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BackgroundGait impairments including shuffling gait and hesitation are common in people with Parkinson’s disease (PD), and have been linked to increased fall risk and freezing of gait. Nowadays the gait metrics mostly focus on the spatiotemporal characteristics of gait, but less is known of the angular characteristics of the gait, which may provide helpful information pertaining to the functional status and effects of the treatment in PD. ObjectiveThis study aimed to quantify the angles of steps during walking, and explore if this novel step angle metric is associated with the severity of PD and the effects of the treatment including the acute levodopa challenge test (ALCT) and deep brain stimulation (DBS). MethodsA total of 18 participants with PD completed the walking test before and after the ALCT, and 25 participants with PD completed the test with the DBS on and off. The walking test was implemented under two conditions: walking normally at a preferred speed (single task) and walking while performing a cognitive serial subtraction task (dual task). A total of 17 age-matched participants without PD also completed this walking test. The angular velocity was measured using wearable sensors on each ankle, and three gait angular metrics were obtained, that is mean step angle, initial step angle, and last step angle. The conventional gait metrics (ie, step time and step number) were also calculated. ResultsThe results showed that compared to the control, the following three step angle metrics were significantly smaller in those with PD: mean step angle (F1,48=69.75, P

Autophagy has been implicated in stroke. Our previous study showed that the FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion (I/R). However, whether the Akt/FoxO3 signaling pathway plays a regulatory role in autophagy in cerebral I/R-induced oxidative stress injury is still unclear. The present study aims to investigate the effects of the Akt/FoxO3 signaling pathway on autophagy activation and neuronal injury in vitro and in vivo. By employing LY294002 or insulin to regulate the Akt/FoxO3 signaling pathway, we found that insulin pretreatment increased cell viability, decreased reactive oxygen species production, and enhanced the expression of antiapoptotic and autophagy-related proteins following [H.sub.2][O.sub.2] injury in HT22 cells. In addition, insulin significantly decreased neurological deficit scores and infarct volume and increased the expression of antiapoptotic and autophagy-related proteins following I/R injury in rats. However, LY294002 showed the opposite effects under these conditions. Altogether, these results indicate that Akt/FoxO3 signaling pathway activation inhibited oxidative stress-mediated cell death through activation of autophagy. Our study supports a critical role for the Akt/FoxO3 signaling pathway in autophagy activation in stroke. Key words: Akt/FoxO3 signaling pathway, autophagy, apoptosis, hydrogen peroxide, stroke, Introduction Stroke, which is widely considered to be a leading cause of disability and death, causes a tremendous global health and economic burden (Virani et al. 2021). Cerebral ischemia/reperfusion (I/R) [...]

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide ([H.sub.2][O.sub.2]) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced [H.sub.2][O.sub.2]-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced [H.sub.2][O.sub.2]-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3- methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation, and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on [H.sub.2][O.sub.2]-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit [H.sub.2][O.sub.2]-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain. Key words: FoxO3 transcription factors, autophagy, apoptosis, hydrogen peroxide, oxidative stress, neurodegenerative diseases, HT22 cells. On a implique l'autophagie dans les maladies neurodegeneratives. Les facteurs de transcription FoxO3 (pour << Forkhead box O3 >>) favorisent l'autophagie dans le coeur et entrainent une inhibition des dommages oxydatifs. Dans les presents travaux, nous etudions le role des FoxO3 dans la regulation de l'autophagie apres des lesions liees au stress oxydatif dans des lignees cellulaires d'hippocampe de souris (HT22). La presente etude confirme que des lesions causees par le peroxyde d'hydrogene ([H.sub.2][O.sub.2]) peuvent engendrer de l'autophagie et l'activation des FoxO3 dans les cellules HT22. De plus, la surexpression des FoxO3 entrainait une augmentation de l'activation de l'autophagie engendree par le [H.sub.2][O.sub.2] et une inhibition complete des dommages dans les cellules neuronales, tandis que la repression (<< knockdown >>) des FoxO3 entrainait une diminution de l'activation de l'autophagie engendree par le [H.sub.2][O.sub.2] et une exacerbation des lesions dans les cellules neuronales. L'inhibition de l'autophagie par le 3-methyladenine (3-MA) entrainait une diminution de la viabilite des cellules, une augmentation de la production de derives reactifs de l'oxygene, une aggravation de la condensation des noyaux et une diminution de l'expression de proteines antiapoptotiques et liees a l'autophagie, ce qui montre que l'autophagie pourrait avoir des effets protecteurs contre les effets des lesions engendrees par le [H.sub.2][O.sub.2] dans les cellules HT22. En outre, la surexpression des FoxO3 permettait de prevenir l'exacerbation des dommages engendres par le 3-MA dans le cerveau. Dans leur ensemble, ces resultats montrent que l'activation des FoxO3 pourrait engendrer de l'autophagie et attenuer les dommages engendres par le [H.sub.2][O.sub.2] dans les cellules HT22. Notre etude montre le role essentiel des FoxO3 dans la regulation de l'autophagie dans le cerveau. [Traduit par la Redaction] Mots-cles : facteurs de transcription FoxO3, autophagie, apoptose, peroxyde d'hydrogene, stress oxydatif, maladies neurodegeneratives, cellules HT22., Introduction Neurodegenerative diseases are associated with irreversible and progressive damage to the nervous system (Rekatsina et al. 2020). These diseases are primarily prevalent in the elderly, and the incidence rate [...]