We compared the serum levels of microRNA-155 (miR-155) between subjects with normal response to hepatitis B vaccine and nonresponders. Results showed that serum expression of miR-155 was significantly higher in nonresponders than in responders (6.40 versus 2.55;Z= 2.125,P= 0.034), suggesting that overexpression of miR-155 is correlated with nonresponsiveness to hepatitis B vaccine.

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.

Background: Antibody–drug conjugates (ADCs), as a new type of targeted drug, have been widely used in breast cancer patients in recent years. However, while achieving better efficacy, its hepatotoxicity should not be ignored. Objectives: To clarify the incidence of hepatotoxicity associated with ADCs and compare the incidence of hepatotoxicity of ADCs with different drugs. Design: We performed a systematic review and meta-analysis to summarize the clinical trials and combined the data using meta-analysis. Methods: We searched the PubMed, Embase, and Web of Science databases up to March 12, 2023. The primary outcome was the incidence of ADC-related hepatotoxicity in breast cancer patients. The data were merged using Stata 17.0 software. Results: ADCs caused a high incidence of all grades of hepatotoxicity. Sacituzumab govitecan caused the highest incidence of all grades of alanine aminotransferase (ALT) elevation at 25.30% (95% confidence interval (CI): 19.29–31.82). Trastuzumab deruxtecan caused the highest incidence of all grades of aspartate aminotransferase (AST) elevation. The highest incidence of AST elevation was 31.89% (95% CI: 18.56–46.85). Conversely, trastuzumab emtansine caused the highest incidence of grade ⩾3 AST and ALT elevation (incidence rates were 3.95% (95% CI: 2.39–5.85) and 3.42% (95% CI: 1.95–5.24), respectively). Conclusion: Hepatotoxicity is an adverse reaction that cannot be ignored when ADCs are used for treating breast cancer. Moreover, clinicians should pay more attention to the assessment of patients’ liver function and monitoring of liver indices, particularly ALT and AST, when using ADCs.