Colorectal cancer is one of the most leading causes of death. Searching for new therapeutic targets for colorectal cancer is urgently needed. SHU00238, an isoxazole derivative, was reported to suppress colorectal tumor growth through microRNAs. But the underlying mechanisms still remain unknown. Here, we explored the mechanism of SHU00238 on colorectal cancer by RT-PCR, CCK-8, flow cytometry, mirTarBase, and GO enrichment analysis. We screened partial microRNAs regulated by SHU00238 in colorectal cancer cells. Furthermore, we identified that miR-4701-3p and miR-4793-3p can reverse the acceleration of SHU00238 on colorectal cancer cell apoptosis in HCT116 Cells. Finally, we found that SMARCA5, MBD3, VPS53, EHD4 are estimated to mediate the regulation of miR-4701-3p and miR-4793-3p on colorectal cancer cell apoptosis, which targets ATP-dependent chromatin remodeling pathway and endocytic recycling pathway. Taken together, our study reveals that SHU00238 promotes colorectal cancer cell apoptosis through miR-4701-3p and miR-4793-3p, which provide a potential drug target and therapeutic strategy for colorectal cancer.

Muscle atrophy is a common complication of heart failure. At present, there is no specific treatment to reverse the course of muscle atrophy. Exercise training, due to the safety and easy operation, is a recommended therapy for muscle atrophy induced by heart failure. However, the patients with muscle atrophy are weak in mobility and may not be able to train for a long time. Therefore, it is necessary to explore novel targets of exercise protection for muscle atrophy, so as to improve the quality of life and survival rate of patients with muscular atrophy induced by heart failure. This article aims to review latest studies, summarize the evidence and limitations, and provide a glimpse into the future of exercise for the treatment of muscle atrophy induced by heart failure. We wish to highlight some important findings about the essential roles of exercise sensors in muscle atrophy induced by heart failure, which might be helpful for searching potential therapeutic targets for muscle wasting induced by heart failure.

Background and aims: Antibiotic use in early life is increasingly being scrutinized for its potential effects on health, particularly its association with inflammatory bowel disease (IBD). The weaning period is a critical developmental window for maturation of the intestinal barrier, immune system and gut microbiota. However, it remains unknown how administering antibiotics to male mice starting at weaning affects the susceptibility of their future offspring to IBD. Methods: Three-week-old weaned male mice were used to investigate the effects of short-term (1 week) and long-term (6 weeks) administration with ampicillin and cefixime on colitis susceptibility in adulthood and in the subsequent F1 generation. Paternal and F1 offspring were administered dextran sodium sulfate (DSS) to induce colitis. Quantitative real-time polymerase chain reaction, immunoblotting, immunofluorescence staining, and histological examination were used to assess mRNA and protein expression and morphological changes. Full 16S rRNA and miRNA sequencing was used to assess changes in the gut microbiota compositions and the mechanisms of intergenerational transmission of intestinal phenotypes. A dual-luciferase reporter assay was used to decipher the direct regulation of miR-10b-5p and miR-200b-3p on Occludin 3′ UTR. Results: Both short- and long-term antibiotic administration during the weaning period significantly alleviated DSS-induced colitis in male paternal mice, with long-term administration conferring a more pronounced protective effect. Interestingly, the protective effect against DSS-induced colitis was observed in LONG_F1 offspring, which was more pronounced in F1 males than in F1 females. Mechanistically, the protective effect was associated with increased expression of Occludin in epithelial cells, which was negatively modulated by miR-10b-5p and miR-200b-3p. This effect was inherited via the sperm. Furthermore, long-term antibiotic administration significantly altered the gut microbiota of paternal males, increasing the abundance of certain beneficial bacteria, such as Lactobacillus gasseri and Parabacteroides merdae , while promoting the enrichment of antibiotic-resistant strains. Conclusions: Long-term antibiotic administration initiated at the weaning stage in male mice improves colitis in adulthood and in their offspring that associates with decreasing miR-10b-5p and miR-200b-3p expression, thus providing a theoretical basis for optimizing the use of antibiotics and prevention of IBD.