Xi'an Jiaotong University Health Science Center

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its dismal prognosis and limited therapeutic options. In this study, we investigated the role of miR-301a in facilitating crosstalk between the Hedgehog (Hh) and HIPPO/YAP signaling pathways during the progression of PDAC. Our findings revealed that miR-301a served as a central regulatory node, targeting Gli1 within the Hh pathway and STK4 within the HIPPO/YAP pathway. Immunohistochemical and molecular analyses confirmed dysregulation of pathway components in pancreatic cancer, underscoring the pivotal role of miR-301a. Functional assays demonstrated the impact of miR-301a on cell proliferation and apoptosis, particularly in synergy with TNF-α. Overall, our study elucidated the intricate interplay between the Hh and HIPPO/YAP pathways mediated by miR-301a, providing valuable insights into potential therapeutic strategies for intervening in PDAC.

This study compared the efficacy of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) and the Childbirth Attitudes Questionnaire (CAQ) in assessing fear of childbirth (FOC) among hospitalized pregnant women, aiming to identify a practical screening tool. A total of 184 pregnant women were recruited from the Northwest Women's and Children's Hospital using convenience sampling. Data were collected through the General Demographic Questionnaire, Fear of Birth Scale (FOBS), W-DEQ, and CAQ. Using the FOBS as a reference, the diagnostic performance of the W-DEQ and CAQ was evaluated via receiver operating characteristic curves and Bayesian discriminant analysis. The area under the curve (AUC) for the W-DEQ (0.888) was significantly higher than that of the CAQ (0.789; Z = -2.189, p < 0.05). Optimal cutoff values were 80.5 for the W-DEQ and 31.5 for the CAQ. Cross-validation revealed accuracy rates of 75.6% and 70.7%, respectively. The incidence of FOC, as assessed by the W-DEQ, CAQ, and FOBS, was 29.9%, 43.9%, and 37.2%. Both tools demonstrated good reliability and validity, but the W-DEQ showed superior performance. It is recommended as the preferred tool for assessing FOC among pregnant women in China due to its comprehensive evaluation capacity.

Methotrexate (MTX)-induced pulmonary fibrosis is associated with high morbidity and mortality, with limited treatment options available. This study investigates whether disulfiram (DSF) can mitigate MTX-induced pulmonary fibrosis and explores the underlying mechanisms.

Eight-week-old male mice were divided into control, DSF, MTX, and MTX+DSF groups and treated for 8 weeks. Weight, food, and water intake were monitored. Post-treatment, lung tissues were analyzed using HE and Masson staining, and electron microscopy. Real-time qPCR and ELISA were employed to assess inflammatory markers such as IL-1β and TNF-α in lung tissues and serum. PCR, ELISA, and Western blot were used for fibrotic markers including Col1α1, α-SMA, and hydroxyproline. Type 2 alveolar epithelial cell line MLE12 cells were similarly grouped, followed by RNA sequencing and bioinformatics analysis to elucidate the mechanisms by which DSF exerts anti-MTX-induced pulmonary fibrosis effects. ELISA and Western blot were used to measure E-cadherin and α-SMA expression.

DSF significantly reduced MTX-induced alveolar septal thickening, pulmonary fibrosis, and inflammatory cell infiltration. It also decreased the expression of inflammatory factors IL-1β and TNF-α, as well as the expression of Col1α1, α-SMA, and others. RNA-seq revealed that DSF induces changes in multiple signaling pathways associated with pulmonary fibrosis, particularly in extracellular matrix-related genes. ELISA and Western blot showed decreased E-cadherin and increased α-SMA in the MTX group, which was partially restored with DSF treatment.

DSF alleviates MTX-induced pulmonary fibrosis by reducing epithelial-mesenchymal transition (EMT) in type 2 alveolar epithelial cells. Disulfiram shows potential as a therapeutic agent for MTX-induced pulmonary fibrosis.