Inflammation and apoptosis are considered as two major pathological causes of human sarcopenia. The current understanding based on different models recognizes that apoptosis does not trigger inflammation, while emerging evidence indicates that inflammation can induce apoptosis. Here, we provide solid evidence to suggest that the inflammation-dependent downregulation of miR-532 causes apoptosis through targeting a proapoptotic gene BAK1 (BCL2 antagonist/killer 1). To identify miRNAs and genes that are aberrantly expressed in the muscle tissues of sarcopenia patients, we conducted two independent microarray analyses. In total, we identified 53 miRNAs and 69 genes with differential expression levels. Of these aberrantly expressed miRNAs, miR-532-3p showed the most obvious changes in sarcopenia tissues, and more importantly, it can be repressed by the well-known inflammatory inducer lipopolysaccharide (LPS) in vitro. According to gene-based microarray results and the predicted targets of miR-532-3p, we presumed that BAK1 was a putative target of miR-532-3p. Further in vitro and in vivo analyses verified that miR-532-3p could directly bind to the three prime untranslated region (3'-UTR) of BAK1 through the seed sequence CUCCCAC. In addition, we found that NFKB1 (also known as p50), a subunit of the transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), could specifically bind to the promoter region of miR-532-3p and repress its expression. Further analysis revealed that the activation of TLR4 (Toll-like receptor 4) signaling led to the translocation of p50 from the cytoplasm to the nucleus, where it repressed miR-532-3p expression and thus led to an increase of BAK1. The accumulated BAK1 activated its downstream apoptotic signaling pathways and resulted in apoptosis, eventually causing the pathogenesis underlying sarcopenia. Overall, our results uncovered a new mechanism by which the inflammation-dependent downregulation of miR-532-3p contributed to the pathogenesis of sarcopenia through mediating BAK1 expression.

In mammals, specificity protein 1 (SP1) was the first Cys2-His2 zinc finger transcription factor to be isolated within the specificity protein and Krüppel-like factor (Sp/KLF) gene family. SP1 regulates gene expression by binding to Guanine–Cytosine (GC)-rich sequences on promoter regions of target genes, affecting various cellular processes. Additionally, the activity of SP1 is markedly influenced by posttranslational modifications, such as phosphorylation, acetylation, glycosylation, and proteolysis. SP1 is implicated in the regulation of apoptosis, cell hypertrophy, inflammation, oxidative stress, lipid metabolism, plaque stabilization, endothelial dysfunction, fibrosis, calcification, and other pathological processes. These processes impact the onset and progression of numerous cardiovascular disorders, including coronary heart disease, ischemia-reperfusion injury, cardiomyopathy, arrhythmia, and vascular disease. SP1 emerges as a potential target for the prevention and therapeutic intervention of cardiac ailments. In this review, we delve into the biological functions, pathophysiological mechanisms, and potential clinical implications of SP1 in cardiac pathology to offer valuable insights into the regulatory functions of SP1 in heart diseases and unveil novel avenues for the prevention and treatment of cardiovascular conditions.

Aims: Cardiomyocyte apoptosis is an important factor leading to the occurrence and development of heart failure (HF), which is associated with high mortality of patients with cardiovascular diseases. This study aims to investigate the underlying mechanisms of HF in terms of expression and regulation patterns using bioinformatics and experimental validation. Methods and results: Two HF datasets were collected: a dataset GSE112056 downloaded from the GEO database (including mRNA and miRNA sequencing data) and another is the laboratory-owned mRNA dataset. Differential mRNAs and miRNAs in the two datasets were screened using the raw Bayesian approach method. Gene Ontology was used to perform functional enrichment analysis of the differential mRNAs and co-expression network analysis of the differential mRNAs, combined with nuclear transcription factors in the differential miRNAs and mRNAs for target gene prediction. A HF cell model was constructed using mouse cardiomyocytes (HL-1), and the role and mechanism of miRNA-103-3p-Hlf (hepatic leukaemia factor) in the process of HF was verified by cell transfection, luciferase reporter gene, WB, and qPCR. We found that Hlf gene expression was decreased in the HF model group and strongly correlated with FYCO1 (FYVE and coiled-coil domain-containing protein 1) gene, a phenomenon enriched in apoptotic autophagy-related pathways. MiR-103-3p expression was up-regulated in the HF model group, and its targeting correlation with Hlf was confirmed by luciferase activity assay. In the HL-1 cell model, miR-103-3p significantly promoted apoptosis and inhibited autophagy in HL-1 cells (all P < 0.05), and overexpression of the Hlf gene reversed this phenomenon, inhibiting apoptosis and promoting autophagy in HL-1 cells (all P < 0.05). Conclusions: MiR-103-3p affects myocardial cells apoptosis and autophagy by targeting Hlf, playing as a potential therapeutic biomarker for HF progression.

The mevalonate (MVA) pathway serves an important role in ventricular remodeling. Targeting the MVA pathway has protective effects against myocardial fibrosis. The present study aimed to investigate the mechanism behind these effects. Primary cultured cardiac fibroblasts from C57BL/6 mice were treated in vitro in 5 groups: i) negative control; ii) angiotensin II (Ang II) model (1x10‑5 mol/l); iii) Ang II + rosuvastatin (ROS); iv) Ang II + alendronate (ALE); and v) Ang II + fasudil (FAS). Collagen and crystal violet staining were used to assess morphological changes in cardiac fibroblasts. Reverse transcription quantitative PCR and western blotting were used to analyze the expression of key signaling molecules involved in the MVA pathway. Collagen staining in the ALE, FAS, and ROS groups was weak compared with the Ang II group, while the rate of cell proliferation in the ROS, ALE, and FAS groups was slower compared with that in the Ang II group. In addition, the expression of key signaling molecules in the MVA pathway, including transforming growth factor‑β1 (TGF‑β1), heat shock protein 47 (HSP47), collagen type I α1 (COL1A1), vascular endothelial growth factor 2 (VEGF2) and fibroblast growth factor 2 (FGF2), was decreased in the FAS and ROS groups compared with the Ang II model. Compared with the Ang II group, 3‑Hydroxy‑3‑Methylglutaryl‑CoA reductase (HMGCR) gene expression was significantly lowered in the drug intervention groups, whereas farnesyl pyrophosphate synthase (FDPS) expression was downregulated in the ALE group, but elevated in the FAS and ROS groups. Compared with that in the Ang II group, ras homolog family member A (RhoA) expression was downregulated in the FAS and ROS groups, whilst mevalonate kinase expression was reduced in the ROS group. Protein expression of TGF‑β1, COL1A1 and HSP47 were decreased following intervention with each of the three drugs compared with the Ang II group. Overall, rosuvastatin, aledronate and fasudil decreased the proliferation of myocardial fibroblasts and inhibited collagen synthesis. Rosuvastatin had the strongest protective effects against myocardial fibrosis compared with the other drugs tested, suggesting this to be a potential agent for the clinical treatment of cardiovascular disease.

A glucose-responsive and biodegradable copolymer, poly(ε-caprolactone)-b-poly(2-phenylboronic ester-1,3-dioxane-5-ethyl)methylacrylate (PCL-b-PPBDEMA), was synthesized by the combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The diblock copolymer could be easily prepared as a membrane containing insulin via a solution casting approach. The crystalline behaviour and thermal properties were investigated by POM and DSC. The results indicated that the PPBDEMA segments could destroy the crystallizability of the PCL segments. Glucose molecules could react with PPBDEMA, which led to the breakage of the phenylboronic acid molecules from the PBDEMA groups. PCL-b-PPBDEMA copolymer membranes as intelligent carriers could realize controlled insulin release via adjusting the glucose concentration. At the physiological pH, the membrane revealed a higher release rate of insulin after immersion in glucose solutions with high concentrations than that in glucose solutions with lower concentrations. In vitro cytotoxicity assays showed that the membrane is almost noncytotoxic.

BACKGROUND:Bariatric procedures such as left gastric artery ligation (LGAL) and sleeve gastrectomy (SG) have emerged as important procedures for treating morbid obesity. In this study, we compared the effects of LGAL vs. SG on obesity-induced adipose...