Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04774-9
Previous studies have confirmed that scald injuries can lead to disturbances in hepatic lipid metabolism, and bone marrow-derived mesenchymal stem cells (BMSCs) have emerged as a promising therapeutic strategy for alleviating such disorders. However, research focusing on the regulation and restoration of liver lipid metabolic processes remains limited. In this study, we investigated the effects of BMSCs on hepatic lipid metabolism disorders induced by scald injury in rats through integrated transcriptomic and metabolomic analyses. The results demonstrated that portal vein infusion of BMSCs markedly improved body weight recovery, reduced hepatic lipid accumulation, normalized serum lipid profiles, and attenuated liver injury following scalding. Combined transcriptomic and metabolomic data further suggested that the therapeutic mechanism may involve inhibition of NF-κB/Gadd45a signaling in hepatocytes, restoration of sphingolipid metabolism, enhancement of hepatic lipid conversion, and suppression of adipocyte lipolysis. Overall, this study provides a theoretical basis for the potential clinical application of BMSCs in treating hepatic lipid metabolism disorders secondary to severe burn injury.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025146
Actin-bundling protein Fascin1 (FSCN1) is encoded by the Fscn1 gene and is crucial for cytoskeletal remodeling and cellular migration. Although a previous study linked Fscn1 deficiency to neonatal lethality in mice, the underlying metabolic mechanism remains unclear. In this study, we report that systemic knockout (KO) of Fscn1 leads to 52.2% mortality within 24 h post-birth, accompanied by severe hypoglycemia in KO pups compared with their littermates. Remarkably, this lethality is fully rescued by oral glucose administration, indicating a glucose supply-dependent survival mechanism. Surviving Fscn1-KO neonates display persistent developmental deficits, including growth retardation and depleted lipid stores, despite intact canonical insulin-regulated hepatic gluconeogenic pathways. Transcriptomic profiling of P0 livers reveals that Fscn1 loss predominantly disrupts metabolic pathways, with the glycerol phosphate shuttle being the most significantly downregulated module. Mechanistically, Fscn1-KO livers exhibit markedly reduced protein levels of glycerol-3-phosphate dehydrogenase isoforms (GPD1/GPD2), key enzymes bridging glycolysis and gluconeogenesis. Consistently, glycerol tolerance tests demonstrate impaired glycerol-to-glucose conversion in Fscn1-KO mice, confirming defective glycerol-driven gluconeogenesis. Our findings establish FSCN1 as a novel cytoskeletal-metabolic integrator essential for neonatal survival by sustaining hepatic glucose production from glycerol, thus revealing an unexpected role of actin dynamics in coordinating metabolic adaptation during early postnatal development.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025080
Macrophages are key players in the pathology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Existing studies and our previous studies have documented the role of CD206-positive M2 macrophages in the inflammatory process of AAV. Inflammasome activation is a critical pathway through which macrophages release inflammatory factors. In this study, we investigate the role of the inflammasome in macrophages in AAV and explore the role of CD206 in this process. We recruit newly diagnosed AAV patients and disease controls from our department. The expression and localization of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) and CD206 in the kidney are determined via immunofluorescence experiments. Myeloperoxidase (MPO)-ANCA immunoglobulin G (MPO-ANCA IgG) is purified from new-onset AAV patients with MPO-ANCA and used to treat lipopolysaccharide (LPS)-primed macrophages in vitro. Our findings reveal that NLRP3 expression is significantly elevated in the kidneys of active AAV patients, accompanied by increased cleaved caspase-1 and N-terminal gasdermin-D (GSDMD) levels in peripheral blood mononuclear cells (PBMCs). In vitro, MPO-ANCA IgG induces NLRP3 inflammasome activation and interleukin (IL)-1β production in macrophages, which is associated with increased MPO expression and JNK signaling pathway activation. Immunofluorescence analysis demonstrates partial colocalization of CD206 and NLRP3 in AAV kidneys. Furthermore, silencing of MRC1 gene, which encodes CD206, reduces inflammasome activation induced by MPO-ANCA IgG. In conclusion, our study provides evidence that MPO-ANCA IgG contributes to NLRP3 inflammasome activation and macrophage pyroptosis, with CD206 playing a critical role in this process. These findings elucidate the mechanisms underlying inflammation in AAV and suggest potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024060
Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04774-9
Scald injuries annually affect over 2 million individuals in the United States, with approximately 3,400 deaths and an economic burden exceeding 573 million USD. Thermal burns and scalds constitute more than 90% of cases, driving systemic complications that result in roughly 250,000 global deaths annually. These outcomes are largely attributed to profound metabolic disturbances, including systemic inflammation and hepatic lipid dysregulation. Bone marrow-derived mesenchymal stem cells (BMSCs) have emerged as a potential therapeutic strategy, yet their specific impact on liver lipid metabolism post-scald remains poorly defined. This study employed integrated transcriptomic and metabolomic analyses to investigate BMSC-mediated restoration of hepatic lipid homeostasis in a rat scald model. Portal vein infusion of BMSCs significantly improved body weight recovery, reduced hepatic lipid accumulation, normalized serum lipid profiles, and attenuated liver injury. Mechanistically, the therapeutic effect was associated with inhibition of NF-κB/Gadd45a signaling in hepatocytes, restoration of sphingolipid metabolism, enhanced hepatic lipid conversion, and suppression of adipocyte lipolysis. These findings delineate a molecular pathway through which BMSCs ameliorate scald-induced hepatic lipid metabolic dysfunction, providing a theoretical foundation for clinical translation in severe burn injury.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21204
BACKGROUND: In tissue engineering bone construction, the physical properties of the scaffold can directly affect the activity and repair effect of seed cells, among which extracellular matrix hardness is a key factor affecting seed cell proliferation activity. Primary cilia and YAP proteins have been shown to be classical mechanoreceptors and downstream transduction factors, which may directly mediate this mechanism. OBJECTIVE: To investigate the regulatory effect of extracellular matrix hardness on the proliferation activity of bone marrow stromal stem cells and the related mechanisms. METHODS: Bone marrow stromal stem cells were passaged and seeded under different hardness of polydimethylsiloxane extracellular matrix conditions (soft, median, and rigid) for culture. Cell proliferation activity was detected using CCK-8 assay. Transcriptional activity of proliferation genes c-myc and CCND1 was measured using qRT-PCR. Activation of Wnt/β-catenin pathway was evaluated using western blot assay. Primary cilia and YAP protein expression levels were evaluated by acetylated α-tubulin and YAP immunofluorescence staining. After passage, bone marrow stromal stem cells were inoculated on polydimethylsiloxane-based membranes of different hardness (soft and hard) for culture. Then siRNA was used to interfere with YAP protein expression. Western blot assay was used to detect YAP, phosphorylated GSK-3β, and β-catenin protein expression. qRT-PCR was used to detect the transcriptional activity of c-myc and CCND1. The length of primary cilia was analyzed after immunofluorescence staining of acetylated α-tubulin. RESULTS AND CONCLUSION: The cell proliferation activity, c-myc and CCND1 transcriptional activity under rigid polydimethylsiloxane conditions were significantly higher than those under soft and median hardness, and the activation of Wnt/β-catenin pathway was stronger. Immunofluorescence staining showed that rigid polydimethylsiloxane induced shortening of primary cilia and increased YAP-positive cells. After siRNA interference of YAP expression, the differences in YAP, phosphorylated GSK-3β, β-catenin protein expression, and c-myc and CCND1 transcriptional activity between groups disappeared, accompanied by the disappearance of primary cilia length differences. The results indicate that extracellular matrix stiffness regulates the proliferation activity of bone marrow stromal stem cells through a novel YAP protein/primary cilia mechanism.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21333
BACKGROUND: Periprostatic adipose tissue is the white visceral adipose tissue that is closest to the prostate, which is part of the prostate cancer tumor microenvironment and plays a key role in the occurrence and progression of prostate cancer. OBJECTIVE: To investigate the ability of adipose-derived stem cells derived from periprostatic adipose tissue to form three-dimensional cell sheets. METHODS: Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy. Adipose-derived stem cell suspensions were prepared using a combination of enzymatic digestion and mechanical dissection. Adipose-derived stem cell proliferation was assessed using a CCK-8 assay. Expression of stem cell-associated antigens CD34/CD44/CD45/CD90/CD105 was determined by flow cytometry. Multidirectional differentiation potential of the stem cells was assessed using osteogenic/adipogenic/chondrogenic differentiation assays. Adipose-derived stem cells were cultured for three weeks in low-glucose DMEM containing 100 μg/mL vitamin C and 10% fetal bovine serum to construct cell sheets, followed by histological analysis and scanning electron microscopy. RESULTS AND CONCLUSION: Adipose-derived stem cells from periprostatic adipose tissue exhibited a long spindle or fusiform shape, aligned growth, and consistent morphology. Primary culture reached 95% confluence at 9-10 days with good cell viability, and no obvious senescence was observed up to passage 15. Flow cytometry showed expression rates of CD44, CD90, and CD105 at 98.24%, 84.99%, and 89.14%, respectively, while CD34 and CD45 were expressed at 0.64% and 1.02%. After 3 weeks of osteogenic, adipogenic, and chondrogenic induction, the cells could differentiate into osteoblasts, adipocytes, and chondrocytes. After continuous culture for 3 weeks, the cells formed a three-dimensional cell sheet with a smooth surface and uniform texture, rich in extracellular matrix components such as fibronectin and type I collagen. Scanning electron microscopy revealed a flat surface with aligned long spindle-shaped cells and abundant extracellular matrix deposition between cells. This study successfully isolated adipose-derived stem cells from periprostatic adipose tissue of prostate cancer patients and constructed a three-dimensional cell sheet by stimulating extracellular matrix secretion with vitamin C over 3 weeks of continuous culture.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025080
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening systemic autoimmune disease characterized by necrotizing small vessel vasculitis, with pauci-immune glomerulonephritis being the most severe manifestation. Macrophages, particularly CD206-positive M2 subsets, are central to AAV pathology, yet the mechanistic link between inflammasome activation and CD206 remains undefined. This study investigates NLRP3 inflammasome activity and pyroptosis in CD206+ macrophages exposed to myeloperoxidase (MPO)-ANCA immunoglobulin G (IgG). Newly diagnosed AAV patients and disease controls were recruited; renal NLRP3 and CD206 expression were assessed by immunofluorescence. MPO-ANCA IgG was purified from new-onset AAV patients and applied to lipopolysaccharide (LPS)-primed macrophages in vitro. Results demonstrate significantly elevated NLRP3 expression in active AAV kidneys, accompanied by increased cleaved caspase-1 and N-terminal gasdermin-D (GSDMD) in peripheral blood mononuclear cells (PBMCs). In vitro, MPO-ANCA IgG induces NLRP3 inflammasome activation and interleukin (IL)-1β production, associated with increased MPO expression and JNK signaling pathway activation. Immunofluorescence reveals partial colocalization of CD206 and NLRP3 in AAV kidneys. Silencing of MRC1, encoding CD206, reduces inflammasome activation induced by MPO-ANCA IgG. These findings establish that MPO-ANCA IgG contributes to NLRP3 inflammasome activation and macrophage pyroptosis, with CD206 playing a critical role. The study elucidates mechanisms underlying AAV inflammation and suggests potential therapeutic targets.