Purpose: The main purpose of this study is to demonstrate the effects of epithelial to mesenchymal transition activating transcription factor silencing (EMT-ATF silencing) on migration, invasion, drug resistance and tumor-forming abilities of various pancreatic cancer cell lines. Additionally, the contribution of small molecule inhibitors of EMT (SD-208 and CX4945) to the effects of gene silencing was evaluated. Methods: EMT activating transcription factors “Snail, Slug and Twist” were silenced by short hairpins on Panc-1, MIA PaCa-2, BxPC-3, and AsPC-1 pancreatic cancer cell lines. The changes in migration, invasion, laminin attachment, cancer stem-like cell properties and tumor-forming abilities were investigated. Chemosensitivity assays and small molecule inhibitors of EMT were applied to the metastatic pancreatic cancer cell line AsPC-1. Results: EMT-ATF silencing reduced EMT and stem cell-like characteristics of pancreatic cancer cell lines. Following EMT-ATF silencing amongst the four PC cell lines, AsPC-1 showed the best response and was chosen for further chemoresistance and combinational therapy applications. EMT downregulated AsPC-1 cells showed less resistance to select chemotherapeutics compared to the control group. Both small molecule inhibitors enhanced the outcomes of EMT-ATF silencing. Conclusion: Overall it was found that EMT-ATF silencing, either by EMT-ATF silencing or with the enhancement by small molecules, is a good candidate to treat pancreatic cancer since it simultaneously minimizes metastasis, stem cell properties, and drug resistance.

The intricate interplay between the intestinal microbiota and the immune system has emerged as a central theme in understanding autoimmune disease pathogenesis. This review comprehensively explores the role of gut microbiota in shaping immune development, establishing immune tolerance, and contributing to both local and systemic immune regulation. This review synthesizes the modulatory effects of microbial metabolites (eg, short-chain fatty acids and indole derivatives) on regulatory T cells (Tregs) and inflammatory pathways. The concept of “dysbiosis” is examined from functional and compositional perspectives, linking microbial imbalances to autoimmune disorders (IBD, MS, RA, and T1D). Microbiota-targeted therapeutic interventions (probiotics, prebiotics, FMT) are also evaluated. The synthesis of the literature confirms that microbial metabolites have a direct impact on Treg differentiation and inflammatory pathways. Dysbiosis, through functional and compositional disruptions, is strongly associated with the pathogenesis of various autoimmune disorders, including Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis, and Type 1 Diabetes. Therapeutic interventions such as probiotics, prebiotics, and Fecal Microbiota Transplantation show promising potential in restoring microbial and immune homeostasis. This review highlights the role of the gut-immune axis in autoimmune diseases. Despite current challenges, such as individual variability and determining causality, future directions toward precision microbiota and immune modulation are promising. This study provides a robust foundation for researchers and clinicians seeking to understand and therapeutically target the gut-immune axis.

Background: Highly aggressive and resistant to chemotherapy, pancreatic cancers are the fourth leading cause of cancer-related deaths in the western world. The absence of effective chemotherapeutics is leading researchers to develop novel drugs or repurpose existing chemicals. Alexidine Dihydrochloride (AD), an orally bioavailable bis-biguanide compound, is an apoptosis stimulating reagent. It induces mitochondrial damage by inhibiting a mitochondrial-specific protein tyrosine phosphatase, PTPMT1. The aim of this study was to test AD as a novel compound to induce apoptosis in a human pancreatic adenocarcinoma cell lines, Panc-1, MIA PaCa-2, AsPC-1, and Psn-1. Methods: After the IC50 value of the AD was determined by cytotoxicity assay, apoptosis was observed by a variety of methods, including the detection of early apoptosis marker Annexin V and the proteomic profile screening by apoptosis array. Multicaspase and mitochondrial depolarization were measured, and changes in the cell cycle were analyzed. Results: AD is found to initiate apoptosis by activating the intrinsic pathway and inhibit the cell cycle in pancreatic cancer cell lines. Conclusions: In conclusion, considering its anti-cancer properties and bioavailability, Alexidine dihydrochloride can be considered as a potential candidate against pancreatic adenocarcinomas.