Shanshan Zhou

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although considerable progress has been made in the diagnosis, treatment and prognosis of CVD, there is still a critical need for novel diagnostic biomarkers and new therapeutic interventions to decrease the incidence of this disease. Recently, there is increasing evidence that circulating miRNAs (miRNAs), i.e. endogenous, stable, single-stranded, short, non-coding RNAs, can be used as diagnostic biomarkers for CVD. Furthermore, miRNAs represent potential novel therapeutic targets for several cardiovascular disorders. In this review we provides an overview of the effects of several CVD; including heart failure, acute myocardial infarction, arrhythmias and pulmonary hypertension; on levels of circulating miRNAs. In addition, the use of miRNA as therapeutic targets is also discussed, as well as challenges and recommendations in their use in the diagnosis of CVD.

Heart failure (HF) is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS) in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2-) related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF.

Hyperglycemia-induced inflammation and apoptosis have important roles in the pathogenesis of diabetic cardiomyopathy. We recently found that a novel curcumin derivative, C66, is able to reduce the high glucose (HG)-induced inflammatory response. This study was designed to investigate the protective effects on diabetic cardiomyopathy and its underlying mechanisms. Pretreatment with C66 significantly reduced HG-induced overexpression of inflammatory cytokines via inactivation of nuclear factor-κB in both H9c2 cells and neonatal cardiomyocytes. Furthermore, we showed that the inhibition of Jun NH2-terminal kinase (JNK) phosphorylation contributed to the protection of C66 from inflammation and cell apoptosis, which was validated by the use of SP600125 and dominant-negative JNK. The molecular docking and kinase activity assay confirmed direct binding of C66 to and inhibition of JNK. In mice with type 1 diabetes, the administration of C66 or SP600125 at 5 mg/kg significantly decreased the levels of plasma and cardiac tumor necrosis factor-α, accompanied by decreasing cardiac apoptosis, and, finally, improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. Thus, this work demonstrated the therapeutic potential of the JNK-targeting compound C66 for the treatment of diabetic cardiomyopathy. Importantly, we indicated a critical role of JNK in diabetic heart injury, and suggested that JNK inhibition may be a feasible strategy for treating diabetic cardiomyopathy.

Gut microbiota** play important roles in the health and disease status of both humans and animals. Little is known about whether heat stress changes the composition of the gut microbiota in chicken. The aim of this study was to investigate the effects of heat stress on changes in caecal microbiota, including changes in growth performance as well as HSP70 and cortisol levels. Sixty 14-day-old female broilers were equally divided into 2 treatment groups with different housing temperatures for 28 D: a control group (C) at 24 to 26°C and a heat stress (HS) group at 34 to 38°C. The caecal contents of the broiler chicken were then extracted on days 1, 3, 7, 14, and 28. Genomic DNA was extracted and amplified based on the V3∼V4 hypervariable region of 16S rRNA high-throughput sequence analyses. The results showed that the average daily gain and average daily feed intake were significantly decreased and that the feed conversion ratio was increased by heat stress. The concentrations of HSP70 and cortisol in the serum were significantly increased. The composition of gut microbiota was influenced by heat stress** through beta diversity analysis and taxon-based analysis. In particular, at the phylum level the composition of Firmicutes, Tenericutes, and Proteobacteria in HS group was increased than that of C group, and Bacteroidetes and Cyanobacteria in HS group were reduced than that of C group. In addition, the composition of Anaeroplasma and Lactobacillus phyla in HS group were increased than that of C group, whereas the Bacteroides, Oscillospira, Faecalibacterium, and Dorea genera in HS group were decreased than that of C group. In conclusion, the gut microbiota in broilers were changed by heat stress. And the changes of the gut microbiota could provide the basis for further research on the heat stress.