Genetic variations in immune mediators and prostate cancer risk: A field synopsis with Bayesian calculations.

OBJECTIVE: Our study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches. METHODS: We performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein-protein networks were designed for the genes and products enrolled in the results. RESULTS: As results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein-protein networks reinforced the findings on IL1B and IL18 genes. CONCLUSION: In conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.

Gene variations related to the hepatocellular carcinoma: Results from a field synopsis and Bayesian revaluation.

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein-protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Epiisopiloturine, an imidazole alkaloid, reverses inflammation and lipid peroxidation parameters in the Crohn disease model induced by trinitrobenzenosulfonic acid in Wistar rats.

Epiisopiloturine (EPI) is an important imidazole alkaloid because of its pharmacological properties. The aim of this study was to investigate the effects of epiisopiloturine on inflammatory parameters of the colonic mucosa in a rat model of Crohn's disease (CD). For this, we induced colitis using trinitrobenzenosulfonic acid and determined myeloperoxidase (MPO), interleukin 1 ß (IL-1ß), glutathione (GSH), and malondialdehyde (MDA) levels in the intestinal mucosa. The location and expression of the inflammatory markers in the colon were investigated by immunohistochemistry for NO synthase induced (iNOS), interleukin 1 beta (IL-1ß), and cyclooxygenase-2 (COX-2) and western blotting (iNOS and COX-2), respectively. Compared with TNBS alone, epiisopiloturine at 1 mg/kg reduced the macroscopic and microscopic scores, wet weight of the colon, and neutrophilic infiltration and expression of the pro-inflammatory cytokine IL-1ß. Epiisopiloturine at 1 mg/kg maintained or restored GSH levels and simultaneously decreased MDA levels. Animals treated with epiisopiloturine exhibited reduced immunostaining for IL-1ß, iNOS, and COX-2 and reduced cell count per field. Epiisopiloturine reduced the expression of COX-2 and iNOS in the colon. Based on these findings, we conclude that epiisopiloturine at 1 mg/kg may be an important pharmacological tool against intestinal inflammatory diseases due to its inhibitory action on key enzymes and products involved in inflammation.