Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase inAkkermansia, whereas the opposite was observed forEscherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt⁺CD3⁻group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.

Emerging research has revealed regulation of colorectal cancer metabolism by bacteria. Fusobacterium nucleatum (Fn) plays a crucial role in the development of colorectal cancer, however, whether Fn infection modifies metabolism in patients with colorectal cancer remains unknown. Here, LC-MS/MS-based lipidomics identified the upregulation of cytochrome P450 monooxygenases, primarily CYP2J2, and their mediated product 12,13-EpOME in patients with colorectal cancer tumors and mouse models, which increased the invasive and migratory ability of colorectal cancer cells in vivo and in vitro by regulating the epithelial–mesenchymal transition (EMT). Metagenomic sequencing indicated a positive correlation between increased levels of fecal Fn and serum 12,13-EpOME in patients with colorectal cancer. High levels of CYP2J2 in tumor tissues also correlated with high Fn levels and worse overall survival in patients with stage III/IV colorectal cancer. Moreover, Fn was found to activate TLR4/AKT signaling, downregulating Keap1 and increasing NRF2 to promote transcription of CYP2J2. Collectively, these data identify that Fn promotes EMT and metastasis in colorectal cancer by activating a TLR4/Keap1/NRF2 axis to increase CYP2J2 and 12,13-EpOME, which could serve as clinical biomarkers and therapeutic targets for Fn-infected patients with colorectal cancer. Significance: This study uncovers a mechanism by which Fusobacterium nucleatum regulates colorectal cancer metabolism to drive metastasis, suggesting the potential biomarker and therapeutic utility of the CYP2J2/12,13–EpOME axis in Fn-infected patients.

Chemotherapy has an essential role not only in advanced solid tumor therapy intervention but also in society’s health at large. Chemoresistance, however, seriously restricts the efficiency and sensitivity of chemotherapeutic agents, representing a significant threat to patients’ quality of life and life expectancy. How to reverse chemoresistance, improve efficacy sensitization response, and reduce adverse side effects need to be tackled urgently. Recently, studies on the effect of ultrasonic microbubble cavitation on enhanced tissue permeability and retention (EPR) have attracted the attention of researchers. Compared with the traditional targeted drug delivery regimen, the microbubble cavitation effect, which can be used to enhance the EPR effect, has the advantages of less trauma, low cost, and good sensitization effect, and has significant application prospects. This article reviews the research progress of ultrasound-mediated microbubble cavitation in the treatment of solid tumors and discusses its mechanism of action to provide new ideas for better treatment strategies.

The role of tumor size in predicting prognosis in upper tract urothelial carcinoma (UTUC) patients remains poorly defined. To assess the prognostic value of tumor size in patients with UTUC through a systematic review and meta-analysis. A comprehensive literature search of the PubMed and Embase databases were performed to identify all relevant articles published up to December 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Available hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were analyzed to evaluate the association between tumor size and survival outcomes. A total of 35 articles representing 32 292 patients met the eligibility criteria and were finally included for the meta-analysis. Tumor size was significantly associated with poor outcomes in terms of overall survival (HR = 1.42, 95% CI = 1.28–1.58), cancer-specific survival (HR = 1.66, 95% CI = 1.47–1.88), recurrence-free survival (HR = 1.25, 95% CI = 1.13–1.38), and intravesical recurrence (HR = 1.12, 95% CI = 1.04–1.20). There was between-study heterogeneity in the effect of tumor size on all these meta-analyses, with p < 0.10 and I² generally >50%. Subgroup analyses illustrated that the association of tumor size with adverse prognosis in UTUC patients is not affected by treatment modalities. Segmental resection of ureter, whether receiving lymph node dissection, cutoff of tumor size, and region of population were potential sources of heterogeneity. The funnel plot test indicated no significant publication bias in the meta-analysis of survival outcomes. This study shows that larger tumor size is associated with an increased risk of overall and cancer-specific mortality, and disease recurrence in UTUC. Integration of tumor size with other prognostic indicators may help in risk stratification and individualized treatment of UTUC. Through a systematic review and meta-analysis, this study found that larger tumor size is associated with an increased risk of overall and cancer-specific mortality, and disease recurrence in patients with upper tract urothelial carcinoma.