BACKGROUND/AIMS Stabilization of the hypoxia-inducible factor (HIF-1α) is proposed to provide a protective host-response to C. difficile intoxication. Here, we aimed to elucidate whether nitric oxide and/or reactive oxygen species produced during C. difficile toxin exposure could influence HIF-1α stability and initiate protection against epithelial cell damage. METHODS/RESULTS HIF-1α and indu...

Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor that plays an important role in the carcinogenesis and development of nasopharyngeal carcinoma. In this research, a novel biodegradable D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was prepared as a delivery system for small interfering ribonu...

The cellular response to hypoxia is primarily regulated by the hypoxia-inducible factors (HIFs). HIF-1α is also a major mediator of tumor physiology, and its abundance is correlated with therapeutic resistance in a broad range of cancers. Accumulation of HIF-1α under hypoxia is mainly controlled by the oxygen-sensing HIF prolyl 4-hydroxylases (EGLNs, also known as PHDs). Here, we identified a h...

Accumulating evidence strongly implicates the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the pathophysiology of multiple neurological disorders, but the downstream gene targets of PGC-1α in the brain have remained enigmatic. Previous data demonstrate that PGC-1α is primarily concentrated in inhibitory neurons and that PGC-1α is required f...

Aspartyl-(Asparginyl)-β-Hydroxylase (AAH) promotes cell motility by hydroxylating Notch. Insulin and insulin-like growth factor, type 1 (IGF-I) stimulate AAH through Erk MAPK and phosphoinositol-3-kinase-Akt (PI3K-Akt). However, hypoxia/oxidative stress may also regulate AAH. Hypoxia inducible factor-1 alpha (HIF-1α) regulates cell migration, signals through Notch, and is regulated by hypoxia/o...

Pancreatic cancer exhibits the poorest prognosis among all tumors and is characterized by high resistance to the currently available chemotherapeutic agents. Our previous studies have suggested that stromal components could promote the chemoresistance of pancreatic cancer cells (PCCs). Here, we explored the roles of pancreatic stellate cells (PSCs) and the SDF-1α/CXCR4 axis in pancreatic cancer...

The human cell line D98S can be cultivated indefinitely in the presence of up to 3 x 10(-5)M 5-bromodeoxyuridine (BUDR), without loss of cell viability. During this time, BUDR is incorporated into both strands of the DNA molecules, replacing up to 45 per cent of the thymidine and thereby rendering the cells highly sensitive to UV light and to x-rays. Cells grown for a limited period of time in ...

Hormone antagonist therapy for estrogen receptor positive (ER+) breast cancer patients post radical surgery and radiation therapy has a poor prognosis and also causes bone loss. 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is a potent antitumor agent in pre-clinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less...