Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

BACKGROUND:The treatment of autologous pericardium transplantation has been widely applied in clinics, mainly involving cardiovascular repair and reconstruction, the treatment of ocular surface disease. The study addressing protection effects of autologous pericardium transplantation on the heart with ischemia injury is rarely reported. The investigations on the safety and protection effects of autologous pericardial transplantation on the heart with ischemia injury are of important significance.
OBJECTIVE:To explore effect of autologous pericardial transplantation on cardiac electrical activity and the protective effects on myocardial ischemia.
METHODS:Rongchang pork pigs and Sprague-Dawley rats were randomly divided into three groups:autologous pericardium transplantation, myocardial ischemia, and myocardial ischemia+autologous pericardium transplantation. The model of myocardial ischemia was established by ligation of the left anterior descending coronary artery in the groups of myocardial ischemia and myocardial ischemia+autologous pericardium transplantation. The model of transplantation was established by autologous pericardium transplant with flap in the groups of autologous pericardium transplantation and myocardial ischemia+autologous pericardium transplantation.
RESULTS AND CONCLUSION:Porcine electrocardiogram monitoring results showed that, superventricular premature beat was frequently observed in each group of pigs;the ventricular premature beat was occasional observed in autologous pericardium transplantation group, ventricular tachycardia and ventricular fibril ation did not appear. Compared with myocardial ischemia group, the ventricular premature beat decreased and the heart function was improved in myocardial ischemia+autologous pericardium transplantation group (P<0.05). Rat electrocardiogram monitoring results showed that, the ventricular fibril ation did not appear in autologous pericardium transplantation group, the lethal ventricular fibril ation did not appear in myocardial ischemia and myocardial ischemia+autologous pericardium transplantation groups. Compared with myocardial ischemia group, the heart function was improved, the apoptosis index decreased, the expressions of Bcl-2 protein increased, the expressions of Caspase-3 protein decreased in myocardial ischemia+autologous pericardium transplantation group (P<0.05). The autologous pericardium transplantation with flap cannot induce malignant ventricular arrhythmia and is relatively safe;the ventricular premature beat is reduced, the cardiac function is improved, which is possibly related to the inhibition of apoptosis in myocardial ischemic area.

BACKGROUND: Electrical stimulation at different intensity, frequency and time on the human body may produce a variety of pathophysiological reactions. OBJECTIVE: To observe the effects of surface electric-impulse stimulation on heart rhythm and heart rate in mice. METHODS: Thirty Kunming mice were randomly divided into three groups, each group contained 10 mice. Electrical stimulation at different voltage, time and frequency was respectively applied to the three groups. The stimulus power was supplied by BL-420F Data Acquisition & Analysis System. The II lead electrocardiogram was recorded. The systemic reactions and local body changes of mice were observed.