Replicating human characteristics: A promising animal model of central fatigue.

Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.

Differential gene screening and bioinformatics analysis of epidermal stem cells and dermal fibroblasts during skin aging.

To explore the differentially expressed genes (DEGs) and potential therapeutic targets of skin aging in GEO database by bioinformatics methods. Dermal fibroblasts and skin aging related data sets GSE110978 and GSE117763 were downloaded from GEO database, and epidermal stem cells and skin aging related data sets GSE137176 were downloaded. GEO2R was used to screen DEGs of candidate samples from the three microarrays, GO function analysis and KEGG pathway analysis were performed. Protein interaction network was constructed using String database, and hub gene was obtained by Cytoscape. NetworkAnalys was used to analyze the coregulatory network of DEGs and MicroRNA (miRNA), interaction with TF, and protein-chemical interactions of DEGs. Finally, DSigDB was used to determine candidate drugs for DEGs. Six DEGs were obtained. It mainly involves the cytological processes such as response to metal ion, and is enriched in mineral absorption and other signal pathways. Ten genes were screened by PPI analysis. Gene-miRNA coregulatory network found that Peg3 and mmu-miR-1931 in DEGs were related to each other, and Cybrd1 was related to mmu-miR-290a-5p and mmu-miR-3082-5p. TF-gene interactions found that the transcription factor UBTF co-regulated two genes, Arhgap24 and Mpzl1. Protein-chemical Interactions analysis and identification of candidate drugs show results for candidate drugs. Try to explore the mechanism of hub gene action in skin aging progression, and to discover the key signaling pathways leading to skin aging, which may be a high risk of skin aging.