Linagliptin's impact on lymphatic barrier and lymphangiogenesis in oral cancer with high glucose.

OBJECTIVES: Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier-related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction. MATERIALS AND METHODS: A CAL-27-LEC co-culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability. Western blotting and RT-qPCR detected protein and mRNA expression under different conditions, respectively. CCK-8, scratch wound healing, and transwell assays revealed cell migration and proliferation. Tube formation experiment tested capacity for endothelial tube formation. Immunohistochemical staining analyzed tissue sections from 43 oral cancer individuals with/without diabetes. RESULTS: In high-glucose co-culture system, we observed increased lymphatic barrier permeability and decreased expression of ZO-1 and occludin, two tight-junction proteins; conversely, the expression of PAR2, a high permeability-related protein, was increased. Following linagliptin treatment, the expression levels of VEGF-C, VEGFR-3, and PAR2 decreased, while those of ZO-1 and occludin increased. Considerably higher levels of LYVE-1 expression in individuals with diabetes than in those without diabetes. CONCLUSIONS: By ameliorating the high glucose-induced disruption of the lymphatic endothelial barrier, linagliptin may reduce lymphangiogenesis and exhibit an inhibitory effect on lymphatic metastasis in oral cancer patients with diabetes.

Downregulation of VAP-1 in OSCC suppresses tumor growth and metastasis via NF-κB/IL-8 signaling and reduces neutrophil infiltration.

BACKGROUND: Vascular adhesion protein-1 (VAP-1) is believed to play a role in inflammation. Studies have suggested that VAP-1-mediated activation of inflammation is dependent on NF-κB, leading to secretion of the interleukin (IL)-8; however, no reports have addressed the association between VAP-1 and NF-κB/IL-8 signaling in oral squamous cell carcinoma (OSCC). This study aimed to investigate the role of VAP-1 in OSCC and further explore whether VAP-1 is involved in the regulation of neutrophil infiltration in the tumor microenvironment (TME). METHODS: Immunochemistry staining was used to observe VAP-1 expression. CCK-8 and Transwell assays were used to measure cell proliferation, migration, and invasion. OSCC xenograft mouse models were used for in vivo verification of the VAP-1 function. The expression of NF-κB and IL-8 were determined by qRT-PCR and western blot. ELISA for IL-8 was also conducted. The relationship between VAP-1 expression and neutrophil infiltration was analyzed by immunofluorescence. RESULTS: VAP-1 was overexpressed in human OSCC tissues. Downregulation of VAP-1 suppressed OSCC cells proliferation, migration, and invasion in vitro and inhibited tumor proliferation and metastasis in vivo. Additionally, downregulation of VAP-1 inhibited NF-κB/IL-8 signaling in vitro and in vivo. VAP-1 expression was positively correlated with neutrophil infiltration in human OSCC tissues. Moreover, blocking VAP-1 decreased neutrophil infiltration by reducing IL-8 production. CONCLUSIONS: VAP-1 downregulation in OSCC suppresses tumor growth and metastasis by inhibiting NF-κB/IL-8 signaling and reducing neutrophil infiltration in the TME, suggesting that VAP-1 may be a potential therapeutic target for OSCC.

Exploring mechanisms affecting environmental risk coping behaviors: evidence from China.

Environmental risk issues pose a threat to human life and well-being. In order to reduce environmental risks, environmental risk response strategies have become increasingly vital. As the group most affected by environmental risks, the public environmental risk coping behaviors affect the effectiveness of environmental risk management. However, the public adoption of such behaviors mainly depends on their willingness. Therefore, the key to effective governance lies in guiding the public to voluntarily adopt appropriate environmental risk coping behaviors. The theory of environmental psychology provides relevant references for this. The internal psychological motivations of the public (including attitudes and subjective norms etc.) affect their choices of environmental risk behavior. The main purpose of this research is to explore the determinants underlying environmental risk coping behaviors using extending the theory of planned behavior by additional constructs (trust, risk perception, interaction satisfaction). The research applies a questionnaire survey method to collect data from the public living in the vicinity of two locations in China-an industrial area and a waste incineration plant in a Chinese city. The result of SEM shows that the public's trust in governments has a positive influence on the intention to collaborate, while the public's trust in the government and enterprises is negatively correlated with their intention to engage in confrontational behavior. Also, there is a positive correlation between confrontational intention and confrontational behavior, while the intention to cooperate may not necessarily result in collaborative behavior. Risk perception is not related to trust and the intention to collaborate, but it positively affects the intention to confront. The reason for the public to willingly take collaborative actions is not because they have perceived a high level of risk, and the public's high trust in the government can enhance their intention to take collaborative actions. It is thus clear that government credibility plays an important guiding role in public risk responsive behavior. The research findings provide policy recommendations for guiding public environmental risk coping behavior.