Inhibition of epithelial ferroptosis in colonic tissues relieved clinical symptoms and improved endoscopic presentations in inflammatory bowel disease (IBD). Kumatakenin, the main ingredient of traditional Chinese medicinal cloves and Alpinia purpurata, is reported to possess therapeutic benefits. However, whether kumatakenin could inhibit ferroptosis and further alleviate colitis remains unclear. Here, we measured the effects of kumatakenin on ferroptosis of colonic epithelial cells from colitis mice. The colitis model was induced in mice by oral intake of 2.5% dextran sulfate sodium in drinking water. RNA sequencing was performed to investigate the mechanism underlying kumatakenin-mediated effects on colitis. The results showed that different doses of kumatakenin significantly alleviated symptoms and suppressed intestinal inflammation in the colitis mouse model. Kumatakenin supplementation decreased cellular iron levels and suppressed ferroptosis in epithelial cells from colitis mice. RNA sequencing, qPCR, and pharmacological inhibition assays showed that kumatakenin reduced cellular iron levels and suppressed ferroptosis in epithelial cells from colitis mice at least partially by upregulating expression of enolase (Eno-3). Furthermore, kumatakenin decreased iron levels in epithelial cells by modulating the Eno3-iron regulatory protein (IRP1) axis. Molecular docking results revealed that kumatakenin could bind Eno3 via hydrogen bonding with the amino acid residues Thr208, Val206, and Pro203. This work will provide a scientific basis for the clinical use of kumatakenin in the treatment of colitis.

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ScopeSystemic heat stress (or heatstroke; HS) induces germ cell death and spermatogenesis disorders in men and male mammals. Also, it affects the immune environment of the circulatory system promoting gut inflammation and intestinal permeability, leading to pathogenic infection. In this study, the crosstalk between the gut and testis (gut‐testis axis) under HS is explored, by examining the effects of intestinal immune status on the health of the male reproductive system in mice.Methods and resultsA mouse model of systemic heat stress is established to investigate the effect of probiotics on testis health. The results reveal that pro‐inflammatory factor receptor activation pathway and pathogen infection response pathway are significantly upregulated in HS testes, leading to necroptosis, while pro‐inflammatory factor and endotoxin are detected locally in the intestine and then entered the blood. The study then uses probiotics to intervene in gut microbiota, which results in milder gut microbial changes, lower inflammatory responses in the HS gut, and less necroptosis in the HS testes.ConclusionProbiotics‐based remodeling of gut microbiota (GM) reduces the proliferation of abnormal bacteria and decreases the spread of gut‐derived inflammatory mediators into the blood circulation under long‐term systemic heat stress, which relieves inflammation on germ cells.

BackgroundThis study aimed to assess the commutability of frozen pooled human serum (PHS), high concentration of Immunoglobulin M (IgM) pure diluted materials (HPDM), commercialized pure materials (CPM), and dilutions of ERM‐DA470k/IFCC in IgM detection using the CLSI and IFCC approaches, to support standardization or harmonization of IgM measurement.MethodsTwenty‐four serum samples, relevant reference materials (PHS, HPDM, CPM), and different ERM‐DA470k/IFCC dilutions were analyzed in triplicate using six routine methods. The commutability of the relevant reference materials was carried out following CLSI EP30‐A and IFCC bias analysis.ResultsAccording to the CLSI approach, low, medium, and high concentrations of PHS, HPDM, and CPM were commutable on 10, 13, 15, 13, and 8 of 15 assay combinations, respectively. Using the IFCC approach, low, medium, and high concentrations of PHS, HPDM, and CPM were commutable on 10, 11, 9, 15, and 10 of 15 assay combinations, respectively. The ERM‐DA470k/IFCC dilutions with D‐PBS and RPMI‐1640 Medium were commutable on 13 of 15 assay combinations according to CLSI and were commutable on all 15 assay combinations using IFCC approach.ConclusionsHigh concentration of PHS were commutable on all six detection systems using the CLSI approach. Low and medium concentration of PHS showed unsatisfied commutability. HPDM, not CPM have good commutability, has the potential to become reference materials. ERM‐DA470k/IFCC diluted with different medium showed different commutability.