Diabetic cardiomyopathy (DCM), a common consequence of longstanding diabetes mellitus, is initiated by death of cardiomyocyte. Hyperglycemia-induced reactive oxygen species (ROS) overproduction is a major contributor of the chronic low-grade inflammation that characterizes as the DCM. ROS may promote the activation of nucleotide-binding oligomerization domain like receptor (NLR) pyrin domain containing 3 (NLRP3) inflammasome, a novel regulator of inflammation and cell death, by nuclear factor-kB (NF-κB) and thioredoxin interacting/inhibiting protein (TXNIP). NLRP3 inflammasome regulates the death of cardiomyocyte and activation of fibroblast in DCM, which is involved in the structural and functional disorder of DCM. However, comprehensive understanding of molecular mechanisms linking NLRP3 inflammasome and disorder of cardiomyocyte and fibroblast in DCM is lacking. Here, we review the molecular mechanism(s) of NLRP3 inflammasome activation in response to hyperglycemia in DCM.

Randomized controlled trials of exercise training in patients with HF and symptoms of depression were identified. The depression data were pooled using meta-analysis, and 19 studies were identified, with a total of 3447 patients, of which 16 (3226 patients) provided data for the meta-analysis. Exercise training demonstrated significant reductions in the symptoms of depression [standardized mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to −0.21], and its antidepressive effect was consistent in a number of HF groups, such as in ages under and over 65 years (SMD −0.14, 95% CI −0.22 to −0.07 vs. SMD −0.44, 95% CI −0.61 to −0.27) and EFs of <50% (SMD −0.38, 95% CI −0.56 to −0.20), as well as in a range of interventional strategies, including the aerobic mode (SMD −0.40, 95% CI −0.61 to −0.19), centre, home, or combined setting (SMD −0.61, 95% CI −0.95 to −0.27 vs. SMD −0.25, 95% CI −0.44 to −0.07 vs. SMD −0.13, 95% CI −0.21 to −0.05), and short or longer training programmes (≤12 weeks, SMD −0.50, 95% CI −0.73 to −0.27; 12-26 weeks, SMD −0.47, 95% CI −0.82 to −0.11; >26 weeks, SMD −0.12, 95% CI −0.20 to −0.04). The beneficial effects were preserved when blind design trials were considered (SMD −0.14, 95%

Autoimmunity is involved in the valvular damage caused by rheumatic heart disease (RHd). Increased evidence has linked microRNAs (miRNAs/miRs) to autoimmune disease. Signal transducer and activator of transcription 3 (STAT3) and sphingosine-1-phosphate receptor 1 (S1PR1) and suppressor of cytokine signaling 1 (SOcS1) have been widely studied for their roles in autoimmunity and inflammation. Thus, the current study aims to investigate the role played by miR-155-5p in RHd-induced valvular damage via the S1PR1, SOcS1/STAT3 and interleukin (IL)-6/STAT3 signaling pathways. An RHd rat model was induced by inactivated Group A streptococci and complete Freund's adjuvant. A recombinant adeno-associated virus (AAV-miR155-inhibitor) was used to inhibit the expression of miR-155-5p in the heart. Inflammation and fibrosis were assessed by hematoxylin and eosin staining and Sirius red staining. The expression of miR-155-5p in valvular tissues and serum exosomes was detected by reverse transcription-quantitative PcR. S1PR1, SOcS1, STAT3, phosphorylated STAT3, IL-6 and IL-17 protein expression was detected by western blotting and immunohistochemistry. The relationships between miR-155-5p and S1PR1 and SOcS1 were detected by dual luciferase assays. cytokine concentrations were measured by ELISA. The expression of miR-155-5p in valve tissues and serum exosomes was increased along with decreased S1PR1 and activated SOcS1/STAT3 signaling in the RHd model. The expression of IL-6 and IL-17 was increased in the valves and the serum. dual luciferase assays showed that miR-155-5p directly targeted S1PR1 and SOcS1. Inhibition of valvular miR-155-5p through AAV pretreatment increased S1PR1 expression and inhibited activation of the SOcS1/STAT3 signal pathway as a result of attenuated valvular inflammation and fibrosis as well as a decrease in IL-6 and IL-17 in the valves and serum. These results suggest that inhibition of miR-155-5p can reduce RHd-induced valvular damage via the S1PR1, SOcS1/STAT3 and IL-6/STAT3 signaling pathways.