Skeletal muscles underpin myriad human activities, maintaining an intricate balance between protein synthesis and degradation crucial to muscle mass preservation. Historically, disruptions in this balance—where degradation overshadows synthesis—have marked the onset of muscle atrophy, a condition diminishing life quality and, in grave instances, imperiling life itself. While multiple protein degradation pathways exist—including the autophagy-lysosome, calcium-dependent calpain, and cysteine aspartate protease systems—the ubiquitin-proteasome pathway emerges as an especially cardinal avenue for intracellular protein degradation, wielding pronounced influence over the muscle atrophy trajectory. This paper ventures a panoramic view of predominant muscle atrophy types, accentuating the ubiquitin-proteasome pathway’s role therein. Furthermore, by drawing from recent scholarly advancements, we draw associations between the ubiquitin-proteasome pathway and specific pathological conditions linked to muscle atrophy. Our exploration seeks to shed light on the ubiquitin-proteasome pathway’s significance in skeletal muscle dynamics, aiming to pave the way for innovative therapeutic strategies against muscle atrophy and affiliated muscle disorders.
Neuroimaging-based functional connectivity (FC) analyses have revealed significant developmental trends in specific intrinsic connectivity networks linked to cognitive and behavioral maturation. However, knowledge of how brain functional maturation is associated with FC dynamics at rest is limited. Here, we examined age-related differences in the temporal variability of FC dynamics with data publicly released by the Nathan Kline Institute (NKI; n = 183, ages 7–30) and showed that dynamic inter-region interactions can be used to accurately predict individual brain maturity across development. Furthermore, we identified a significant age-dependent trend underlying dynamic inter-network FC, including increasing variability of the connections between the visual network, default mode network (DMN) and cerebellum as well as within the cerebellum and DMN and decreasing variability within the cerebellum and between the cerebellum and DMN as well as the cingulo-opercular network. Overall, the results suggested significant developmental changes in dynamic inter-network interaction, which may shed new light on the functional organization of typical developmental brains.
There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders.
The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth’s environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.
The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study w...
Skeletal muscle (SKM) has crucial roles in locomotor activity and posture within the body and also functions have been recognized as an actively secretory organ. Numerous bioactive molecules are secreted by SKM and transported by extracellular vesicles (EVs), a novel class of mediators of communication between cells and organs that contain various types of cargo molecules including lipids, proteins and nucleic acids. SKM-derived EVs (SKM-EVs) are intercellular communicators with significant roles in the crosstalk between SKM and other organs. In this review, we briefly describe the biological characteristics, composition, and uptake mechanisms of EVs, particularly exosomes, comprehensively summarize the regulatory effects of SKM-EVs on the function of, which include myogenesis, muscle repair and regeneration, as well as metabolic regulation. Furthermore, we explore the impact of SKM- EVs on various organs including bone, the cardiovascular system, adipose tissue, and nervous system. As emerging evidence suggests that SKM-EVs are involved in the development and regulation of type 2 diabetes (T2D), systemic inflammation, and other chronic diseases, we also highlight the potential of SKM-EVs as therapeutic targets and diagnostic biomarkers, emphasizing the need for further research to elucidate the complex mechanisms underlying intercellular communication in physiological and pathological contexts.