Ginger-Derived Extracellular Vesicles: A Natural Solution for Alopecia.

BACKGROUND: Ginger (Zingiber officinale (L.) Rosc), as an edible plant-derived nanoparticle, offers several advantages, such as a high return rate, low budget, no ethical barriers, and good for health. Ginger-Derived Extracellular Vesicles (GDEVs) are nanoscale vesicles isolated from ginger. METHODS: In this study, GDEVs were used to treat the alopecia mouse model, and its main active components and potential mechanism of action were investigated. The LC-MS/MS analysis of GDEVs revealed the presence of 1299 chemical compounds, among which auxiliary components were identified. Interestingly, the crux of the analysis lies in the discovery of 13 specific ingredients that play a pivotal role in hair proliferation. The aim of this study was to investigate the protective effect of GDEVs on hair loss. These advantages make ginger-derived nanoparticles a promising solution to overcome technical limitations associated with mammalian nanoparticles. This study elucidates the mechanism of action of GDEVs in the treatment of alopecia. However, the active ingredients and mechanism of action of GDEVs in the treatment of hair loss are unknown. RESULTS: GDEVs were isolated from ginger using the differential centrifugal method. Network pharmacological analysis of the GDEVs revealed that the anti-hair loss effect of GDEVs on alopecia was closely linked to its ability to reduce inflammation and promote the proliferation of hair follicle stem cells. Subsequently, it was applied to the balding areas of hair-loss mice using a brush. The results demonstrated that the application of GDEVs led to a rapid recovery of the balding areas and promoted the growth of healthier hair. CONCLUSION: This experiment reported that GDEVs can effectively suppress the inflammatory activity in the alopecia model mice.

BMP9 and COX-2 form an important regulatory loop in BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) can self-renew and differentiate into osteogenic, chondrogenic, adipogenic and myogenic lineages. It's reported that bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic BMPs to initiate the commitment of MSCs to osteoblast lineage. Cyclooxygenase-2 (COX-2) is critical for bone fracture healing and osteogenic differentiation in MSCs. However, the relationship between COX-2 and BMP9 in osteogenesis remains unknown. Herein, we investigate the role of COX-2 in BMP9-induced osteogenesis in MSCs. We demonstrate that COX-2 is up-regulated as a target of BMP9 in MSCs. Both COX-2 inhibitor (NS-398) and COX-2 knockdown siRNAs can effectively decrease alkaline phosphatase (ALP) activities induced by BMP9 in MSCs. NS-398 also down-regulates BMP9-induced expression of osteopontin and osteocalcin, so does the matrix mineralization. The in vivo studies indicate that knockdown of COX-2 attenuates BMP9-induced ectopic bone formation. In perinatal limb culture assay, NS-398 is shown to reduce the hypertropic chondrocyte zone and ossification induced by BMP9. Mechanistically, knockdown of COX-2 significantly inhibits the BMP9 up-regulated expression of Runx2 and Dlx-5 in MSCs, which can be rescued by exogenous expression of COX-2. Furthermore, knockdown of COX-2 apparently reduces BMP9 induced BMPR-Smad reporter activity, the phosphorylation of Smad1/5/8, and the expression of Smad6 and Smad7 in MSCs. NS-398 blocks the expression of BMP9 mediated by BMP9 recombinant adenovirus. Taken together, our findings suggest that COX-2 plays an important role in BMP9 induced osteogenic differentiation in MSCs; BMP9 and COX-2 may form an important regulatory loop to orchestrate the osteogenic differentiation in MSCs.

All-trans retinoic acid inhibits tumor growth of human osteosarcoma by activating Smad signaling-induced osteogenic differentiation.

Osteosarcoma (OS) is one of the most common malignant bone tumors. Despite the advancement of diagnosis and treatment for OS, the prognosis remains poor. We investigated the proliferation inhibitory effect of all-trans retinoic acid (ATRA) for human OS and the possible mechanism underlying this effect. We examined the proliferation inhibition and apoptosis-inducing effects of ATRA in 143B OS cells. We validated this effect by exogenously expressing the retinoic acid receptor alpha (RARα) in 143B OS cells and injecting the cells into nude mice. We explored the possible mechanism for the proliferation inhibitory effect of ATRA on OS cells and multipotential progenitor cells by detecting osteogenic markers. We demonstrated that the endogenous retinoic acid receptor and retinoid X receptor are all detectable in the commercially available OS cell lines and in primary osteosarcoma cells. ATRA inhibits the proliferation of OS cells in a concentration-dependent manner, as well as induces apoptosis in 143B OS cells. The exogenous expression of RARα inhibits the tumor growth and cell proliferation in vivo. The alkaline phosphatase activity, protein levels of osteopontin (OPN) and osteocalcin (OCN) are all promoted by ATRA in OS cells and mouse embryonic fibroblasts (MEFs), at least by activating the Smad signaling pathway. Collectively, our results strongly indicate that ATRA can inhibit the tumor growth of OS by promoting osteogenic differentiation in OS cells, which is mediated in part by activating Smad signaling. Therefore, combination of ATRA with other current chemotherapy agents may be a promising therapy strategy for OS treatment.

Berberine inhibits the proliferation of colon cancer cells by inactivating Wnt/ß-catenin signaling.

Colon cancer is one of the most common malignancies, mainly initiated by the abnormal activation of Wnt/ß-catenin signaling. In this study, we investigated the proliferation inhibitory effect of berberine on colon cancer cells and the molecular basis underlying this effect. With the viability, apoptosis and cell cycle assay, we demonstrated that berberine can inhibit proliferation, induce apoptosis and cell cycle arrest in colon cancer cells. In in vivo investigation, we demonstrated that berberine can prevent the colon cancer formation initiated by dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in rats. We employed western blotting, reverse transcription and polymerase chain reaction, special antagonist, overexpression and knockdown techniques to dissect the possible molecular mechanisms mediating the function of berberine. We found that the protein levels of ß-catenin in the nucleus and cytoplasm were all reduced after treating the colon cancer cells with berberine, and this may not result from accelerating the degradation of ß-catenin in the cytoplasm, but from inhibiting the mRNA expression of ß-catenin. Our results indicate that berberine can be a potential chemoprevention and chemotherapy agent for human colon cancer by targeting Wnt/ß-catenin signaling.