Integrating network pharmacology and experimental verification to explore the pharmacological mechanisms of phlorizin against osteoarthritis.

To study the pharmacological effects and mechanisms of phlorizin in the treatment of osteoarthritis (OA) through network pharmacological analysis, molecular docking, and experimental validation. First, we screened out the relevant targets related to phlorizin and OA from the public database. The key targets, biological processes, and signaling pathways of phlorizin against OA were identified by protein-protein interaction (PPI) network, Gene Ontology (GO), and Encyclopedia of Kyoto Genes and Genomes (KEGG) pathway enrichment analysis. Subsequently, molecular docking was performed to predict the binding activity between phlorizin and key targets. Finally, we evaluated the effects of phlorizin on hydrogen peroxide-induced OA in rats and validated its possible mechanism of action based on the findings of the network pharmacology analysis. Network pharmacology revealed a total of 235 cross-targets involved in the treatment of OA. Phlorizin's anti-OA effect was found to be primarily mediated through oxidoreductase activity, with JAK-STAT and NF-κB signaling pathways playing a regulating role, according to pathway enrichment analysis. Phlorizin demonstrated a strong affinity for NF-κB1 targets through molecular docking. Moreover, in vitro experiments demonstrated that phlorizin could enhance intracellular antioxidant enzyme activities with good ROS scavenging ability and significantly reduce the expression of NF-κB1 and inflammatory cytokines. Phlorizin can inhibit the progression of OA. The potential underlying mechanism involves inhibiting the NF-κB pathway to reduce inflammation and promote intracellular antioxidant action.

Baicalin nanodelivery system based on functionalized metal-organic framework for targeted therapy of osteoarthritis by modulating macrophage polarization.

Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

Estrogen and Estrogen Receptor Modulators: Potential Therapeutic Strategies for COVID-19 and Breast Cancer.

Owing to the ongoing coronavirus disease 2019 (COVID-19) pandemic, we need to pay a particular focus on the impact of coronavirus infection on breast cancer patients. Approximately 70% of breast cancer patients express estrogen receptor (ER), and intervention therapy for ER has been the primary treatment strategy to prevent the development and metastasis of breast cancer. Recent studies have suggested that selective estrogen receptor modulators (SERMs) are a potential therapeutic strategy for COVID-19. With its anti-ER and anti-viral combined functions, SERMs may be an effective treatment for COVID-19 in patients with breast cancer. In this review, we explore the latent effect of SERMs, especially tamoxifen, and the mechanism between ER and virus susceptibility.

Analyzing the synergistic adverse effects of BPA and its substitute, BHPF, on ulcerative colitis through comparative metabolomics.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes long-term inflammation and ulcers in the colon and rectum. Approximately 3 million adults were diagnosed with IBD in the US in 2015, and its incidence rate is estimated to increase by 4-6 times in 2030. Industrial pollutants are largely responsible for this significant increase in UC cases. Several epidemiological and animal studies have demonstrated the correlation between pollutants and gastrointestinal diseases, but detailed molecular mechanisms responsible for adverse effects of environmental pollutants on UC are still unknown. In the present study, we used a dextran sulfate sodium (DSS)-induced colitis mouse model, comparative metabolomics analysis, and systematic bioinformatics analysis to delineate the synergistic adverse effects of bisphenol A (BPA) and its substitute fluorene-9-bisphenol (BHPF) on UC. Subsequently, a significant alteration in gut metabolites was observed by the BPA and BHPF treatments. Furthermore, the bioinformatics analysis indicated deregulation of sugar and fatty acid metabolisms in the DSS-induced colitis model by the BPA and BHPF treatments, respectively. Additionally, both the treatments induced an inflammatory response in the model. Particularly, some DSS-deregulated metabolites, which play important roles in gut inflammation, were synergistically induced or reduced by the BPA and BHPF treatments. To the best knowledge of the authors, the synergistic adverse effects of the BPA and BHPF treatments on UC were demonstrated for the first time through gut metabolism alterations. Therefore, the present study provides novel insights in the role of environmental pollutants, such as BPA and BHPF, in UC development.