BACKGROUND In severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia. METHODS The frequency of anaemia (haematocrit <30%), and temporal changes in haematocrit were evaluated in 1,191 malarious children following ACTs. "Haematocrit ...

BACKGROUND In recent years, miRNAs have been suggested to play key roles in the formation and development of human glioma. The aim of this study is to investigate the effect and mechanism of miR-184 expression on the malignant behavior of human glioma cells. METHODS The relative quantity of miR-184 was determined in human glioma cell lines, and the expression of hypoxia-inducible factor-1 alp...

INTRODUCTION Hypoxia induced factors (HIFs) are at the heart of the adaptive mechanisms cancer cells must implement for survival. HIFs are regulated by four hydroxylases; Prolyl hydroxylase (PHD)-1,-2,-3 and factor inhibiting HIF (FIH). We aimed to investigate the prognostic impact of these oxygen sensors in NSCLC. METHODS Tumor tissue samples from 335 resected stages I to IIIA NSCLC patients...

Gankyrin (also called p28 or PSMD10) is an oncoprotein commonly overexpressed in hepatocellular carcinomas. It consists of 7 ankyrin repeats and interacts with multiple proteins including Rb, Cdk4, MDM2 and NF-κB. To assess the oncogenic activity in vivo, we produced transgenic mice that overexpress gankyrin specifically in the hepatocytes. Unexpectedly, 5 of 7 F2 transgenic mice overexpressing...

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...

Recently, Shin et al reported that the proteasomal inhibitor bortezomib inhibits the hypoxic response by stimulating the factor-inhibiting HIF-1 (FIH)–mediated repression of hypoxiainducible factor-1 (HIF-1).1 The essence of this study is that bortezomib enhances the FIH function and the repression is dependent on asparagine 803 (N803). Both conclusions are in contradiction to previously publis...

The activity and levels of the metazoan HIF (hypoxia-inducible factor) are regulated by its hydroxylation, catalysed by 2OG (2-oxoglutarate)- and Fe(II)-dependent dioxygenases. An oxygen consumption assay was developed and used to study the relationship between HIF hydroxylase activity and oxygen concentration for recombinant forms of two human HIF hydroxylases, PHD2 (prolyl hydroxylase domain-...

Activation of the hypoxia-inducible factor (HIF) pathway is a critical step in the transcriptional response to hypoxia. Although many of the key proteins involved have been characterised, the dynamics of their interactions in generating this response remain unclear. In the present study, we have generated a comprehensive mathematical model of the HIF-1α pathway based on core validated component...

Hypoxia and inflammation share an interdependent relationship (1). Many recent publications implicate hypoxia-elicited inflammation, or inflammation during hypoxic conditions in the outcomes of a wide array of human diseases (2). On the one hand, inflammatory disease states are frequently characterized by tissue hypoxia, or stabilization of hypoxiadependent transcription factors, such as hypoxi...