Objective To explore the relationship and its mechanism of emphysema induced by different ways of rearing and tobacco smoke exposure with the atherosclerosis formation. Methods Forty-eight SD rats were randomly divided into 6 groups (n= 8 ,each):a normal diet + tobacco smoke exposure (TSE) group ,a fat-rich diet + TSE group ,a limit intake + TSE group ,a normal diet group ,a fat-rich diet group ,and a limit intake group for 24 weeks. Lee's index ,serum tumor necrosis factor-α (TNF-α) ,interleukin-6 (IL-6 ) ,adiponectin (APN ) levels ,mean linear intercept (MLI) ,mean alveoli number (MAN) ,the aortic pathology change ,vascular endothelial growth factor (VEGF) of aorta ,and bone morphogenetic protein-2 (BMP-2) level were collected. Results Tobacco smoke exposure ,fat-rich diet ,and limit intake increased the severity of emphysema. The microscopic features of aorta showed an early atherosclerosis in the tobacco smoke exposure groups , but no atherosclerosis in the non-smoking groups. Interactions between tobacco smoke exposure and different ways of rearing on serum APN level (F= 10.68 ,P< 0.05) were found.In the tobacco smoke exposure groups ,Pearson correlation analysis showed positive correlations of aortic VEGF and BMP-2 levels with MLI ,serum TNF-α and IL-6 levels (r= 0.431 ,0.471 ,0 ,448 ,0.449 ,0.428 , 0.447 ,all P<0.05) ,and an negative correlation with MAN (r= -0.411 ,-0.442 ,P<0.05). Conclusions Both tobacco smoke exposure and different ways of rearing can influence the formation of emphysema. There is a positive correlation between the severities of emphysema and atherosclerosis , and systemic inflammation may be involved.

The intestinal microbiota participates in maintaining the homeostasis of the intestinal environment, and the imbalance caused by changes in its composition or distribution and activity is called intestinal microbiota imbalance. Carotid atherosclerosis, especially vulnerable carotid plaques, will increase the risk of ischemic stroke. Researches have shown that intestinal microbiota can participate in the occurrence and development of carotid artery plaques through its metabolites as signaling molecules, and targeted drugs that improve intestinal microbiota imbalance are expected to become a new treatment modality for vulnerable carotid artery plaques.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment