Insulin can regulate the expression of eNOS gene, mediated by the activation of PI-3 kinase, in endothelial cells and microvessels. Thus, insulin may chronically modulate vascular tone. The activation of PKC in the vascular tissues as in insulin resistance and diabetes may inhibit PI-3 kinase activity and eNOS expression and may lead to endothelial dysfunctions in these pathological states.

The aim of this study was to evaluate whether high-intensity endurance training would alleviate exercise-induced oxidative stress. Nine untrained male subjects (aged 19-21 years) participated in a 12-week training programme, and performed an acute period of exhausting exercise on a cycle ergometer before and after training. The training programme consisted of running at 80% maximal exercise heart rate for 60 min.day-1, 5 days.week-1 for 12 weeks. Blood samples were collected at rest and immediately after exhausting exercise for measurements of indices of oxidative stress, and antioxidant enzyme activities [superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT)] in the erythrocytes. Maximal oxygen uptake (VO2max) increased significantly (P < 0.001) after training, indicating an improvement in aerobic capacity. A period of exhausting exercise caused an increase (P < 0.01) in the ability to produce neutrophil superoxide anion (O2.-) both before and after endurance training, but the magnitude of the increase was smaller after training (P < 0.05). There was a significant increase in lipid peroxidation in the erythrocyte membrane, but not in oxidative protein, after exhausting exercise, however training attenuated this effect. At rest, SOD and GPX activities were increased after training. However, there was no evidence that exhausting exercise enhanced the levels of any antioxidant enzyme activity. The CAT activity was unchanged either by training or by exhausting exercise. These results indicate that high-intensity endurance training can elevate antioxidant enzyme activities in erythrocytes, and decrease neutrophil O2.- production in response to exhausting exercise. Furthermore, this up-regulation in antioxidant defences was accompanied by a reduction in exercise-induced lipid peroxidation in erythrocyte membrane.

Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with 99mTc-HMPAO under physiologic conditions and monitored in vivo distribution of 99mTc-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with 99mTc-HMPAO for 1 hr incubation, followed by removal of free 99mTc-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with 99mTc-HMPAO, the radiochemical purity of 99mTc-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in 99mTc-HMPAO-ENVs. 99mTc-HMPAO-ENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5 hr. SPECT/CT images of the mice injected with 99mTc-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with 99mTc-HMPAO showed high brain uptake until 5 hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.

Radiomics has been spotlighted as imaging biomarker for estimation of intratumoral heterogeneity (ITH) which is regarded as the main reason for resistance to tumor treatment. Although a number of studies has shown clinical evidences that separate measurement of metabolic ITH by texture features (TFs) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has prognostic ability in various tumors, there has been no consensus regarding the best parameter representing ITH. Besides, it is yet uncertain that TFs are useful for estimation of histopathologic markers, prediction of response to neoadjuvant chemotherapy (NAC), or prognostic ability in breast cancer. To depart from the traditional approach, we evaluated the clinical usefulness of integrated metabolic radiomics using unsupervised clustering with 109 TFs measured from pretreatment 18F-FDG PET/CT scans of 73 patients with locally advanced breast cancer (LABC) underwent NAC before surgery. Our study shows that metabolic radiomics patterns of LABC are associated with Ki67 expression, achievement of pathologic complete response after NAC, and risk of recurrence. Integrated metabolic radiomics has potential for clinically relevant pretreatment biomarker with predictive and prognostic ability for personalized management in LABC.