Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems.

Glycolysis is the initial step of glucose catabolism and is up-regulated in cancer cells (the Warburg Effect). Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems, and the molecular mechanisms underlying the shifts remain unknown. With proteomics, we observed increased glycolysis in disused human diaphragm muscle. In disused muscle, lung cancer, and H(2)O(2)-treated myotubes, we show up-regulation of the rate-limiting glycolytic enzyme muscle-type phosphofructokinase (PFKm, >2 fold, P<0.05) and accumulation of lactate (>150%, P<0.05). Using microRNA profiling, we identify miR-320a as a regulator of PFKm expression. Reduced miR-320a levels (to ∼50% of control, P<0.05) are associated with the increased PFKm in each of these diverse systems. Manipulation of miR-320a levels both in vitro and in vivo alters PFKm and lactate levels in the expected directions. Further, miR-320a appears to regulate oxidative stress-induced PFKm expression, and reduced miR-320a allows greater induction of glycolysis in response to H(2)O(2) treatment. We show that this microRNA-mediated regulation occurs through PFKm's 3' untranslated region and that Ets proteins are involved in the regulation of PFKm via miR-320a. These findings suggest that oxidative stress-responsive microRNA-320a may regulate glycolysis broadly within nature.

Medical comorbidities predict the need for colectomy for complicated and recurrent diverticulitis.

OBJECTIVE: The objective of this study was to identify risk factors for recurrent or complicated diverticulitis requiring colectomy. METHODS: A total of 112 patients were admitted to the West Haven Veterans Affairs Medical Center with the diagnosis of colonic diverticular disease from January 1998 to December 2006. Patients' records were assessed for demographics, past medical history, and physical and biochemical features of presentation. Student t tests, analysis of variance, and chi-square analysis were used to compare binary and categoric data. RESULTS: The medical records of 112 patients admitted to the West Haven Veterans Affairs hospital with the diagnosis of diverticulitis were analyzed retrospectively. A total of 97.3% were male (n = 109), with a mean age of 63.3 years, and a significant smoking history greater than 30 pack-years was present in 70.5% (n = 79) of patients. Eighty-four percent (n = 94) of patients presented with localized abdominal pain and 69.6% (n = 78) had abdominal tenderness without peritoneal signs. Computed tomography was performed in 85.7% (n = 96) of cases. A total of 23.2% (n = 26) of patients proceeded to laparotomy, with free perforation being the most common indication (38.4%, n = 12) followed by a history of 2 or more antecedent attacks of diverticulitis (23.1%, n = 6). Analysis of variance showed that serum albumin levels were significantly lower in the group undergoing colectomy compared with those who did not (3.4 vs 4.1 mg/dL; P = .016). The need for colectomy owing to complicated or recurrent attacks correlated with glucocorticoid use (P < .001) and a history of chronic obstructive pulmonary disease (P < .038), but not with diabetes mellitus, collagen vascular disease, or inflammatory bowel disease. CONCLUSIONS: The rules regarding the treatment of diverticulitis are evolving. Comorbid conditions such as hypoalbuminemia, chronic obstructive pulmonary disease, and glucocorticoid use may predispose patients to recurrent or complicated attacks of diverticulitis requiring colectomy. Stratification and reduction of risks may reduce the overall morbidity and mortality of diverticulitis.