Dysregulation of polyamine metabolism has been implicated in cancer initiation and progression; however, the mechanism of polyamine dysregulation in cancer is not fully understood. In this study, we investigated the role of MUC1, a mucin protein overexpressed in pancreatic cancer, in regulating polyamine metabolism. Utilizing pancreatic cancer patient data, we noted a positive correlation between MUC1 expression and the expression of key polyamine metabolism pathway genes. Functional studies revealed that knockdown of spermidine/spermine N1-acetyltransferase 1 ( SAT1 ), a key enzyme involved in polyamine catabolism, attenuated the oncogenic functions of MUC1, including cell survival and proliferation. We further identified a regulatory axis whereby MUC1 stabilized hypoxia-inducible factor (HIF-1α), leading to increased SAT1 expression, which in turn induced carbon flux into the tricarboxylic acid cycle. MUC1-mediated stabilization of HIF-1α enhanced the promoter occupancy of the latter on SAT1 promoter and corresponding transcriptional activation of SAT1 , which could be abrogated by pharmacological inhibition of HIF-1α or CRISPR/Cas9-mediated knockout of HIF1A . MUC1 knockdown caused a significant reduction in the levels of SAT1-generated metabolites, N1-acetylspermidine and N8-acetylspermidine. Given the known role of MUC1 in therapy resistance, we also investigated whether inhibiting SAT1 would enhance the efficacy of FOLFIRINOX chemotherapy. By utilizing organoid and orthotopic pancreatic cancer mouse models, we observed that targeting SAT1 with pentamidine improved the efficacy of FOLFIRINOX, suggesting that the combination may represent a promising therapeutic strategy against pancreatic cancer. This study provides insights into the interplay between MUC1 and polyamine metabolism, offering potential avenues for the development of treatments against pancreatic cancer.

There is insufficient evidence to confirm the efficacy of ustekinumab (UST) in promoting fistula closure in perianal fistulizing Crohn’s disease (CD) patients. We aimed to evaluate the efficacy of UST in a real-world setting. The data were retrospectively analyzed. Intestinal clinical and endoscopic changes were evaluated. Fistula radiological outcomes were determined using the Van Assche score. A total of 108 patients were included, 43.5% of whom had complex perianal fistulas. Intestinal clinical and endoscopic remission was achieved in 65.7% and 31.5% of patients, respectively. The fistula clinical remission and response rates were 40.7% and 63.0%, respectively, with a significant reduction in Perianal Crohn’s disease Activity Index [5.0(3.0, 8.0) vs. 7.5(5.0, 10.0), p < 0.001] and Crohn’s Anal Fistula Quality of Life [23.5(9.3, 38.8) vs. 49.0(32.3, 60.0), p < 0.001]. Radiological healing, partial response, no change, and deterioration were observed in 44.8%, 31.4%, 13.4%, and 10.4% of patients, respectively. The cut-off UST trough concentration for predicting fistula clinical remission was 2.11 μg/mL with an area under the curve of 0.795, a sensitivity of 93.3%, and a specificity of 67.6%. UST is efficacious in promoting radiological fistula closure in patients with perianal fistulizing CD. A UST trough concentration over 2.11 μg/mL was correlated with a higher likelihood of perianal fistula clinical remission.

The affordances of social media, have significantly transformed how patients seek and process health information online, including those with chronic diseases like irritable bowel disease (IBD). Few studies have explored how information processing may impact symptom management. Guided by social cognitive theory, this study investigates how Chinese and U.S. patients (N = 838) process health information in a cross-cultural setting and the impact on symptom management. It finds that efficient information processing improves treatment understanding and symptom management for IBD patients, regardless of their cultural backgrounds. It also reveals a U-shaped quadratic relationship between IBD severity and emotional and peer support, indicating varying support needs at different IBD stages. These findings provide valuable insights for healthcare professionals, patients, and caregivers in designing interventions for chronic diseases. The study underscores the importance of recognizing the dynamics of health information processing and the need for a more nuanced approach to patient support and care.

The pathogenesis and vital factors of early and progressive stages of stomach adenocarcinoma (STAD) have not been fully elucidated. In order to discover novel and potential targets to guide effective treatment strategies, a comprehensive bioinformatics study was performed, and the representative results were then validated by quantitative polymerase chain reaction (qPCR) and immunohistochemical (IMC) staining in clinical samples. A total of 4,627, 4,715, and 3,465 differentially expressed genes (DEGs) from overall-, early-, and progressive-stage STAD were identified, respectively. Prognostic models of 5-year OS were established for overall-, early-, and progressive-stage STAD, and ROC curves demonstrated AUC values for each model were 0.73, 0.87, and 0.92, respectively. Function analysis revealed that mRNAs of early-stage STAD were enriched in chemical stimulus-related pathways, whereas remarkable enrichment of mRNAs in progressive-stage STAD mainly lay in immune-related pathways. Both qPCR and IHC data confirmed the up-regulation of IGFBP1 in the early-stage and CHAF1A in progressive-stage STAD compared with their matched normal tissues, indicating that these two representative targets could be used to predict the prognostic status of the patients in these two distinct STAD stages, respectively. In addition, seven mRNAs (F2, GRID2, TF, APOB, KIF18B, INCENP, and GCG) could be potential novel biomarkers for STAD at different stages from this study. These results contributed to identifying STAD patients at high-risk, thus guiding targeted treatment with efficacy in these patients.

Introduction: Immunogenic cell death (ICD) is a sort of regulated cell death (RCD) sufficient to trigger an adaptive immunological response. According to the current findings, ICD has the capacity to alter the tumor immune microenvironment by generating danger signals or damage-associated molecular patterns (DAMPs), which may contribute in immunotherapy. It would be beneficial to develop ICD-related biomarkers that classify individuals depending on how well they respond to ICD immunotherapy.Methods and results: We used consensus clustering to identify two ICD-related groupings. The ICD-high subtype was associated with favorable clinical outcomes, significant immune cell infiltration, and powerful immune response signaling activity. In addition, we developed and validated an ICD-related prognostic model for PDAC survival based on the tumor immune microenvironment. We also collected clinical and pathological data from 48 patients with PDAC, and patients with high EIF2A expression had a poor prognosis. Finally, based on ICD signatures, we developed a novel PDAC categorization method. This categorization had significant clinical implications for determining prognosis and immunotherapy.Conclusion: Our work emphasizes the connections between ICD subtype variations and alterations in the immune tumor microenvironment in PDAC. These findings may help the immune therapy-based therapies for patients with PDAC. We also created and validated an ICD-related prognostic signature, which had a substantial impact on estimating patients' overall survival times (OS).