Exploring the possible mechanism of low-dose naloxone exposure improving the immune microenvironment of gastric cancer tumors

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Introduction Gastric cancer, one of the most common cancers digestive tract, has high incidence and mortality rates. Until recently, surgery been effective method treatment for gastric cancer. Surgery, however, inevitably results in dysfunction autonomic nervous system, entry tumor cells into bloodstream, immunosuppression during perioperative period, all which increase risk complications patients with Opioid receptors play an important role proliferation secretion cytotoxic factors by immune cells. Opiate usage inhibits cell function, reduces release factors, enables to evade thereby increasing complications. antagonists may reverse opioid-mediated several ways. However, studies on molecular biology opioid receptor relation their ability improve function cancer are limited. Methods We first analyzed genome atlas stomach adenocarcinoma (TCGA-STAD) dataset determine correlation between changes toll-like 4 (TLR4) expression A transwell co-culture system was established using CD8 + T mouse forestomach carcinoma (MFC) were treated different concentrations naloxone concentration killing then performed western blotting quantitative realtime polymerase chain reaction lymphocyte activation gene 3 (Lag3), perforin 1 (Prf1), programmed death ligand (PD-1), T-cell immunoglobulin mucin domain (TIM-3), TLR4/AKT/mTOR An MFC-derived allograft model used study vivo Flow cytometry, ELISA, WB, PCR examine number populations spleen, cells, receptors, AKT/mTOR, checkpoint proteins, respectively, Results found that strongly correlated TLR4 surface Low-dose (LDN) increased cytotoxicity, inhibited exhaustion, Lag3, Prf1, Tim3 expression, AKT mTOR downregulated following LDN administration. Conclusion improved kill reduced exhaustion. The mechanism underlying these LDN-mediated phenomena involve regulation factor via pathway, or further affecting

Language: Английский

Drugs repurposed against morphine and heroin dependence: molecular docking, DFT, MM-GBSA-based MD simulation studies

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(2)

Published: April 17, 2025

Language: Английский