Inflammatory activation and intestinal flora imbalance play an essential role in the development and progression of colorectal cancer (CRC). Berberine (BBR) has attracted great attention in recent years due to its heath-related benefits in inflammatory disorders and tumors, but the intricate mechanisms have not been fully elucidated. In this study, the effects and the mechanism of BBR on colon cancer were investigated in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated carcinogenesis mice model. Our results showed that pre-administration of BBR showed a decrease in weight loss, disease activity index (DAI) score, and the number of colon tumors in mice, compared with the model group. The evidence from pathological examination indicated that the malignancy of intestinal tumors was ameliorated after pre-administration of BBR. Additionally, pre-administration with BBR suppressed the expression of pro-inflammatory factors (interleukin (IL)-6, IL-1β, cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α) and the cell-proliferation marker Ki67, while expression of the tight junction proteins (ZO-1 and occludin) were increased in colon tissue. Moreover, the levels of critical pathway proteins involved in the inflammatory process (p-STAT3 and p-JNK) and cell cycle regulation molecules (β-catenin, c-Myc and CylinD1) exhibited lower expression levels. Besides, 16S rRNA sequence analysis indicated that pre-administration of BBR increased the ratio of Firmicutes/Bacteroidetes (F:M) and the relative abundance of potentially beneficial bacteria, while the abundance of cancer-related bacteria was decreased. Gavage with Lactobacillus rhamnosus can improve the anti-tumor effect of BBR. Overall, pre-administration of BBR exerts preventive effects in colon carcinogenesis, and the mechanisms underlying these effects are correlated with the inhibition of inflammation and tumor proliferation and the maintenance of intestinal homeostasis.

Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.

Staphylococcus aureus (S. aureus), an important opportunistic pathogen in human and animal, causes a series of diseases in the impairing of immunity of host and even then death. Alpha‐hemolysin (Hla), a primary virulence factor, plays a major role in the pathogenic progress of S. aureus, especially in pneumonia. Prim‐O‐glucosylcimifugin (POG), a nature chromone compound, is an active ingredient in many Chinese Medicines. In this study, POG investigated the inhibitory effect of the secretion of Hla in S. aureus strain USA300 at the subinhibitory concentrations. The hemolysis assays and western blotting assays showed that POG can decrease the production of Hla in the USA300 growth cell cultures in a dose‐dependent manner. The results of RT‐PCR revealed that reduction of Hla was related to inhibit the transcription of hla and RNAIII. In the cells experiment, POG was proved to protect A549 cells from Hla‐medicated injury. In conclusion, POG was shown the capacity of decreased the production of S. aureus Hla. POG can be developed as a candidate agent to treat S. aureus infections against Hla.