Objective. Curcumin is an active extract from turmeric. The aim of this study was to identify the underlying mechanism of curcumin on PCa cells and the role of autophagy in this process. Methods. The inhibitory effect of curcumin on the growth of PANC1 and BxPC3 cell lines was detected by CCK‐8 assay. Cell cycle distribution and apoptosis were tested by flow cytometry. Autophagosomes were tested by cell immunofluorescence assay. The protein expression was detected by Western blot. The correlation between LC3II/Bax and cell viability was analyzed. Results. Curcumin inhibited the cell proliferation in a dose‐ and time‐dependent manner. Curcumin could induce cell cycle arrest at G2/M phase and apoptosis of PCa cells. The autophagosomes were detected in the dosing groups. Protein expression of Bax and LC3II was upregulated, while Bcl2 was downregulated in the high dosing groups of curcumin. There was a significant negative correlation between LC3II/Bax and cell viability. Conclusions. Autophagy could be triggered by curcumin in the treatment of PCa. Apoptosis and cell cycle arrest also participated in this process. These findings imply that curcumin is a multitargeted agent for PCa cells. In addition, autophagic cell death may predominate in the high concentration groups of curcumin.

Structural disruption of gut microbiota is closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). Previous research has demonstrated that both curcumin (CUR) and metformin (MET) have a therapeutic effect against NAFLD and play a role in modulating the gut microbiota. However, there is a lack of direct comparison between the two medications in terms of the therapeutic efficacy and the regulatory effect on gut microbiota. In this study, we administered either CUR or MET to rats with high-fat diet (HFD)-induced obesity to observe changes in body parameters, biochemical parameters, liver, and ileum pathology and gut microbiota, and used next generation sequencing and multivariate analysis to evaluate the structural changes of gut microbiota in a NAFLD rat model before and after CUR and MET intervention. It was found that both CUR and MET attenuated hepatic ectopic fat deposition, alleviated inflammatory factors, and improved intestinal barrier integrity in HFD-fed rats. More importantly, CUR and MET reduced the Firmicutes/Bacteroidetes ratio and reverted the composition of the HFD-disrupted gut microbiota. Both CUR and MET treatments effectively modified the gut microbiome, enriched the abundance of beneficial bacteria and reduced opportunistic pathogens in obese rats. The abundance of Butyricicoccus was increased while the abundance of Dorea was decreased in HFD + CUR group. Besides, some beneficial bacteria such as Prevotella were increased in MET-treated animals. Spearman’s correlation analysis showed that Helicobacter, Akkermansia, Desulfovibrio, Romboutsia, Corynebacterium, Lactobacillus, Ruminococcaceae_unclassified, Lachnospiraceae_unclassified, and Clostridiales_unclassified showed significantly positive correlations with TG, TC, LDL-C, GLU, IL-6, IL-1β, and TNF-α, and negative correlations with HDL-C (both p < 0.05). However, Prevotella and Stomatobaculum showed an opposite trend. In summary, CUR and MET showed similar effects in alleviating hepatic steatosis, improving intestinal barrier integrity and modulating gut microbiota in HFD-induced obesity rats, and therefore may prove to be a novel adjunctive therapy for NAFLD.

Ferroptosis is a regulated cell death nexus linking metabolism, redox biology and diseases including cancer. The aim of the present study was to identify a ferroptosis-related gene prognostic signature for pancreatic cancer (PCa) by systematic analysis of transcriptional profiles from Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Altogether 14 ferroptosis-relevant genes with potential prognostic values were identified, based on which a risk score formula was constructed. According to the risk scores, we classified the patients into a high- and a low-risk score group. It was verified in Gene Expression Omnibus (GEO) and ICGC(International Cancer Genome Consortium) datasets. The Kaplan-Meier survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS) (P < 0.0001). The area under the receiver operating curve (ROC) for 12, 18 and 24 months was about 0.8 in all patients. The result of immune status analysis revealed that the signature significantly associated with the immune infiltration and immune checkpoint blockade (ICB) proteins. In addition, we used quantitative real time PCR (q-rtPCR) and Human Protein Atlas (HPA) to validate the expression of the key genes. Collectively, the signature is valuable for survival prediction of PCa patients. As the signature also has relevance with the immune characteristics, it may help improve the efficacy of personalized immunotherapy.

Aim: This study aims to evaluate the efficacy of Lacticaseibacillus rhamnosus LRa05 supplementation in enhancing Helicobacter pylori (H. pylori) eradication rate and alleviating the gastrointestinal side effects associated with bismuth quadruple therapy.Methods: H. pylori-positive patients were randomized to receive levofloxacin-based bismuth quadruple therapy combined either probiotic LRa05 or a placebo for two weeks, followed by LRa05 (1 × 10¹⁰ CFU) or maltodextrin for the next two weeks. H. pylori infection was detected by ¹³C breath test pre- and post-treatment. Blood and stool samples were collected at week 0 and week 4 for routine and biochemical analysis, and serum inflammatory markers. Gastrointestinal symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS). Intestinal microbiota was analyzed using 16S rRNA sequencing. The research was listed under the Chinese Clinical Trial Registry (ChiCTR2300072220), and written informed consent was obtained from all participants.Results: The LRa05 group exhibited a trend toward higher H. pylori eradication rates (86.11%) compared to the placebo group (82.86%), though the difference was not statistically significant. Significant reductions in neutrophil count, alanine aminotransferase, aspartate aminotransferase, pepsinogen I, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) (p < 0.05) suggest that LRa05 supplementation may mitigate inflammation, enhance liver function, and potential aid in early cancer prevention. GSRS symptom scores showed that LRa05 alleviated abdominal pain, acid reflux, bloating, and diarrhea, enhancing patient compliance. Furthermore, 16S rRNA sequencing showed that LRa05 countered the antibiotic-induced disruption of gut microbiota diversity, primarily by increasing beneficial bacteria.Conclusion: Although LRa05 did not significantly improve the success rate of H. pylori eradication therapy, it has the potential to improve liver function and reduced levels of inflammatory markers such as IL-6 and TNF-α in the body, regulating the inflammatory response. In addition, it played a positive role in alleviating the adverse symptoms and gut microbiota disturbances caused by eradication therapy, providing a possible way to improve the overall health of patients and demonstrating promising clinical potential.Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2300072220.

Introduction: Constipation-predominant irritable bowel syndrome (IBS-C) is a functional bowel disease that affects 10–20% of the population worldwide. Curcumin (CUR) is widely used in traditional Chinese medicine to treat IBS, but its mechanism of action needs further investigation.Methods: In this study, we used mosapride (MOS) as a positive control to evaluate the changes in gut microbiota in IBS-C rat models after treatment with CUR or MOS by analyzing 16S rDNA variation. In addition, we used enzyme immunoassay kits and immunohistochemical analysis to investigate whether CUR or MOS influenced serotonin (5-HT), substance P (SP), and vasoactive intestinal peptide (VIP) levels in the serum and colon of IBS-C rats.Results: The study showed that rats supplemented with CUR showed significantly increased fecal weight, fecal water content, small intestine transit rate and significantly decreased serum levels of 5-HT, VIP and SP compared to the IBS group (p < 0.05). In addition, treatment with CUR changed the relative abundance of Blautia, Sutterella, Acetanaerobacterium and Ruminococcus2 in the gut microbiota.Discussion: This study showed that the efficacy of CUR on IBS-C was possibly by modulating the microbiota and lowering the serum levels of HT, SP, and VIP.