Exploring effective methods to lessen myocardial ischemia-reperfusion injury still has positive significance. The adenosine A2a receptor (A2aR) has played a crucial part in cardiac ischemia-reperfusion injury. Previous studies revealed that the adenosine A2a receptor regulated autophagy, but the specific mechanism in myocardial ischemia-reperfusion injury was still unclear. We established an ischemia-reperfusion model (30 min of ischemia and 2 h of reperfusion) in vivo and a model with oxygen-glucose deprivation for 6 h and reoxygenation for 18 h (OGDR) in vitro. The ischemia-reperfusion injury resulted in prolonged QTc interval, left ventricular systolic dysfunction, and myocardial infarction. In vitro model, we found that the OGDR-induced autophagosomes and apoptosis caused myocardial cell death, as evidenced by a significant increase in the generation of lactate dehydrogenase and creatine kinase-MB. Furthermore, overactivated autophagy with rapamycin showed an anti-apoptotic effect. The interaction between autophagy and apoptosis in myocardial ischemia-reperfusion injury was complex and variable. We discovered that the activation of adenosine A2a receptor could promote the expression of Bcl-2 to inhibit the levels of Beclin-1 and LC3II. The number of autophagosomes exceeded that of autolysosomes under OGDR, but the result reversed after A2aR activation. Activated A2aR with its agonist CGS21680 before reperfusion saved cellular survival through anti-apoptosis and anti-autophagy effect, thus improving ventricular contraction disorders, and visibly reducing myocardial infarction size. The myocardial protection of adenosine A2a receptor after ischemia may involve the cAMP-PKA signaling pathway and the interaction of Bcl-2-Beclin-1.

Hepatocellular carcinoma (HCC) remains a significant health burden to date. Its early diagnosis and treatment are complicated by the lack of early diagnosis markers and multidrug resistance. microRNA regulation of HCC oncogenes are among the new diagnostic and therapeutic strategies being explored, although the mode of delivery of a therapeutic dose of the miRNA remains a challenge. In this study, we explored the use of exosomes from umbilical mesenchymal stem cells transfected with miR-27a-3p to interact with the oncogene GOLM1 in HCC and inhibit HCC progression both in vitro and in vivo. We first determined and compared the expression levels of miR-27a-3p in blood, various cell lines and tissues of HCC and their corresponding normal controls. We then employed bioinformatics analysis to determine the gene target for miR-27a-3p in HCC and later transfected upregulated miR-27a-3p in mesenchymal stem cells, and treated HCC cells with exosomes extracted from the transfected stem cells. We then created mouse models of HCC using balbc/nude mice and equally treated them with exosomes from miR-27a-3p transfected stem cells. The results showed that miR-27a-3p is downregulated in blood, cell lines, and tissues of HCC patients compared to normal controls. Exosomes from the miR-27a-3p transfected mesenchymal stem cells prevented HCC cell proliferation, invasion, and metastasis both in vitro and in vivo. Upregulation of miR-27a-3p prevented HCC through interacting with and downregulating GOLM1 as its target oncogene. In conclusion, miR-27a-3p is a potential therapeutic target for HCC acting through GOLM1.

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Induction chemotherapy (IC) prior to concurrent chemo-radiotherapy is the recommended treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, the optimum number of IC cycles for improved survival outcomes is still not known. Here, we assessed the efficacy of 2 or more cycles of IC for unresectable stage III NSCLC patients from our hospital. Data on unresectable stage III NSCLC patients treated with IC + concurrent chemo-radiotherapy at our hospital between 2018 and 2022 were retrieved and analyzed, and survival outcomes compared between IC = 2 and IC > 2 patients. Univariate and multivariate Cox regression, and Chi-square or Fisher exact test were used to assess prognosis and acute toxicity profiles. One hundred twenty-six patients were recruited; 90 for IC = 2 and 36 for IC > 2. Median follow-up time was 26 months [IQR 16-38]. Three-year overall survival was not statistically significant between the 2 groups (77.8% vs 75.0%, P = .453). Distant metastasis free survival, loco-regional recurrence free survival and progression free survival were also not significant, (90.0% vs 86.1%, P = .068), 97.8% vs 97.2%, P = .056), and (73.3% vs 66.7%, P = .446) respectively. Univariate and multivariate Cox regression analysis revealed smoking, T_stage, N_stage, and IC_regimen as independent prognostic factor for overall survival, while drinking and T_stage were risk factors for progression free survival. In summary, 2 cycles of platinum-based IC was effective for stage III unresectable NSCLC and adding more than 2 cycles did not offer extra survival benefits.