The development of safe and effective radioprotective agents with minimal side effects, particularly for high-dose exposure, remains a global priority. E0703, a novel steroidal compound structurally derived from estradiol, has shown promising radioprotective efficacy with limited estrogenic activity in prior pharmacodynamic studies. In this study, E0703 was found to significantly increase the abundance of Akkermansia muciniphila (AKK) in the intestines of both irradiated and non-irradiated mice. Co-administration of E0703 and AKK markedly improved the 7-day survival rate of mice exposed to a lethal 8.5 Gy dose of radiation. E0703 induced beneficial transcriptional changes in AKK, with enrichment in metabolic pathways such as amino acid biosynthesis, aminoacyl-tRNA biosynthesis, the tricarboxylic acid (TCA) cycle, and fatty acid biosynthesis. These alterations supported the production of glucosamine 6-phosphate (GlcN-6-P) by AKK, which contributed to intestinal tissue regeneration following irradiation. Single-cell transcriptomic analysis revealed that E0703 significantly increased the proportion of intestinal stem cells and goblet cells by Day 5 post irradiation. Mechanistically, E0703 modulated the oxidative phosphorylation pathway in these cell types, including regulation of Muc2 production. E0703 also enhanced AKK abundance in irradiated mice, particularly in the presence of mucin, thereby elevating the availability of GlcN-6-P—a critical substrate for intestinal organoid repair. These findings indicate that E0703 exerts direct effects on goblet cells and AKK, promoting host–microbe interactions that facilitate intestinal regeneration and improve survival following radiation exposure.
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Original Research
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To investigate the clinical manifestations of traditional Chinese medicine (TCM) and their associations with TCM constitutions in individuals who have migrated to plateau areas, and to provide a scientific basis for plateau health management.
Migrants living in areas above 3000 m were selected as research subjects. Data were collected by using TCM symptom assessment scales and constitution assessment scales. Descriptive statistical analysis was conducted to determine the incidence and severity of symptoms among individuals with different migration durations, and core symptoms were identified. Factor analysis was performed by using SPSS software to extract symptom clusters and explore the correlation between core symptoms and TCM constitutions.
Among individuals who migrated to plateau areas, the incidence of discomfort symptoms was 83.44%. The five most common symptoms were dry skin (67.94%), forgetfulness (56.03%), dry mouth (52.06%), yellow urine (48.73%), and insomnia (47.14%). In the top 10 symptoms with the highest increase in incidence, yellow urine (33.51%) and forgetfulness (26.33%) were both present in the top 10 symptoms across different migration durations. Factor analysis extracted 5, 2, 4, and 6 symptom clusters from the overall population, individuals who migrated within 1 year, those who migrated for 1-2 years, and those who migrated over 2 years, respectively. Qi-deficiency constitution (QDC), blood stasis constitution (BSC), qi stagnation constitution (QSC), phlegm-dampness constitution (PDC), and dampness-heat constitution (DHC) were significantly positively correlated with forgetfulness.
Migrating to plateau areas can induce discomfort symptoms, and both the number and incidence of symptoms increase with longer migration durations. The number and incidence of high-frequency symptoms (incidence≥30%) increase with prolonged migration time. There are differences in the composition and severity of symptom clusters across different migration durations. QDC, BSC, QSC, PDC, and DHC are closely related to forgetfulness and can be considered risk constitutions for forgetfulness. Timely attention to changes in symptom clusters and constitutions can help prevent and mitigate the occurrence and development of symptoms.
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