、生理作用的分子机制、病理意义以及采用药物干预糖基化终产物的形成和生物学效应等方面进行了综述。     

Insulin-producing cells derived from stem/progenitor cells: therapeutic implications for diabetes mellitus

One of the most common diseases of the pancreas is diabetes mellitus. The current treatment of exogenous insulin supply is not fully capable of achieving tight control of glucose regulation, leading to long-term complications. Hence, recent success in islet transplantation-based therapies for diabetes mellitus and the extreme shortage of pancreatic islets have motivated recent efforts to develop renewable sources of islet-replacement tissue. Of clinical interest, I review the recent progress on stem cell-based strategies for diabetes in view of regenerative medicine.     

Immunohistochemical localization of advanced glycosylation end products in coronary atheroma and cardiac tissue in diabetes mellitus.

Advanced glycosylation end products (AGEs) accumulate on long-lived extracellular matrix proteins and have been implicated in the micro- and macrovascular complications of diabetes mellitus. Within the arterial wall, AGE-modified proteins increase vascular permeability, inactivate nitric oxide activity, and induce the release of growth-promoting cytokines. Recently developed anti-AGE antibodies were used in an immunohistochemical analysis of coronary arteries obtained from type II diabetic and nondiabetic patients. High levels of AGE reactivity were observed within the atherosclerotic plaque present in vessels from selected patients with diabetes. Considered together with the pathological effects of AGEs on vascular wall homeostasis, these data support the role of advanced glycosylation in the rapidly progressive atherosclerosis associated with diabetes mellitus.     

Autologous stem cell transplantation for early type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is the result of the autoimmune response against pancreatic insulin producing beta cells. This autoimmune response begins months or even years before the first presentation of signs and symptoms of hyperglycemia and at the time of clinical diagnosis near 30% of beta-cell mass still remains. In daily clinical practice, the main therapeutic option for T1DM is multiple subcutaneous insulin injections that are shown to promote tight glucose control and reduce much of diabetic chronic complications, especially microvascular complications. Another important aspect related to long-term complications of diabetes is that patients with initially larger beta-cell mass suffer less microvascular complications and less hypoglycemic events than those patients with small beta-cell mass. In face of this, beta-cell preservation is another important target in the management of type 1 diabetes and its related complications. For many years, various immunomodulatory regimens were tested aiming at blocking autoimmunity against beta-cell mass and at promoting beta-cell preservation, mainly in secondary prevention trials. In this review, we summarize some of the most important studies involving beta-cell preservation by immunomodulation and discuss our preliminary data on autologous nonmyeloablative hematopoietic stem cell transplantation in newly-diagnosed T1DM.     

2型糖尿病及其并发症患者生活质量影响因素的研究

目的:了解2型糖尿病及其并发症患者的生命质量状况,并探讨其影响因素。方法:采用自编2型糖尿病患者生活质量量表(Qualityoflifescaleforpatientswithtype2diabetesmellitus,DMQLS)评价352例2型糖尿病和74例糖尿病伴并发症的患者的生命质量,并研究其影响因素。结果:糖尿病并发症组在疾病维度、生理维度、社会维度、心理维度、满意度维度5个领域及总分方面均显著低于无并发症组(P<0.01),性别、年龄、文化程度、收入、体力和脑力活动都不同程度地影响生活质量的不同方面,独居方式、自费和农民职业的患者生活质量显著低于其他组患者(P<0.01)。结论:完善糖尿病患者的医疗保健和服务系统,减少并发症的发生,加强心理和行为的健康教育和支持系统可改善糖尿病人的生活质量。     

Mechanisms behind the anti-inflammatory actions of insulin

The epidemic of diabetes mellitus is worsening worldwide. Diabetes mellitus is a chronic metabolic disease characterized by inappropriate recurrent or persistent hyperglycemia. Numerous studies have demonstrated that hyperglycemia, the most significant predictor of poor clinical outcome in diabetes mellitus patients, can directly promote an inflammatory response and oxidative stress. Although there are various causes of DM, all eventually lead to absolute or relative insulin deficiency and death of pancreatic β-cells. Thus, insulin inevitably becomes the primary medication used to treat the disease and prevent diabetic complications in all DM patients. Interestingly, an emerging body of evidence suggests that insulin suppresses the inflammatory process, not only through preventing hyperglycemia but also by modulating key inflammatory molecules. In this review, we discuss the findings of studies done in vitro as well as clinical trials that have demonstrated an anti-inflammatory action of insulin and that have pointed to mechanisms responsible for this effect. Further, we discuss how the anti-inflammatory action of insulin bears on our current understanding of the pathophysiology and complications of both type 1 and type 2 diabetes.