CTNNB x HIF-1α x Wnt

Glioblastoma multiforme (GBM) is a rapidly progressing brain malignancy, with its progression closely tied to a hypoxic microenvironment. Hypoxia-inducible factor-1α (HIF-1α) acts as a vital regulator in tumor adaptation to low oxygen levels, and its relationship with the Wnt/β-catenin signaling pathway exerts significant functions in the malignant properties of GBM. In this research, Western blot and qRT-PCR were applied to check β-catenin and HIF-1α expression in GBM. How HIF-1α influenced GBM cell behavior was investigated in vitro through the construction of U251 cell models with HIF-1α overexpression and knockdown, accompanied by assessments of cell proliferation, migration, invasion, and apoptosis. Additionally, co-immunoprecipitation (Co-IP) experiments were leveraged for checking the interaction of β-catenin and HIF-1α. This study demonstrated that HIF-1α and β-catenin were markedly upregulated in GBM tissues relative to normal controls, and their expression was positively correlated at the transcriptional level. In oxygen-limited environments, HIF-1α expression was significantly enhanced, and the Wnt signaling pathway was activated through stabilizing β-catenin. Functional experiments showed that HIF-1α overexpression facilitated cell proliferation, migration, and invasion, while inhibiting apoptosis; conversely, HIF-1α knockdown led to a significant reduction in these processes. Taken together, HIF-1α regulates the Wnt/β-catenin signaling pathway via its engagement with β-catenin, thereby promoting GBM proliferation and invasion, and inhibiting apoptosis. These findings emphasize the importance of HIF-1α in GBM advancement and suggest novel therapeutic strategies targeting HIF-1α and the Wnt/β-catenin pathway.

Defective bone repair is a pressing issue in the field of bone regeneration due to donor shortages and the associated complications of bone grafting. Artificial bone repair materials offer more options and are attracting extensive attention from researchers. However, achieving efficient osteogenesis in clinical practice remains a challenge. Here, dual drug-releasing nanofibre membranes (NMs) for bone repair was fabricated by coaxial electrostatic spinning. Strontium-doped hydroxyapatite (SrHA) and desferrioxamine (DFO) were loaded into the shell and core of the NMs for slow and sustained release, respectively. Our results showed that the DFO/SrHA NMs significantly enhanced cell proliferation, angiogenesis and osteogenic differentiation of rat bone mesenchymal stem cells through the synergism of DFO and SrHA. This synergy results from the slow and sustained release of DFO and SrHA via NMs, which maintains the drug concentration in the effective range for a long time, ensuring long-term stable activation of the HIF-1 α and Wnt/β-catenin signalling pathways. Overall, the DFO/SrHA NMs provides a promising strategy for defective bone repair by enhancing osteogenic differentiation.

Traditional Chinese medicine, especially Bushen Huoxue decoction, has demonstrated good therapeutic effects in the treatment of intervertebral disc degeneration and osteoarthritis, but its mechanism of action in osteoporosis remains unclear. This study aimed to explore its potential mechanisms against osteoporosis.

Active components of Bushen Huoxue decoction were identified through searching the TCM databases. Osteoporosis-related genes were retrieved from three disease databases. Common targets were used to construct a PPI network. Functional enrichment analyses (GO and KEGG), molecular docking, molecular dynamics simulations, and literature validation were performed.

A total of 112 active compounds and 343 potential targets were identified. Key bioactive ingredients included quercetin, luteolin, kaempferol, wogonin, and baicalein. The decoction appeared to act via multiple pathways, such as TNF, NF-κB, MAPK, PI3K/Akt, Wnt/β-catenin, HIF-1, FoxO, AMPK, mTOR, and VEGF, affecting inflammation, metabolism, cell proliferation, survival, and angiogenesis.

Bushen Huoxue decoction likely exerted anti-osteoporotic effects through a multi-- component, multi-target, and multi-pathway approach, consistent with current understanding of osteoporosis mechanisms. However, as this study was based on network pharmacology and computational analysis, experimental validation is needed.

Bushen Huoxue decoction showed promise as a potential treatment for osteoporosis through complex regulatory mechanisms. The findings provided a theoretical basis for further pharmacological research and TCM-based drug development.