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Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1ß), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.
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BACKGROUND: Globally, HCC presents a significant health burden, characterized by high incidence and mortality rates. Epidemiological studies have increasingly suggested a link between dietary patterns and the risk of hepatocellular carcinoma (HCC), yet consensus on this relationship remains elusive. OBJECTIVE: This study aims to synthesize existing literature and provide a comprehensive analysis of the association between dietary patterns and HCC risk through meta-analytical methods. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library databases was conducted to identify studies examining common dietary patterns in relation to HCC, published up to August 2023. Study quality was rigorously evaluated using the Newcastle-Ottawa Scale. We employed a random effects model to synthesize effect sizes, calculating hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 13 papers, of these 10 investigating a priori dietary patterns(index-based dietary patterns) and 3 focusing on a posterior dietary patterns (data-driven dietary patterns). Analysis of a priori dietary patterns revealed that higher scores in the Healthy Eating Index (HEI) & alternative HEI (HR = 0.67, 95% CI: 0.54-0.85), Dietary Approaches to Stop Hypertension (DASH) (HR = 0.77, 95% CI: 0.66-0.91), and the Mediterranean diet (HR = 0.65, 95% CI: 0.56-0.75) were associated with a reduced risk of HCC. Conversely, pro-inflammatory dietary patterns were linked with an increased risk (HR = 2.21, 95% CI: 1.58-3.09). In a posterior dietary patterns, a vegetable-based diet was negatively correlated with HCC risk (HR = 0.63, 95% CI: 0.49-0.81). CONCLUSION: This meta-analysis underscores a significant association between dietary patterns and the risk of HCC. Adherence to healthy dietary patterns characterized by high in vegetables, whole grains, legumes, nuts, and low in red and processed meats may confer a protective effect against HCC, whereas inflammatory diets appear to elevate risk.
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Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy. Tumor-infiltrating lymphocyte (TIL) therapy, a form of adoptive cellular therapy (ACT), involves isolating T lymphocytes from tumor tissues, in vitro expansion, and reintroduction into the body to target and eliminate tumor cells. This article presents an overview of the development and application of TIL therapy in CRC, as well as the associated challenges.
RESUMO
Correct usage and maintenance of the enteral nutrition feeding pump system is always a challenge in nutrition support for patients with colorectal cancer (CRC). However, there are few studies on the sustained accuracy improvement of the enteral nutrition feeding system in discharged CRC patients. Here, we established a seven-month quality control circle (QCC) activity with the theme of improving the performance of home enteral feeding pumps (EFP) and examined the effect of QCC activity on the nutritional state and quality of life in discharged CRC patients. We enrolled 100 discharged CRC patients treated with home enteral nutrition from Zhejiang Cancer Hospital between March 2020 and December 2021. The patients were randomly split into two research groups: one participated in the QCC activity (n = 50) and the other did not (n = 50). QCC analysis indicated that the top 3 causes of EFP inaccurate usage are the simple and boring contents of training, various types of pumps, no examination rules, and lack of management. Furthermore, both intra- and inter-group comparisons showed that QCC significantly improved the patients' pass rate of nutrition pump operation from 52 to 70% after 1-month of activity, which gradually improved and got the highest (90%) after 3 months (p < 0.05). Interestingly, the established QCC activity significantly increased the patient-generated subjective global assessment (PG-SGA) and Barthel index (BI) scores, body fat mass (BFM) and superior longitudinal muscle (SLM) by intra- and inter-group comparisons. In this study, we clarified the main causes of inaccurate EFP usage and established a QCC process to improve the pass rate of EFP usage. It finally leads to the improvement of nutritional state and quality of life in CRC patients.
