This study investigates the role of circular RNA (circRNA) hsa_circ_0000515 in cervical cancer and the underlying mechanism associated with microRNA-326 (miR-326). hsa_circ_0000515 and ETS transcription factor ELK1 (ELK1) were initially over-expressed and miR-326 was down-regulated in cervical cancer tissues and cells. Low hsa_circ_0000515 expression was found to be associated with favorable prognosis of patients with cervical cancer. A series of mimics, inhibitors, over-expression plasmids or siRNAs were introduced into cervical cancer cells to alter the expression of hsa_circ_0000515, miR-326 and ELK1. In vitro experiments exhibited that silencing of hsa_circ_0000515 or upregulation of miR-326 resulted in suppressed proliferation and invasion, along with induced apoptosis and autophagy of cervical cancer cells. Dual-luciferase reporter assay, RNA pulldown and RIP assays highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-326 to increase ELK1. Furthermore, enhancement of ELK1 expression resulted in enhanced proliferation and invasion but repressed apoptosis and autophagy of cervical cancer cells. In vivo experiments further confirmed the suppressed tumor growth by hsa_circ_0000515 silencing. Our findings demonstrated that hsa_circ_0000515 acts as a tumor promoter in cervical cancer. The study provides evidence for targeting hsa_circ_0000515 for therapeutic purposes in treating cervical cancer.

Background and purpose:Chronic proliferative responses of different vascular cell types have been involved in the pathogenesis of atherosclerosis. However, their functional role remains to be established. Sirolimus reduces neointimal proliferation after balloon angioplasty and chronic graft vessel disease. These studies were undertaken to investigate the effects of this anti-proliferative drug on atherogenesis. Experimental approach: Low-density lipoprotein receptor-deficient (LDL r-KO) mice on a cholesterol-rich diet were randomized to receive placebo or sirolimus (0.1; 0.3; or 1 mg·kg -1 ) in their diet for 8 or 16 weeks. Results: In both studies, plasma levels of the drug increased in a dose-dependent fashion, animals gained weight normally and, among groups, plasma lipids levels did not differ significantly. Compared with placebo, plasma levels of interleukin-6, monocyte chemoattractant protein-1, interferon g, tumour necrosis factor a and CD40, and their mRNA levels in aortic tissue were significantly reduced in sirolimus-treated mice. This effect resulted in a significant and dose-dependent reduction in atherosclerotic lesions, in both the root and aortic tree. Also these lesions contained less monocyte/macrophages and smooth muscle cells, but more collagen. Conclusions and implications:The present results demonstrated that at low doses, sirolimus was an effective and safe anti-atherogenic agent in the LDL r-KO mice. It attenuated the progression of atherosclerosis and modulated the plaque phenotype by reducing the pro-inflammatory vascular responses typical of the disease.

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID‐19 has not been studied. We analysed 70 COVID‐19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID‐19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID‐19 combined with HBV infection. Compared with COVID‐19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28‐69)vs 21(14‐30), P = .000; 40(25‐54) vs 23(18‐30), P = .000; 34.0(27.2‐38.7) vs 37.2(31.1‐41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co‐infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co‐infected patients group. Age and c‐reactive protein (CRP) level were independent risk factors for recovery of patients with COVID‐19 combined with HBV infection. The original characteristics of COVID‐19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID‐19.

There is growing evidence that oxidative stress plays critical roles in the pathogenesis of cardiac remodeling. In the present study, we established a rat model of passive smoking and investigated the antioxidant effects of hydrogen sulfide (H2S) on smoking-induced left ventricular remodeling. Cardiac structure and function were evaluated using 2-dimensional echocardiography. Myocardial fibrosis was detected by Masson's trichrome staining and immunohistochemistry. Oxidative stress was assessed by measuring malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities, and reactive oxygen species generation in the myocardium. Neonatal rat cardiomyocytes transfected with specific siRNA and exposed to cigarette smoke condensate and H2S donor sodium hydrosulfide were used to confirm the involvement of Nrf2 and PI3K/Akt signaling in the antioxidant effects of H2S. Our results indicated that H2S could protect against left ventricular remodeling in smoking rats via attenuation of oxidative stress. Moreover, H2S was also found to increase the phosphorylation of Akt and GSK3β and decrease the nuclear expression of Fyn, which consequently leads to nuclear translocation of Nrf2 and elevated expression of HO-1 and NQO1. In conclusion, H2S may exert antioxidant effects on left ventricular remodeling in smoking rats via PI3K/Akt-dependent activation of Nrf2 signaling.

Abstract. The mechanisms that control the morphologic organization of endothelial cells (ECs) into new blood vessels are not well understood. Recent studies revealed that the small G proteins of the Rho family are key regulators of cell migration, involving reorganization of the actin cytoskeleton, cell migration and the regulation of gene transcription. We hypothesized that RhoA GTPase, a member of the Rho family, may play an important role in EC organization during angiogenesis, the process of new vessel formation in preexisting tissues. To test this hypothesis, we investigated the effects of RhoA on human umbilical vein endothelial (HUVE) cell migration and angiogenesis in vitro, by stably transfecting HUVE cells with sense RhoA expression plasmid through the Lipofect-2000 system. Wound assay in vitro and 3-dimensional cell culture were used to detect the migration and angiogenesis capacity of HUVE cells. The morphological changes of transfected cells were revealed under confocal and phase contrast microscopy. Our results demonstrated that the increased expression of RhoA in HUVE cells significantly enhanced the morphogenetic changes and cytoskeletal reorganization of the transfected cells, and also enhanced cell migration and angiogenic capacity in vitro, suggesting that RhoA plays an important role in the process of HUVE cell migration and angiogenesis in vitro.