Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04378-3
Background Myocardial infarction (MI) is a severe disease that often associated with impaired angiogenesis and increased myocardial apoptosis. Mesenchymal stromal cells (MSCs) have been a promising candidate for treating myocardial infarction. However, functional heterogeneity of MSCs leads to inconsistent therapeutic efficiency and the current MSCs-based therapy lacks the concept and implementation of precision medicine. In this study, we compared the cardioprotective effect of UCMSCs and ADMSCs targeting the angiogenesis in a mouse MI model and screened out optimum MSCs candidate for precise clinical application. Methods The gene expression profiles of UCMSCs and ADMSCs were investigated through RNA sequencing analysis. To compare their angiogenic potential, we performed tube formation assay, Matrigel plug assays, and aortic ring assay, and analyzed pro-angiogenic genes via qPCR. Subsequently, UCMSCs and ADMSCs were respectively injected into myocardium after MI surgery in mice. On day 28 post-MI, echocardiography was performed to assess cardiac function. Histological analysis was performed to assess MSCs retention, angiogenesis, and myocardial apoptosis. Additionally, the anti-apoptosis effects mediated by MSCs were further evaluated using flow cytometry in hypoxia H9C2 and HL-1 cells. Results The RNA sequencing analysis revealed differences in gene expression related to angiogenesis and apoptosis pathways between UCMSCs and ADMSCs. UCMSCs presented greater pro-angiogenesis activity than ADMSCs in vitro and in vivo. Both of UCMSCs and ADMSCs improved cardiac function, decreased infarction area and inhibited cardiomyocyte apoptosis while promoting angiogenesis post-MI in mice. Notably, ADMSCs exerted a better cardioprotective function than UCMSCs and stronger anti-apoptotic effect on residual cardiomyocytes.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026039
Patients with peripheral artery disease (PAD) commonly experience chronic limb-threatening ischemia (CLTI) in the end stage, leading to severe functional impairment of the limbs, amputation, and even death. Among the various disease factors contributing to PAD, diabetes is significantly associated with PAD risk, leading to more severe symptoms and a poorer prognosis. Promoting angiogenesis at ischemic sites and improving blood flow are key to the recovery of limbs from ischemic injury. Angiogenic therapies based on cells and small-molecule drugs are considered important and promising strategies. Cell-based therapies can be classified based on cell source into allogeneic therapies and autologous therapies. Autologous cells offer the advantage of not requiring immunosuppression but may be limited by factors such as cell unavailability and scarcity due to autologous factors. Allogeneic cells, while offering a more abundant cell source, present drawbacks, including immune incompatibility and ethical concerns, which restrict their application. Small chemical molecules offer advantages such as convenience, low cost, ease of synthesis and storage, and rapid action without the need for introducing exogenous genes. They circumvent the high costs associated with cell therapies and potential side effects from allogeneic cell transplantation, holding significant promise and potential in both biomedical research and clinical applications. Fibroblasts are a cell type with functional and transcriptional heterogeneity and cellular fate plasticity, making them a promising source of seed cells for clinical tissue and organ repair and regeneration. Small molecules have become recognized as crucial tools for the induction of cellular reprogramming. In our laboratory’s previous research, a novel small chemical molecule probe, CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl)piperazin-1-yl)styryl)-1-methylpyridin-1-ium iodide), was identified as an inhibitor of prolyl-4-hydroxylase 2 (PHD2). CPP induces the differentiation of cultured human dermal fibroblasts into vascular endothelial cells (VECs) via the PHD2/hypoxia-inducible factor-1α/hairy-related transcription factor 1 (PHD2/HIF1α/HEY1) signaling pathway. The differentiated VECs exhibited therapeutic efficacy in treating lower limb ischemia in mice, indicating that CPP holds promise as a therapeutic candidate for limb ischemia. In this study, we aimed to investigate the capability of CPP to directly induce angiogenesis in vivo under conditions of vascular injury. Critical limb ischemia (CLI) occurs at the end stage of PAD. To evaluate the in situ therapeutic effects of CPP on CLI, a CLI model was established using C57BL/6 mice (Hubei Research Center of Laboratory Animals, Wuhan, China). CPP was synthesized and provided by the laboratory of Professor Baoxiang Zhao at Shandong University (Jinan, China). Following surgery, continuous subcutaneous multipoint injections of CPP were administered for 14 d to mimic localized drug treatment (Figure 1A). Laser speckle blood flow imaging was used to assess lower limb perfusion on days 0, 7, and 14 (Figure 1B, upper panel). The results showed that by day 7 post-surgery, both CPP concentrations significantly enhanced perfusion in the ischemic limb compared to the control group. From days 7 to 14, perfusion changes in both CPP-treated groups plateaued. Meanwhile, the control group showed increased perfusion. Throughout the treatment period, no significant differences were observed between the 1 and 10 mg/kg/day CPP treatment groups (Figure 1C,D). On day 14, the capillary density in the skin and muscle was significantly higher in the 1 mg/kg/day CPP group than in the control group. Although the 10 mg/kg/day group had a slightly higher density than the control, the difference was not statistically significant (Figure 1E–G). In addition, the organ toxicity
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025093
YY1 is a crucial transcription factor and plays significant roles in biological processes. However, the mechanisms of YY1 action in ischemia-reperfusion injury and its regulatory role in ferroptosis have not been extensively studied. This study aims to elucidate the molecular mechanism by which NEDD4L-mediated degradation of YY1 through ubiquitination suppresses SLC7A11 transcription, leading to the promotion of cellular ferroptosis and exacerbation of hepatic ischemia-reperfusion injury (IRI), via the integration of multiple omics sequencing datasets. An IRI-I/R mouse model is established, followed by proteomic sequencing to identify proteins that are differentially expressed during IRI. The altered expression of YY1 is validated, and in vivo and in vitro experiments are used to assess its impact on IRI damage. The E3 ligase NEDD4L, which regulates YY1 ubiquitination, is identified and validated via the UbiBrowser 2.0 database. The ubiquitination types of YY1 and its sites are screened and confirmed through in vitro experiments. Transcriptional sequencing of YY1-overexpressing cell lines is conducted to analyze the involvement of the downstream transcription factor SLC7A11 in IRI, followed by validation of its regulatory role. The results show that YY1 is downregulated in liver tissues during IRI and is expressed primarily in liver cells. YY1 overexpression alleviates liver tissue and liver cell IRI both in vitro and in vivo. Upregulation of E3 ligase expression during IRI promotes the K63-linked ubiquitination of YY1 at the K339 site, leading to proteasomal degradation of YY1. RNA-seq analysis and experimental validation demonstrate that YY1 suppresses IRI-induced ferroptosis via the transcriptional regulation of downstream target genes. YY1 positively regulates SLC7A11 transcription, inhibits IRI-induced ferroptosis and ameliorates liver injury. In summary, the E3 ubiquitin ligase NEDD4L facilitates YY1 protein degradation through ubiquitination, suppressing the transcription of the ferroptosis inhibitor SLC7A11, thus promoting IRI-related ferroptosis and exacerbating liver injury.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026039
Peripheral artery disease (PAD) often progresses to chronic limb-threatening ischemia (CLTI), leading to severe limb dysfunction and amputation. Angiogenic therapies using small molecules offer advantages over cell-based approaches. Here, we investigated the in vivo angiogenic effects of CPP, a small chemical molecule previously shown to induce differentiation of human dermal fibroblasts into vascular endothelial cells via the PHD2/HIF1α/HEY1 pathway. In a mouse model of critical limb ischemia (CLI), subcutaneous multipoint injections of CPP (1 or 10 mg/kg/day) for 14 days significantly enhanced blood perfusion in ischemic limbs by day 7, with the 1 mg/kg dose increasing capillary density in skin and muscle by day 14. High-dose CPP showed no organ toxicity. In diabetic db/db mice, intraperitoneal CPP (1 or 5 mg/kg/day) for 30 days restored capillary density in skin and gastrocnemius muscle, counteracting diabetes-induced vascular rarefaction. These findings demonstrate that CPP promotes in situ angiogenesis and perfusion recovery in ischemic and diabetic conditions, highlighting its potential as a therapeutic agent for PAD.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21299
BACKGROUND: Neurogenic heterotopic ossification frequently occurs within 1 to 3 months following spinal cord injury or traumatic brain injury, characterized by abnormal bone formation in periarticular soft tissues. The precise pathogenesis remains unclear, underscoring the urgent need for systematic research to inform clinical management. OBJECTIVE: To summarize recent advances in animal models of neurogenic heterotopic ossification and elucidate its underlying mechanisms, with a particular focus on the pathological differentiation of osteogenic precursor cells, remodeling of the local tissue microenvironment, and the interplay between neural regulation and neurogenic heterotopic ossification formation. METHODS: PubMed, CNKI, and SinoMed were searched from inception to January 2025. Chinese search terms included 'neurogenic heterotopic ossification, spinal cord injury, traumatic brain injury, heterotopic ossification'; English search terms included 'Neurogenic Heterotopic Ossification, spinal cord injury, Traumatic brain injury, ossification, heterotopic, Central nervous system'. Literature related to animal models and mechanisms of neurogenic heterotopic ossification was included to summarize key pathogenic processes. RESULTS AND CONCLUSION: The recruitment and aberrant osteogenic differentiation of osteogenic precursor cells (mainly fibro-adipogenic progenitors) are regulated by local microenvironmental factors such as hypoxia, inflammation, and angiogenesis. Neurotrophic factors, calcitonin gene-related peptide, and substance P promote aberrant ossification through neuro-immune interactions. Future research should construct a systematic molecular map, explore core signaling pathways, and develop novel targeted interventions to achieve early identification and individualized treatment of neurogenic heterotopic ossification, thereby improving patient outcomes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21414
BACKGROUND: Transforaminal lumbar interbody fusion is one of the main surgical methods for treating degenerative lumbar diseases such as lumbar disc herniation, lumbar spinal stenosis, and lumbar spondylolisthesis. Hidden blood loss refers to the concealed loss of blood volume in patients, which is often overlooked by people. OBJECTIVE: To evaluate the perioperative blood loss during transforaminal lumbar interbody fusion using a new method, calculate the hidden blood loss based on the new method, and analyze its risk factors. METHODS: The medical records of 93 patients with lumbar degenerative diseases (lumbar spinal stenosis, lumbar disc herniation, and lumbar spondylolisthesis) who were hospitalized in the Department of Spine Surgery of Second Affiliated Hospital of Soochow University from October 2023 to October 2024 were retrospectively analyzed. The general data of patients were collected, such as age, gender, height, body mass, body mass index, and whether they had hypertension and diabetes; surgical data, such as the number of surgical segments, operation time, and American Society of Anesthesiologists anesthesia grade; laboratory tests, such as prothrombin time, activated partial thromboplastin time, international normalized ratio, platelet count, fibrinogen, and D-dimer level. Pearson or Spearman correlation analysis was used to explore the correlation between patient characteristics and postoperative hidden blood loss, and multivariate linear regression analysis was utilized to determine the independent risk factors for postoperative hidden blood loss. RESULTS AND CONCLUSION: (1) The average hidden blood loss calculated by the new method for transforaminal lumbar interbody fusion was (284.24±352.76) mL, accounting for 58.6% of total blood loss; while the traditional method calculated an average hidden blood loss of (165.77±339.89) mL, accounting for 34.15% of total blood loss, with a significant difference between the two (P < 0.05). (2) In univariate analysis, hidden blood loss was positively correlated with the number of segments (r=0.213, P=0.040) and operation time (r=0.210, P=0.043), and negatively correlated with platelet count (r=-0.324, P=0.018). (3) In multivariate linear regression analysis, decreased platelet count was an independent risk factor for hidden blood loss (P=0.016). (4) These findings suggest that the new method provides a more accurate estimation of hidden blood loss, and hidden blood loss is an important component of perioperative total blood loss; increased number of segments, prolonged operation time, and decreased platelet count are risk factors for hidden blood loss in transforaminal lumbar interbody fusion, with decreased platelet count being an independent risk factor.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21381
BACKGROUND: Currently, the biomechanical differences between cervical rotation manipulation and cervical rotation-traction manipulation for the treatment of cervical radiculopathy have not been systematically elucidated. OBJECTIVE: To compare the biomechanical differences between cervical rotation manipulation and cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy caused by cervical disc herniation, and to provide a basis for the rational selection of manipulation in clinical practice. METHODS: A 27-year-old Asian male patient with cervical spondylotic radiculopathy caused by left posterior cervical disc herniation compressing the nerve root was recruited. The CT scan data of the skull and cervical spine were extracted to construct a finite element model of the head and full cervical spine. After model validation, the key parameters of cervical rotation manipulation and rotation-traction manipulation were loaded into the model, and the effects of the two manipulations on the stress of intervertebral disc, facet joints, spinal cord and nerve roots, disc displacement, and intervertebral foramen volume were compared. RESULTS AND CONCLUSION: (1) In terms of Von-Mise stress, the maximum stresses of cervical rotation manipulation on the annulus fibrosus, nucleus pulposus, and facet joints were 0.903, 0.139, and 2.186 MPa, respectively, which were significantly increased by 18%, 13%, and 30% compared with rotation-traction manipulation (0.765, 0.123, 1.682 MPa); while the maximum stress on the spinal cord and nerve roots was 2.547 MPa, which was 7% lower than that of rotation-traction manipulation (2.738 MPa). (2) In terms of displacement, the maximum forward displacement of the herniated side of the intervertebral disc by cervical rotation manipulation was 1.067 mm, which was 11.1% more than that of rotation-traction manipulation (0.960 mm). (3) In terms of intervertebral foramen volume changes, both manipulations increased the volume after implementation compared with before, with rotation manipulation increasing by 15.5% and rotation-traction manipulation increasing by 19.8%, the latter being more effective in expanding the intervertebral foramen volume. (4) It is suggested that cervical rotation manipulation has advantages in promoting the forward displacement of the herniated disc, but it produces higher stress on the intervertebral disc and facet joints, which may easily cause disc damage; rotation-traction manipulation will cause slightly higher stress on the spinal cord and nerve roots, but it can more effectively expand the intervertebral foramen volume and reduce the risk of disc structural damage. In clinical treatment, the advantages and disadvantages of the two manipulations should be carefully weighed and selected based on the patient's specific condition.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21368
BACKGROUND: In the process of applying artificial intelligence to orthopedic imaging, the technical system exhibits a clear hierarchical structure: machine learning is the primary pathway to achieving artificial intelligence, while convolutional neural networks, a branch of deep learning, have become the core model for image analysis. Clarifying this technical lineage helps to systematically review the research evolution and trends in this field through bibliometric methods. OBJECTIVE: To comprehensively analyze the research status and development trends of artificial intelligence in the field of orthopedic imaging based on bibliometric methods, providing ideas and methods for future research. METHODS: By searching the Web of Science Core Collection database, with keywords including artificial intelligence, deep learning, convolutional neural network, and orthopedic imaging, a total of 460 relevant English articles published between 2015 and 2025 were included. CiteSpace 6.4.R1, VOSviewer 1.6.20, and Bibliometrix software were used to conduct visual analysis from dimensions such as annual publication volume, country and institution distribution, author collaboration network, keyword co-occurrence, clustering, and burst word evolution. RESULTS AND CONCLUSION: (1) The number of publications in this field has steadily increased over the past 10 years. (2) China and the United States are the main publishing countries, with the United States showing outstanding performance in citation frequency and international collaboration influence; Sichuan University, the University of California, and Harvard University constitute a core collaborative institutional network. (3) Research hotspots mainly focus on bone age assessment, automated image segmentation, and the application of deep learning in fracture detection and osteoarthritis diagnosis. Related keywords such as bone age assessment, automated segmentation, and deep learning have continued to burst, indicating the evolutionary trajectory of research focus. (4) The research enthusiasm for artificial intelligence in orthopedic imaging continues to rise, with intelligent segmentation, disease grading, and multimodal data fusion being important future research directions. (5) This paper systematically reviews the field from a macro perspective, providing a reference for promoting the deep integration of artificial intelligence technology in orthopedic clinical practice; through bibliometric analysis, it constructs a knowledge map of the application of artificial intelligence in orthopedic imaging, systematically summarizes the research status and hotspots in this field, and aims to provide reference and guidance for future related research.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21587
BACKGROUND: Modern medicine often uses benzodiazepines for the treatment of insomnia complicated by anxiety; however, long-term use can lead to drug dependence and adverse reactions. Traditional Chinese medicine, based on syndrome differentiation and holistic treatment, demonstrates definite efficacy and high safety, offering multi-pathway and multi-target comprehensive effects, thereby providing new ideas and directions for the treatment of this condition. OBJECTIVE: To investigate the effects of Yuping Shen’an Granules on hippocampal neuronal autophagy in mice with insomnia and anxiety via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. METHODS: Ultra-high performance liquid chromatography-tandem mass spectrometry was used to identify the components of Yuping Shen’an Granules, and network pharmacology was used to predict key pathways. Ninety male C57BL/6J mice were randomly divided into normal group, model group, low-, medium-, and high-dose Yuping Shen’an Granules groups [3.125, 6.25, 12.5 g/(kg·d)], eszopiclone group [0.06 mg/(kg·d)], recovery-model group, recovery-model + PI3K inhibitor group [10 mg/(kg·d)], recovery-Yuping Shen’an [12.5 g/(kg·d)] + inhibitor group [10 mg/(kg·d)], with 10 mice per group. Except for the normal group, all groups were exposed to chronic unpredictable mild stress for 14 days and intraperitoneal injection of para-chlorophenylalanine for 4 days to establish a mouse model of insomnia with anxiety. Behavioral assessments included open field and pentobarbital sodium sleep tests; hematoxylin-eosin and Nissl staining were used to observe hippocampal pathological changes; enzyme-linked immunosorbent assay was used to detect levels of 5-hydroxytryptamine, γ-aminobutyric acid, dopamine, and norepinephrine; immunofluorescence was used to detect microtubule-associated protein light chain 3B expression; western blotting was used to detect PI3K/AKT/mTOR pathway-related proteins, autophagy-related proteins (P62, Beclin-1, microtubule-associated protein light chain 3B), and 5-hydroxytryptamine receptor 1A protein expression; transmission electron microscopy was used to observe the number of autophagosomes. RESULTS AND CONCLUSION: ① Ultra-high performance liquid chromatography-tandem mass spectrometry identified 2,276 components of Yuping Shen’an Granules, and 35 main components were screened out; ② Network pharmacology analysis showed that the PI3K/AKT/mTOR pathway was a potential target; ③ Compared with the normal group, the model group showed increased exploratory behavior, prolonged sleep latency (P < 0.01), significant hippocampal neuronal damage, decreased levels of 5-hydroxytryptamine and γ-aminobutyric acid, increased levels of dopamine and norepinephrine (P < 0.01), upregulated microtubule-associated protein light chain 3B fluorescence and protein expression (P < 0.01), downregulated phosphorylated PI3K/AKT/mTOR, P62, and 5-hydroxytryptamine receptor 1A expression, upregulated Beclin-1 and microtubule-associated protein light chain 3B expression (P < 0.05), and increased number of autophagosomes; ④ Compared with the model group, the recovery-model + inhibitor group showed aggravated damage, while the high-dose Yuping Shen’an Granules group and recovery-Yuping Shen’an + inhibitor group significantly reversed the above changes, improving behavioral indicators, alleviating neuronal damage, increasing 5-hydroxytryptamine and γ-aminobutyric acid levels, decreasing dopamine and norepinephrine levels (P < 0.05), and reversing autophagy-related protein expression (P < 0.05), with reduced autophagosomes. These results indicate that Yuping Shen’an Granules improve insomnia with anxiety symptoms by activating the PI3K/AKT/mTOR pathway, regulating neurotransmitter balance, and inhibiting excessive autophagy in hippocampal neurons.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025093
Hepatic ischemia-reperfusion injury (IRI) remains a major clinical challenge in liver transplantation and resection, with ferroptosis emerging as a critical cell death modality. This study investigates the mechanistic role of the transcription factor YY1 and its regulation by the E3 ubiquitin ligase NEDD4L in hepatic IRI. Using an established mouse IRI model and proteomic sequencing, YY1 was identified as significantly downregulated in injured liver tissues, predominantly in hepatocytes. In vivo and in vitro overexpression of YY1 attenuated IRI-induced liver damage and ferroptosis. Mechanistically, NEDD4L, an E3 ligase upregulated during IRI, was found to interact with YY1 and catalyze K63-linked ubiquitination at lysine 339, leading to proteasomal degradation of YY1. Transcriptomic analysis and validation revealed that YY1 positively regulates the transcription of SLC7A11, a key ferroptosis inhibitor. Consequently, NEDD4L-mediated degradation of YY1 suppresses SLC7A11 expression, promoting ferroptosis and exacerbating hepatic injury. These findings delineate a novel NEDD4L-YY1-SLC7A11 axis in IRI pathogenesis, offering potential therapeutic targets. The study acknowledges limitations, including the need for validation in human liver samples and further in vivo confirmation of some in vitro findings. This research provides a mechanistic framework for developing targeted interventions against hepatic IRI.