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Mitochondria are important for energy production and cardiomyocyte homeostasis. OMA1, a metalloendopeptidase, initiates the proteolytic process of the fusion-allowing protein OPA1, to deteriorate mitochondrial structure and function. In this study, mouse embryonic fibroblasts (MEFs) and neonatal mouse cardiomyocytes (NMCMs) subjected to hypoxia-reperfusion injury (HRI) and/or H 2 O 2 were used to mimic oxidative stress in the heart following ischemia-reperfusion injury (IRI). In vitro experiments demonstrated that HRI or stimulation with H 2 O 2 induced self-cleavage of OMA1 and the subsequent conversion of OPA1 from its long form to its short form, leading to mitochondrial fragmentation, cytochrome c release and apoptosis. By using Molecular Operating Environment (MOE) software to simulate the binding interaction of 2295 phytochemicals against OMA1, epigallocatechin gallate (EGCG) and betanin were selected as candidates of OMA1 inhibitor. We found that EGCG directly interacted with OMA1 and potently inhibited self-cleavage of OMA1, leading to attenuated OPA1 cleavage. This study, therefore, suggests to use OMA1 inhibition induced by EGCG to treat cardiac IRI.

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BackgroundProstate cancer is a common type of malignant tumor invading the male reproductive-urinary system, which has increasing incidence worldwide. Androgen receptor variant 7 (AR-V7) participates in regulating prostate cancer cell proliferation and gene expression. This study aimed to investigate the expression of AR-V7 in circulated tumor cells (CTCs) in patients with prostate cancer and to assess its correlation with drug sensitivity against enzalutamide or abiraterone.Material/MethodsBlood samples of prostate cancer patients were collected for separating CTCs, in which mRNA expression level of full-length AR and AR-V7 was measured to analyze their correlation with enzalutamide or abiraterone resistance. Progression-free survival (PFS) of patients with different AR-V7 expression levels was compared. AR-V7 was overexpressed in transfected prostate cancer cells, and its effects on proliferation were analyzed by clonal formation assay.ResultsqRT-PCR showed AR-V7 overexpression in a total of 13 patients; 76.92% of these patients developed drug resistance, the distal metastasis of which was significantly higher than that in the group with AR-V7 downregulation, with lower PFS (p<0.01). In cultured prostate cancer cells, AR-V7 upregulation resulted in a significantly higher clonal formation rate than in the control group with enzalutamide-containing medium (p<0.05).ConclusionsIn prostate cancer cells, AR-V7 expression is correlated with drug resistance, as AR-V7 upregulation leads to enhanced proliferation potency of cancer cells, indicating unfavorable prognosis of patients.