Gut microbiota in muscular atrophy development,progression,and treatment:New therapeutic targets and opportunities

Skeletal muscle atrophy is a debilitating condition that significantly affects quality of life and often lacks effective treatment options.Muscle atrophy can have various causes,including myogenic,neurogenic,and other factors.Recent investigation has underscored a compelling link between the gut microbiota and skeletal muscle.Discerning the potential differences in the gut microbiota associated with muscle atrophy-related diseases,understanding their influence on disease development,and recognizing their potential as intervention targets are of paramount importance.This review aims to provide a comprehensive overview of the role of the gut microbiota in muscle atrophy-related diseases.We summarize clinical and pre-clinical studies that investigate the potential for gut microbiota modulation to enhance muscle performance and promote disease recovery.Furthermore,we delve into the intricate interplay between the gut microbiota and muscle atrophy-related diseases,drawing from an array of studies.Emerging evidence suggests significant differences in gut microbiota composition in individuals with muscle atrophy-related diseases compared with healthy individuals.It is conceivable that these alterations in the microbiota contribute to the pathogenesis of these disorders through bacterium-related metabolites or inflammatory signals.

Generation and Characterization of a Transgenic Zebrafish Expressing the Reverse Tetracycline Transactivator

Conditional expression of a target gene during zebrafish development is a powerful approach to elucidate gene functions. The tetracycline-controlled systems have been successfully used in the modulation of gene expression in mammalian cells, but few lines of zebrafish carrying these systems are currently available. In this study, we had generated a stable transgenic zebrafish line that ubiquitously expressed the second-generation of reverse Tet transactivator （rtTA-M2）. Southern blotting analysis and high-throughput genome sequencing verifed that a single copy of rtTA-M2 gene had stably integrated into the zebrafish genome. After induction with doxycycline （Dox）, a strong green fluorescent protein （GFP） was seen in rtTA-transgenic eggs injected with pTRE--EGFP plasmids. The fluorescent signal gradually decreased after the withdrawal of Dox and disappeared. However, leaky expression of GFP was undetectable before Dox- induction. Additionally, transgenic embryos expressing rtTA-M2 exhibited no obvious defects in morphological phenotypes, hatching behavior and expression patterns of developmental marker genes, suggesting that rtTA-M2 had little effect on the development of transgenic zebrafish. Moreover, expressed Dickkopf-1 （DKK1） in pTRE-DKKl-injected embryos led to alterations in the expression of marker genes associated with Wnt signaling. Thus, this rtTA-transgenic zebrafish can be utilized to dissect functions of genes in a temporal manner.

New glimpses of caveolin-1 functions in embryonic development and human diseases

Caveolin-1(Cav-1)isoforms,including Cav-1αand Cav-1β,were identified as integral membrane proteins and the major components of caveolae.Cav-1 proteins are highly conserved during evolution from Caenorhabditis elegans to human and are capable of interacting with many signaling molecules through their caveolin scaffolding domains to regulate the activities of multiple signaling pathways.Thus,Cav-1 plays crucial roles in the regulation of cellular proliferation,differentiation and apoptosis in a cell-specific and contextual manner.In addition,Cav-1 is essential for embryonic development of vertebrates owing to its regulation of BMP,Wnt,TGF-βand other key signaling molecules.Moreover,Cav-1 is mainly expressed in terminally differentiated cells and its abnormal expression is often associated with human diseases,such as tumor progression,cardiovascular diseases,fibrosis,lung regeneration,and diseases related to virus.In this review,we will further discuss the potential of Cav-1 as a target for disease therapy and multiple drug resistance.