Nrf2 signaling in diabetic nephropathy, cardiomyopathy and neuropathy: Therapeutic targeting, challenges and future prospective.

Western lifestyle contributes to an overt increase in the prevalence of metabolic anomalies including diabetes mellitus (DM) and obesity. Prevalence of DM is rapidly growing worldwide, affecting many individuals in both developing and developed countries. DM is correlated with the onset and development of complications with diabetic nephropathy (DN), diabetic cardiomyopathy (DC) and diabetic neuropathy being the most devastating pathological events. On the other hand, Nrf2 is a regulator for redox balance in cells and accounts for activation of antioxidant enzymes. Dysregulation of Nrf2 signaling has been shown in various human diseases such as DM. This review focuses on the role Nrf2 signaling in major diabetic complications and targeting Nrf2 for treatment of this disease. These three complications share similarities including the presence of oxidative stress, inflammation and fibrosis. Onset and development of fibrosis impairs organ function, while oxidative stress and inflammation can evoke damage to cells. Activation of Nrf2 signaling significantly dampens inflammation and oxidative damage, and is beneficial in retarding interstitial fibrosis in diabetic complications. SIRT1 and AMPK are among the predominant pathways to upregulate Nrf2 expression in the amelioration of DN, DC and diabetic neuropathy. Moreover, certain therapeutic agents such as resveratrol and curcumin, among others, have been employed in promoting Nrf2 expression to upregulate HO-1 and other antioxidant enzymes in the combat of oxidative stress in the face of DM.

Time estimation and beta segregation: An EEG study and graph theoretical approach.

Elucidation of the neural correlates of time perception constitutes an important research topic in cognitive neuroscience. The focus to date has been on durations in the millisecond to seconds range, but here we used electroencephalography (EEG) to examine brain functional connectivity during much longer durations (i.e., 15 min). For this purpose, we conducted an initial exploratory experiment followed by a confirmatory experiment. Our results showed that those participants who overestimated time exhibited lower activity of beta (18-30 Hz) at several electrode sites. Furthermore, graph theoretical analysis indicated significant differences in the beta range (15-30 Hz) between those that overestimated and underestimated time. Participants who underestimated time showed higher clustering coefficient compared to those that overestimated time. We discuss our results in terms of two aspects. FFT results, as a linear approach, are discussed within localized/dedicated models (i.e., scalar timing model). Second, non-localized properties of psychological interval timing (as emphasized by intrinsic models) are addressed and discussed based on results derived from graph theory. Results suggested that although beta amplitude in central regions (related to activity of BG-thalamocortical pathway as a dedicated module) is important in relation to timing mechanisms, the properties of functional activity of brain networks; such as the segregation of beta network, are also crucial for time perception. These results may suggest subjective time may be created by vector units instead of scalar ticks.