Cancer metastasis accounts for the major cause of cancer-related deaths. How disseminated cancer cells cope with hostile microenvironments in secondary site for full-blown metastasis is largely unknown. Here, we show that AMPK (AMP-activated protein kinase), activated in mouse metastasis models, drives pyruvate dehydrogenase complex (PDHc) activation to maintain TCA cycle (tricarboxylic acid cycle) and promotes cancer metastasis by adapting cancer cells to metabolic and oxidative stresses. This AMPK-PDHc axis is activated in advanced breast cancer and predicts poor metastasis-free survival. Mechanistically, AMPK localizes in the mitochondrial matrix and phosphorylates the catalytic alpha subunit of PDHc (PDHA) on two residues S295 and S314, which activates the enzymatic activity of PDHc and alleviates an inhibitory phosphorylation by PDHKs, respectively. Importantly, these phosphorylation events mediate PDHc function in cancer metastasis. Our study reveals that AMPK-mediated PDHA phosphorylation drives PDHc activation and TCA cycle to empower cancer cells adaptation to metastatic microenvironments for metastasis.

Much controversy persists regarding the optimal techniques for myocardial protection during heart surgery. Numerous studies have compared warm cardioplegia with cold cardioplegia for myocardial preservation, but the outcomes were inconclusive. The aim of this meta-analysis of randomised controlled trials (RCTs) was to compare the beneficial and harmful effects of warm and cold cardioplegia during heart surgery. Electronic databases and manual bibliographical searches were conducted. A meta-analysis of all RCTs comparing warm cardioplegia to cold cardioplegia perfusion during cardiac surgery was performed. Data for clinical events (in-hospital death, myocardial infarction (MI), low output syndrome, postoperative use of intra-aortic balloon pump, stroke and atrial fibrillation), postoperative cardiac index, postoperative creatine kinase-MB (CK-MB) and cardiac troponin release were extracted, and we summarised the combined results of the data of the RCTs as relative risk (RR), with 95% confidence intervals. A total of 41 RCTs including 5,879 patients were assessed in this study. We found that there was no statistical difference between patients receiving warm cardioplegia and cold cardioplegia in the incidences of clinical events. Warm cardioplegia was associated with improved postoperative cardiac index. CK-MB and cardiac troponin concentrations after surgery were significantly lower in the warm group as compared with the cold group. Using warm cardioplegia for myocardial protection during heart surgery resulted in similar incidences of clinical events, significant improvement in postoperative cardiac index and reduction in postoperative enzyme release as compared with cold cardioplegia.

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Glucose-insulin-potassium (GIK) has long been used as adjuvant treatment for patients with serious cardiovascular disease. Although many studies have reported their results based on GIK therapy in the setting of heart surgery, the outcomes remain controversial and inconclusive. The aim of this meta-analysis of randomized controlled trials (RCTs) was to determine the clinical effects of GIK in adult cardiac surgery patients. Electronic databases and manual bibliographical searches were conducted. A meta-analysis of all RCTs comparing GIK with control in heart surgery was performed. Data for all-causes mortality (within 2 months after surgery), perioperative myocardial infarction, postoperative inotropic support, atrial fibrillation, cardiac index, durations of intensive unit care stay and total hospital stay were extracted, and we summarized the combined results of the data of the RCTs as relative risk (RR), with 95% confidence intervals (CIs). A total of 33 RCTs including 2113 patients were assessed in this study. GIK infusion was associated with significantly fewer perioperative myocardial infarctions (RR = 0.63, 95% CI 0.42-0.95), less inotropic support requirement (RR = 0.66, 95% CI 0.45-0.96), better postoperative cardiac index (weighted mean difference (WMD) = 0.43, 95% CI 0.31-0.55), and reduced length of stay in the intensive care unit (WMD = -7.96, 95% CI -13.36 to -2.55). Further analysis showed that diabetic patients were benefited from GIK with glycemic control, but not GIK infusion without glucose control. GIK significantly reduced myocardial injury and improved hemodynamic performance in patients undergoing cardiac surgery. Glycemic control with GIK might be required for cardiac surgery patients with diabetes.