EGCG protects cardiomyocytes against hypoxia-reperfusion injury through inhibition of OMA1 activation.

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 H2O2 were used to mimic oxidative stress in the heart following ischemia-reperfusion injury (IRI). In vitro experiments demonstrated that HRI or stimulation with H2O2 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.

Expression of Androgen Receptor Variant 7 (AR-V7) in Circulated Tumor Cells and Correlation with Drug Resistance of Prostate Cancer Cells.

BACKGROUND Prostate 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 AND METHODS Blood 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. RESULTS qRT-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). CONCLUSIONS In 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.

[Orchidopexy increases the levels of serum anti-Müllerian hormone and inhibin B in cryptorchidism patients].

OBJECTIVE: To investigate the levels of serum anti-Müllerian hormone (AMH) and inhibin B (INHB) in patients with unilateral cryptorchidism before and after orchidopexy. METHODS: This study included 58 cases of unilateral cryptorchidism treated by orchidopexy and 32 healthy controls. Before and at 6 months after surgery, we measured the length and circumference of the penis, the volume of the undescended testis, and levels of serum AMH and INHB. RESULTS: There were statistically significant differences between the unilateral cryptorchidism and healthy control groups in the levels of serum AMH (ï¼»102.80 ± 17.35 vs 108.76 ± 13.64ï¼½ ng/ml, P<0.05) and INHB (ï¼»70.24 ± 5.73ï¼½ vs ï¼» 77.72 ± 5.94ï¼½ pg/ml, P<0.05) at the baseline, but not at 6 months after orchidopexy (AMH: ï¼»109.76 ± 17.25ï¼½ vs ï¼»108.03 ± 14.13ï¼½ ng/ml, P>0.05; INHB: ï¼»75.76 ± 5.94ï¼½ vs ï¼»77.63 ± 5.99ï¼½ pg/ml, P>0.05). No remarkable differences were observed between the unilateral cryptorchidism and healthy control groups in the preoperative penile length (ï¼»2.05 ± 0.23ï¼½ vs ï¼»2.11 ± 0.22ï¼½ cm, P>0.05), penile circumference (ï¼»3.91 ± 0.23ï¼½ vs ï¼»3.99 ± 0.20ï¼½ cm, P>0.05) and volume of the undescended testis (ï¼»0.45 ± 0.02ï¼½ vs ï¼»0.46 ± 0.02ï¼½ ml, P>0.05), or in the postoperative penile length (ï¼»2.09 ± 0.23ï¼½ vs ï¼»2.16 ± 0.22ï¼½ cm, P>0.05), penile circumference (ï¼»4.00 ± 0.25ï¼½ vs ï¼»3.98 ± 0.19ï¼½ cm, P>0.05) and volume of the undescended testis (ï¼»0.45 ± 0.02ï¼½ vs ï¼»0.45 ± 0.02ï¼½ ml, P>0.05). Compared with the baseline, the cryptorchidism patients showed markedly increased levels of serum AMH (ï¼»102.80 ± 17.35ï¼½ vs ï¼»109.76 ± 17.25ï¼½ ng/ml, P<0.05) and INHB (ï¼»70.24 ± 5.73ï¼½ vs ï¼»75.76 ± 5.94ï¼½ pg/ml, P<0.05) after orchidopexy. CONCLUSIONS: Orchidopexy can elevate the levels of serum AMH and INHB and protect the testicular function of cryptorchidism patients.

[Clinical application of the disposable circumcision suture device in male circumcision].

OBJECTIVE: To investigate the safety and efficiency of the disposable circumcision suture device (DCSD) in the surgical treatment of phimosis and redundant prepuce. METHODS: We randomly assigned 249 outpatients with phimosis or redundant prepuce to be treated with DCSD (n = 129) and by conventional circumcision (CC, n = 120), respectively. Then we compared the safety and efficiency of the two strategies. RESULTS: Comparisons between DCSD and CC showed that the operation time was (4.02 +/- 0.69) vs (30.8 +/- 4.05) min, blood loss was (1.07 +/- 1.29) vs (8.72 +/- 2.15) ml, intraoperative pain score was 0.81 +/- 0.81 vs 2.42 +/- 1.15, 24-hour postoperative pain score was 1.84 +/- 1.02 vs 4.99 +/- 1.36, postoperative complication rate was 13. 95% (18/129) vs 9.17% (11/120), wound healing time was (13.99 +/- 9.06) vs (17.48 +/- 3.49) d, satisfaction with the penile appearance was 98.4% (127/129) vs 95% (109/120), and treatment cost was (2215.62 +/- 17.67) vs (576.47 + 15.58) Y RMB. DCSD exhibited obvious superiority over CC for shorter operation time, less blood loss, milder intraoperative pain, sooner wound healing, and better penile appearance, but it also had a higher rate of postoperative complications (P > 0.05) and involved more treatment cost than the latter (P < 0.05). CONCLUSION: The disposable circumcision suture device affords ideal clinical effects and therefore deserves clinical popularization.

circCRKL suppresses the progression of prostate cancer cells by regulating the miR-141/KLF5 axis.

BACKGROUND: Prostate cancer (PCa) is a prevalent human malignancy in males. Circular RNA circCRKL (Hsa_circ_0001206) was reported to be lowly expressed in PCa tissues. However, the regulatory role of circCRKL in PCa is poorly defined. METHODS: Levels of circCRKL, microRNA-141 (miR-141), and Kruppel-like factor (KLF5) were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell cycle progression, apoptosis, migration, and invasion were examined by Flow cytometry, Wound healing, and transwell assays. The underlying relationship between miR-141 and circCRKL or KLF5 was predicted by starBase, and then verified by a dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. The protein level of KLF5 was assessed by western blot assay. The biological role of circCRKL was detected by a xenograft tumor model in vivo. RESULTS: CircCRKL and KLF5 were decreased, and miR-141 was increased in PCa tissues and cells. The functional analysis discovered that the overexpression of circCRKL repressed cell cycle progression, migration, invasion, and boosted apoptosis of PCa cells. Mechanically, circCRKL could positively regulate KLF5 expression by sponging miR-141. In addition, circCRKL upregulation could hinder PCa tumor growth in vivo. CONCLUSION: These findings revealed that circCRKL inhibited the progression of PCa through upregulating KLF5 expression by sponging miR-141, elucidating a novel regulatory pathway in PCa cells. Our research suggested an underlying circRNA-targeted therapy for PCa.