Antigen-specific immunotherapies in type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the destruction of pancreatic beta cells, in which immune system disorder plays an important role. Finding a cure for T1DM and restoring beta cell function has been a long-standing goal. Research has shown that immune regulation with pancreatic islet auto-antigens may be the most specific and safe treatment for T1DM. Immunological intervention using diabetogenic auto-antigens as a target can help identify T1DM in high-risk individuals by early screening of autoantibodies (AAbs) before the loss of pancreatic islet function and thus achieve primary prevention of T1DM. However, induction of self-tolerance in patients with pre-diabetes can also slow down the attack of autoimmunity, and achieve secondary prevention. Antigen-based immune therapy opens up new avenues for the prevention and treatment of T1DM. The zinc transporter 8 (ZnT8) protein, presents in the serum of pre-diabetic and diabetic patients, is immunogenic and can cause T1D autoimmune responses. ZnT8 has become a potential target of humoral autoimmunity; it is of great significance for the early diagnosis of T1D. ZnT8-specific CD8+ T cells can be detected in most T1DM patients, and play a key role in the progression of T1D. As an immunotherapy target, it can improve the dysfunction of beta cells in T1DM and provide new ideas for the treatment of T1D. In this review, we summarize research surrounding antigen-specific immunotherapies (ASI) over the past 10 years and the ZnT8 antigen as an autoimmune target to induce self-tolerance for T1DM.

Novel insights into the consequences of obesity: a phenotype-wide Mendelian randomization study.

Obesity is thought to significantly impact the quality of life. In this study, we sought to evaluate the health consequences of obesity on the risk of a broad spectrum of human diseases. The causal effects of exposing to obesity on health outcomes were inferred using Mendelian randomization (MR) analyses using a fixed effects inverse-variance weighted model. The instrumental variables were SNPs associated with obesity as measured by body mass index (BMI) reported by GIANT consortium. The spectrum of outcome consisted of the phenotypes from published GWAS and the UK Biobank. The MR-Egger intercept test was applied to estimate horizontal pleiotropic effects, along with Cochran's Q test to assess heterogeneity among the causal effects of instrumental variables. Our MR results confirmed many putative disease risks due to obesity, such as diabetes, dyslipidemia, sleep disorder, gout, smoking behaviors, arthritis, myocardial infarction, and diabetes-related eye disease. The novel findings indicated that elevated red blood cell count was inferred as a mediator of BMI-induced type 2 diabetes in our bidirectional MR analysis. Intriguingly, the effects that higher BMI could decrease the risk of both skin and prostate cancers, reduce calorie intake, and increase the portion size warrant further studies. Our results shed light on a novel mechanism of the disease-causing roles of obesity.

Acute suppurative thyroiditis with thyroid metastasis from oesophageal cancer.

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RNA-Seq Revealed Novel Non-proliferative Retinopathy Specific Circulating MiRNAs in T2DM Patients.

Background: Diabetic retinopathy (DR) is a common diabetes complication and was considered as the major cause of blindness among young adults. MiRNAs are a group of small non-coding RNAs regulating the expression of target genes and have been reported to be associated with the development of DR in a variety of molecular mechanisms. In this study, we aimed to identify miRNAs that are differentially expressed (DE) in the serum of DR patients. Methods: We recruited 21 type 2 diabetes mellitus (T2DM) inpatients of Chinese Han ancestry, consisting of 10 non-proliferative DR patients (DR group) and 11 non-DR T2DM patients (NDR group). MiRNA was extracted from fasting peripheral serum and quantified by RNA-seq. The expression levels of miRNA were evaluated and compared between the two groups, with adjustments made for age differences. The validated target genes of miRNAs were subjected to a pathway analysis. We also constructed a weighted polygenic risk score using the DE miRNA and evaluated its predictive power. Results: Five miRNAs were DE between DR and NDR groups (p-Value ≤ 0.01, LFC ≥ 2 or LFC ≤-2). These included miR-4448, miR-338-3p, miR-190a-5p, miR-485-5p, and miR-9-5p. In total, these miRNAs were validated to regulate 55 target genes. Four target genes were found to overlap with the NAD metabolism, sirtuin, and aging pathway, which was thought to control the vascular growth and morphogenesis. The predictive power of our polygenic risk score was apparently high (AUC = 0.909). However, it needs to be interpreted with caution. Conclusion: In this study, we discovered novel DR-specific miRNAs in human serum samples. These circulating miRNAs may represent the pathological changes in the retina in response to diabetes and may serve as non-invasive biomarkers for early DR risk prediction.