Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03856-4
Mesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03938-3
Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026002
The newly discovered midnolin-proteasome pathway is a unique ubiquitin-independent mechanism for degrading nuclear proteins, which is crucial for maintaining cellular protein homeostasis. The Catch domain of midnolin is essential for substrate recognition and binding, yet the underlying mechanism for its broad substrate specificity remains elusive. Transcription factor IRF4, essential for the functions of B and T cells, is a substrate of midnolin. This study presents comprehensive biochemical and structural analyses of the human midnolin Catch domain in complexes with both wild-type and mutant IRF4 peptides. The crystal structure of the Catch-IRF4 complex reveals that the Catch domain creates a substrate-binding groove at the interface of the Catch1 and Catch2 subdomains, recognizing and binding to the 215-QVTGTFYAC-223 sequence motif of IRF4. The binding motif of IRF4 forms a β-strand that is embedded into the substrate-binding groove, resulting in an antiparallel five-stranded β-sheet. The interactions between the IRF4 peptide and the Catch domain are predominantly hydrophobic and exhibit high spatial complementarity. Additionally, the biochemical, modeling and structural data indicate that the V2 and A8 positions of the IRF4 sequence motif can be substituted with other hydrophobic or small polar residues (G/A/V/L/I/M/P/F/Y/C/S/T), but not with large polar and charged residues (D/N/E/Q/H/K/R). The G4 position can be replaced by Ser, while the F6 position can be substituted with Tyr. These results suggest that the Catch domain can recognize and bind to a variety of substrates containing the sequence motif x[G/A/V/L/I/M/P/F/Y/C/S/T]x[G/S]x[F/Y]x[G/A/V/L/I/M/P/F/Y/C/S/T]x or briefly the G/SxF/Y motif (where x represents polar residues) located in an unstructured or loop region on the protein surface, and the hydrophobic interactions and spatial complementarity between the binding motifs of substrates and the Catch domain govern the substrate specificity. Collectively, these findings elucidate the molecular basis for midnolin’s broad substrate specificity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025081
Resident CD24+LCN2+ liver progenitor cells (LPCs) reportedly contribute to the expanding ductular reaction and macrophage-mediated inflammation associated with chronic liver damage. Both ductular reactions and macrophage-driven inflammation are associated with liver fibrosis and injury in various mouse liver disorders. This study aims to investigate the molecular phenotypes of LPCs and their regulatory mechanisms in humans with non-alcoholic steatohepatitis (NASH). Single-cell RNA sequencing (scRNA-seq) datasets are used to characterize the status and molecular phenotypes of LPCs in clinical NASH samples. To elucidate the regulatory mechanisms of LPCs, CellChat and NicheNet are employed to assess cell-cell communication between LPCs and other cell types. The findings are validated using RNA sequencing datasets associated with NASH progression, NASH mouse models (CDAHFD and HFD), and human NASH liver samples. Results show that resident CD24+LCN2+ LPCs are identified and found to be significantly enriched in NASH patients. Cell communication analyses predict strong interactions between LPCs and proinflammatory macrophage subtypes. Additionally, in NASH, the liver recruits peripheral blood mononuclear cell (PBMC)-derived macrophages and polarizes them into proinflammatory subtypes. The macrophage subtype MP-2 is identified as the primary recipient of LPC-derived signals, exhibiting marked hyperactivation of the NF-κB pathway and a strong association with liver fibrosis. Finally, the MP-2 markers COL10A1 and TPPP3 are characterized and validated. In summary, this study reveals that resident CD24+LCN2+ LPCs are activated in NASH and contribute to fibrosis progression by promoting the activation of the proinflammatory COL10A1+TPPP3+ macrophage subtype.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025242
Drug-induced liver injury (DILI) caused by anti-tuberculosis drugs is a serious clinical problem that can lead to acute liver failure and even death. Current diagnosis relies on lagged indicators such as serum transaminase levels, which rise only 48–72 hours after liver injury. This study is the first to systematically analyze the microRNA expression profile of serum exosomes in patients with anti-tuberculosis drug-induced liver injury (TB-DILI) to discover early diagnostic markers. A total of 12 tuberculosis patients and 6 normal controls were included. Serum exosomes were isolated and characterized, and small RNA sequencing identified 701 miRNAs, with 128 differentially expressed between TB-DILI and TB groups. Notably, miR-122-5p was upregulated and has shown early warning value. Target gene prediction and enrichment analysis revealed involvement in GTPase activity regulation, cell migration, and BMP signaling. These findings suggest that exosomal miRNAs, particularly miR-122-5p, may serve as early diagnostic biomarkers for TB-DILI.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025197
Acute myeloid leukemia (AML) is a clinically aggressive hematologic malignancy characterized by high relapse rates and treatment resistance, highlighting the need for novel biomarkers to improve clinical outcomes. In this study, we explore the roles of nuclear receptor-interacting protein 1 (NRIP1) in AML, focusing on its associations with tumor progression and immune infiltration. Analysis of public AML gene expression datasets reveals that NRIP1 expression is significantly increased in AML patients. Those with high NRIP1 expression have markedly shorter overall survival than those with low expression. Furthermore, NRIP1 expression is significantly associated with the infiltration of diverse immune cells, including B cells, dendritic cells, T cells, mast cells, eosinophils, and T helper cells, suggesting that NRIP1 may be a regulator of immune cell infiltration. Functional enrichment analysis indicates that NRIP1 and its interacting partners are involved in tumorigenesis, immune microenvironment remodeling, and metabolic reprogramming. Survival analysis confirms the prognostic value of NRIP1. Importantly, functional validation in AML cell lines confirms that NRIP1 knockdown suppresses proliferation and induces apoptosis. Our study identifies NRIP1 as a multifaceted regulator that promotes AML by driving tumor progression, regulating immune cell infiltration, and modulating ferroptosis, highlighting its role as a novel prognostic biomarker.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024024
Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024068
Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024186
Pyruvate dehydrogenase kinase 1 (PDK1) is a new therapeutic target that is dysregulated in multiple tumors. This study aims to explore the potential role and regulatory mechanism of PDK1 in epithelial ovarian cancer (EOC). We detect PDK1 expression in EOC tissues and cells using qRT-PCR and western blot analysis, and the effects of PDK1 on EOC cell malignant behaviors are explored. RNA sequencing analyses are performed to explore the differentially expressed genes in PDK1-silenced EOC cells. Furthermore, tumor-bearing mouse models are established to assess the impacts of PDK1 and BGN on EOC tumor growth and metastasis in vivo. The results show that PDK1 is upregulated in EOC tissues and cell lines. Biglycan (BGN) is downregulated in PDK1-silenced EOC cells, and its expression is positively correlated with PDK1 levels in EOC tissues. PDK1 depletion inhibits EOC cell proliferation, migration and invasion. Mechanistically, PDK1 and BGN are colocalized in the cytoplasm of EOC cells and interact with each other. PDK1 positively regulates BGN expression by enhancing BGN mRNA stability. BGN overexpression partially reverses the anti-tumor effects of PDK1 depletion on EOC cell malignant behaviors. PDK1 has also been revealed to upregulate BGN to activate the NF-κB oncogenic pathway in EOC cells. Additionally, PDK1 accelerates tumor growth and metastasis by modulating BGN expression. In conclusion, PDK1 functions as an oncogene, facilitating EOC progression by upregulating BGN and activating the NF-κB pathway. These findings may provide valuable biomarkers for the diagnosis and treatment of EOC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024056
Biological control of pests and pathogens has attracted much attention due to its green, safe and effective characteristics. However, it faces the dilemma of insignificant effects in large-scale applications. Therefore, an in-depth exploration of the metabolic potential of biocontrol fungi based on big omics data is crucial for a comprehensive and systematic understanding of the specific modes of action operated by various biocontrol fungi. This article analyzes the preferences for extracellular carbon and nitrogen source degradation, secondary metabolites (nonribosomal peptides, polyketide synthases) and their product characteristics and the conversion relationship between extracellular primary metabolism and intracellular secondary metabolism for eight different filamentous fungi with characteristics appropriate for the biological control of bacterial pathogens and phytopathogenic nematodes. Further clarification is provided that Paecilomyces lilacinus, encoding a large number of hydrolase enzymes capable of degrading pathogen protection barrier, can be directly applied in the field as a predatory biocontrol fungus, whereas Trichoderma, as an antibiosis-active biocontrol control fungus, can form dominant strains on preferred substrates and produce a large number of secondary metabolites to achieve antibacterial effects. By clarifying the levels of biological control achievable by different biocontrol fungi, we provide a theoretical foundation for their application to cropping habitats.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024181
MicroRNAs (miRNAs) have emerged as essential regulators that play important roles in the development of multiple systems. Recent studies have identified significant roles for miRNAs in the progression of cardiac hypertrophy. This study aims to investigate the effects of miR-133b-3p on angiotensin II (Ang II)-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Our experimental results reveal that miR-133b-3p expression is significantly decreased in both animal and cell models of cardiac hypertrophy induced by Ang II. Overexpression of miR-133b-3p reverses the hypertrophic manifestations and apoptosis induced by Ang II. Through bioinformatics analysis and dual-luciferase reporter assays, CDIP1 (cell death inducing p53 target 1) is identified as a direct target of miR-133b-3p, and the overexpression of miR-133b-3p reduces CDIP1 expression. Additionally, CDIP1 silencing suppresses cardiomyocyte hypertrophy and apoptosis induced by Ang II. In summary, these results suggest that miR-133b-3p may serve as a potential diagnostic marker for cardiac hypertrophy and that the upregulation of miR-133b-3p inhibits cardiac hypertrophy by targeting CDIP1.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024014
Intrahepatic cholangiocarcinoma (ICC) accounts for approximately 15% of primary liver cancers, and the incidence rate has been increasing in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to identify signature genes. The aim of this study is to screen the signature genes of ICC and find the potential target for the treatment of ICC. We find that UBA3 is highly expressed in ICC, and knockdown of UBA3 inhibits ICC proliferation, invasion and migration. Mechanistic experiments show that UBA3 promotes ICC proliferation, invasion and migration by affecting ANXA2 through the MAPK signaling pathway. UBA3 is a target of bufalin, and bufalin targeting UBA3 inhibits ICC development and progression through the MAPK signaling pathway. In conclusion, our study shows that bufalin inhibits ICC by targeting UBA3, which has emerged as a new biomarker and potential therapeutic target for ICC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024132
Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025242
Drug-induced liver injury (DILI) caused by anti-tuberculosis drugs is a serious clinical problem that can lead to acute liver failure and even death. Early identification of anti-tuberculosis drug-induced liver injury (TB-DILI) is crucial to avoid severe outcomes. Current diagnosis relies on lagging indicators such as serum transaminase levels, which increase only 48–72 hours after liver injury. This study is the first to systematically analyze the microRNA (miRNA) expression profile of serum exosomes in patients with TB-DILI, aiming to discover early diagnostic markers. Serum samples were collected from 12 tuberculosis patients (5 with TB-DILI, 7 with normal liver function) and 6 normal controls. Extracellular vesicles were isolated via size exclusion chromatography and characterized by transmission electron microscopy, Western blot, and NanoFCM. Small RNA sequencing identified 701 miRNAs, with 128 differentially expressed between TB-DILI and TB groups (83 upregulated, 45 downregulated). Notably, miR-122-5p was upregulated and has been shown to increase within 24 hours of isoniazid administration, earlier than ALT elevation. Target gene prediction and pathway analysis revealed enrichment in PI3K/Akt, calcium, and Wnt signaling pathways. Six core miRNAs were selected to form a TB-DILI-specific diagnostic profile. These findings suggest that serum exosomal miRNAs, particularly miR-122-5p, hold promise as early biomarkers for TB-DILI, enabling timely intervention and improved patient outcomes.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026002
The newly discovered midnolin-proteasome pathway is a unique ubiquitin-independent mechanism for degrading nuclear proteins, which is crucial for maintaining cellular protein homeostasis. The Catch domain of midnolin is essential for substrate recognition and binding, yet the underlying mechanism for its broad substrate specificity remains elusive. Transcription factor IRF4, essential for the functions of B and T cells, is a substrate of midnolin. This study presents comprehensive biochemical and structural analyses of the human midnolin Catch domain in complexes with both wild-type and mutant IRF4 peptides. The crystal structure of the Catch-IRF4 complex reveals that the Catch domain creates a substrate-binding groove at the interface of the Catch1 and Catch2 subdomains, recognizing and binding to the 215-QVTGTFYAC-223 sequence motif of IRF4. The binding motif of IRF4 forms a β-strand that is embedded into the substrate-binding groove, resulting in an antiparallel five-stranded β-sheet. The interactions between the IRF4 peptide and the Catch domain are predominantly hydrophobic and exhibit high spatial complementarity. Additionally, the biochemical, modeling and structural data indicate that the V2 and A8 positions of the IRF4 sequence motif can be substituted with other hydrophobic or small polar residues (G/A/V/L/I/M/P/F/Y/C/S/T), but not with large polar and charged residues (D/N/E/Q/H/K/R). The G4 position can be replaced by Ser, while the F6 position can be substituted with Tyr. These results suggest that the Catch domain can recognize and bind to a variety of substrates containing the sequence motif x[G/A/V/L/I/M/P/F/Y/C/S/T]x[G/S]x[F/Y]x[G/A/V/L/I/M/P/F/Y/C/S/T]x or briefly the G/SxF/Y motif (where x represents polar residues) located in an unstructured or loop region on the protein surface, and the hydrophobic interactions and spatial complementarity between the binding motifs of substrates and the Catch domain govern the substrate specificity. Collectively, these findings elucidate the molecular basis for midnolin’s broad substrate specificity.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21260
BACKGROUND: As a group of ubiquitous exogenous compounds in the environment, endocrine disrupting chemicals can interfere with endocrine system function and contribute to various diseases. In recent years, the correlation between exposure to endocrine disrupting chemicals and type 1 diabetes risk has become a research hotspot, but the exact underlying mechanisms remain unclear. OBJECTIVE: To review the research progress on the association between endocrine disrupting chemicals and type 1 diabetes in terms of epidemiological studies, animal experiments, and related mechanism studies. METHODS: The literature retrieval was conducted on CNKI and PubMed databases from January 2000 to January 2025 with the keywords of “endocrine disrupting chemicals; EDCs; type 1 diabetes; T1DM” in Chinese and English, respectively. A total of 55 articles were selected for the review. RESULTS AND CONCLUSION: Typical endocrine disrupting chemicals such as bisphenol A, pesticides and heavy metals can promote the development of type 1 diabetes through various pathways, including inducing immune dysregulation, activating oxidative stress, and epigenetic regulation. However, existing studies are limited by issues such as non-unified exposure assessment methods, an unclear dose-response relationship, and population heterogeneity. Future research should focus on identifying critical exposure windows and integrating multi-omics approaches to provide new strategies for the prevention of type 1 diabetes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21477
BACKGROUND: Hernandezine has shown promising therapeutic effects due to its anti-inflammatory bioactivity in diseases such as suppression of tumors, antiplatelet agglutination and diabetes. However, there are no basic studies on the effects and molecular mechanism of Hernandezine on macrophage phenotype and osteoclast activation. OBJECTIVE: To investigate the role of Hernandezine on the regulation of macrophage polarization, osteoclast activation and osteoporosis. METHODS: (1) Cellular experiments: RAW264.7 was used as macrophage model and divided into four groups: Control group, lipopolysaccharide group, lipopolysaccharide + 2.5 μmol/L Hernandezine group, lipopolysaccharide + 5 μmol/L Hernandezine group. Macrophage polarization was induced in the latter three groups using a complete medium supplemented with lipopolysaccharide. The two drug-treated groups received 2.5 and 5 μmol/L Hernandezine, respectively. RAW264.7 cells were induced toward osteoclast differentiation using a complete medium supplemented with nuclear factor κB receptor activator ligand. Macrophage polarization was assessed via qRT-PCR and immunofluorescence for inflammatory cytokine expression. The effects of Hernandezine on osteoclast differentiation were evaluated using qRT-PCR, tartrate-resistant acid phosphatase staining, and F-actin staining. (2) In vivo experiments: Twenty-four female C57BL/6J mice were randomly divided into four groups: sham operation, ovariectomy, ovariectomy + 5 mg/kg Hernandezine, and ovariectomy + 10 mg/kg Hernandezine. The latter three groups underwent bilateral ovariectomy to establish an osteoporosis model. The two drug-treated groups received intraperitoneal injections of Hernandezine at 5 or 10 mg/kg every two days post-surgery. After 8 weeks, femurs were collected for Micro-CT scanning, bone parameter analysis, and hematoxylin-eosin staining to evaluate bone loss. RESULTS AND CONCLUSION: Hernandezine inhibited lipopolysaccharide-induced pro-inflammatory gene expression in macrophages by downregulating the transcription of Toll-like receptor 4/nuclear factor κB signaling pathway-related genes, exhibiting a concentration-dependent effect, with 5 μmol/L showing more significant inhibition. Hernandezine also inhibited the expression of genes related to osteoclast activation and bone resorption, and suppressed osteoclast activation in vitro in a concentration-dependent manner. In vivo, Hernandezine reduced bone loss in estrogen-deficient osteoporotic mice, with the 10 mg/kg group showing better recovery. CONCLUSION: This study confirms that Hernandezine inhibits macrophage pro-inflammatory phenotype transformation and osteoclast activation by downregulating the Toll-like receptor 4/nuclear factor κB signaling pathway, and alleviates excessive bone loss in estrogen-deficient osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21519
BACKGROUND: Schatzker type II fractures often involve the posterolateral plateau, resulting in weakened bone strength, increased fixation challenges, and increased risk of postoperative collapse. Optimizing treatment strategies to balance stability and minimize trauma is urgently needed. OBJECTIVE: To evaluate the clinical efficacy of simple lateral L-shaped plate fixation for osteoporotic Schatzker type II tibial plateau fractures involving the posterolateral aspect, and to compare its biomechanical properties with those of lateral L-shaped plate combined with posterior T-shaped plate fixation using finite element analysis. METHODS: A retrospective analysis was conducted on 39 patients with osteoporotic Schatzker type II tibial plateau fractures involving the posterolateral aspect treated between January 2018 and December 2023 at the Department of Joint Surgery, The Second Affiliated Hospital of Soochow University. Patients were divided into L-shaped plate group (simple lateral L-shaped plate fixation, n=24) and combined group (lateral L-shaped plate combined with posterior T-shaped plate fixation, n=15). Clinical outcomes including operation time, intraoperative blood loss, bone mineral density, preoperative tibial plateau collapse, time from injury to surgery, postoperative radiological parameters (tibial plateau varus angle, posterior slope angle), knee range of motion, Hospital for Special Surgery score, and Lysholm score were compared between groups. Additionally, finite element models of Schatzker type II tibial plateau fractures were constructed based on CT data of a healthy adult male knee. Models were divided into non-osteoporotic group (A: simple L-shaped plate; B: L-shaped plate + T-shaped plate) and osteoporotic group (C: simple L-shaped plate; D: L-shaped plate + T-shaped plate). Under axial loads of 250, 500, and 750 N, overall displacement, tibial stress, and internal fixation stress were analyzed. RESULTS AND CONCLUSION: (1) Clinical results: There were no significant differences in age, sex, body mass index, bone mineral density, preoperative tibial plateau collapse, or time from injury to surgery between the two groups (P > 0.05). The L-shaped plate group had significantly shorter operation time and less intraoperative blood loss than the combined group (P < 0.0001). Immediate postoperative tibial plateau varus angle and posterior slope angle showed no significant differences between groups (P > 0.05). At final follow-up, the varus angle in the L-shaped plate group was smaller than that in the combined group (P=0.04), while the posterior slope angle still showed no significant difference (P > 0.05). At final follow-up, knee range of motion, Hospital for Special Surgery score, and Lysholm score showed no significant differences between groups (P > 0.05). (2) Finite element results: Under the same load, whether in non-osteoporotic or osteoporotic bone models, the use of T-shaped plate auxiliary fixation (groups B/D) exhibited superior performance in overall displacement and tibial and internal fixation stress compared with simple L-shaped plate fixation (groups A/C). (3) These findings suggest that for osteoporotic Schatzker type II fractures involving the posterolateral tibial plateau, simple lateral L-shaped plate fixation can achieve satisfactory reduction stability and functional recovery, with clinical outcomes comparable to double-plate technique. Finite element analysis indicates that double-plate fixation has better mechanical properties, but considering that simple lateral L-shaped plate fixation has significantly less surgical trauma and good clinical results, routine addition of posterior T-shaped plate is not necessary.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21577
BACKGROUND: Recent studies have shown that Chlorella possesses potential value in treating rheumatoid arthritis. The pathological progression of rheumatoid arthritis is closely associated with an imbalance in oxidative stress, abnormal macrophage polarization, aggressive activation of fibroblast-like synoviocytes, and disturbances in the vascular endothelial system. However, the optimization of extraction processes for peptides derived from Chlorella and their regulatory effects on key pathological links of rheumatoid arthritis remain to be systematically validated. OBJECTIVE: To optimize the extraction process of antioxidant peptides from Chlorella, clarify their antioxidant activity and biosafety, and explore their regulatory effects on pathological phenotypes of rheumatoid arthritis-related cells (RAW 264.7 mouse monocyte macrophage leukemia cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells), providing experimental evidence for the treatment of rheumatoid arthritis with Chlorella peptides. METHODS: (1) Chlorella peptide extract was prepared by bromelain enzymatic hydrolysis combined with phosphomolybdic acid precipitation. Using peptide yield as the evaluation index, the extraction process parameters were optimized by single-factor experiments, including solid-liquid ratio, enzymatic hydrolysis time, and reaction system pH. (2) The peptide content was determined by BCA method, antioxidant capacity was detected by ABTS method, and biosafety of peptides on RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells was evaluated by CCK-8 method. (3) An inflammatory model of RAW 264.7 cells induced by lipopolysaccharide was established. The effects of peptides on intracellular reactive oxygen species levels and M1/M2 polarization phenotypes were detected by DCFH-DA staining, flow cytometry, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (4) An activation model of fibroblast-like synoviocytes induced by tumor necrosis factor-alpha was established. The effects of peptides on migration, proliferation, invasion, and related gene expression of fibroblast-like synoviocytes were detected by wound healing assay, EdU proliferation assay, Transwell invasion assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (5) An abnormal activation model of human umbilical vein endothelial cells induced by vascular endothelial growth factor A was established. The effects of peptides on migration, tube formation, and expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes were detected by wound healing assay, Transwell assay, tube formation assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. RESULTS AND CONCLUSION: (1) The optimal extraction process for Chlorella peptides was solid-liquid ratio of 2:1 (g:100 mL), enzymatic hydrolysis time of 60 minutes, and reaction system pH of 6.5, yielding the highest peptide yield. (2) Chlorella peptides exhibited concentration-dependent antioxidant activity and showed no obvious toxicity to RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells in the concentration range of 1-10 μg/mL, indicating good biocompatibility. (3) Chlorella peptides dose-dependently inhibited lipopolysaccharide-induced reactive oxygen species generation in RAW 264.7 cells, downregulated M1 pro-inflammatory genes such as interleukin-1 beta and tumor necrosis factor-alpha, upregulated M2 anti-inflammatory genes such as interleukin-10 and arginase 1, and promoted macrophage polarization from M1 to M2 phenotype. (4) Chlorella peptides significantly inhibited tumor necrosis factor-alpha-induced migration, proliferation, and invasion of fibroblast-like synoviocytes, and downregulated the expression of interleukin-6, matrix metalloproteinase 13, tumor necrosis factor receptor superfamily member 11A, and C-X-C motif chemokine ligand 12. (5) Chlorella peptides effectively inhibited vascular endothelial growth factor A-induced migration and tube formation of human umbilical vein endothelial cells, and reduced the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes. These results indicate that Chlorella peptides regulate multiple pathological links of rheumatoid arthritis through anti-oxidative stress, regulation of macrophage polarization, inhibition of aggressive phenotype of fibroblast-like synoviocytes, and improvement of vascular endothelial disorders, suggesting potential therapeutic value for rheumatoid arthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21576
BACKGROUND: Exercise therapy is a non-drug management strategy for diabetic patients and can significantly improve endothelial function. However, its effect on endothelial progenitor cells and its specific biological mechanism are still unclear. OBJECTIVE: To explore the effects of voluntary wheel running on the function of endothelial progenitor cells in type 2 diabetic rats and reveal the possible mechanisms of action. METHODS: (1) Animal experiment: Sixty Wistar rats were randomly divided into four groups. The control group (n=15) underwent neither modeling nor any exercise intervention. In the model group (n=15), a rat model of type 2 diabetes was established using a high-fat diet combined with streptozotocin induction, with no exercise intervention after modeling. In the model exercise group (n=15), model rats underwent voluntary wheel running for 5 days per week over 8 weeks. In the model exercise + gene silencing group (n=15), after establishing the type 2 diabetes model, rats received tail vein injection of insulin-like growth factor 1 receptor-specific small interfering RNA adenovirus recombinant, and 4 hours later underwent voluntary wheel running for 5 days per week over 8 weeks. After exercise intervention, fasting blood glucose, serum insulin-like growth factor 1 and insulin levels, and insulin resistance index were measured. Thoracic aortic endothelial diastolic function was assessed by in vitro vascular ring assay. (2) Cell experiment: After exercise intervention, bone marrow endothelial progenitor cells were isolated and cultured from each group. Cell proliferation, migration, and tube formation abilities were detected by MTT assay, scratch test, and Matrigel tube formation assay. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of insulin-like growth factor 1 receptor in cells. Western blot was used to detect the protein expression of insulin-like growth factor 1, insulin-like growth factor 1 receptor, phosphorylated phosphatidylinositol-3 kinase, and phosphorylated protein kinase B. RESULTS AND CONCLUSION: (1) Animal experiment: Compared with the control group, the model group showed increased fasting blood glucose, insulin levels, and insulin resistance index (P < 0.05), and decreased insulin-like growth factor 1 level (P < 0.05). Compared with the model exercise group, the model group and the model exercise + gene silencing group showed increased fasting blood glucose, insulin levels, and insulin resistance index (P < 0.05), and the model group showed decreased insulin-like growth factor 1 level (P < 0.05). The vascular endothelial diastolic function in the model group, model exercise group, and model exercise + gene silencing group was weaker than that in the control group (P < 0.05), and the model exercise group showed stronger vascular endothelial diastolic function than the model group and the model exercise + gene silencing group (P < 0.05). (2) Cell experiment: The proliferation, migration, and tube formation abilities of bone marrow endothelial progenitor cells and the mRNA expression of insulin-like growth factor 1 receptor in the model group were lower than those in the control group. The proliferation, migration, and tube formation abilities of bone marrow endothelial progenitor cells and the mRNA expression of insulin-like growth factor 1 receptor in the model exercise group were higher than those in the model group and the model exercise + gene silencing group (P < 0.05). The protein expression of insulin-like growth factor 1, insulin-like growth factor 1 receptor, phosphorylated phosphatidylinositol-3 kinase, and phosphorylated protein kinase B in the model group was lower than that in the control group (P < 0.05). The protein expression of insulin-like growth factor 1 receptor, phosphorylated phosphatidylinositol-3 kinase, and phosphorylated protein kinase B in the model exercise group was higher than that in the model group and the model exercise + gene silencing group (P < 0.05), and the protein expression of insulin-like growth factor 1 was higher than that in the model group (P < 0.05). (3) These results indicate that voluntary wheel running can improve the function of endothelial progenitor cells in type 2 diabetic rats, and the mechanism is related to the activation of the insulin-like growth factor 1 receptor-mediated phosphatidylinositol-3 kinase/protein kinase B signaling pathway.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04948-z
Osteoporosis (OP) is characterized by diminished bone mass and pathological marrow adiposity, driven by imbalanced osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The translocator protein (TSPO), a multifunctional mitochondrial protein, has an undefined role in bone metabolism. This study integrated bioinformatic analyses of human and mouse OP datasets with experimental validation in BMSCs from osteoporotic patients and mouse models. TSPO was significantly upregulated in OP BMSCs. Gain- and loss-of-function experiments in human BMSCs demonstrated that TSPO overexpression suppressed proliferation, migration, and osteogenesis while promoting senescence and adipogenesis; TSPO knockdown enhanced cellular fitness and osteogenic capacity. Mechanistically, TSPO acted as an upstream regulator of the PI3K/AKT/GSK-3β signaling axis, suppressing downstream phosphorylation and inhibiting β-catenin-mediated osteogenic transcription. In ovariectomized (OVX) mice, local TSPO silencing via AAV-9 improved bone microarchitecture, enhanced bone formation, and reduced marrow adiposity, concomitant with reactivation of the PI3K/AKT/GSK-3β/β-catenin pathway. These findings identify TSPO as a key pathogenic regulator that impairs osteogenesis by disrupting PI3K/AKT/β-catenin signaling. Targeting TSPO presents a novel anabolic strategy for osteoporosis, potentially addressing the unmet clinical need for therapies that restore bone formation.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04918-5
Intervertebral disc (IVD) degenerative disease is a prevalent and debilitating spinal condition. Current treatments provide only symptomatic relief and fail to halt disease progression or restore native biomechanical function. Regenerative medicine strategies, particularly those harnessing endogenous progenitor cells, offer a promising avenue for biological repair and functional homeostasis. The identification of intervertebral disc progenitor cells (IVD-PCs) has revealed a potential cellular reservoir for self-repair, given their demonstrated stemness attributes, including clonogenicity and multipotent differentiation. However, clinical translation of IVD-PCs is significantly hampered by an incomplete understanding of their inherent heterogeneity, hierarchical organization, and, most critically, the dynamic interplay with their unique microenvironment, which dictates their fate decisions. This review synthesizes recent advances in deciphering the molecular signatures and functional plasticity of IVD-PCs. We emphasize how key physicochemical, mechanical, and cellular cues within the IVD niche orchestrate progenitor cell behavior—ranging from maintenance and activation to aberrant differentiation—during both homeostasis and degeneration. Furthermore, we propose forward-looking insights to bridge critical knowledge gaps, aiming to propel the development of novel progenitor cell-based therapeutics for IVD degeneration.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025232
Midnolin (MIDN) is a newly recognized master regulator that drives ubiquitin-independent proteasomal degradation, yet the mechanisms governing its own turnover remain enigmatic. Here, we demonstrate that MIDN is ubiquitinated and identify RNF126 as the cognate E3 ligase. RNF126 physically associates with MIDN and catalyzes its ubiquitination, and mass spectrometry mapping reveals that this process occurs primarily at non-canonical cysteine, serine, and threonine residues (C230, C236, S237, T239, and S241) rather than at lysine residues. This non-classical ubiquitination targets MIDN for 26S-proteasomal degradation. In vivo dissection of the RNF126-MIDN axis shows that it governs EGR1 abundance and, consequently, the tumor-suppressor proteins PTEN and p53, thereby restraining the progression of testicular germ-cell tumors (TGCTs). Our findings reveal an unappreciated layer of MIDN regulation and identify the RNF126-MIDN ubiquitination cascade as a potential therapeutic vulnerability in TGCTs and related malignancies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025081
Non-alcoholic steatohepatitis (NASH) represents a progressive form of metabolic dysfunction-associated steatotic liver disease with limited therapeutic options. Ductular reactions and macrophage-driven inflammation are associated with liver fibrosis in various chronic liver disorders. This study investigates the molecular phenotypes of resident CD24+LCN2+ liver progenitor cells (LPCs) and their regulatory mechanisms in human NASH. Single-cell RNA sequencing datasets were employed to characterize LPC status in clinical NASH samples. CellChat and NicheNet analyses assessed cell-cell communication between LPCs and other cell types. Findings were validated using RNA sequencing datasets associated with NASH progression, NASH mouse models (CDAHFD and HFD), and human NASH liver samples. Results demonstrate that resident CD24+LCN2+ LPCs are significantly enriched in NASH patients. Cell communication analyses predict strong interactions between LPCs and proinflammatory macrophage subtypes. In NASH, the liver recruits peripheral blood mononuclear cell-derived macrophages and polarizes them into proinflammatory subtypes. The macrophage subtype MP-2 is identified as the primary recipient of LPC-derived signals, exhibiting marked hyperactivation of the NF-κB pathway and strong association with liver fibrosis. The MP-2 markers COL10A1 and TPPP3 are characterized and validated. This study reveals that resident CD24+LCN2+ LPCs are activated in NASH and contribute to fibrosis progression by promoting activation of the proinflammatory COL10A1+TPPP3+ macrophage subtype. These findings delineate a cellular crosstalk axis that may serve as a therapeutic target for NASH fibrosis.