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.

Effects of compound Caoshi silkworm granules on stable COPD patients and their relationship with gut microbiota: A randomized controlled trial.

BACKGROUND AND PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) usually experience recurrent acute exacerbations. These patients, especially those with stable COPD, require an effective intervention for treating exacerbations. This study aimed to evaluate the efficacy of Compound Caoshi silkworm granules (CCSGs) in stable COPD patients and to investigate their potential mechanism. METHODS: A randomized controlled trial was performed at Jinhua Hospital, Zhejiang University. Patients were enrolled in this study if they met the criterion of stable COPD. A total of 40 patients were randomly divided into the following 2 groups: Group A (n = 20, routine treatment (RT) group) and Group B (n = 20, RT plus CCSGs [RT plus CCSGs] group). The duration of treatment was 3 months. Stool samples were collected from all patients on day 0 and the gut microbiota was analyzed using 16s rRNA sequencing. The St. George's Respiratory Questionnaire (SGRQ) scores and lung function were assessed at month 0 and month 3. RESULTS: The components of gut microbiota differed between stable COPD patients and the healthy population. The RT plus CCSGs group showed improved SGRQ scores compared to the RT group. There was no difference in forced expiratory volume-one second, forced vital capacity, and forced expiratory volume-one second/forced vital capacity between the two groups. Furthermore, the abundance of gut microbiota in patients with the top 10 SGRQ scores (Group N) differed from the abundance of gut microbiota in those with the lowest 10 SGRQ scores (Group T). CONCLUSION: CCSGs have beneficial effects in the improvement of symptoms in stable COPD patients over a 3-month treatment period. The potential underlying mechanism may be attributable to the difference in gut microbiota among patients. However, more research is needed to confirm this conclusion.