Recent studies have shown a close relationship between the gut microbiota and Crohn’s disease (CD). This study aimed to determine whether mesenchymal stem cell (MSC) treatment alters the gut microbiota and fecal metabolite pathways and to establish the relationship between the gut microbiota and fecal metabolites. Patients with refractory CD were enrolled and received 8 intravenous infusions of MSCs at a dose of 1.0 × 10⁶ cells/kg. The MSC efficacy and safety were evaluated. Fecal samples were collected, and their microbiomes were analyzed by 16S rDNA sequencing. The fecal metabolites at baseline and after 4 and 8 MSC infusions were identified by liquid chromatography-mass spectrometry (LC--MS). A bioinformatics analysis was conducted using the sequencing data. No serious adverse effects were observed. The clinical symptoms and signs of patients with CD were substantially relieved after 8 MSC infusions, as revealed by changes in weight, the CD activity index (CDAI) score, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). Endoscopic improvement was observed in 2 patients. A comparison of the gut microbiome after 8 MSC treatments with that at baseline showed that the genus Cetobacterium was significantly enriched. Linoleic acid was depleted after 8 MSC treatments. A possible link between the altered Cetobacterium abundance and linoleic acid metabolite levels was observed in patients with CD who received MSCs. This study enabled an understanding of both the gut microbiota response and bacterial metabolites to obtain more information about host-gut microbiota metabolic interactions in the short-term response to MSC treatment.

Pyroptosis is a programmed cell death caused by inflammation. Multiple studies have suggested that Mycobacterium tuberculosis infection causes tissue pyroptosis. However, there are currently no protective drugs against the inflammatory damage caused by pyroptosis. In this study, anti-pyroptotic effects of the natural compound astaxanthin (ASTA) were explored in a simulated pulmonary tuberculosis-associated inflammatory environment. The results showed that ASTA maintained the stability of MLE-12 lung epithelial cell numbers in the inflammatory environment established by lipopolysaccharide. The reason is not to promote cell proliferation but to inhibit lipopolysaccharide-induced pyroptosis. The results showed that ASTA significantly inhibited the expression of key proteins in the caspase 4/11-gasdermin D pathway and the release of pyroptosis-related inflammatory mediators. Therefore, ASTA inhibits inflammation-induced pyroptosis by inhibiting the caspase 4/11-gasdermin D pathway and has the potential to protect lung tissue from tuberculosis-related inflammatory injury. ASTA, a functional food component, is a promising candidate for protection against tuberculosis-associated inflammatory lung injury.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the most prevalent chronic liver disease worldwide, with an increasing incidence rate. MAFLD is a heterogeneous disease that can have a low or high-risk profile for developing severe liver disease in its natural course. Recent evidence has highlighted the critical role of RNA methylation modification in the pathogenesis of various liver diseases. However, it remains unclear whether the RNA N1-methyladenosine (m¹A) modification of immune cells could potentially contribute to the pathogenesis and heterogeneity of MAFLD. To address this issue, we conducted an integrated bioinformatics analysis of MAFLD bulk and single-cell RNA sequencing (scRNA-seq) data to pinpoint m¹A regulators in the network. This was followed by a description of the immune landscape, pathway enrichment analysis, and molecular subtyping. The expression patterns of m¹A regulatory genes stratify MAFLD into two molecular subtypes, Cluster 1 and Cluster 2. These subtypes demonstrate different immune cell infiltration with distinct inflammation characteristics, which suggest different immune-inflammatory responses in the liver. Notably, Cluster 2 is associated with pro-inflammation and may be more likely to lead to progressive stages of MAFLD. Through intersection analysis of weighted gene co-expression network analysis (WGCNA) and m¹A regulatory genes, three true hub genes (ALKBH1, YTHDC1, and YTHDF3) were identified, all of which were strongly correlated with infiltrating immune cells. The specific signaling pathways involved in the three core genes were derived from genomic variation analysis. Furthermore, scRNA-seq data from 33,168 cells from six liver samples identified 26 cell clusters and eight cell types, with endothelial cells, macrophages, and monocytes showing the most significant differences between MAFLD and normal controls. The cell-cell communication network between immune cells and non-parenchymal cells was extremely sophisticated and changed significantly in MAFLD. In summary, these findings demonstrate the involvement of m¹A in MAFLD heterogeneity and emphasize the crucial role of m¹A modulation of immune cells in regulating inflammation in MAFLD. These results may suggest potential therapeutic strategies for MAFLD.

Background: Mesenchymal stem cells (MSCs) have shown positive therapeutic effects on various diseases; however, their functionality can decline during in vitro expansion. Selenium (Se) supplementation has emerged as a strategy for enhancing MSC culture. This study evaluated the effects of different forms of selenium (Na₂SeO₄, SeMet, ebselen, and chitosan-coated selenium nanoparticles (CS-SeNPs)) on the biological functions of MSCs. Methods: Human umbilical cord-derived MSCs (HUC-MSCs) were cultured in media supplemented with various selenium compounds at specific concentrations. To investigate their biological effects, we assessed cell proliferation, morphology, surface marker expression, and differentiation potential. Furthermore, to elucidate the underlying mechanisms, we analyzed key markers of cellular senescence, including p16, p21, IL-6, IL-8, p27, p53, and reactive oxygen species (ROS) levels. Results: All the selenium treatments promoted hUC-MSC proliferation at specific concentrations. CS-SeNPs and Na₂SeO₄ exhibited relatively high bioavailability, whereas ebselen and SeMet demonstrated relatively low toxicity. The optimal concentration (0.5 μM CS-SeNPs or 0.25 μM Na₂SeO₄) significantly enhanced proliferation without altering the hUC-MSC morphology, phenotype, or differentiation capacity. Both CS-SeNPs and Na₂SeO₄ effectively promoted hUC-MSC proliferation and reduced the senescence of hUC-MSCs by downregulating key senescence-related effectors: the cell cycle inhibitors p16, p21, p27, and p53; and the levels of ROS and senescence-associated secretory phenotype factors (IL-6 and IL-8). Conclusions: Selenium supplementation is an effective strategy for improving MSC expansion and alleviating senescence. The beneficial effects are dependent on the specific selenium compound used, with CS-SeNPs and Na₂SeO₄ showing particularly strong potential for enhancing the bioavailability and function of hUC-MSCs during in vitro cultivation.