Anti-HIF1A monoclonal antibody, clone FTFF233

Tissue oxygen (O-2) levels vary during development and disease; adaptations to decreased O-2 (hypoxia) are mediated by hypoxia-inducible factor (HIF) transcription factors. HIFs are active in the skeleton, and stabilizing HIF-alpha isoforms cause high bone mass (HBM) phenotypes. A fundamental limitation of previous studies examining the obligate role for HIF-alpha isoforms in the skeleton involves the persistence of gene deletion as osteolineage cells differentiate into osteocytes. Because osteocytes orchestrate skeletal development and homeostasis, we evaluated the influence of Vhl or Hif1a disruption in osteocytes. Osteocytic Vhl deletion caused HBM phenotype, but Hif1a was dispensable in osteocytes. Vhl cKO mice revealed enhanced canonical Wnt signaling. B cell development was reduced while myelopoiesis increased in osteocytic Vhl cKO, revealing a novel influence of Vhl/HIF-alpha function in osteocytes on maintenance of bone microarchitecture via canonical Wnt signaling and effects on hematopoiesis.

Background: Berberine has multitudinous anti-cancer stem cells effects making it a highly promising candidate substance for the next-generation cancer therapy. However, berberine modes of action predispose it to significant side-effects that probably limit its clinical testing and application. Materials and Methods: HeLa cells were treated with two concentrations of berberine (30 and 100 mu M) for 24 hours to assess the functioning of the NFE2L2/AP-1, NF kappa B and HIF1A pathways using 22 RNAs expression qPCR-based analysis. Results: Berberine effects appeared to he highly dose-dependent, with the lower concentration being capable of suppressing the NF kappa B functioning and the higher concentration causing severe signaling side-effects seen in the HIF1A pathway and the NFE2L2 sub-pathways, and especially and more importantly in the AP-1 sub-pathway. Conclusion: The results of the study suggest that berberine has clinically valuable anti-NF kappa B effects however jeopardized by its side effects on the HIF1A and especially NFE2L2/AP-1 pathways, its therapeutic window phenomenon and its cancer type-specificity. These, however, may be ameliorated using the cocktail approach. provided there is enough data on signaling effects of berberine.