Int J Med Sci
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Increasing studies have shown that N6-methyladenosine (m6A) modification plays an important role in cardiovascular diseases. In this study, we systematically investigated the regulatory mode of m6A genes in myocardial infarction (MI) by combining bioinformatics analysis of clinical samples with animal experiments. We utilized gene expression data of clinical samples from public databases to examine the expression of m6A genes in heart tissues and found a large difference between the healthy control group and MI group. ⋯ Through GO enrichment analysis, we found that most differentially expressed genes between the two clusters were profibrotic. By means of WGCNA, we inferred that GJA4 might be a core molecule in the m6A regulatory network of MI. This study demonstrates that m6A regulators probably affects the immune-inflammatory response and fibrosis to regulate the process of MI, which provides a potential therapeutic target.
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Background: Focal adhesion kinase (FAK) is activated by mechanical stimulation and plays a vital role in distraction osteogenesis (DO), a well-established but lengthy procedure for repairing large bone defects. Both angiogenesis and osteogenesis contribute to bone regeneration during DO. However, the effects of ZINC40099027 (ZN27), a potent FAK activator, on angiogenesis, osteogenesis, and bone regeneration in DO remain unknown. ⋯ The ERK1/2-specific inhibitor PD98059 significantly hindered the effects of ZN27, suggesting the participation of FAK-ERK1/2 signaling in ZN27-enhanced angiogenesis and osteogenesis. As indicated by improved radiological and histological features, ZN27 induced active angiogenesis within the distraction area and accelerated bone regeneration in a rat DO model. Conclusion: Our results show that ZN27 targets FAK-ERK1/2 signaling to stimulate both angiogenesis and osteogenesis, and ZN27 accelerates bone regeneration in DO, suggesting the therapeutic potential of ZN27 for repairing large bone defects in the mechanobiological environment during DO.
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Background and Objectives: The rat Optimized Peritoneal Adhesion Model (OPAM) was developed to provoke adhesion formation with high reproducibility in incidence and extent. In a recent study, the starch-based hemostats 4DryField PH and Arista AH were tested for their capabilities to prevent adhesion formation, the former one certified for adhesion prevention and hemostasis, the latter one only certified for hemostasis. As two further starch-based hemostats, i.e., HaemoCer PLUS and StarSil, have officially been certified for adhesion prevention in the meantime, the present study was conducted to examine their efficacy. ⋯ When comparing 4DryField PH, HaemoCer PLUS and StarSil, 4DryField PH was significantly more effective in preventing peritoneal adhesions. The results of the macroscopic investigation were confirmed by histopathological evaluations. Conclusions: Only 4DryField PH but neither HaemoCer PLUS nor StarSil were capable to effectively prevent adhesion formation, corroborating the assumption that starch-based hemostats do not generally have the capability to act as effective adhesion prevention devices.
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Vascular calcification (VC) is a known predictor of cardiovascular events in patients with atherosclerosis and chronic renal disease. However, the exact relationship between VC and cardiovascular mortality remains unclear. Herein, we investigated the underlying mechanisms between VC progression, arterial stiffness, and cardiac dysfunction. ⋯ Hearts demonstrated higher levels of ANP, BNP, MMP2, and lower levels of bcl2/bax. Moreover, calcified rat VSMC media induced H9C2 apoptosis and upregulated genes expression linked to cardiac dysfunction. Our data provide evidence that VC accelerates cardiac dysfunction, partially by inducing cardiomyocytes apoptosis.
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Evidence presented that osteoporosis is closely related to the dysfunction of bone mesenchymal stem cells (BMSCs). But most studies are insufficient to reveal what actually happens to the osteoporotic BMSCs. In this study, BMSCs were harvested from ovariectomized and sham-operated rats. ⋯ In addition, potential miRNA-mRNA and lncRNA-mRNA regulatory networks were illustrated. The changes in osteoporotic BMSCs covered a large set of biological processes, including cell viability, differentiation, immunoreaction, bone repairment and estrogen defect. This study enriched the pathophysiological mechanisms of BMSCs and osteporosis, as well as provided dozens of attractive RNA targets for further treatment.