Background: The T helper 17 (Th17)/T regulatory (Treg) cell imbalance is involved in the course of obesity and type 2 diabetes mellitus (T2DM). In the current study, the exact role of glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on regulating the Th17/Treg balance and the underlying molecular mechanisms are investigated in obese diabetic mice model. Methods: Metabolic parameters were monitored in db/db mice treated with/without exenatide during 8-week study period. The frequencies of Th17 and Treg cells from peripheral blood and pancreas in db/db mice were assessed. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway in Th17 and Treg cells from the spleens of male C57BL/6J mice was detected by western blotting. In addition, the expression of glucagon-like peptide-1 receptor (GLP-1R) in peripheral blood mononuclear cells (PBMCs) of male C57BL/6J mice was analyzed. Results: Exenatide treatment improved β-cell function and insulitis in addition to glucose, insulin sensitivity and weight. Increased Th17 and decreased Treg cells in peripheral blood were present as diabetes progressed while exenatide corrected this imbalance. Progressive IL-17 + T cell infiltration of pancreatic islets was alleviated by exenatide intervention. In vitro study showed no significant difference in the level of GLP-1R expression in PBMCs between control and palmitate (PA) groups. In addition, PA could promote Th17 but suppress Treg differentiation along with down-regulating the phosphorylation of PI3K/Akt/FoxO1, which was reversed by exenatide intervention. FoxO1 inhibitor AS1842856 could abrogate all these effects of exenatide against lipid stress. Conclusions: Exenatide could restore systemic Th17/Treg balance via regulating FoxO1 pathway with the progression of diabetes in db/db mice. The protection of pancreatic β-cell function may be partially mediated by inhibiting Th17 cell infiltration into pancreatic islets, and the resultant alleviation of islet inflammation.

Ischaemia caused by lower extremity artery stenosis is the main cause of peripheral artery disease (PAD) in patients with diabetes. Trimetazidine (TMZ) has traditionally been used as an anti-ischae...

Introduction. Diagnosis of uveitis is challenging due to the multitude of possible pathogenies. Identifying infectious and non-infectious uveitis is of great clinical significance. Recently, metagenomic next-generation sequencing (mNGS) was used to detect infectious and non-infectious uveitis, but its efficacy has not been widely evaluated. Hypothesis. Compared with routine diagnostic tests (RDTs), mNGS is more effective in identifying infectious and non-infectious uveitis. Aim. To describe the microbiological diagnostic performance of mNGS in detecting infectious and non-infectious uveitis. Methodology. Patients with suspected infectious uveitis of uncertain pathogenesis were tested by mNGS and RDTs. Infectious and non-infectious uveitis were grouped according to the final diagnosis based on comprehensive analysis of the test results and the effect of therapy. The test results were used to assess the performance of mNGS in actual clinical practice. Results. Fifty-eight cases were enrolled in this project, including 32 cases of infectious uveitis and 26 cases of non-infectious uveitis. The sensitivity of mNGS was 96.88%, which was much higher than that of RDTs. The detected pathogenic micro-organisms included bacteria, fungi, viruses, Toxoplasma gondii and Bartonella. Consequently, mNGS showed a high negative predictive value (NPV) of 94.74%, indicating that an mNGS negative should be a true negative result most of the time, but a low positive predictive value (PPV) of 79.49%. Conclusions. mNGS showed extremely high sensitivity but low specificity, which increased the detection rate of infectious uveitis pathogens but might result in false positives. The excellent NPV suggested that the identification of non-infectious uveitis is of considerable clinical importance.