Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04540-x
Background Trained immunity with human bone marrow mesenchymal stem cells (hBMSC) is a promising approach to liver regeneration. This study aimed to clarify the trained-hBMSC (T-hBMSC) in restoring tissue immuno-microenvironment in fulminant hepatic failure (FHF) mice. Methods hBMSC trained with tumor necrosis factor-α and interferon-γ were phenotypically characterized in vitro. FHF mouse models were established in male Balb/c mice via tail vein injection of concanavalin A. The therapeutic potential of T-hBMSC was evaluated through transplantation into FHF mice. Transcriptomic analysis was performed to elucidate the mechanism of liver regeneration post-transplantation of T-hBMSC. Results T-hBMSC with the characteristics of trilineage differentiation potential showed that pro-inflammatory (IL1β, IL8, both p < 0.0001) and immunoregulatory genes (PDL1, IDO1, both p < 0.0001) were significantly upregulated compared to untrained-hBMSC (UT-hBMSC). Time-trajectory analysis revealed downregulation of pro-inflammatory genes (IL6, IL8, and IL1α) and upregulation of immunomodulatory genes (IDO1) in T-hBMSC upon mimic-stimulation, characterized by distinct transcriptional programs. The liver function (ALT, AST) and inflammatory cytokines (IL6, MCP1, both p < 0.01) levels were significantly improved in the T-hBMSC-treated mice. The survival status of the T-hBMSC group was superior to the UT-hBMSC group, although there was no statistical significance. Histological analysis confirmed reduced necrosis and fewer infiltrating CD45+ immune cells in the T-hBMSC-treated mice. Significant downregulation of immune response (TNF & IL-17 signaling pathways and neutrophil chemotaxis) and upregulation of metabolic pathways were observed in the T-hBMSC group, associated with enhanced liver regeneration. The proportion of anti-inflammatory F4/80+CD163+ macrophages was increased in the liver of T-hBMSC group.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03949-0
Background The selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phenotype and function. We analyze and emphasize from the perspectives of clinical and commercial application why research on customized culture media is critical for the success of enterprises developing novel cellular therapeutics. Methods We cultured hUC-MSCs with identical cell seeding densities in different formulations of SFM and SCM until passage 10 and examined the changes in cell phenotype and function. We analyzed the results with the commercial application requirments of the cellular therapy industry to assess the potential impact of customized culture media on inter-batch consistency, efficacy, stability, biosafety, and cost-effectiveness of industrial-scale cell production. Results hUC-MSCs cultured in SCM and SFM exhibit consistent cell morphology and surface molecule expression, but hUC-MSCs cultured in SFM demonstrate higher activity, superior proliferative capacity, and greater stability. Furthermore, hUC-MSCs cultured in different SFM exhibit differences in cell activity, proliferative capacity, senescent rate, and S/M ratio of cell cycle, while maintaining a normal karyotype after long-term in vitro cultivation. Moreover, [abstract truncated]
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025222
Poultry production faces escalating challenges from intensive farming practices, where stressors, including high stocking density, pathogen exposure, and dietary fluctuations, disrupt intestinal integrity, microbiota balance, and antioxidant defenses. These disruptions impair nutrient absorption, growth performance, and immune function, leading to significant economic losses. Although antibiotics have historically mitigated such issues, growing restrictions due to antimicrobial resistance necessitate natural alternatives. Fungal polysaccharides (FP)—notably lentinan (LNT) from Lentinula edodes and polysaccharide from Ganoderma lucidum (GLP), are promising candidates owing to their immunomodulatory, antioxidant, and prebiotic properties. However, existing research focuses predominantly on individual FP, neglecting potential synergies in blended formulations. Structurally, LNT (β-(1→3)-D-glucan backbone) enhances rumen volatile fatty acid production and fiber degradation, whereas GLP (heterogeneous α/β-glycans) potently activates the Nrf2/HO-1 antioxidant pathway and modulates Th1/Th2 immunity. These divergent mechanisms imply complementary effects when combined. In our previous experiments on broiler feeding, we reported that a combination of GLP (68.32% polysaccharide content, composed of mannose, glucose, arabinose, rhamnose, and galactose at a molar ratio of 1.00:16.37:18.82:1.42:17.42) and LNT (76.52% polysaccharide content, composed of mannose, galacturonic acid, arabinose, galactose, glucose, and rhamnose at a molar ratio of 1.00:15.22:8.23:2.05:1.78:4.26) at a 1:1 ratio maximally promoted broiler growth (unpublished data), but their impacts on intestinal morphology, antioxidant signaling, and the microbiota remain uncharacterized. We therefore hypothesize that mixed FP synergistically may enhance intestinal health by simultaneously improving nutrient absorption, activating antioxidant pathways, and stabilizing microbial ecosystems. To investigate the effects of mixed FP on intestinal development, 240 one-day-old Arbor Acres male broilers were randomly assigned to the 0 mg/kg FP (Control), 200 mg/kg FP (Group I), 400 mg/kg FP (Group II), and 600 mg/kg FP (Group III) groups. Broilers were housed in three-tier battery cages (0.7 m × 0.7 m × 0.4 m; 12 broilers/cage), with five replicate cages per experimental group maintained under identical conditions. The experiments were approved by the College of Animal Science and Technology in Anhui Agricultural University (approval number: SYXK 2016-007). All the cages were subjected to a 16 h light: 8 h dark cycle with ad libitum access to water and twice-daily feeding (09:00/16:00) of basal diets (Supplementary Table S1). On day 42, the duodenum, jejunum, and ileum segments were collected, fixed in 4% paraformaldehyde, sectioned at 5 μm, and stained with hematoxylin-eosin. Villus height (VH), crypt depth (CD), and VH/CD ratios were measured via Case Viewer software. The results revealed that Group II significantly increased VH and VH/CD across all the intestinal segments while reducing CD (Figure 1A; P < 0.05 vs the control); these findings suggest enhanced nutrient absorption capacity and intestinal health. To evaluate antioxidant capacity and signaling pathway activation, intestinal tissues were homogenized in PBS (1:9, w/v). The total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) activities were determined via commercial kits (Nanjing Jiancheng Bioengineering Institute, Nanjing, China)). For gene expression analysis, total RNA was extracted and reverse-transcribed. The qPCR was performed via specific primers for HO-1, NQO1, CAT, Nrf2, and Keap1, with β-actin used as the reference gene (primer sequences and product sizes are listed in Supplementary Table S2). The results demonstrated that Group II significantly elevated antioxidant enzyme activities (P < 0.05), upregulated HO-1, NQO1, CAT, and Nrf2, and
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261618
This study systematically interrogated the China National Intellectual Property Administration patent database to identify candidate core herb combinations and therapeutic targets for ischemic stroke (IS), integrating cluster analysis, network pharmacology, molecular docking, molecular dynamics simulations, single-cell RNA sequencing, spatial transcriptomics, and CellOracle-based in silico knockdown. A core herb combination of Polygalae Radix, Acori Tatarinowii Rhizoma, Rhei Radix et Rhizoma, and Curcumae Radix was identified, yielding nine representative active components (1-hydroxyacoronene, aristolone, calamendiol, β-asarone, α-asarone, kaempferol, thymol, eugenol, caffeic acid) and six candidate targets (TNF, IL-6, AKT1, EGFR, MAPK1, PTGS2). Molecular docking and dynamics simulations indicated binding tendencies, with kaempferol-PTGS2 and kaempferol-EGFR complexes showing stability under simulated conditions. Single-cell and spatial transcriptomics revealed spatial concordance between high candidate target expression regions and macrophage/astrocyte distribution. CellOracle predicted that Jun/Fos and STAT3 transcription factors may regulate post-ischemic inflammatory responses and cell state transitions. The study constructs a mechanistic evidence chain linking core herbs, active components, candidate targets, and spatiotemporal validation, offering a modern biological interpretation of the 'Tongfu Xingshen' therapeutic principle. However, findings remain computational and require experimental validation; limitations include single-timepoint single-cell data (24 h post-MCAO), reliance on public databases, and lack of in vivo/in vitro efficacy experiments.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025222
Poultry production faces escalating challenges from intensive farming practices, where stressors disrupt intestinal integrity, microbiota balance, and antioxidant defenses, leading to economic losses. Although antibiotics have historically mitigated such issues, growing restrictions due to antimicrobial resistance necessitate natural alternatives. Fungal polysaccharides (FP), notably lentinan (LNT) from Lentinula edodes and polysaccharide from Ganoderma lucidum (GLP), are promising candidates owing to their immunomodulatory, antioxidant, and prebiotic properties. However, existing research focuses predominantly on individual FP, neglecting potential synergies in blended formulations. We hypothesized that mixed FP synergistically enhance intestinal health by simultaneously improving nutrient absorption, activating antioxidant pathways, and stabilizing microbial ecosystems. To investigate, 240 one-day-old Arbor Acres male broilers were randomly assigned to control (0 mg/kg FP) and treatment groups receiving 200, 400, or 600 mg/kg mixed FP (1:1 ratio of GLP and LNT). On day 42, intestinal segments were collected for morphological analysis, antioxidant enzyme activities, gene expression, and cecal microbiota composition. Results showed that 400 mg/kg FP significantly increased villus height and VH/CD ratio across all intestinal segments while reducing crypt depth, indicating enhanced nutrient absorption. Antioxidant enzyme activities (T-AOC, T-SOD, GSH-Px) were elevated, and mRNA expression of HO-1, NQO1, CAT, and Nrf2 was upregulated, with Keap1 downregulated, suggesting activation of the Keap1-Nrf2 pathway. Microbiota analysis revealed increased alpha diversity (Shannon and Simpson indices) and altered composition, with elevated abundances of beneficial genera such as Butyricimonas and Alistipes, and increased Verrucomicrobiota phylum. These findings demonstrate that mixed FP supplementation at 400 mg/kg improves intestinal health, antioxidant capacity, and microbiota diversity in broilers, offering a natural alternative to antibiotics.