Galangin Promotes Tendon Repair Mediated by Tendon-Derived Stem Cells through Activating the TGF-ß1/Smad3 Signaling Pathway.

Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor ß1 (TGF-ß1) and p-Smad3 to activate the TGF-ß1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-ß receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-ß1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.

Bidirectional two-sample mendelian randomization analysis identifies causal associations between age at menarche and sarcopenia-related traits.

BACKGROUND: Observational studies have shown that the age of menarche is associated with sarcopenia, but confounding factors make the causal relationship difficult to infer. OBJECTIVE: Therefore, we conducted a bidirectional two-sample Mendelian randomized (MR) analysis to evaluate the potential causal relationship between age at menarche and sarcopenia-related traits (hand grip strength, lean mass, walking pace). METHODS: We obtained the latest aggregate statistics from the Genome-wide association studies (GWAS) database on the age of menarche of 182,416 participants from ReproGen, the appendicular lean mass of 244,730 participants from EMBL's European Bioinformatics Institute, the left-hand grip strength of 401,026 participants, the right-hand grip strength of 461,089 participants and the usual walking pace of 459,915 participants from the UK Biobank. The inverse variance weighting (IVW) method and other MR methods were used to evaluate the bidirectional causal relationship between the age of menarche and sarcopenia. RESULTS: The forward MR results showed that the age of menarche predicted by the gene was positively correlated with left-hand grip strength (IVWß=0.041, P = 2.00 × 10-10), right-hand grip strength (IVWß=0.053, P = 1.97 × 10-18), appendicular lean mass (IVWß=0.012, P = 4.38 × 10-13) and usual walking pace (IVWß=0.033, P = 1.62 × 10-8).In the reverse MR analysis, we also found that the usual walking pace was positively correlated with the age of menarche predicted by genes (IVWß=0.532, P = 1.65 × 10-4). Still, there was no causal relationship between grip strength and appendicular lean mass and the age at menarche. CONCLUSION: Our results show that earlier menarche will increase the risk of sarcopenia. In addition, people with higher muscle function tend to have menarche later. These findings may provide a reference for prevention strategies and interventions for menarche in advance and sarcopenia.

Xanthorrhizol Ameliorates Oxidative Stress and Inflammation in Freund's Complete Adjuvant-Induced Rheumatoid Arthritis in Rats.

Rheumatoid arthritis (RA) is an inflammatory disease and a common cause of disability. This study is aimed to ascertain the therapeutic potentials of the xanthorrhizol against Freund's complete adjuvant (FCA)-stimulated RA in rats. The RA was initiated in the rats via injecting FCA (0.1 ml) subcutaneously and then treated with xanthorrhizol (20 mg/kg) for 25 days. The hematological markers were investigated using the automated hematological analyzer. The organ index (spleen and thymus) and paw volume were inspected by standard methods. The ALP, SGOT, and SGPT activities were examined using kits. The levels of inflammatory biomarkers, i.e., IL-1ß, IL-6, IL-10, and TNF-α, were inspected using assay kits. The status of MDA, SOD, CAT, GSH, COX-2, iNOS, and NF-κB was quantified using respective assay kits. The xanthorrhizol treatment appreciably improved the body weight and hematological parameters and reduced the arthritis score, organ index, and paw volume in the RA rats. The levels of RBCs and Hb were effectively improved, and activities of ALP, SGOT, and SGPT were decreased by the xanthorrhizol in the RA rats. The RA rats treated with 20 mg/kg of xanthorrhizol demonstrated the depleted IL-1ß, IL-6, and TNF-α levels. The antioxidant markers SOD, CAT, and GSH were improved, and inflammatory biomarker levels such as COX-2, iNOS, and NF-κB were decreased by the xanthorrhizol in the RA rats. Overall, these outcomes witnessed that the xanthorrhizol effectively ameliorated the oxidative stress and inflammatory responses and attenuated the RA in rats. Hence, it could be a talented anti-arthritic medication to treat RA.