MicroRNAs,Parkinson’s Disease,and Diabetes Mellitus

Parkinson’s disease (PD) is a neurodegenerative disorder that affects 1% of the population over the age of 60. Diabetes Mellitus (DM) is a metabolic disorder that affects approximately 25% of adults over the age of 60. Recent studies showed that DM increases the risk of developing PD. The link between DM and PD has been discussed in the literature in relation to different mechanisms including mitochondrial dysfunction, oxidative stress, and protein aggregation. In this paper, we review the common microRNA (miRNA) biomarkers of both diseases. miRNAs play an important role in cell differentiation, development, the regulation of the cell cycle, and apoptosis. They are also involved in the pathology of many diseases. miRNAs can mediate the insulin pathway and glucose absorption. miRNAs can also regulate PD-related genes. Therefore, exploring the common miRNA biomarkers of both PD and DM can shed a light on how these two diseases are correlated, and targeting miRNAs is a potential therapeutic opportunity for both diseases.     

Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study

Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (≥ 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs 31.2%), coronary heart disease (17.1% vs 8.0%), and chronic kidney diseases (6.2% vs 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol·L⁻¹ (interquartile range (IQR): 5.80–9.29) vs 5.46 mmol·L⁻¹ (IQR: 5.00–6.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol·L⁻¹ (IQR: 1.67–2.76) vs 1.75 mmol·L⁻¹ (IQR: 1.27–2.01)), and systolic pressure (130 mmHg (IQR: 120–142) vs 122 mmHg (IQR: 110–137)) (1 mmHg = 133.3 Pa) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.     

基于ASP．NET的糖尿病网站设计与实现

网站根据湘雅二医院内分泌研究所中南大学糖尿痛中心的需求．结合当代计算机数据库管理技术和ASP．NET编程技术设计开发糖尿病网站系统。该网站采用B／S架构模式．SQLServer2005作为数据库管理系统,对网站进行设计和实现。通过网站树立了糖尿病中心形象,提高了糖尿病中心的知名度,人们可以不受地域和时间限制了解糖尿病中心的医疗信息,从中获得服务,网站也加强了糖尿病中心对科研资料的有效利用和资源共享。     

Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we elucidate the mechanisms of NET formation and their different implications in disease. We focused on autoinflammatory and cardiovascular disorders as the leading cause of death. Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms. Furthermore, NETosis can be considered as a source of autoantigens and maintains an inflammatory milieu promoting autoimmune diseases. Indeed, there is further need for research into the balance between NET induction, inhibition, and degradation in order to pharmacologically target NETs and their compounds without impairing the patient’s immune defense. This review may be of interest to both basic scientists and clinicians to stimulate translational research and innovative clinical approaches.     

Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice

Soluble epoxide hydrolase (sEH) is abundant in the brain, is upregulated in type 2 diabetes mellitus (DM2), and is possible mediator of ischemic injury via the breakdown of neuroprotective epoxyeicosatrienoic acids (EETs). Prophylactic, pre-ischemic sEH blockade with 4-[[trans-4-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]cyclohexyl]oxy]-benzoic acid (tAUCB) reduces stroke-induced infarct in normal and diabetic mice, with larger neuroprotection in DM2. The present study tested whether benefit occurs in normal and DM2 mice if tAUCB is administered after stroke onset. We performed 60 min middle cerebral artery occlusion in young adult male C57BL mice divided into four groups: normal or DM2, with t-AUCB 2 mg/kg or vehicle 30 min before reperfusion. Endpoints were (1) cerebral blood flow (CBF) by laser Doppler, and (2) brain infarct at 24 h. In nondiabetic mice, t-AUCB reduced infarct size by 30% compared to vehicle-treated mice in the cortex (31.4 ± 4 vs. 43.8 ± 3 (SEM)%, respectively) and 26% in the whole hemisphere (26.3 ± 3 vs. 35.2 ± 2%, both p < 0.05). In contrast, in DM2 mice, tAUCB failed to ameliorate either cortical or hemispheric injury. No differences were seen in CBF. We conclude that tAUCB administered after ischemic stroke onset exerts brain protection in nondiabetic but not DM2 mice, that the neuroprotection appears independent of changes in gross CBF, and that DM2-induced hyperglycemia abolishes t-AUCB-mediated neuroprotection after stroke onset.     

Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.     

Cloud based intelligent system for delivering health care as a service

The promising potential of cloud computing and its convergence with technologies such as mobile computing, wireless networks, sensor technologies allows for creation and delivery of newer type of cloud services. In this paper, we advocate the use of cloud computing for the creation and management of cloud based health care services. As a representative case study, we design a Cloud Based Intelligent Health Care Service (CBIHCS) that performs real time monitoring of user health data for diagnosis of chronic illness such as diabetes. Advance body sensor components are utilized to gather user specific health data and store in cloud based storage repositories for subsequent analysis and classification. In addition, infrastructure level mechanisms are proposed to provide dynamic resource elasticity for CBIHCS. Experimental results demonstrate that classification accuracy of 92.59% is achieved with our prototype system and the predicted patterns of CPU usage offer better opportunities for adaptive resource elasticity.     

Enhanced healing of full-thickness diabetic wounds using bioactive glass and Yunnan baiyao ointments

In order to accelerate the chronic wounds healing, we investigated the healing effects of bioactive glass and Yuunan baiyao ointments in streptozotocin-induced diabetic rats. The ointments were prepared by mixing 45S5 bioactive glass powder （16% weight） with Vaseline and different weight percentages of Yurman baiyao. Full-thickness defect wounds were created on the back of 130 SD rats and were randomly divided into 8 groups. The wound healing rates were calculated at 4, 7, 10, 14 and 21 days after surgery. The samples were harvested for further observations. Considering the wound closure rate, group 6 （with 5% Yuunan baiyao） has better wound healing performance than other diabetic groups. The lower inflammatory response was observed by gross observation and confirmed by the results of H＆E staining and TEM observation. Besides, the proliferation of fibroblasts, the formation of granulation tissue, as well as the vascularization, were improved in group 6 compared to other diabetic groups. All results suggest that bioactive glass and Yunnan baiyao ointments can accelerate the recovery of diabetes-impaired skin wounds, and comparing to other diabetic groups, group 6 （with 5% Yunnan baiyao） has better healing effect.     

Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: Potential applications to cardiovascular disease and diabetes

Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular disease (CVD)—the leading cause of death in the United States. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed toward treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary MS-based approaches—mass spectrometric immunoassay (MSIA) and MS/MS as MRM—for the analysis of plasma proteins and PTMs of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the high density lipoprotein (HDL) proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on HDL proteins from T2DM patients to provide examples of how these MS approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation, and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice.     

Glycated proteome: From reaction to intervention

Glycation, a nonenzymatic reaction between reducing sugars and proteins, is a proteome wide phenomenon, predominantly observed in diabetes due to hyperglycemia. Glycated proteome of plasma, kidney, lens, and brain are implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative diseases, cancer, and aging. This review discusses the strategies to characterize protein glycation, its functional implications in different diseases, and intervention strategies to protect the deleterious effects of protein glycation.