HIF-1-Dependent Reprogramming of Glucose Metabolic Pathway of Cancer Cells and Its Therapeutic Significance.

Normal cells produce adenosine 5'-triphosphate (ATP) mainly through mitochondrial oxidative phosphorylation (OXPHOS) when oxygen is available. Most cancer cells, on the other hand, are known to produce energy predominantly through accelerated glycolysis, followed by lactic acid fermentation even under normoxic conditions. This metabolic phenomenon, known as aerobic glycolysis or the Warburg effect, is less efficient compared with OXPHOS, from the viewpoint of the amount of ATP produced from one molecule of glucose. However, it and its accompanying pathway, the pentose phosphate pathway (PPP), have been reported to provide advantages for cancer cells by producing various metabolites essential for proliferation, malignant progression, and chemo/radioresistance. Here, focusing on a master transcriptional regulator of adaptive responses to hypoxia, the hypoxia-inducible factor 1 (HIF-1), we review the accumulated knowledge on the molecular basis and functions of the Warburg effect and its accompanying pathways. In addition, we summarize our own findings revealing that a novel HIF-1-activating factor enhances the antioxidant capacity and resultant radioresistance of cancer cells though reprogramming of the glucose metabolic pathway.

Effectiveness of group cognitive-behavioral therapy in reducing self-stigma in Japanese psychiatric patients.

OBJECTIVE: There is evidence that the stigma surrounding mental illness may be greater in Japan than elsewhere. However, few Japanese studies have focused on self-stigma (the internalization of social stigma), and few interventions to reduce self-stigma exist. To remedy this deficiency, we evaluated the efficacy of group cognitive-behavioral therapy (CBT) in reducing self-stigma and examined the relationship between cognitive restructuring and self-stigma. METHODS: We administered a 10-session group CBT program to 46 Japanese outpatients with anxiety and depressive symptoms (36 men, 10 women; mean age=38.57 years, SD=8.33; 20 diagnosed with mood disorders; 24 with neurotic, stress-related, or somatoform disorders; and 2 with other disorders). A pretest-posttest design was used to examine the relationship between cognitive restructuring and self-stigma. Outcomes were measured using the Japanese versions of the Devaluation-Discrimination Scale, Dysfunctional Attitude Scale, Beck Depression Inventory-II, State-Trait Anxiety Inventory State-Form, and Rosenberg's Self Esteem Scale. RESULTS: Participants exhibited significant improvements in depression, anxiety, and maladjusted cognitive bias and reductions in self-stigma. Cognitive bias was significantly correlated with self-stigma. CONCLUSIONS: Group CBT is effective in improving both emotional symptoms and self-stigma in outpatients with anxiety and depressive symptoms. Reduction in self-stigma plays a mediating role in alleviating emotional symptoms and improving cognition.

The periodontopathogenic bacterium Eikenella corrodens produces an autoinducer-2-inactivating enzyme.

Eikenella corrodens produces autoinducer-2 (AI-2) in the mid log phase, and AI-2 activity decreases dramatically during the stationary phase. We investigated the mechanism underlying this decrease in AI-2 activity. To analyze the mechanism, we extracted and purified AI-2 from the supernatant of mid-log-phase culture. Simultaneously, the stationary-phase culture supernatant was fractionated by ammonium sulfate precipitation. On incubating purified AI-2 and 4-hydroxy-5-methyl-3(2H)-furanone (MHF) with each fraction, the 30% fraction decreased both AI-2 and MHF activities. The data suggest that AI-2 and MHF were rendered inactive in the same manner. Heat and/or trypsin treatment of the 30% fraction did not completely arrest AI-2 inactivation, suggesting that partially heat-stable proteins are involved in AI-2 inactivation. We observed that an enzyme converted MHF to another form. This suggests that E. corrodens produces an AI-2 inactivating enzyme, and that AI-2 can be degraded or modified by it.