Propolis has been shown to modulate the angiogenesis in both in vitro and in vivo models. Thus, we aimed to evaluate the antiangiogenic properties of an ethanolic extract of Chilean propolis (EEP) and Pinocembrin (Pn). Migration, formation of capillary-like structures of endothelial cells, and sprouting from rat aortic rings were used to assess the antiangiogenic properties of EEP or Pn. In add...

Hypoxia Inducible transcription Factors (HIFs) are principally regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the HIFα subunit, facilitating its proteasome-mediated degradation. Observations that HIFα hydroxylation can be impaired even when oxygen is sufficient emphasise the importance of understanding the complex nature of PHD regulation. Here,...

Mammalian erythropoiesis is a conserved process tightly controlled by the hypoxia-inducible factor (HIF1) pathway. In this study, a small molecule inhibitor (PHI-1) of prolyl-hydroxylase-2 (PHD2) enzyme involved in regulating HIF1α levels was orally administered to male BALB/c mice at 10 and 30 mg/kg. A systems pharmacology model was developed based on the measured PHI-1 plasma exposures, kidne...

Hypoxia occurs in cancer, prolonged exercise, and long-term ischemia with durations of several hours or more, and the hypoxia-inducible factor 1 (HIF1) pathway response to these conditions differs from responses to transient hypoxia. We used computational modeling, validated by experiments, to gain a quantitative, temporal understanding of the mechanisms driving HIF1 response. To test the hypot...

Abstract Glioblastoma (GBM) is an aggressive brain tumor with no cure. Standard treatment includes adjuvant, concomitant temozolomide (TMZ) and radiation, but most patients do not survive more than 15 months. Tumor adaptations to contribute glioblastoma chemoresistance recurrence, hypoxia inducible factor subunit alpha (HIF1α) downstream effectors are implicated in attenuated therapeutic respon...

BACKGROUND The use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. The purpose of this study was to clarify the molecular mechanisms involved in FDG uptake. MATERIAL AND METHODS Fifty patients with gastric cancer who underwent FDG-PET and gastrectomy were studied. Snap-froze...

Upon antigen stimulation, the bioenergetic demands of T cells increase dramatically over the resting state. Although a role for the metabolic switch to glycolysis has been suggested to support increased anabolic activities and facilitate T cell growth and proliferation, whether cellular metabolism controls T cell lineage choices remains poorly understood. We report that the glycolytic pathway i...

PURPOSE Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF. EXPERIMENTAL DESIGN/RESULTS Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became eviden...

The problem of hypoxia adaptation in high altitudes is an unsolved brainteaser in the field of the life sciences. As one of the best chicken breeds with adaptability to highland environment, the Tibet chicken, is genetically different from lowland chicken breeds. It is well known that hypoxia has significant impact on growth by inducing the expression of the alpha subunit of the heterodimeric t...

Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type-specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia-induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detec...