Exosomes are extracellular nanovesicles secreted by a variety of cell types such as cardiomyocyte, hepatocytes, and stem cells. They carry specific sets of mRNA, microRNA, and proteins, which play a role in intercellular communication in almost each physiological and pathological process. Exosomes, which are released after tissue cell injury, can initiate repair/regeneration responses by triggering inflammation and active fibroblast, and finally lead to tissue fibrosis. However, exosomes released by stem cells can retard tissue fibrosis by enhancing cell survival and reducing apoptosis. In this paper, we reviewed the research progress in the relationship between exosomes and tissue fibrosis.

Objective To examine the effects of exercise intensity and duration on the structure,function and fibrosis of the left and right ventricular,and to discuss the potential mechanism in these processes.Methods Forty-eight male Sprague-Dawley rats were randomly divided into a sedentary(Sed)group,a moderate exercise(ME)group and an intensive exercise(IE) group,each of 16.Rats in Sed group were not given any training,while those in ME group and IE group run on treadmill at the speed of 15.2 m/min with the slope gradient of 5° and 28 m/min with the slope gradient of 10 degree 1 hour per day,5 days per week.Eight and 16 weeks after the training,we recorded the body weight and measure end-diastolic diameter,end-diastolic wall thickness,and ejection fraction of both ventriculars using the ultrasonic testing.All rats were then sacrificed after blood sampling.Elisa was used to measure serum cTnI concentration,and sirius red staining was applied to evaluate collagen volume fraction of both ventriculars.Results Eight or sixteen weeks after the training,the average bi-ventricular end-diastolic diameter of ME and IE rats was bigger than Sed group.There were no differences in end-diastolic diameter of both ventricular between ME group and IE group after sixteen-week training,but the left ventricular end-diastolic diameter of IE group was greater than ME group.As exercise intensive increased and time accumulated,the end-diastolic wall thickness of both ventriculars increased but without statistical significance.At sixteen-week intervention,the bi-ventricular ejection fraction of IE rats was significantly lower than Sed and ME groups,while there was a decreasing trend eight weeks earlier without significant differences.After 8 or 16 weeks of training,the serum cTnI was significantly higher in IE rats than Sed group or ME group,but there was no significant differences between ME group and Sed group.After 16 weeks' exercises,the average bi-ventricular collagen volume fraction of ME or IE group was greater than that after 8 weeks' exercises.The average collagen volume fraction of the right ventricular was greater than Sed group at the same time points,and after sixteenweek training the right ventricular collagen volume fraction in IE group was significantly greater than ME group.However,there were no significant differences in the measurement of the left side among different groups.The serum cTnI was negatively correlated with the left and right ventricular systolic function(r=-0.327,P=0.029 and r=-0.582,P=0.000).Moreover,it was positively correlated with the right ventricular collagen volume fraction moderately,but had no correlation with the left ventricular collagen volume fraction.Conclusion(1)Sixteen-week moderate and intensive exercise result in left ventricular dilation,and the dilation increases with the increase of the exercise intensity.Only 8 weeks' exercise at the same intensity can lead to right ventricular dilation,but exercise intensity has little influence on the right ventricular dilation.(2)Long-term moderate or intensive endurance exercises may cause bi-ventricular hypertrophy potentially.The left ventricular hypertrophy and dilation may not be synchronous with hypertrophy followed by dilation,while the right ventricular hypertrophy and dilation is synchronous.(3)The temporary decrease in bi-ventricular systolic function after intensive endurance exercise may be caused by ventricular injury,with more serious injury in the right ventricular than in the left.Moderate exercises don't cause ventricular injury,thus there is little or no influence on ejection fraction.(4) Long-term (8 or 16 weeks)moderate or intensive endurance exercises can increase the right ventricular collagen volume fraction,which may indicate cardiac fibrosis following right ventricular injury but not in the left ventricular.The bi-ventricular collagen volume fraction at sixteenth week in ME and IE rats are greater than corresponding rats at eighth week.It may result from the hypertrophy of bi-ventricular cardiomyocyte after 8-week training,followed by increase in the extracellular matrix but not cardiac fibrosis.

Objective To explore the expression level of miR-21 in exercise-induced right ventricular (RV) fibrosis,and to analyze the role of miR-21 in exercise-induced right ventricular fibrosis.Methods Seventy-two male Sprague-Dawley rats were randomly divided into a sedentary (Sed) group,a moderate exercise (ME) group and an intensive exercise (IE) group,each of 24.Rats in the Sed group were free of exercises,while those in ME and IE groups ran an hour on treadmill at 5°and 10° slopes at the speed of 15.2 m/min and 28 m/min respectively for 8 weeks,12 weeks or 16 weeks every day,5days per week.Twenty-four hours after the last training,all rats were sacrificed after blood sampling.The right ventricles were removed,and the collagen volume fraction (CVF) was tested using Sirius red staining,Collagen Ⅰ (Col Ⅰ) content was quantified using Immunofluorescence.The expression level of miR-21 was measured using the reverse transcription-polymerase chain reaction (RT-PCR).Results Af ter 12 weeks (P＜0.05,P＜0.05) and 16 weeks (P＜0.01,P＜0.01) of intensive exercises,the average CVF in the right ventricular was significantly higher than that of Sed and ME rats.Compared to Sed and ME groups,12 weeks (P＜0.01,P＜0.01) and 16 weeks (P＜0.01,P＜0.01) of intensive exercises significantly increased RV collagen Ⅰ content.Compared to the Sed group,the expression of miR-21 in RV increased significantly in the IE group (P＜0.01,P＜0.05 and P＜0.05).After 16-week intensive exercises,the miR 21 expression was positively correlated with the RV Col Ⅰ content.Conclusion The right ventricular fibrosis induced by long-term intensive exercises is associated with increased miR-21 expression level.Therefore,miR-21 is a potent therapeutic target and novel biomarker of the exercise-induced right ventricular fibrosis.

Objective:To investigate the relationship between the expression of serum exsomal miRNA-155-5p (miR-155-5p) and prognosis in patients with esophageal squamous cell carcinoma (ESCC).Methods:A total of 336 samples from ESCC patients in Fujian Provincial Cancer Hospital from October 2014 to December 2015 were collected. The relative expression levels of serum exsomal miR-155-5p were detected by using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). Cut-off value of the expression levels of serum exsomal miR-155-5p was determined by using X-tile software. Based on the optimal cut-off value, patients were divided into miR-155-5p low expression group and miR-155-5p high expression group. The survival curve was drawn by using Kaplan-Meier method and Cox proportional hazards regression model was used to make survival analysis.Results:The cut-off value of serum exsomal miR-155-5p expression level was 2.340. According to the cut-off value, patients were divided into miR-155-5p low expression group (<2.340) of 51 cases and miR-155-5p high expression group (≥2.340) of 285 cases. There were no statistical differences in age ( χ2 = 0.020, P = 0.887), gender ( χ2 = 0.283, P = 0.595), tumor location ( χ2 = 0.063, P = 0.977), differentiation grade ( P = 0.474), clinical staging ( χ2 = 3.996, P = 0.136) and surgery treatment ( χ2 = 0.941, P = 0.332) of patients in both groups. ESCC patients in serum exsomal miR-155-5p high expression had a higher risk of death compared with patients in miR-155-5p low expression group ( HR = 1.763, 95% CI 1.049-2.961, P = 0.032). Conclusion:The high expression level of serum exsomal miR-155-5p is associated with poor prognosis in ESCC patients and it could be used as a prognostic new marker in ESCC patients.

Studies have shown that m6A modifying enzymes regulated the expression of related factors by m6A methylation modification,and then participated in the regulation of adipogenesis,adipocyte hypertrophy,adipose tissue browning and thermogenesis.This article reviews the research progress of m6A methylation modification on the regulation of adipose tissue metabolism.

BACKGROUND AND OBJECTIVES: Intense exercise (IE) induced myocardial fibrosis (MF) showed contradictory findings in human studies, making the relationship between IE and the development of MF unclear. This study aims to demonstrate exercise induced MF is associated with cardiac damage, and inflammation is essential to the development of exercise induced MF. METHODS: Sprague-Dawley rats were submitted to daily 60-minutes treadmill exercise sessions at vigorous or moderate intensity, with 8-, 12-, and 16-week durations; time-matched sedentary rats served as controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum cardiac troponin I (cTnI) concentration. After completion of the exercise protocol rats were euthanized. Biventricular morphology, ultrastructure, and collagen deposition were then examined. Protein expression of interleukin (IL)-1β and monocyte chemotactic protein (MCP)-1 was evaluated in both ventricles. RESULTS: After IE, right but not left ventricle (LV) MF occurred. Serum cTnI levels increased and right ventricular damage was observed at the ultrastructure level in rats that were subjected to long-term IE. Leukocyte infiltration into the right ventricle (RV) rather than LV was observed after long-term IE. Long-term IE also increased protein expression of pro-inflammation factors including IL-1β and MCP-1 in the RV. CONCLUSIONS: Right ventricular damage induced by long-term IE is pathological and the following inflammatory response is essential to the development of exercise induced MF.
Animals ; Collagen ; Enzyme-Linked Immunosorbent Assay ; Fibrosis ; Heart Injuries ; Heart Ventricles ; Humans ; Inflammation ; Interleukins ; Leukocytes ; Monocytes ; Rats ; Rats, Sprague-Dawley ; Troponin I

BACKGROUND AND OBJECTIVES: Intense exercise (IE) induced myocardial fibrosis (MF) showed contradictory findings in human studies, making the relationship between IE and the development of MF unclear. This study aims to demonstrate exercise induced MF is associated with cardiac damage, and inflammation is essential to the development of exercise induced MF. METHODS: Sprague-Dawley rats were submitted to daily 60-minutes treadmill exercise sessions at vigorous or moderate intensity, with 8-, 12-, and 16-week durations; time-matched sedentary rats served as controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum cardiac troponin I (cTnI) concentration. After completion of the exercise protocol rats were euthanized. Biventricular morphology, ultrastructure, and collagen deposition were then examined. Protein expression of interleukin (IL)-1β and monocyte chemotactic protein (MCP)-1 was evaluated in both ventricles. RESULTS: After IE, right but not left ventricle (LV) MF occurred. Serum cTnI levels increased and right ventricular damage was observed at the ultrastructure level in rats that were subjected to long-term IE. Leukocyte infiltration into the right ventricle (RV) rather than LV was observed after long-term IE. Long-term IE also increased protein expression of pro-inflammation factors including IL-1β and MCP-1 in the RV. CONCLUSIONS Right ventricular damage induced by long-term IE is pathological and the following inflammatory response is essential to the development of exercise induced MF.

Objective To determine the expression of matrix metalloproteinase-1 (MMP-1) and its inhibitor in the development of exercise-induced atrial fibrosis.Methods Totally 48 eight-week-old male adult sprague-dawley rats were randomly divided into a control(C) group and a highly intensive exercise(H) group,each of 24.Group C was fed normally,while group H took one hour treadmill running with the gradient of 10°and speed of 28 m/min every weekday,lasting 5 weeks.The mRNA and protein expression of MMP-1 and matrix metalloproteinase tissue inhibitor-1 (TIMP-1) were detected using the real-time PCR and Western blotting.Results The MMP-1 expression of group H increased significantly after 8 weeks' training,compared to the control group.However,there was no significant difference in MMP-1 expression between group C and H after 12 or 16 weeks of training.The MMP-1 mRNA expression decreased with the extending of exercise,and that of group H after 16 weeks' training was significantly lower than 8 weeks' (P＜0.05).The TIMP-1 expression had an increasing trend without significance after 8-week exercise.After 12 and 16-week exercise,the mRNA and protein expression of TIMP-1 increased significantly(P＜0.01 and P＜0.05).The TIMP-1 mRNA and protein expression increased gradually with the extension of exercise,and the TIMP-1 mRNA expression of group H after 16 weeks of training was significantly higher than that after 8 weeks(P＜0.01).The ratio of MMP-1/TIMP-1 mRNA and protein increased at first and decreased afterwards.The ratio of MMP-1/TIMP-1 of group H after 16 weeks of exercise was significantly lower than group C at the same time point,and group H after 8 weeks' Conclusion After a long-term high-intensity exercise,the MMP-1 expression of atrial first increases and then decreases,while the TIMP-1 expression increases gradually.Moreover,such exercise can induce disbalance between MMP-1 and TIMP-1,maybe due to the molecular pathological mechanism of exercise-induced atrial damage and fibrosis.

OBJECTIVES: In light of the rise in the global aging population, this study investigated the potential of the oxidative balance score (OBS) as an indicator of phenotypic age acceleration (PhenoAgeAccel) to better understand and potentially slow down aging. METHODS: Utilizing data from the National Health and Nutrition Examination Survey collected between 2001 and 2010, including 13,142 United States adults (48.7% female and 51.2% male) aged 20 and above, OBS and PhenoAgeAccel were calculated. Weighted generalized linear regression models were employed to explore the associations between OBS and PhenoAgeAccel, including a sex-specific analysis. RESULTS: The OBS demonstrated significant variability across various demographic and health-related factors. There was a clear negative correlation observed between the higher OBS quartiles and PhenoAgeAccel, which presented sex-specific results: the negative association between OBS and PhenoAgeAccel was more pronounced in male than in female. An analysis using restricted cubic splines revealed no significant non-linear relationships. Interaction effects were noted solely in the context of sex and hyperlipidemia. CONCLUSIONS A higher OBS was significantly associated with a slower aging process, as measured by lower PhenoAgeAccel. These findings underscore the importance of OBS as a biomarker in the study of aging and point to sex and hyperlipidemia as variables that may affect this association. Additional research is required to confirm these results and to investigate the biological underpinnings of this relationship.

Sensory processing is strongly modulated by different brain and behavioral states, and this is based on the top-down modulation. In the olfactory system, local neural circuits in the olfactory bulb (OB) are innervated by centrifugal afferents in order to regulate the processing of olfactory information in the OB under different behavioral states. The purpose of the present study was to explore the organization of neural networks in olfactory-related cortices and modulatory nuclei that give rise to direct and indirect innervations to the glomerular layer (GL) of the OB at the whole-brain scale. Injection of different recombinant attenuated neurotropic viruses into the GL showed that it received direct inputs from each layer in the OB, centrifugal inputs from the ipsilateralanterior olfactory nucleus (AON), anterior piriform cortex (Pir), and horizontal limb of diagonal band of Broca (HDB), and various indirect inputs from bilateral cortical neurons in the AON, Pir, amygdala, entorhinal cortex, hippocampus, HDB, dorsal raphe, median raphe and locus coeruleus. These results provide a circuitry basis that will help further understand the mechanism by which olfactory information-processing in the OB is regulated.