Ventilator-induced lung injury (VILI) may be caused by incorrect mechanical ventilation (MV), and its progression is mainly related to inflammatory reaction, apoptosis and oxidative stress. The Wnt/β-catenin pathway can modulate inflammation and apoptosis, however, its role in VILI is unknown. This research aims to explore the role of the Wnt/β-catenin pathway in VILI. VILI models were established using rats and type II alveolar epithelial cells. GSK-3β, β-catenin and cyclin D1 were determined using western blot and immunofluorescence. Apoptosis of lung tissues was evaluated using TUNEL, flow cytometry, Bax and Bcl2 protein. IL-1β, IL-6 and TNF-α were detected via ELISA. Lung pathological injury was evaluated through hematoxylin and eosin staining. Lung permeability was evaluated by the ratio of dry to wet weight of lung tissue and the total protein level of bronchoalveolar lavage fluid. The results showed that GSK-3β expression was enhanced and β-catenin expression was diminished in lung tissue under MV. SB216763 increased β-catenin and cyclin D1 expression by inhibiting GSK-3β expression and inhibited the inflammatory response and apoptosis of lung, alleviated pulmonary edema and lung tissue permeability, and significantly mitigated lung injury. However, inhibition of β-catenin expression by MSAB attenuated the anti-inflammatory and anti-apoptotic effects of SB216763 in VILI. Overall, this study demonstrates that the Wnt/β-catenin pathway activation in MV may play an anti-inflammatory and anti-apoptotic role, thereby alleviating lung injury and delaying VILI progression, which may be a key point of intervention in VILI.

Background: Mechanical Ventilationventilation (MV) is an essential life support mechanism in the clinic. It may also lead to ventilator-induced acute lung injury (VILI) due to local alveolar overstretching and/or repeated alveolar collapse. However, the pathogenesis of VILI is not completely clear, and its occurrence and development may be related to inflammatory reactions, oxidative stress, apoptosis and other physiological processes. Some studies have found that the apelin/APJ pathway is an endogenous antagonistic mechanism that is activated during Acute respiratory distress syndrome(ARDS), and it can counteract the injury response and prevent uncontrolled lung injury. To prove that apelin-13 plays a protective role in VILI, in this study, we established a rat VILI model to explore whether apelin-13 can attenuate VILI in rats by inhibiting inflammation, cell apoptosis and oxidative stress. Methods: SD rats were divided into four groups: the control group, high tidal volume group, high tidal volume+NS group, and high tidal volume+apelin-13 group. After tracheotomy, autonomous breathing was maintained in the rats. After tracheotomy, the other rats were connected to a small animal ventilator for 4 hours to establish the rat VILI model. The mRNA expression of apelin was measured by real-time quantitative polymerase chain reaction (qRT‒PCR), and the protein expression levels of APJ, the apoptotic protein Bax, Bcl-2 and Akt/P-Akt were measured by Western blotting (WB) and immunofluorescence. The degree of lung injury was evaluated by pathological staining of lung tissue and measuring the wet to dry ratio of lung tissue. The expression of inflammatory factors in alveolar lavage fluid was measured by enzyme-linked immunosorbent assay (ELISA), and the activity of myeloperoxidase (MPO) in lung tissue was measured to evaluate the degree of pulmonary inflammation. Results: The expression of apelin and the APJ receptor was upregulated under VILI conditions. After the rats were treated with apelin-13, the activation of the apelin-APJ signaling pathway, the pathological damage to lung tissues, the degree of cell apoptosis, and the levels of the inflammatory cytokines IL-1, IL-6 and TNF-α were reduced in the VILI model rats. The expression of MPO was decreased, and the activity of MPO was also decreased. Moreover, the Akt/P-Akt signaling pathway is associated with apoptosis. After treatment, the expression of Akt/P-Akt pathway-related proteins increased. Conclusion: During VILI, the apelin/APJ axis plays an endogenous role in ameliorating injury. Overexpression of apelin can significantly reduce the inflammatory response, cell apoptosis and oxidative stress in the lung tissues of VILI model rats and slow the occurrence and development of VILI.

BackgroundDeoxythymidylate kinase (DTYMK) is a rate-limiting enzyme in pyrimidine metabolism. Crucially, it is overexpressed in a variety of tumors and is associated with poor prognosis in liver cancer. The role of DTYMK in lung adenocarcinoma remains poorly understood, particularly with respect to immune infiltration. MethodsThe present study aimed to compare the expression of DTYMK between normal tissues, lung adenocarcinoma, and other cancer types using data obtained via The Cancer Genome Atlas, Tumor Immune Estimation Resource 2.0, Gene Expression Database of Normal and Tumor Tissues 2, and Gene Expression Profiling Interactive Analysis (GEPIA). The prognostic value of DTYMK in patients with lung adenocarcinoma was evaluated using GEPIA and Kaplan–Meier plotter. STRING and GeneMANIA were employed to assess protein and gene interaction with DTYMK. R software and TISIDB were used to analyze the correlation between DTYMK expression and immune infiltration. Finally, we validated DTYMK protein expression in lung adenocarcinoma using the UALCAN and HPA databases. ResultsDTYMK expression was significantly increased in various cancer and lung adenocarcinoma tissues (p < 0.05), and was associated with poor prognosis (p < 0.05) in patients with lung adenocarcinoma. In addition, DTYMK was negatively associated with the vast majority of immune cells in lung adenocarcinoma.ConclusionsIncreased expression of DTYMK is associated with poor prognosis in lung adenocarcinoma patients. DTYMK may serve as a potential prognostic biomarker in lung adenocarcinoma. In addition, DTYMK may influence the progression and prognosis of lung adenocarcinoma by influencing the immune microenvironment of tumors.

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