Protopanaxadiol manipulates gut microbiota to promote bone marrow hematopoiesis and enhance immunity in cyclophosphamide-induced immunosuppression mice.

Protopanaxadiol (PPD) has potential immunomodulatory effects, but the underlying mechanism remains unclear. Here, we explored the potential roles of gut microbiota in the immunity regulation mechanisms of PPD using a cyclophosphamide (CTX)-induced immunosuppression mouse model. Our results showed that a medium dose of PPD (PPD-M, 50 mg/kg) effectively ameliorated the immunosuppression induced by CTX treatment by promoting bone marrow hematopoiesis, increasing the number of splenic T lymphocytes and regulating the secretion of serum immunoglobulins and cytokines. Meanwhile, PPD-M protected against CTX-induced gut microbiota dysbiosis by increasing the relative abundance of Lactobacillus, Oscillospirales, Turicibacter, Coldextribacter, Lachnospiraceae, Dubosiella, and Alloprevotella and reducing the relative abundance of Escherichia-Shigella. Importantly, PPD-M lost the ability to promote bone marrow hematopoiesis and enhance immunity when the gut microbiota was depleted by broad-spectrum antibiotics. Moreover, PPD-M promoted the production of microbiota-derived immune-enhancing metabolites including cucurbitacin C, l-gulonolactone, ceramide, DG, prostaglandin E2 ethanolamide, palmitoyl glucuronide, 9R,10S-epoxy-stearic acid, and 9'-carboxy-gamma-chromanol. KEGG topology analysis showed that the PPD-M treatment significantly enriched the sphingolipid metabolic pathway with ceramide as a main metabolite. Our findings reveal that PPD enhances immunity by manipulating gut microbiota and has the potential to be used as an immunomodulator in cancer chemotherapy.

Assessment of cancer cell migration using a viscosity-sensitive fluorescent probe.

A novel viscosity probe (NV1) was developed for assessing cancer cell migration. NV1 can respond to changes of viscosity rapidly and exhibits high sensitivity in HepG2 cells treated with starvation, rotenone and nystatin. Importantly, NV1 was used for the first time to evaluate the relationship between intracellular viscosity changes and cancer cell migration and proved that increased intracellular viscosity inhibits cell migration while decreased intracellular viscosity promotes cell migration.

Metformin inhibits the tumor-promoting effect of low-dose resveratrol, and enhances the anti-tumor activity of high-dose resveratrol by increasing its reducibility in triple negative breast cancer.

Resveratrol, a natural antioxidant that maintains better bioactivity under hypoxia, has anti-tumor effects, but its underlying mechanism is controversial and the effect on Triple-negative breast cancer (TNBC) remains unclear. Herein, we investigated the anti-TNBC mechanism of resveratrol under a mimic hypoxic tumor microenvironment and explored a method of combining metformin to improve the therapeutic effect. The results showed an inverted "U" shaped relationship between the cell viability and resveratrol concentrations. Low concentrations of resveratrol (LRes) promoted proliferation and migration in MDA-MB-231 cells by activating JAK3/STAT3 signaling pathway, while high concentrations of resveratrol (HRes) inhibited cell growth and induced both autophagy and apoptosis through MAPK signaling pathway. Meanwhile, HRes treatment resulted in the up-regulation of antioxidant-related genes SOD3 and FAM213B, the increase of catalase activity and NAD(P)H level, which leading to a reducing microenvironment in cells. Notably, metformin could inhibit the proliferation and migration induced by LRes, whereas promote apoptosis induced by HRes. Moreover, metformin enhanced the reducing environment via further increasing the catalase activity and NAD(P)H level. These findings conclude the anti-TNBC mechanism of HRes should be attributed to its antioxidant activity and metformin enhances its reducibility. Metformin combined with resveratrol exerts a synergistic therapeutic effect on TNBC and effectively prevents tumor progression.