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Autophagy is essential for the adaptive response to exercise and physiological skeletal muscle functionality. However, the mechanisms leading to the activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle in response to high-intensity exercise remain elusive. Our findings demonstrate that macroautophagy and chaperone-mediated autophagy are stimulated by high-intensity exercise in normoxia (P I O 2 : 143 mmHg) and severe acute hypoxia (P I O 2 : 73 mmHg) in healthy humans. High-intensity exercise induces macroautophagy initiation through AMPKα phosphorylation, which phosphorylates and activates ULK1. ULK1 phosphorylates BECN1 at Ser15, eliciting the dissociation of BECN1-BCL2 crucial for phagophore formation. Besides, high-intensity exercise elevates the LC3B-II:LC3B–I ratio, reduces total SQSTM1/p62 levels, and induces p -Ser349 SQSTM1/p62 phosphorylation, suggesting heightened autophagosome degradation. PHAF1/MYTHO, a novel macroautophagy biomarker, is highly upregulated in response to high-intensity exercise. The latter is accompanied by elevated LAMP2A expression, indicating chaperone-mediated autophagy activation regardless of post-exercise HSPA8/HSC70 downregulation. Despite increased glycolytic metabolism, severe acute hypoxia does not exacerbate the autophagy signaling response. Signaling changes revert within 1 min of recovery with free circulation, while the application of immediate post-exercise ischemia impedes recovery. Our study concludes that macroautophagy and chaperone-mediated autophagy pathways are strongly activated by high-intensity exercise, regardless of PO 2 , and that oxygenation is necessary to revert these signals to pre-exercise values. PHAF1/MYTHO emerges as a pivotal exercise-responsive autophagy marker positively associated with the LC3B-II:LC3B–I ratio. [Display omitted] • It is unknown whether and how macroautophagy and chaperone-mediated autophagy are activated by exercise in human skeletal muscle. • We show that macroautophagy and chaperone-mediated autophagy are activated by acute exercise to exhaustion in normoxia and severe acute hypoxia. • Simultaneously, protein synthesis signaling is blunted. • Macroautophagy and chaperone-mediated autophagy remain activated during ischemic recovery. • MYTHO, a FOXO-regulated protein is markedly upregulated after exercise in normoxia, hypoxia, and post-exercise ischemia. [ABSTRACT FROM AUTHOR]

Chagas disease (CHD) is the highest economic burden parasitosis worldwide and the most important cardiac infection, without therapeutic alternatives to halt or reverse its progression. In CHD-experimental models, antioxidant and anti-inflammatory compounds have demonstrated therapeutic potential in cardiac dysfunction. Theobroma cacao polyphenols are potent natural antioxidants with cardioprotective and anti-inflammatory action, which are susceptible to degradation, requiring technological approaches to guarantee their protection, stability, and controlled release. Here, 21 cocoa polyphenol-rich microencapsulates were produced by spray-drying and freeze-drying techniques using two wall materials (maltodextrin and gum arabic). Chemical (total and individual phenolic content and antioxidant activity), structural (morphology), and biological parameters (cytotoxicity, trypanocidal, antioxidant, and immunomodulatory activities) were assessed to determine the most efficient microencapsulation conditions on Trypanosoma cruzi -infected myocardioblast and macrophage cells. Significant antiproliferative properties against infected cells (superior to benznidazole) were found in two microencapsulates which also exhibited cardioprotective properties against oxidative stress, inflammation, and cell death. [ABSTRACT FROM AUTHOR]

Objective To test the intra-individual reliability in response to anodal transcranial direct current stimulation (AtDCS). Methods 45 healthy subjects received AtDCS (1 mA, 13 min) in two separate sessions, 6–12 months apart. Motor evoked potentials were collected at baseline and then at 5-min intervals after AtDCS for 1 h. Short intracortical inhibition (SICI) was assessed at minutes 6 and 46 after AtDCS. Results AtDCS increased cortical excitability over minutes 0–30 post-stimulation in both sessions, with fair intra-individual reliability. 60% and 64% of subjects responded with the expected increase in cortical excitability in each session, respectively. 69% of the subjects maintained their response pattern between sessions during this timeframe. However, there were no significant effects on cortical excitability over the full hour post AtDCS in either session. SICI showed fair intra-individual reliability 6 min after AtDCS. Conclusion A change in cortical excitability in the first half-hour post-AtDCS may be a good predictor of the response in a subsequent session. Furthermore, minute 15 post-stimulation showed the maximum increase in cortical excitability in both sessions. Significance We show for the first time that intra-individual variability is lower than inter-individual variability, and with fair intra-individual inter-sessional reliability for 30 min after AtDCS-subjects are likely to maintain their response patterns to tDCS between sessions, with implications for experimental and therapeutic applications of tDCS. [ABSTRACT FROM AUTHOR]

Vitamin C is reabsorbed from the renal lumen by one isoform of sodium-vitamin C co-transporters that mediate high affinity sodium-dependent L-ascorbic acid transport. Sodium-vitamin C cotransporter-1 mRNA has been detected in intestine and liver and the S3 segment of the renal proximal tubule. Here, we found that its distribution was broader and all three proximal tubule segments of mouse and human expressed the transporter but the S3 segment had the highest expression. Sodium-vitamin C co-transporter-1 expression was also found in the renal epithelial-derived LLC-PK1 cell line. Ascorbic acid transport in these cells was regulated by a single kinetic component that depended on the sodium concentration, pH and temperature. Reducing ascorbate concentration increased the apical expression of the transporter suggesting the presence of a feedback system for regulation of transporter abundance at the luminal membrane.Kidney International (2008) 74, 1278–1286; doi:10.1038/ki.2008.329; published online 9 July 2008 [ABSTRACT FROM AUTHOR]