Integrin β3 Mediates the Endothelial-to-Mesenchymal Transition via the Notch Pathway

Background/Aims: Neointimal hyperplasia is responsible for stenosis, which requires corrective vascular surgery, and is also a major morphological feature of many cardiovascular diseases. This hyperplasia involves the endothelial-to-mesenchymal transition (EndMT). We investigated whether integrin β3 can modulate the EndMT, as well as its underlying mechanism. Methods: Integrin β3 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). The expression of endothelial markers and mesenchymal markers was determined by real-time reverse transcription PCR (RT-PCR), immunofluorescence staining, and western blot analysis. Notch signaling pathway components were detected by real-time RT-PCR and western blot analysis. Cell mobility was evaluated by wound-healing, Transwell, and spreading assays. Fibroblast-specific protein 1 (FSP-1) promoter activity was determined by luciferase assay. Results: Transforming growth factor (TGF)-β1 treatment or integrin β3 overexpression significantly promoted the EndMT by downregulating VE-cadherin and CD31 and upregulating smooth muscle actin α and FSP-1 in HUVECs, and by enhancing cell migration. Knockdown of integrin β3 reversed these effects. Notch signaling was activated after TGF-β1 treatment of HUVECs. Knockdown of integrin β3 suppressed TGF-β1-induced Notch activation and expression of the Notch downstream target FSP-1. Conclusion: Integrin β3 may promote the EndMT in HUVECs through activation of the Notch signaling pathway

Protective Effects of Sonic Hedgehog Against Ischemia/Reperfusion Injury in Mouse Skeletal Muscle via AKT/mTOR/p70S6K Signaling

Background/Aims: Skeletal muscle ischemia/reperfusion (I/R) injury is a common and severe disease. Sonic hedgehog (Shh) plays a critical role in post-natal skeletal muscle regeneration. In the present study, the role of Shh in skeletal muscle I/R injury and the mechanisms involved were investigated. Methods: The expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice were subjected to systemic administration of cyclopamine or one-shot treatment of a plasmid encoding the human Shh gene (phShh) to examine the effects of Shh on I/R injury. Moreover, mice were subjected to systemic administration of NVP-BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered skeletal muscle protection. Results: We found that the levels of Shh, AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio initially increased and then decreased at different time points post-I/R injury. Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited. Conclusion: Collectively, these data suggest that Shh signaling exerts a protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting skeletal muscle from I/R injury

Ethical dilemma of identity disclosure faced by medical students in clinical clerkships: A nationwide multicenter study in China.

OBJECTIVE:Medical students in China are currently facing a dilemma of whether to clarify their identity as students to patients. Further investigation is needed to support policy-making. The aim was to identify factors influencing medical students' decision on whether or not to clarify their identity to patients and to examine the effects of their decision. METHODS:The study was a cross-sectional nationwide multicenter survey consisting of 947 medical students. A self-designed questionnaire was composed of 19 structured questions investigating the present situation and participants' perception of the ethical dilemma surrounding medical student identity. The questionnaires were distributed randomly in teaching hospitals affiliated with 13 medical schools across China from June 2015 to January 2016. RESULTS:A total of 947 valid questionnaires were retrieved with a valid response rate of 83.7%. Most medical students (71.4%) tended to be ambiguous about their student identity in front of patients. The frequency of encountering distrust and patients' or patient relatives' refusal to allow students to perform procedures was significantly lower for students who explicitly stated their identity than for those who were ambiguous about their identity (p1 y, OR 3.6, 95% CI 2.0-6.5), preceptors' straightforward introduction of the students (OR 8.7, 95% CI 5.4-13.8) and students' acknowledgment of patients' right to know (OR 2.3, 95% CI 1.2-4.5) were related to students' clear self-introduction to patients. CONCLUSION:It is beneficial for medical students to clearly explain their identity to patients in order to decrease patient distrust and prevent the refusal to have certain appropriate procedures performed. Several methods, including emphasizing the role of mentors, developing curriculum for medical students, and creating clear regulations and guidelines for revealing the identity of medical students on the healthcare team can help address and ideally resolve this ethical dilemma of identity disclosure

Adverse events encountered by medical students according to how they introduce themselves to patients.

<p>Adverse events encountered by medical students according to how they introduce themselves to patients.</p

Demographic characteristics of the 947 surveyed medical students.

<p>Demographic characteristics of the 947 surveyed medical students.</p

Optimal bivariate logistic regression model for possible factors influencing how students introduce themselves to patients.

<p>Optimal bivariate logistic regression model for possible factors influencing how students introduce themselves to patients.</p

Chi-square test of factors influencing how students introduce themselves to patients.

<p>Chi-square test of factors influencing how students introduce themselves to patients.</p