Cardiac fibrosis is a common pathophysiological change associated with myocardial infarction (MI), and while there is evidence that miR-130a plays an important role in a variety of fibrotic diseases, its role in the cardiac fibrosis during MI is unclear. Our study aimed to assess miR-130a’s ability to modulate cardiac fibrosis post-MI and uncover its potential molecular mechanisms. miR-130a was significantly downregulated in infarcted myocardium and hypoxic cardiac fibroblasts (CFs), whereas TGF-β, α-SMA, collagen 1 (Col-1), and TGF-β receptor 1 (TGFBR1) were upregulated. We transfected mice with AAV-9 carrying miR-130a and found that miR-130a overexpression statistically improved cardiac function and reduced the area of cardiac fibrosis in mice post-MI. Eukaryotic transcriptome sequencing and dual-luciferase reporter assay results verified that Tgfbr1 was a target gene of miR-130a. miR-130a inhibition heightened Col-1, α-SMA, and TGFBR1 expressions and Smad3 phosphorylation levels in CFs; however, these increments were suppressed by the overexpression of miR-130a. Meanwhile, co-transfection with TGFBR1 weakened miR-130a’s ability to inhibit α-SMA and Col-1 expression. These findings suggest that miR-130a exerts antifibrotic properties by directly targeting TGFBR1 to regulate TGF-β/Smad signaling and inhibit the conversion of CFs to myofibroblasts. Thus, miR-130a is a promising therapeutic target for alleviating cardiac fibrosis. Graphical Abstract

Currently, acute myocardial infarction (AMI) is one of the leading causes of human health issues worldwide. The sudden and continuous occlusion of the coronary artery results in myocardial hypoxic-ischemic necrosis, which is accompanied by inflammatory infiltration and fibrosis, leading to pathological cardiac remodeling. Exosome-based therapy is a promising cell-free approach for repairing the ischemic myocardium. This study aimed to explore the effects and mechanism of human umbilical vein endothelial cells (HUVECs)-derived exosomes on AMI. The results indicated that the localized injection of HUVECs-derived exosomes in the infarcted area could significantly improve cardiac function in AMI mouse models. It could also ameliorate myocardial fibrosis and decrease infarct size after AMI. Additionally, HUVECs-derived exosomes had cardioprotective effects on the H9C2 cells in hypoxic culture conditions, including increased cell viability and decreased lactate dehydrogenase (LDH) release. In both the in-vivo and in-vitro experiments, HUVECs-derived exosomes could effectively inhibit cardiomyocyte apoptosis. The low expression levels of Bcl-2–associated X protein (Bax) and cleaved caspase-3, high expression levels of B-cell lymphoma 2 (Bcl-2), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) were detected in AMI mouse models treated with HUVECs-derived exosomes in-vivo. In conclusion, HUVECs-derived exosomes effectively enhanced cardiac function after AMI and inhibited cardiomyocyte apoptosis, which might be regulated through the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. Graphical Abstract

The benchmark dose (BMD) method has been increasingly used to assess the health risks of cadmium (Cd) in epidemiological studies. The aim of our study was to estimate the threshold levels of urinary Cd (UCd) using the BMD method in a general population of Jiangshan City, Zhejiang Province of China. In our study, a total of 934 people (469 men, 465 women) were recruited and morning urine samples were collected from all the participants. Levels of Cd, creatinine, and renal dysfunction indicators such as retinol binding protein (RBP), β2-microglobulin (β2-MG), and N-acetyl-b-glucosaminidase (NAG) in urine were detected for analysis of BMD and BMD low (BMDL) of UCd. RBP, β2-MG, and NAG in urine all correlated significantly (P < 0.001) with UCd except of age (P = 0.767). When the benchmark response (BMR) was 5%, the BMD/BMDL of UCd for RBP, β2-MG, and NAG was 1.69/ 0.89, 1.24/0.62, 0.85/0.49 μg/g Cr in men and 1.70/0.76, 1.35/0.64, 1.36/0.65 μg/g Cr in women, respectively. If the BMR was set at 10%, the BMD/BMDL of UCd for RBP, β2-MG, and NAG was 2.44/1.59, 2.09/1.30, 1.80/1.04 μg/g Cr in men and 2.43/1.53, 2.10/1.34, 2.31/1.37 μg/g Cr in women, respectively. Our results provided evidence for Cd-induced tubular effects in cadmium non-polluted areas in China. Both β2-MG and NAG were more sensitive than RBP in response to Cd exposure. But β2-MG was the most sensitive indicator in women, and NAG was the most sensitive one in men.

Dilated cardiomyopathy (DCM), a heterogeneous cardiomyopathy, is a major cause of heart failure and heart transplant. Currently, immunotherapy is believed to be an effective treatment method for DCM. However, individual differences are so obvious that the clinical effect is not satisfactory. In order to find immune-related biomarkers of DCM to guide treatment and improve clinical efficacy, we downloaded a GSE120895 dataset from the Gene Expression Omnibus (GEO) database using CIBERSORT and WGCNA algorithms in RStudio and visualizing the protein–protein interaction (PPI) network for key modules by Cytoscape, and finally obtained six hub genes. A GSE17800 dataset was downloaded from the GEO dataset to verify the diagnostic values of hub genes, MYG1, FLOT1, and ATG13, which were excellent. Our study revealed unpublished potential immune mechanisms, biomarkers, and therapeutic targets of DCM.