AP39 inhibits ferroptosis by inhibiting mitochondrial autophagy through the PINK1/parkin pathway to improve myocardial fibrosis with myocardial infarction.

BACKGROUND AND PURPOSE: Research has revealed the involvement of mitochondrial autophagy and iron death in the pathogenesis of myocardial fibrosis. The objective of this study is to investigate whether the mitochondrial-targeted H2S donor AP39 inhibits mitochondrial autophagy and antagonizes myocardial cell iron death through the PINK1/Parkin pathway, thereby improving myocardial fibrosis in rats with myocardial infarction. EXPERIMENTAL APPROACH: A rat model of myocardial infarction was created by intraperitoneal injection of a high dose of isoproterenol, and H9c2 myocardial cells were subjected to hypoxic injury induced by CoCl2. Western blot, RT-PCR, transmission electron microscopy, immunohistochemistry, as well as echocardiography, and studies on isolated hearts were employed. KEY RESULTS: In the hearts of rats with myocardial infarction, there was a significant accumulation of interstitial collagen fibers, accompanied by downregulation of CSE protein expression, activation of the PINK1/Parkin signaling pathway, and activation of mitochondrial autophagy. Intervention with AP39 resulted in a significant improvement of the aforementioned changes, which could be reversed by the addition of PAG. Similar results were observed in vitro experiments. Furthermore, the addition of CCCP reversed the antagonistic effect of AP39 on myocardial cell iron death, while the addition of RSL3 reversed the inhibitory effect of AP39 on collagen production in myocardial cells. CONCLUSION AND IMPLICATIONS: The mitochondrial-targeted H2S donor AP39 can inhibit mitochondrial autophagy through the PINK1/Parkin pathway, antagonize myocardial cell iron death, and improve myocardial fibrosis in rats with myocardial infarction.

Four new diphenyl ether derivatives from a mangrove endophytic fungus Epicoccum sorghinum.

Four new diphenyl ethers, named epicoccethers K-N (1-4), were purified from the fermentation medium of a fungus Epicoccum sorghinum derived from Myoporum bontioides, and identified through HR-ESI-MS and NMR spectral analysis. Except that compound 1 showed moderate antifungal activity against Penicillium italicum and Fusarium graminearum, the other three compounds showed stronger activity against them than triadimefon. All of them showed moderate or weak antibacterial activity towards Staphylococcus aureus and Escherichia coli with O6 and O78 serotypes except that 3 was inactive to E. coli O6.

[Effect of Shexiang Baoxin Pills on isoprenaline-induced myocardial cell hypertrophy and Cx43 expression].

OBJECTIVE: To observe the effects of Shexiang Baoxin Pill (SBP) on isoprenaline (Iso)-induced changes in myocardial cell volume, shape, and connexin 43 (Cx43) expression.
 Methods: H9C2 myocardial cells were randomly divided into a control group, a Iso group and a Iso+SBP group. After 72 h of culture, the average surface area of H9C2 cells was measured under phase contrast microscope. Bicinchoninic acid (BCA) protein assay was carried out to determine the concentration of proteins. The survival rate of myocardial cells was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and the Cx43 expression was detected by Western blot.
 Results: The mean surface area and Cx43 concentration in Iso-treated myocardial cells were increased under the phase contrast microscope (P<0.05). Compared with the Iso group, the mean surface area was decreased, and the Cx43 concentration was reduced in the Iso+SBP group (both P<0.05). Compared with the control group, the Cx43 expression was obviously down-regulated in the H9C2 cells of the Iso group (P<0.05); while compared with the Iso group, the Cx43 expression was obviously up-regulated in the Iso+SBP group (P<0.05).
 Conclusion: Shexiang Baoxin Pills can prevent Iso-induced myocardial hypertrophy and down-regulate Cx43 expression.

Plant Oil-Derived Epoxy Polymers toward Sustainable Biobased Thermosets.

Epoxy polymers (EPs) derived from soybean oil with varied chemical structures are synthesized. These polymers are then cured with anhydrides to yield soybean-oil-derived epoxy thermosets. The curing kinetic, thermal, and mechanical properties are well characterized. Due to the high epoxide functionality per epoxy polymer chain, these thermosets exhibit tensile strength over an order of magnitude higher than a control formulation with epoxidized soybean oil. More importantly, thermosetting materials ranging from soft elastomers to tough thermosets can be obtained simply by using different EPs and/or by controlling feed ratios of EPs to anhydrides.

Efficacy of Ligustrazine Injection as Adjunctive Therapy for Angina Pectoris: A Systematic Review and Meta-Analysis.

BACKGROUND In the past decades, a large number of randomized controlled trials (RCTs) on the efficacy of ligustrazine injection combined with conventional antianginal drugs for angina pectoris have been reported. However, these RCTs have not been evaluated in accordance with PRISMA systematic review standards. The aim of this study was to evaluate the efficacy of ligustrazine injection as adjunctive therapy for angina pectoris. MATERIAL AND METHODS The databases PubMed, Medline, Cochrane Library, Embase, Sino-Med, Wanfang Databases, Chinese Scientific Journal Database, Google Scholar, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and the Chinese Science Citation Database were searched for published RCTs. Meta-analysis was performed on the primary outcome measures, including the improvements of electrocardiography (ECG) and the reductions in angina symptoms. Sensitivity and subgroup analysis based on the M score (the refined Jadad scores) were also used to evaluate the effect of quality, sample size, and publication year of the included RCTs on the overall effect of ligustrazine injection. RESULTS Eleven RCTs involving 870 patients with angina pectoris were selected in this study. Compared with conventional antianginal drugs alone, ligustrazine injection combined with antianginal drugs significantly increased the efficacy in symptom improvement (odds ratio [OR], 3.59; 95% confidence interval [CI]: 2.39 to 5.40) and in ECG improvement (OR, 3.42; 95% CI: 2.33 to 5.01). Sensitivity and subgroup analysis also confirmed that ligustrazine injection had better effect in the treatment of angina pectoris as adjunctive therapy. CONCLUSIONS The 11 eligible RCTs indicated that ligustrazine injection as adjunctive therapy was more effective than antianginal drugs alone. However, due to the low quality of included RCTs, more rigorously designed RCTs were still needed to verify the effects of ligustrazine injection as adjunctive therapy for angina pectoris.