Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

<p>Abstract</p> <p>Background</p> <p>The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown.</p> <p>Methods</p> <p>In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway.</p> <p>Results</p> <p>On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis.</p> <p>Conclusions</p> <p>These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.</p

Barriers to hospital-based phase 2 cardiac rehabilitation among patients with coronary heart disease in China: a mixed-methods study

Abstract Background Coronary heart disease (CHD) has become a leading cause of morbidity and premature death worldwide. Cardiac rehabilitation (CR) was proved to have substantial benefits for patients with CHD. The CR was divided into three phases. Phase 2 is the important part of CR which involves hospital-based structured and closely monitored exercises and activities. However, CR utilization is low worldwide. The barriers to hospital-based phase 2 CR in China have not been well identified. Aims To investigate barriers to hospital-based phase 2 cardiac rehabilitation among coronary heart disease patients in China and to explore the reasons. Methods This study employed an explanatory sequential mixed-methods design. The study was conducted in a university hospital in China from July 2021 to December 2021. Quantitative data was collected through the Cardiac Rehabilitation Barrier Scale. Qualitative data was collected through unstructured face-to-face interviews. Data analysis included descriptive statistics and inductive qualitative content analysis. Results One hundred and sixty patients completed the Cardiac Rehabilitation Barrier Scale and 17 patients participated in unstructured face-to-face interviews. The main barriers identified were distance (3.29 ± 1.565), transportation (2.99 ± 1.503), cost (2.76 ± 1.425), doing exercise at home (2.69 ± 1.509) and time constraints (2.48 ± 1.496). Six themes were identified; logistical factors, social support, misunderstanding of cardiac rehabilitation, program and health system-level factors, impression of CR team and psychological distress. The first four themes confirmed the quantitative results and provide a deeper explanation for the quantitative results. The last two themes were new information that emerged in the qualitative phase. Conclusion This study provides a better understanding of the barriers to hospital-based phase 2 cardiac rehabilitation among coronary heart disease patients in the Chinese context during the Covid-19 pandemic. Innovative programs such as home-based CR, mobile health, and hybrid programs might be considered to overcome some of these barriers. In addition, psychosocial intervention should be included in these programs to mitigate some of the barriers associated with the impression of CR team and psychological distress

Additional file 1 of Effect of mindfulness-based interventions on people with prehypertension or hypertension: a systematic review and meta-analysis of randomized controlled trials

Additional file 1. Supplementary Material

Expression of Nodal on Bronchial Epithelial Cells Influenced by Lung Microbes Through DNA Methylation Modulates the Differentiation of T-Helper Cells

Background/Aims: The previous study in our lab showed that Nodal molecule on bronchial epithelial cells (BECs) was modulated by all kinds of lung microbes. The present study was designed to determine the effects of Nodal on proliferation of BECs and BECs-induced differentiation of T-helper (Th) cells. The epigenetic mechanisms of Nodal expression following treatments of different lung microbes were also identified. Methods: Real-time polymerization chain reaction (PCR) and western blot were used to determine the expression of Nodal. Flow cytometry was used to observe the effects of proliferation of BECs and subsequent BECs-induced differentiation of Th cells. Methylation levels of CpG islands in Nodal promoters were also analyzed by time of flight mass spectrometry. Results: The results showed that Nodal promoted proliferation of BECs and BECs-induced differentiation of Th cell from Th1 to Th2 and Th17. Nodal promoter showed a hyper-methylation in normal BECs. Through methylation modification in the promoter, P. aeruginosa or A.baumanni inhibited the expression of Nodal while RSV promoted the expression of Nodal. Conclusions: Our data showed that Nodal promoted Th2 and Th17 differentiation and inhibited Th1 differentiation which may cause imbalance of airway microenvironment. P. aeruginosa or A.baumanni may be hopeful for the treatment of airway hyperresponsveness by inhibition Nodal expression through DNA methylation modification in the promoter