Intrahepatic cholangiocarcinoma (ICC) is a type of cancer that is difficult to cure; chemoresistance of cholangiocarcinoma cells affect the prognosis of patients who cannot be treated with surgery. The mechanism underlying this chemoresistance remains unknown. Mesenchymal stem cells (MSCs) are known to be important components of the tumor microenvironment. In the present study, a large number of MSCs were observed to infiltrate the tumor sites of ICC; thus, MSCs were isolated from ICC tumor tissues. It was revealed that herpesvirus entry mediator (HVEM) was overexpressed in ICC-MSCs. The present study then investigated the role of HVEM-overexpressing MSCs in the chemoresistance of cholangiocarcinoma cells. It was demonstrated that HVEM-overexpressing MSCs could support cell survival of chemotherapeutic cholangiocarcinoma cells and inhibited their apoptosis. Further investigations revealed that HVEM-overexpressing MSCs could secrete IL-6 and also activated AMPK/mTOR-dependent autophagy of cholangiocarcinoma cells. Thus, it was concluded that ICC-MSC-induced autophagy is the primary cause of chemoresistance in ICC.
Background: Worldwide adoption of electronic cigarettes (e-cigarettes) has increased exponentially over the past decade due to the perception that they may represent a safer alternative to conventional cigarettes (CS) and as an effort to reduce smoking-related diseases. Various types of e-cigarettes from different brands have been emerged in the market with different design and quality. However, whether the safety risks of e-cigarettes held the trends toward positive changes need to be further certified by more scientific evidence. Methods: A systematic comparison study on the selected harmful and potentially harmful constituents (HPHCs) levels, including carbonyls, volatile organic compounds (VOCs), tobacco-specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), and metals in aerosols of two typical commercially available e-cigarettes and one cigarette smoke (CS) in Chinese market were proceeded, together with their cytotoxicity on Jukart, CNE-1, HONE1, Hep-2 cell lines by CCK-8 and colony formation assays. Results: The results showed that the levels of vast majority HPHCs in e-cigarette aerosols are either undetected or obviously lower than those in CS, which indicating the exposure to HPHCs was markedly reduced in the tested e-cigarettes. The CCK-8 and colony formation assay also indicated that the TPM extracts of e-cigarette aerosols also exhibited much weaker cytotoxicity than CS. Conclusion: The comparison of HPHCs levels in e-cigarette aerosols revealed that the use of e-cigarettes could lead to a significant reduction in exposure to harmful substances compared to CS. In tandem, the potential cytotoxicity of e-cigarettes on cell levels also showed potential for improvement compared to smoking. However, more attention needs to be paid to the differences in safety risks between different brands of e-cigarettes.
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