Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04245-1
Background Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, the harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular vesicles produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, and gas neurotransmitters. ApoVs play significant roles in anti-inflammatory responses, anti-tumor activities, and tissue regeneration through intercellular communication, and they have demonstrated potential as drug carriers. In this study, we investigated the potential of bone marrow stem cell (BMSC)-derived ApoVs for treating CLTI. Methods In vivo, we explored the therapeutic effect of ApoVs on a hindlimb ischemia model through Laser Doppler, matrigel plug assay, and histological analysis. In vitro, we analyzed the effects of ApoVs on the proliferation, migration, and angiogenesis of HUVECs and explored the uptake process of ApoVs. In addition, Proteomic analysis, western blotting, quantitative real-time PCR, shRNA, and siRNA were used to analyze ApoVs-induced HUVECs activation and downstream signaling pathways. Results BMSCs transplantation showed improvement in a hind limb ischemia model, and this effect still exists after apoptosis of BMSCs. Subsequently, ApoVs of BMSCs were isolated and found to improve mouse hind limb ischemia in vivo. In vitro, ApoVs can be ingested by HUVECs through dynamin-, clathrin-, and caveolin-mediated endocytosis and promote its proliferation, migration, and angiogenesis. Mechanistically, ApoVs transferred NAMPT to HUVECs, therefore activating the NAMPT/SIRT1/FOXO1 axis, influencing the transcriptional activity of FOXO1, and promoting angiogenesis. Conclusions Our results demonstrate that the transplanted BMSCs can ameliorate hindlimb ischemia by releasing ApoVs during apoptosis. The main mechanism of this effect is promoting the proliferation, migration, and angiogenesis of endothelial cells via the NAMPT/SIRT1/FOXO1 axis.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04202-y
Background Severe hepatic steatosis can exacerbate Ischemia–reperfusion injury (IRI), potentially leading to early graft dysfunction and primary non-function. In this study, we investigated the heterogeneity of different subpopulations of Urine-derived stem cells (USCs) to explore the most suitable cell subtype for treating severe steatotic liver IRI. Methods This study utilized scRNA-seq and Bulk RNA-seq to investigate the transcriptional heterogeneity between Spindle-shaped USCs (SS-USCs) and Rice-shaped USCs (RS-USCs). Additionally, rat fatty Liver transplantation (LT) model, mouse fatty liver IRI model, and Steatotic Hepatocyte Hypoxia-Reoxygenation (SHP-HR) model were constructed. Extracellular vesicles derived from SS-USCs and RS-USCs were isolated and subjected to mass spectrometry analysis. The therapeutic effects of Spindle-shaped USCs Exosomes (SS-USCs-Exo) and Rice-shaped USCs Exosomes (RS-USCs-Exo) were explored, elucidating their potential mechanisms in inhibiting ferroptosis and alleviating IRI. Results Multiple omics analyses confirmed that SS-USCs possess strong tissue repair and antioxidant capabilities, while RS-USCs have the potential to differentiate towards specific directions such as the kidney, nervous system, and skeletal system, particularly showing great application potential in renal system reconstruction. Further experiments demonstrated in vivo and in vitro models confirming that SS-USCs and SS-USCs-Exo significantly inhibit ferroptosis and alleviate severe fatty liver IRI, whereas the effects of RS-USCs/RS-USCs-Exo are less pronounced. Analysis comparing the proteomic differences between SS-USCs-Exo and RS-USCs-Exo revealed that SS-USCs-Exo primarily inhibit ferroptosis and improve cellular viability by secreting exosomes containing Glutathione Peroxidase 4 (GPX4) protein. This highlights the most suitable cell subtype for treating severe fatty liver IRI. Conclusions SS-USCs possess strong tissue repair and antioxidant capabilities, primarily alleviating ferroptosis in the donor liver of fatty liver through the presence of GPX4 protein in their exosomes. This highlights SS-USCs as the most appropriate cell subtype for treating severe fatty liver IRI.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03572-5
Objective In recent years, cell therapy has emerged as a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cell (MSC) differentiation necessary to form such treatment have not been clarified. Methods In this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSC (S0) and four induced stage (S1–S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). Results We found that the number of differentially expressed lncRNAs and mRNAs trended downwards during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signalling pathway, MAPK signalling pathway, HIPPO signalling pathway, PI3K–Akt signalling pathway, and p53 signalling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA CTBP1-AS2 with PROX1 and the lncRNAs AC009014.3 and GS1-72M22.1 with JARID2 mRNA was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs: XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells. Conclusion In this study, HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signalling pathways. The lncRNAs AC009014.3, Gs1-72m21.1, and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalogue for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025171
Obesity-induced metabolic inflammation is a key driver of chronic kidney disease (CKD), with immune dysregulation, particularly among lymphocytes, contributing to early disease pathology. To explore the role of apolipoprotein A4 (Apoa4) in regulating immune cell metabolism and function, we establish high-fat diet-induced obese (DIO) models using wild-type and Apoa4-knockout (KO) mice. KO mice exhibit exacerbated insulin resistance and renal lipid accumulation. Single-cell RNA sequencing reveals that Apoa4 deletion remodeled the renal immune-metabolic landscape. This remodeling broadly compromises the immune functions of T, NK, and B cells, even as it expands the proportions of cytotoxic Gzma+ NK cells and Derl3+ plasma cells. Mechanistically, Apoa4 deletion aggravates metabolic dysregulation and oxidative stress and downregulates the expression levels of key effector genes, including Ifng and Il1b. Furthermore, the regulatory network activities of key transcription factors, such as Lef1 and Runx3 in Cd8+ T cells; Irf8, T-bet, and Eomes in NK cells; and Tcf4, Lmo2, and Xbp1 in B cells, are perturbed. CellChat analysis predicts disruptions in pro-inflammatory (IFN-II and IL-1), immunoregulatory (FASLG), and metabolic regulatory (ENHO and ANGPTL) signaling, alongside enhanced IL-2-mediated suppression. These findings are corroborated by flow cytometry, immunofluorescence staining, and qPCR. Our results establish Apoa4 as a crucial regulator of lymphocyte metabolic and immune homeostasis in the early stages of obesity-associated CKD.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025193
Arsenic, a toxic metalloid, exists in organic or inorganic states within the Earth’s seawater, river water, soil, atmosphere, food sources, and diverse biological tissues [1]. It poses a threat to the health of hundreds of millions of people globally [2]. Arsenic exposure has toxic effects on the cardiovascular system of organisms, thus endangering human health [3]. Research has indicated that the harmful effect of arsenic exposure on the heart is associated with abnormal calcium handling in myocardial cells [4]. The cardiac ryanodine receptor type 2 (RyR2) is a primary channel involved in the surface of the endoplasmic reticulum in cardiac myocytes that regulates the release of Ca2+ during the systolic phase [5]. The integrity of its function is crucial for maintaining calcium homeostasis in cardiac myocytes. However, when myocardial tissue is damaged and undergoes pathological changes, the spatial structure of the RyR2 protein becomes unstable and becomes excessively activated, thereby triggering Ca2+ leakage [6]. Dantrolene (Dan), which serves as a stabilizer of RyR1, is frequently employed in clinical settings for the treatment of malignant hyperpyrexia and relieves spastic muscle tension [7]. Previous studies have demonstrated that dantrolene also has a stabilizing effect on RyR2 [8]. Research has shown that dantrolene can prevent calcium leakage in myocardial cells by stabilizing the tertiary structure of the RyR2 protein and thereby inhibiting the pathological hyperactivity of RyR2 [9]. Therefore, this study hypothesizes that dantrolene, by virtue of this stabilizing effect, can alleviate myocardial injury caused by arsenic exposure to some extent and plays a role in protecting cardiac function. For this purpose, we established an arsenic exposure model and a Dan intervention arsenic exposure model to verify the protective effect of Dan on the myocardial tissue and cardiac function of arsenic-exposed rats.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025169
AXL, a member of the TAM (Tyro3, AXL, and Mertk) subfamily of RTKs, is abundantly expressed in lung tissue and has been implicated in viral infections and lung injury. PROS1, one of the ligands known to activate AXL, functions as an immunomodulator in many diseases. However, the role of PROS1/AXL signaling in influenza A virus (IAV) infection and infection-induced lung injury is largely unknown. In this study, we find that the exogenous administration of PROS1 mitigates lung injury and protects mice from lethal infection by IAVs through the activation of AXL. PROS1 induces the phosphorylation of AXL, which in turn recruits Gab1 and p85, a regulatory subunit of PI3K, to form a complex that activates Gab1 and its downstream PI3K/AKT/mTOR in alveolar macrophages. Gab1 knockdown in vivo, or LY294002 (a PI3K inhibitor), abolishes the PROS1/AXL-induced protective activity against lethal influenza infection in mice. We also show that PROS1/AXL signaling induces M2 polarization of alveolar macrophages through Gab1 activation both in vitro and in vivo. Gab1 knockdown inhibits M2 macrophage accumulation in IAV-infected lungs and attenuates the protective effect of PROS1. These results indicate that PROS1/AXL signaling can activate Gab1 in macrophages and induce macrophage polarization to an anti-inflammatory M2 phenotype, thereby eliciting protective activity against lethal infection with IAVs. These data also highlight the PROS1/AXL signal as a novel therapeutic target for IAV infection.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261627
Machine vision technology (MVT) has emerged as a pivotal non-contact, high-efficiency, and low-cost sensing modality for the traditional Chinese medicinal materials (TCMM) industry. This review systematically examines MVT applications across the entire TCMM industrial chain, spanning seed quality evaluation and sorting, cultivation environment suitability analysis and zoning, plant growth monitoring and field management, harvesting decision-making, primary processing control, and product quality assessment. By integrating conventional visual imaging with multi-source spectral imaging and employing both traditional machine learning and deep learning algorithms, MVT has substantially enhanced production intelligence and quality control capabilities. Nevertheless, persistent challenges impede industrial-scale adoption: technological fragmentation, data silos, lab-bound models with poor field generalizability, and prohibitive implementation costs. Guided by China's 'Artificial Intelligence Plus' strategy, this paper proposes strategic directions including establishing intelligent agent systems covering the full industrial chain, creating collaborative data resource ecosystems, developing lightweight adaptive algorithm models, and innovating inclusive business models. These measures aim to promote deep integration and large-scale application of MVT in the TCMM industry, providing technical support for intelligent, high-quality development of the entire value chain.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21314
BACKGROUND: Preliminary studies have demonstrated that Shaoyang Shenggu Fang can alleviate joint cartilage degeneration and promote cartilage repair, but its specific mechanism for alleviating knee osteoarthritis symptoms remains unclear. The Wnt/β-catenin pathway and oxidative stress play crucial roles in maintaining articular cartilage homeostasis. OBJECTIVE: To investigate the molecular mechanisms by which Shaoyang Shenggu Fang regulates the Wnt/β-catenin pathway to inhibit oxidative stress in cartilage and thereby delay cartilage aging in a rat model of knee osteoarthritis. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups: a blank control group, a model group, a Western medicine group, and a Chinese medicine group. Animal models of knee osteoarthritis were established in all groups except for the blank control group by transecting the anterior cruciate ligament and resecting the anterior horn of the medial meniscus. After 28 days of modeling, the Chinese medicine group was administered concentrated Shaoyang Shenggu Fang at a dose of 16 g/(kg·d) by gavage, the Western medicine group received glucosamine hydrochloride solution at 4 mL/d, and the blank and model groups received the same volume of normal saline. After 4 weeks, hematoxylin-eosin staining and Safranin O-fast green staining were used to observe the degree of cartilage damage and degeneration. ELISA was used to detect serum levels of inflammatory factors and oxidative stress indicators. Western blot was used to detect the expression of p21Cip1, p16INK4a, and Wnt signaling pathway-related proteins in knee cartilage. RESULTS AND CONCLUSION: Compared with the model group, the Western medicine and Chinese medicine groups showed significant improvement in cartilage defects, thinning of the cartilage layer, and decreased density, with significantly lower Mankin scores (P < 0.05). Compared with the model group, serum levels of interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased in the Western medicine and Chinese medicine groups (P < 0.05), while superoxide dismutase and glutathione peroxidase levels were increased and malondialdehyde concentration was decreased (all P < 0.05). In the Chinese medicine group, the expression levels of p21Cip1, p16INK4a, and Wnt5a proteins were significantly decreased (P < 0.05 and P < 0.01), β-catenin and C-Myc protein expression levels were decreased (P < 0.05), and glycogen synthase kinase-3β protein expression was significantly increased (P < 0.05). These results suggest that Shaoyang Shenggu Fang can significantly reduce inflammation and alleviate cartilage aging in rats with knee osteoarthritis, and the potential mechanism may be through regulation of the Wnt/β-catenin pathway to inhibit cartilage oxidative stress.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025171
Obesity-induced metabolic inflammation drives chronic kidney disease (CKD), with lymphocyte dysregulation contributing to early pathology. We established high-fat diet-induced obese (DIO) models in wild-type and Apoa4-knockout (KO) mice to investigate apolipoprotein A4 (Apoa4) in immune-metabolic regulation. KO mice exhibited exacerbated insulin resistance and renal lipid accumulation. Single-cell RNA sequencing (scRNA-seq) of renal immune cells revealed that Apoa4 deletion remodeled the immune-metabolic landscape, compromising T, NK, and B cell functions while expanding cytotoxic Gzma+ NK cells and Derl3+ plasma cells. Mechanistically, Apoa4 deletion aggravated metabolic dysregulation and oxidative stress, downregulating effector genes including Ifng and Il1b. Transcription factor regulatory networks were perturbed: Lef1 and Runx3 in Cd8+ T cells; Irf8, T-bet, and Eomes in NK cells; and Tcf4, Lmo2, and Xbp1 in B cells. CellChat predicted disrupted pro-inflammatory (IFN-II, IL-1), immunoregulatory (FASLG), and metabolic (ENHO, ANGPTL) signaling, with enhanced IL-2-mediated suppression. Flow cytometry, immunofluorescence, and qPCR validated these findings. Sequencing depth averaged 278,276 reads/cell (WT) and 197,768 reads/cell (KO), ensuring robust detection of low-abundance transcripts despite modest cell capture. Apoa4 is a critical regulator of lymphocyte metabolic and immune homeostasis in early obesity-associated CKD.