Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04896-8
Background The development of vascular calcification (VC) in diabetes is closely related to the endothelial-to-mesenchymal transition (EndMT). We found that microRNA-32-5p (miR-32) was elevated in the plasma of calcification patients. However, it is unclear whether miR-32 mediates the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) in type 2 diabetes (T2D) VC. Methods BMSC-EVs were characterized by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining assessed the severity of VC. qRT-PCR and Western blotting evaluated the expression of BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin, while immunofluorescence was used for detecting VE-cadherin and N-cadherin. In vivo validation was performed using miR-32–/– and ApoE–/– mice. RNA sequencing (RNA-seq) and bioinformatics analysis was conducted to explore underlying mechanisms. Results We demonstrated that BMSC-EVs attenuate VC in endothelial cells (ECs) and inhibit EndMT. In vivo, histological analysis showed that treatment with BMSC-EVs significantly reduced the severity of VC associated with T2D. Notably, knockout of miR-32 further enhanced the inhibitory effect of BMSC-EVs on VC. Mechanistically, transcriptomic and functional analyses suggest that the protective effect of BMSC-EVs on VC is associated with regulation of the MAPK/FoxO signaling pathway, potentially mediated by modulation of ferroptosis. Conclusion These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04895-9
Spinal cord injury (SCI) remains a significant global health challenge with limited effective therapeutic options. Exosomes derived from mesenchymal stem cells (MSCs) have emerged as promising neuroprotective agents due to their biocompatibility and immunomodulatory properties. This study investigated the therapeutic potential of hypoxia-conditioned bone marrow MSC (BMSC)-derived exosomes in both in vitro and in vivo SCI models. Hypoxic preconditioning significantly enriched miR-615-3p in bone marrow mesenchymal stem cell (BMSC)-derived exosomes. In spinal neuron injury models, hypoxic exosomes enhanced cell viability, reduced apoptosis, and ameliorated dysfunction of the mitochondria-associated endoplasmic reticulum membranes (MAMs). Mechanistically, miR-615-3p directly targeted and suppressed phosphodiesterase 4 C (PDE4C), activating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. This in turn modulated calcium signaling, attenuated mitochondrial calcium overload, and reduced endoplasmic reticulum stress (ERS). In a mouse model of SCI, short-term treatment with hypoxic exosomes promoted functional recovery within a 14-day post-injury period, as evidenced by improved locomotor performance, reduced lesion volume, attenuated tissue edema, and decreased inflammatory cell infiltration. Furthermore, in vivo administration of hypoxic exosomes upregulated miR-615-3p and downregulated PDE4C expression in injured spinal cord tissues. These results demonstrate that hypoxia-conditioned BMSC-derived exosomes exert neuroprotective effects via the miR-615-3p/PDE4C axis, highlighting their potential as a novel therapeutic strategy for SCI by targeting calcium homeostasis and mitochondrial-ER dysfunction. These findings demonstrate the short-term therapeutic potential of hypoxia-conditioned exosomes in SCI. However, further preclinical studies, including long-term follow-up to assess the durability of recovery and potential late-onset effects, alongside clinical validation, are warranted before clinical translation.
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.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04322-5
Background Nano-zinc oxide (nZnO) has attracted significant attention in bone tissue engineering due to its antibacterial properties, anti-inflammatory effects, biocompatibility, and chemical stability. Although numerous studies have demonstrated the enhancement of osteogenic differentiation by nZnO-modified tissue engineering materials, the underlying mechanisms remain poorly characterized. Methods This study aimed to identify the molecular mechanisms how nZnO promoted osteogenic differentiation and bone regeneration using transcriptome analysis, drug intervention, and shRNA knockdown techniques, etc. First, the study evaluated the in vivo effects of gelatin methacryloyl (GelMA) containing nZnO on bone regeneration using a mouse calvarial defect model. The impact of nZnO exposure on the osteogenic differentiation of mesenchymal stem cells (MSCs) was then assessed. The combined treatment of nZnO and MSCs in GelMA for bone regeneration was assessed in the mouse calvarial defect model thereafter. Results nZnO induced osteoblastic differentiation to promote bone regeneration. nZnO activated the AMP-dependent protein kinase (AMPK)-ULK1 signals to stimulate autophagosomes formation and facilitate autophagy flow, which was the essential pathway to induce osteogenic differentiation. The combined treatment of MSCs and nZnO significantly enhanced bone regeneration in calvarial defect mice. Conversely, AMPK inhibitor Compound C (C.C) reversed the effects on autophagy flow and osteogenic potentiality induced by nZnO. Conclusions These results highlight that nZnO can regulate bone regeneration by activating autophagy through the AMPK/ULK1 signaling pathway, which may provide a novel therapeutic strategy for addressing bone defects using nZnO.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04727-2
Introduction Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells, leading to insulin deficiency. As insulin therapy does not affect disease progression, advancements in immune regulation therapies have emerged, including the reconstitution of the insulin secretory system. Cysteine-rich acidic secretory protein (SPARC) is an extracellular matrix glycoprotein that regulates cell adhesion, facilitating cell migration, and mediating interactions between cells and their extracellular matrix. SPARC is overexpressed during tissue repair and is involved in β-cells survival. However, the potential of SPARC-modified mesenchymal stem cells (MSCs) to improve insulin secretion has not been thoroughly investigated. This study investigated the therapeutic effects of SPARC-MSCs in vivo and in vitro and assessed whether SPARC enhances survival and insulin secretion after β-cells injury. Methods In vivo, we established T1D models in mice and canine using SPARC-MSCs for cell transplantation. In vitro, MIN6 cells were damaged with STZ, and SPARC-MSC supernatant was co-cultured with MIN6 for various assays. Results Our study demonstrated that SPARC enhanced the regenerative capacity and migratory efficiency of MSCs after H2O2 injury and improved their morphology. In STZ-induced canine and mice diabetes models, SPARC-MSCs therapy significantly reduced hyperglycemia, improved oral glucose tolerance test (OGTT), and reversed weight loss in canine. Biochemical analyses showed improved liver function, and histological examination revealed restored islet area was significantly restored. Transcriptome and proteome sequencing indicated significant enrichment in calcium binding and cell migration pathways. Co-culturing SPARC-MSC supernatant with MIN6 cells after STZ injury restored their regenerative ability, enhancing insulin secretion and ATP content under high glucose stimulation. SPARC treatment also significantly increased intracellular Ca2+ levels in MIN6 cells. Conclusion SPARC significantly promotes cell regeneration and stimulates insulin secretion by increasing intracellular ATP and Ca2+ influx. In diabetic canine and mice models, it alleviated hyperglycemia, improved glucose tolerance, and enhanced pancreatic islet area and insulin secretion.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04713-8
The Editors-in-Chief have retracted this article because of concerns regarding the figures presented in this work. An investigation conducted after its publication discovered the following issues: The Control/CD73 panel in Fig. 1 appears to overlap with the Control/Oct4 in the same figure; Figure 5e appears to overlap with the EGF/α-SMA panel in Fig. 6a in [1]; The bottom portion of Fig. 5g appears to overlap with the top portion of the MSC-CM/α-SMA panel in Fig. 6a in [1]; The panels in question represent cells or tissues subject to different experimental conditions. The Editors-in-Chief therefore no longer have confidence in the integrity of the research presented in this article. The authors have not replied to correspondence from the Publisher about this retraction.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04102-7
Background Cancer stem cells (CSCs) have unique metabolic characteristics and are hypothesized to contribute significantly to the recurrence and drug resistance of glioblastoma multiforme (GBM). However, the reliance on mitochondrial metabolism and the underlying mechanism of glioblastoma stem cells (GSCs) remains to be elucidated. Methods To quantify differential mitochondrial protein expression between GSCs and differentiated cells, a mass spectrum screen was applied by the Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) technique. Functional experiments including CCK8, neurosphere formation, flow cytometry, transwell, and wound healing assays were conducted to evaluate GBM cell malignant phenotype. The potential molecular mechanism of FDFT1 was screened by RNA-seq analyses. The candidate target genes were validated through RT-qPCR and western blot analyses. Results As a top candidate, FDFT1 protein expression in GSCs was elevated relative to their differentiated counterparts. Functionally, the knockdown of FDFT1 suppressed the GBM cell proliferation and migration, while simultaneously enhancing sensitivity to temozolomide. Treatment with both the FDFT1 inhibitor (YM-53601) and simvastatin (an HMG-CoA reductase inhibitor) induced apoptosis in GSCs. Mechanistically, FDFT1 was transcriptionally regulated by SREBP2 but not SREBP1. Furthermore, FDFT1 activates the AKT pathway to regulate tumor metabolism and maintain the stemness of tumor cells. Conclusions GSCs exhibit a dependency on FDFT1-mediated mevalonate metabolism. Inhibition of FDFT1 could represent a potent strategy to eliminate GSCs.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04112-5
Correction to: Stem Cell Research & Therapy (2024) 15:440. The original article initially erroneously presented co-author, Min Xu's name as Xu Min; this has since been amended.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03821-1
Background Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. Methods En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. Results The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. Conclusions The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.
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.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04032-4
Background The efficiency of mesenchymal stem cells (MSCs) in treating myocardial infarction (MI) remains inconsistent, which limits their therapeutic applications. Therefore, exploring the mechanism for the inconsistent efficacy of MSCs and identification the criteria for screening MSCs are important for improving the efficiency of MSCs. Methods Mouse model after MI was utilized to test the role of MSCs from different donors and the functional subpopulation in improving cardiac function. Heterogeneity of MSCs was identified using single-cell RNA sequencing (scRNA-seq) of MSC-GY. GSEA and Scissor analyses were used to find the functional subpopulations of MSCs that promote angiogenesis. The role of functional subpopulations in promoting angiogenesis was verified by detecting the secretory proteins, the ratio of N-CADHERIN+/CD168− subpopulations in MSCs, and the tube formation, migration, and proliferation of HUVECs after treatment with conditional medium (CM) derived from different MSCs. Results We found that umbilical cord-derived MSCs (UC-MSCs) from different donors have varied therapeutic efficacy in MI mice and UC-MSCs with higher therapeutic effectiveness exhibited the most potent pro-angiogenic effects by secreting elevated levels of angiogenesis-related proteins, such as MYDGF, VEGFA, and FGF2. ScRNA-seq of 10,463 UC-MSCs revealed that the N-CADHERIN+/CD168− subpopulation was closely associated with pro-angiogenic effects, and the ratio of this cell subpopulation was positively correlated with the angiogenic potential of MSCs. We also found that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in improving cardiac function of MI mice. Conclusions Our study identified that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in treating MI, which was essential for the development and utilization of MSCs in MI treatment.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025253
Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive subtype of renal cell carcinoma and is characterized by poor prognosis and high molecular heterogeneity. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in cancer, yet the functional role of SNHG11 in KIRC remains unclear. In this study, we perform integrated multiomics analysis using data from the TCGA and ICGC cohorts and reveal that SNHG11, a methylation-associated lncRNA, is significantly correlated with poor clinical outcomes. In vitro and in vivo assays demonstrate that SNHG11 promotes tumor proliferation and progression. Mechanistically, SNHG11 enhances oxidative phosphorylation, as evidenced by increased ATP production, disrupted mitochondrial membrane potential, and altered NAD+/NADH ratios. Furthermore, SNHG11 expression is associated with somatic mutation patterns, particularly those involving BAP1 and PBRM1, indicating potential crosstalk between epigenetic regulation and genetic alterations. These findings reveal that SNHG11 is a novel biomarker in KIRC and a potential therapeutic target.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026042
Efficient genome packaging is a critical step in the phage life cycle, directly influencing the viral maturation and infectivity. In tailed phages, this process is driven by a packaging motor composed of a portal protein and a terminase complex. The terminase complex usually consists of a large subunit (TerL) and a small subunit (TerS), which cooperate to recognize, cleave, and translocate genomic DNA into the capsid. However, due to the remarkable diversity and complexity of phage packaging systems, the molecular mechanisms governing TerS-mediated DNA recognition remain poorly understood. Here, we report the 3.51 Å cryo-electron microscopy structure of the TerS from the short-tailed cyanophage Pam5, which infects the host Pseudanabaena mucicola Chao 1806. Pam5 TerS assembles into a nonameric ring with a radially symmetric spiral architecture. Biochemical assays show that Pam5 TerS recognizes the genomic DNA via a specific interaction between the N-terminal helix-turn-helix (HTH) domain of TerS and a 21-bp DNA sequence within the terS gene. In contrast, the TerS from another short-tailed cyanophage, Pam1, which infects the same host, binds to DNA in a sequence-independent manner. These findings reveal that cyanophages, even infecting the same host, could adopt two distinct DNA recognition strategies: HTH-mediated sequence-dependent or sequence-independent modes. This work provides structural and mechanistic insights into the diverse DNA-recognition strategies of TerS and advances our understanding of the evolutionary plasticity of viral genome packaging mechanisms.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025016
CRISPR-Cas nucleases have been extensively used in molecular detections, especially highly sensitive nucleic acid detections. In these detections, Cas nucleases are programmed by the guide RNA to respond to the detection targets and cleave the chemically labelled molecular beacons by the trans-cleavage activity to produce the detection signal. To improve sensitivity, nucleic acid amplification technologies are usually introduced to give a pre-amplification of the nucleic acid targets, increasing the detection sensitivity extraordinarily. Polymerase chain reaction (PCR) technology has been used for pre-amplification in laboratories, and isothermal amplification technologies are applied to meet point-of-care testing (POCT) needs because they avoid the use of sophisticated thermal cycling devices. The recombinase polymerase amplification (RPA) technology that amplifies nucleic acid targets isothermally at 37–42°C has been combined with CRISPR-Cas nucleases to establish advantageous nucleic acid detection assays, e.g., the SHERLOCK, which combines with Cas13a, and the DETECTR, which combines with Cas12a. It has been challenging to integrate Cas nucleases and RPA in a one-pot reaction system because the cleavage activity of Cas stimulated by even small amounts of the targets can interfere with amplification by digesting the primers or the newly amplified fragments. Thus, many assays based on Cas nucleases and RPA are in a two-step setting, with pre-amplification and Cas cleavage being isolated as two independent procedures. The two-step setting ensures that amplification and cleavage occur under favorable conditions but sacrifices operational convenience and introduces the risk of cross-contamination. In efforts to establish one-pot RPA-Cas assays, many strategies have been applied, including the use of photocontrolled guide RNA to activate the Cas nuclease at a preferred timepoint, the use of a suboptimal protospacer adjacent motif (PAM) to suppress Cas activity, the generation of dynamic aqueous multiphase with sucrose or glycerol to partially separate the two reactions, and extensive optimization of the RPA-CRISPR reaction system to achieve a subtle balance between the two reactions. In this study, a one-pot CRISPR-Cas12b and RPA combined assay with a temperature switch (CRATS) was established utilizing the reaction temperature difference between RPA and CRISPR-Cas12b cleavage. The Cas12b used in this study, AaCas12b, is a type V-B CRISPR‒Cas nuclease from Alicyclobacillus acidiphilus. It has a bi-lobed architecture consisting of an α-helical recognition lobe containing the REC domains and a nuclease lobe containing the WED, RuvC and Nuc domains. As a dual-RNA-guided DNA endonuclease, Cas12b can be guided by a chimeric single-guide (sg) RNA, and its trans-cleavage activity is specifically activated by the DNA target and results in nonspecific cleavage of single-stranded (ss) DNA molecules, which can be used to produce detection signals if the ssDNA is appropriately labelled as the molecular beacon. As the temperature for RPA is 37°C and the trans-cleavage of Cas12b is active at 60°C, CRATS uses temperature switching to adjust the major on-going reaction in the one-pot system and realizes sequential amplification of the target and cleavage reactions for signal detection. The detection target of this study, monkeypox virus, is an infectious pathogen that has caused the announcement of the Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) twice in recent years. In this one-pot CRATS assay, the reaction reagents of CRISPR-Cas12b and RPA are mixed in a single tube. After the addition of the sample containing the detection target, the reaction was carried out at 37°C for 20 min for amplification, followed by 60°C for 20 min for Cas12b cleavage. The fluorescently labelled molecular beacon is cleaved by Cas12b to release the FAM fluorophore from quenching, producing a fluorescence signal that is visualized under blue light. CRATS shows a high sensitivity of 100 copies of the target DNA per reaction and good specificity, providing a novel strategy of temperature switching to integrate CRISPR-Cas and RPA in a one-pot reaction system. Moreover, it provides a POCT-friendly tool for the detection of the important infectious pathogen monkeypox virus.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025121
Carfilzomib (Cfz) is a second-generation proteasome inhibitor approved for the treatment of relapsed/refractory multiple myeloma (RRMM). Previous studies have shown that Cfz is associated with a higher incidence of severe adverse cardiac effects than bortezomib (Btz); however, the underlying mechanisms remain to be elucidated. The aim of this study is to identify key regulators of cardiotoxicity induced by Cfz and to investigate the mechanisms by which these factors exert their effects. We establish a mouse model of cardiac toxicity induced by Cfz and confirm the phenotype through cardiac functional analysis, morphology assessment, myocardial fibrosis, and apoptosis analysis. We subsequently perform RNA sequencing to identify differentially expressed genes (DEGs) and further validate their functions and mechanisms. We find that Cfz induces myocardial hypertrophy and myocardial injury, along with the suppression of SENP1 expression in mouse heart tissues and in vitro cultured neonatal rat cardiomyocytes. Suppression of SENP1 exacerbates Cfz-induced injury and remodeling in cardiomyocytes by directly binding to and deconjugating the SUMO1-mediated SUMOylation of the RNA helicase DDX17. This process leads to a reduction in K-48 ubiquitin-linked polyubiquitination and degradation of DDX17, resulting in increased expressions of anti-apoptotic genes and maintenance of mitochondrial homeostasis. Therefore, the overexpression of SENP1 using AAV vectors alleviates Cfz-induced cardiotoxicity in mice. In summary, our findings reveal a previously unknown role of the SENP1-DDX17 axis in protecting against cardiotoxicity induced by Cfz, providing a potential foundation for developing therapeutic strategies to mitigate cardiac side effects in the clinical management of MM patients.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025026
Ulcerative colitis (UC) is a chronic inflammatory disease with an increasing prevalence worldwide. Naringenin (NAR) has been proven effective in preventing UC, but its mechanism has not been fully elucidated. In this study, network pharmacology and bioinformatics methods are used to screen the genes associated with NAR and UC. A mouse model of dextran sulfate sodium (DSS)-induced UC is established. After treatment with NAR, the disease activity index (DAI) is scored, and colonic histopathology is observed via hematoxylin-eosin (HE) staining. The expressions of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and inflammation-related factors in the colons of UC mice are examined via western blot analysis and immunohistochemistry (IHC). The results of the animal experiments reveal that the model group of UC mice present the most severe weight loss and the highest DAI scores. After the administration of NAR, weight loss is alleviated, and DAI scores are reduced (P < 0.05). NAR improves pathological manifestations in the mouse colon, such as reducing inflammatory cell infiltration and restoring goblet cell loss (P < 0.05). NAR significantly increases the protein expression levels of Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) in the colon (P < 0.05) but decreases the protein expression levels of nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) (P < 0.05), thus alleviating the inflammatory response in UC model mice.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025079
This is a corrigendum to the original article published in Acta Biochim Biophys Sin (Shanghai) 2021, 53(12): 1670–1680. In the original version, errors were found in Figure 2 and Figure 6. The correct figures are shown in this corrigendum. The authors apologize for the error.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026049
Esophageal squamous cell carcinoma (ESCC) represents a common malignancy of the digestive system. Circular RNAs (circRNAs) are a distinct class of single-stranded non-coding RNAs that are essential in the progression of various tumors given that they can act as microRNA (miRNA) sponges in a manner similar to that of mRNAs. In this study, circ_0006156 is screened to be highly expressed in ESCC tissues through high-throughput sequencing and quantitative real-time polymerase chain reaction. Subsequent in vitro and in vivo experiments are conducted to validate its biological functions. Furthermore, the regulatory relationships among circ_0006156, miR-202-5p, and TGFBR1 are investigated using RNA antisense purification, miRNA sequencing, RNA immunoprecipitation, fluorescence in situ hybridization, dual-luciferase reporter assay, and bioinformatics analyses. The results show significant overexpression of circ_0006156 in ESCC tissues, with relatively shorter overall survival observed in patients with high circ_0006156 expression. circ_0006156 is further identified to directly bind to miR-202-5p. miR-202-5p inhibits the proliferation, migration, and invasion of ESCC cells in vitro and partially rescues the effects induced by circ_0006156. Consistent results are reported by subcutaneous xenograft tumor experiments in nude mice. In addition, circ_0006156 is confirmed to act as an endogenous sponge for miR-202-5p, which results in a relieved suppression of its target gene TGFβR1. In summary, circ_0006156 can regulate TGFβR1 expression by sponging miR-202-5p, which may further activate the TGFβ/Smad pathway and promote ESCC progression. Collectively, circ_0006156 functions as a novel oncogenic RNA in ESCC and may serve as a potential tumor marker.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026043
Pentatrichomonas hominis is a zoonotic protozoan belonging to the family Trichomonadidae that primarily inhabits the cecum and colon. Although traditionally regarded as an opportunistic pathogen, P. hominis is increasingly recognized for its pathogenic potential, including roles in animal diarrheal disease and the induction of intestinal epithelial damage and chronic inflammation in mice. A previous study further identified a significant correlation between P. hominis infection and colorectal cancer, underscoring its growing clinical and public health significance. This parasite infects a wide range of hosts, among which dogs, displaying infection rates as high as 47.4%, are regarded as a potential zoonotic reservoir because of their close contact with humans. Consequently, establishing reliable detection methods for P. hominis in dogs is essential for veterinary practice and public health surveillance. Current methods for detecting P. hominis infections in dogs mainly include direct smear microscopy and polymerase chain reaction (PCR)-based techniques. Although direct smear microscopy is straightforward, it frequently exhibits low sensitivity. In comparison, PCR demonstrates high sensitivity and specificity, yet it relies on specialized equipment, trained operators, and extended processing time. Recently, reported nucleic acid detection approaches, such as recombinase polymerase amplification coupled with lateral flow dipstick (RPA-LFD) and RPA-CRISPR/Cas12a assays, have enhanced the efficiency and accessibility of molecular detection for P. hominis. However, these methods still necessitate nucleic acid extraction, controlled temperature conditions, and operational complexity. In addition, some emerging detection technologies, such as microfluidic chips and nanozyme-based detection systems, offer advantages of high throughput and sensitivity but have not yet been widely applied in the field of detection of parasitic infection. Although immunoassays, including enzyme-linked immunosorbent assay (ELISA) and colloidal gold immunochromatographic strips, have been successfully used for the detection of infections of some intestinal protozoans, such as Giardia, there have been no reports on their application for detecting P. hominis infections, primarily due to the lack of specific detection antigens. To address the detection need, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used as the primary discovery tool to identify specific detected antigens. Using this targeted proteomics approach, we precisely identified immunoreactive proteins and selected glyceraldehyde 3 phosphate dehydrogenase (GAPDH), an immunogenic and species-specific antigen in related parasites, as the candidate antigen. Based on this identified antigen, we subsequently developed and evaluated the detection performance in both indirect ELISA and colloidal gold immunochromatographic strips using recombinant GAPDH. This study aimed to identify novel antigens for immunodetection of P. hominis and to establish a practical, on-site method for detecting dog infections, thereby facilitating further epidemiological and clinical research.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025147
CD47, a cell surface transmembrane glycoprotein, is an innate immune checkpoint that suppresses phagocytic clearance. Emerging evidence suggests that CD47 has noncanonical functions. However, its involvement in chemotherapy resistance is not well understood. Our study reveals that cisplatin treatment upregulates CD47 expression across multiple cancer cell lines. Cisplatin induces the expression of CD47 through the ATM/NF-κB signaling pathway. Genetic ablation of CD47 dramatically sensitizes cancer cells to cisplatin. Mechanistically, CD47 depletion potentiates cisplatin-induced DNA damage, as demonstrated by elevated γH2AX formation and ATM phosphorylation. Knockdown of CD47 inhibits the expression of DNA repair genes ERCC1, FANCA, and BRCA2 through the ATM/NF-κB pathway. Remarkably, CD47 blockade with neutralizing antibodies recapitulates these effects, synergistically potentiating cisplatin’s DNA-damaging capacity while suppressing DNA repair capacity. CD47 blockade also potentiates cisplatin’s tumor inhibitory effect in vivo. These findings establish a novel mechanism whereby CD47 promotes cisplatin resistance through transcriptional regulation of DNA repair pathway, providing rationale for combining CD47-targeted therapies with conventional chemotherapy. This dual approach could simultaneously overcome immune evasion while enhancing treatment efficacy.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024095
Eimeria spp. can invade different intestines of chickens. Among them, Eimeria acervulina (E. acervulina, Ea) is the most virulent, and it is characterized by disruption of the intestinal nutrient uptake mechanism, leading to weight loss and even death. As a result, coccidia have caused a heavy burden on the poultry industry [1]. Currently, understanding the invasion mechanism of E. acervulina in host cells is the basis for developing the most effective preventive method for coccidiosis. However, the specific mechanism of E. acervulina invasion is unclear, so the interactions between parasite and host cells need to be studied in depth. Serine thiol proteinase inhibitors widely exist in bacteria, viruses and parasites. It can protect against the dissolution of host proteins and the development of pathogens in the process of pathogen invasion [2]. The serine protease inhibitor (SERPIN) of Toxoplasma gondii, which has the ability to inhibit trypsin activity, was the first SERPIN to be studied in parasites. SERPIN in T. gondii may play an important role in protecting against the degradation of host intestinal proteases and reducing the ability of host proteins to hydrolyse T. gondii [3]. SERPIN in T. gondii can also promote the growth of tachyzoites in the host. Subsequently, a 79-amino acid protease inhibitor, SERPIN, which can completely inhibit the activity of bacterial subtilisin, was found in Neospora caninum [4]. SERPIN plays an important role not only in parasite physiology but also in the interactions with the host. Real-time quantitative PCR analysis at all developmental stages of E. tenella showed that SERPIN1 is highly expressed in sporozoites [5]. Previous studies have shown that the secreted SERPIN protein in sporozoites may also regulate the host immune pathway. In Schistosoma mansoni, SERPIN can inhibit neutrophil proteases and regulate the degradation of tissues to promote the migration of parasites in the host [6]. SERPIN secreted by parasites can also be used to protect themselves from degradation by host proteases, thus manipulating the host response to parasites. Studies have shown that they are mainly involved in physiological processes such as blood sucking, digestion, reproduction and immune response and affect the interaction between parasites and hosts [7]. SERPIN from Trichinella spiralis (TsSPI) is not directly involved in the growth and reproduction of parasites but regulates the interaction between T. spiralis and its host to a certain extent. TsSPIs can regulate the polarization of macrophages and subsequently affect the balance among host inflammatory factors to regulate the host immune response and create a favorable environment for the colonization of Trichinella spiralis in the host [8]. Taeniasis solium SERPIN can play a biological role by participating in the inflammatory and apoptotic pathways of the host [9]. Previous studies have shown that SERPIN plays important roles during host-cell invasion, and 66 related proteins that interact with E. tenella SERPIN on the host have been preliminarily screened [10]. However, few studies have focused on the binding partner of Ea-SERPIN. To identify the ligand-binding partner molecules that may play an important role in the invasion process of E. acervulina, a yeast two-hybrid system was used to screen the associated proteins from the yeast complementary DNA (cDNA) library of chicken duodenal epithelium cells using Ea-SERPIN as bait. In this study, a close genetic relationship was identified between E. acervulina and E. maxima and between E. acervulina and T. gondii. The protein homology of SERPIN between E. acervulina and E. maxima was 87%, and that between E. acervulina and Toxoplasma gondii was 43% (Supplementary Figure S1). The yeast cDNA library of chicken duodenal epithelium cells in the pGADT7 vector was constructed using a Matchmaker Library Construction and Screening kit (Clontech, Palo Alto, USA) as the prey. Preys containing a Gal4 activation domain (AD prey) were transformed into the yeast strain Y187. The efficiency of transformation and the size of the insert fragment satisfied the quality requirements of the yeast library. For yeast two-hybrid screening, SERPIN was amplified by polymerase chain reaction (PCR) using the forward primer 5′-CCC CATATGATGGCATTATTAAGTAAATTAACTCG-3′ and the reverse primer 5′-CCCCTGCAGTTACTGCTGTGCAGCTGTCGGGTCAG-3′ from E. acervulina cDNA and then ligated into the NdeI-PstI sites of pGBKT7 as a bait. The recombinant plasmid was transformed into Y2H GOLD yeast cells, and the transformants were separately grown on plates containing minimal yeast medium without tryptoph
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024122
The main protease (Mpro) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. PF-00835231 is a promising inhibitor of SARS-CoV-2 Mpro. Here, we report the inhibitory potency of PF-00835231 against SARS-CoV-2 Mpro and seven Mpro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral Mpros. In addition, the crystal structures of SARS-CoV-2 Mpro, SARS-CoV Mpro, MERS-CoV Mpro, and seven SARS-CoV-2 Mpro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveals key determinants essential for inhibition and elucidates the binding modes of different coronaviral Mpros. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into Mpro inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023286
Thioredoxin-interacting protein (TXNIP) is a crucial thioredoxin-binding protein that is recognized as a tumor suppressor in diverse malignancies, such as breast cancer, lung cancer, hepatocellular carcinoma, and thyroid cancer. However, the specific role and molecular mechanisms of TXNIP in the pathogenesis and progression of pancreatic cancer cells have not been determined. In this study, we investigate the relationship between TXNIP expression and overall survival prognosis in pancreatic cancer patients. Mechanistic studies are conducted to reveal the role of TXNIP in pancreatic cancer cell proliferation, migration, and regulation during malignancy. Our findings indicate that patients with high TXNIP expression have a more favorable prognosis. In vitro experiments with pancreatic cell lines show that overexpression of TXNIP suppresses the proliferation and migration of pancreatic cancer cells. Furthermore, we find that TXNIP inhibits the activation of the MAPK signaling pathway, thereby decreasing the malignant potential of pancreatic cancer. In conclusion, our study reveals TXNIP as a promising new predictive marker and therapeutic target for pancreatic cancer.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024075
Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor β (TGFβ) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFβ-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024175
Myocardial hypertrophy (MH) is an important factor contributing to severe cardiovascular disease. Previous studies have demonstrated that specific deletion of the protein arginine methyltransferase 1 (PRMT1) leads to MH, but the exact mechanism remains unclear. Serine/arginine-rich splicing factor 1 (SRSF1) affects the development and progression of cardiovascular disease by selectively splicing downstream signaling proteins. The present study is designed to determine whether PRMT1 is involved in MH by regulating SRSF1 and, if so, to explore the underlying mechanisms. Adult male mice and H9C2 cardiomyocytes are treated with isoprenaline (ISO) to establish MH models. The expression levels of PRMT1 are significantly decreased in the ISO-induced MH models, and inhibiting PRMT1 worsens MH, whereas overexpression of PRMT1 ameliorates MH. SRSF1 serves as the downstream target of PRMT1, and its expression is markedly elevated in MH. Moreover, SRSF1 increases the mRNA expressions of CaMKIIδ A and CaMKIIδ B, decreases the mRNA expression of CaMKIIδ C by altering the selective splicing of CaMKIIδ, and further participates in MH. In addition, there is an interaction between PRMT1 and SRSF1, whereby PRMT1 reduces the phosphorylation level of SRSF1 via methylation, thus further altering its functional activity and eventually improving MH. Our present study demonstrates that PRMT1 relieves MH by methylating SRSF1, which is expected to provide a new theoretical basis for the pathogenic mechanism of MH and potential drug targets for reducing MH and associated cardiovascular disease.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024018
Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024112
FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase expressed in hematopoietic cells. Internal-tandem duplication domain (ITD) mutation and tyrosine kinase domain (TKD) mutation are the two most common mutations in acute myeloid leukemia (AML). Post-translational modifications (PTMs) of FLT3, such as glycosylation and ubiquitination, have been shown to impact various aspects of the protein in both wild-type (WT) and mutant forms of FLT3. In this review, we describe how the glycosylation status of FLT3 affects its subcellular localization, which significantly impacts the activation of downstream signaling, and the impact of specific ubiquitination on FLT3 function and stability, which may be associated with disease progression. Moreover, potential novel therapeutic strategies involving a combination of FLT3 tyrosine kinase inhibitors and drugs targeting glycosylation or ubiquitination are discussed.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023285
Cisplatin (CDDP) is a widely used chemotherapeutic agent that has remarkable antineoplastic effects. However, CDDP can cause severe acute kidney injury (AKI), which limits its clinical application. Agrimol B is the main active ingredient found in Agrimonia pilosa Ledeb and has a variety of pharmacological activities. The effect of agrimol B on CDDP-induced renal toxicity has not been determined. To investigate whether agrimol B has a protective effect against CDDP-induced AKI, we first identify Sirtuin 1 (Sirt1) as a critical target protein of agrimol B in regulating AKI through network pharmacology analysis. Subsequently, the AKI mouse model is induced by administering a single dose of CDDP via intraperitoneal injection. By detecting the serum urea nitrogen and creatinine levels, as well as the histopathological changes, we confirm that agrimol B effectively reduces CDDP-induced AKI. In addition, treatment with agrimol B counteracts the increase in renal malondialdehyde level and the decrease in superoxide dismutase (SOD), catalase and glutathione levels induced by CDDP. Moreover, western blot results reveal that agrimol B upregulates the expressions of Sirt1, SOD2, nuclear factor erythroid2-related factor 2, and downstream molecules, including heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1. However, administration of the Sirt1 inhibitor EX527 abolishes the effects of agrimol B. Finally, we establish a tumor-bearing mouse model and find that agrimol B has a synergistic antitumor effect with CDDP. Overall, agrimol B attenuates CDDP-induced AKI by activating the Sirt1/Nrf2 signaling pathway to counteract oxidative stress, suggesting that this compound is a potential therapeutic agent for the treatment of CDDP-induced AKI.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024089
Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is clinically characterized by short stature, delayed bone age and central distribution of body fat, and it has also been proven to be mildly heritable. Treatment with recombinant human growth hormone (r-hGH) is primary and safe for GHD children, and a dose of 0.15‒0.20 mg/kg each week results in a considerable increase in height velocity, with noteworthy growth during the first year of therapy [1]. Previous studies have shown that serum IGF-1 is strongly correlated with the growth response [2]. Therefore, IGF-1 can serve as a clinical indicator for monitoring compliance, efficacy and safety. However, the response to GH therapy shows significant individual variation, which is strongly associated with genetic factors. The prevalence rate of severe childhood GHD-related short stature varies from 1:4000 to 1:10,000 [3], while approximately 3%‒4% of the population in China suffers from short stature with an increasing trend. Therefore, an open-label, prospective, multicentric, noncomparative, nonrandomized phase IV interventional study (NCT01187550, Merck Serono Study 27709) was conducted to investigate the relationship between the prospective biomarkers of GHD patients and the individual variation in the primary therapeutic response following 4 weeks of r-hGH therapy. Given the significance of predicting GHD treatment response and the gaps in previous research, we sought to adopt a comprehensive strategy to accurately predict the therapeutic response utilizing the transcriptome, single nucleotide polymorphisms (SNPs) and clinical factors. We employed continuous variables and standard deviation scores of differences in serum IGF-1 levels after 4 weeks of r-hGH therapy (ΔIGF-1) as targets to filter possible influencing variables. Furthermore, we compared several potential machine learning techniques, validated by PCA and PLS-DA, and ultimately applied the elastic net algorithm to determine the optimized predictive factors with consistent effect sizes. Additionally, expression quantitative trait locus (eQTL) analysis and differentially expressed gene (DEG) analysis were conducted to identify significant biomarkers for GHD treatment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024118
Lung cancer is the leading cause of cancer mortality in China and worldwide, and metastasis is the main cause of patient death. Cancer cells invade and migrate from the primary tumor, enter the circulation system through intravasation, and become circulating tumor cells (CTCs). CTCs that survive in blood vessels extravasate and invade target organs to become disseminated tumor cells (DTCs). DTCs proliferate in target organs to metastasize to distant organs. The previous view was that metastasis is the final stage of cancer progression. Normal cells first transform into tumor cells and then into invasive cancer cells; thus, metastasis occurs. Therefore, the possibility of metastasis is closely related to the size of the primary tumor. This is reflected in the TNM stage (T, tumor size; N, extent of spread to regional lymph nodes; M, metastasis to distant organs), which is often referenced in clinical diagnosis. However, an increasing number of studies are currently challenging this view. A previous study showed that the metastasis of malignant tumors occurs in the early stages of cancer. When patients are diagnosed with primary cancer, dissemination occurs. CTCs already exist in the blood vessels of early-stage lung cancer patients, and in early-stage lung cancer patients, DTCs are likely to be the main source of late-stage metastasis in some cancers; they do not proliferate in target organs, so they cannot be eliminated by surgery, radiotherapy or chemotherapy. As a result, even if the lesions are removed through surgery in these patients, metastasis is still found months or years later, which affects the patient’s quality of life and reduces the patient’s survival period. These observations prompt scientists in the field of metastasis to pay more attention to the prevention and treatment of DTCs when formulating metastasis prevention strategies. To determine whether DTCs exist in different states after entering the target organ, we used a mouse lung cancer metastasis model to generate CTC-TJH-01 cells, which are circulating tumor cells derived from the peripheral blood of early-stage lung adenocarcinoma patients who extravasate into target organs and become DTCs. Then, we observed the distribution and proliferation of DTCs in the lungs. Combined with traditional Chinese medicine theory, our findings can improve clinical medication regimens and promote innovations in metastasis prevention and treatment strategies. We observed the potential distribution and proliferation status of DTCs in the lungs in a mouse lung cancer metastasis model. A lung colonization assay was performed by injecting 5 × 105 CTC-TJH-01 cells into the lateral tail vein of NOD/SCID mice, and vimentin was used as a lung tumor marker. Immunofluorescence staining was performed, and CTC-TJH-01 cells that reached the lungs through the peripheral circulation were evenly spread over 24 h. This finding showed that cancer cells can move to distant sites through the circulation, especially the lungs, which are rich in blood vessels, and stay there in the form of DTCs. However, after 12 weeks, there were only a few visible metastases in the lungs, and many tumor cells in the visible metastases were Ki67-positive. Immunohistochemistry revealed other Vimentin-positive tumor cells in the lungs, but as the number of cells decreased, the Ki67 positivity rate also decreased, and a single tumor cell was negative for Ki67. This finding shows that an unsuitable microenvironment induces DTC apoptosis, and only a very small number of DTCs mediate the formation of an immunosuppressive microenvironment and then proliferate to form metastatic lesions. In addition, DTCs that survive have different proliferation rates; some proliferate to form metastases, while others remain dormant somewhere as individuals. These metastases of different sizes that coexist in the lungs may also have different responses to radiotherapy and chemotherapy due to their different proliferation rates. This may also explain why early-stage lung cancer patients still develop metastasis after standard clinical treatment. Before disseminated tumor cells proliferate and form visible metastases, they generally cannot be detected clinically through conventional diagnostic methods or tumor biomarkers, and patients at this stage often have no clinically significant symptoms; this stage can be called the “metastasis subclinical stage”. Tian et al. proposed the pathogenesis theory of “hidden toxicity due to vital Qi deficiency” for this stage of lung cancer metastasis. According to this theory, DTCs in a dormant state are already present in the metastatic target organs of patients with early-stage lung cancer after surgery. Immunosenescence or stress mediates immune dysfunction, leading to the activation and proliferation of dormant DTCs, which in turn leads to the occurrence of clinical metastasis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024016
Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation. Furthermore, accumulated intracellular iron activates various signaling pathways or risk factors for AS, such as abnormal lipid metabolism, oxidative stress, and inflammation, which can eventually lead to the disordered function of macrophages, vascular smooth muscle cells, and vascular endothelial cells. However, the molecular pathways through which ferroptosis affects AS development and progression are not entirely understood. This review systematically summarizes the interactions between AS and ferroptosis and provides a feasible approach for inhibiting AS progression from the perspective of ferroptosis.
Chinese Journal of Pathophysiology•2025•DOI: 10.3969/j.issn.1000-4718.2025.09.002
AIM: To investigate whether melatonin can ameliorate acute myocardial infarction (AMI) by inhibiting ferroptosis. METHODS: H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI. Then cells were treated with melatonin and ferroptosis inducer erastin. The cell activity, reactive oxygen species (ROS), lipid peroxidation, mitochondrial membrane potential (MMP), and ferroptosis related protein expression were detected. A rat model of AMI induced by isoprenaline (ISO) injection was established to evaluate the effects of melatonin, in which the myocardial infarction size, cardiac injury, pathological changes, oxidative stress, iron ion and ferroptosis related protein expression were examined. RESULTS: Melatonin decreased the oxidative stress, lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia, but these effects could be impeded by the ferroptosis inducer erastin. Furthermore, in vivo experiments, we also found that melatonin improved the myocardial infarction size, cardiac injury, pathological changes, oxidative stress, and alleviated iron ion accumulation and ferroptosis. CONCLUSION: The cardioprotective effects of melatonin in AMI are associated with the inhibition of ferroptosis.
Chinese Journal of Pathophysiology•2025•DOI: 10.3969/j.issn.1000-4718.2025.06.001
AIM: Regulatory T cells (Tregs) are a specialized subset of CD4+ T cells primarily involved in immunosuppressive functions. AMP-activated protein kinase (AMPK) serves as a metabolic sensor that governs the differentiation, maturation, and immune functions of Tregs through metabolic reprogramming. However, the impact of AMPKα1 (the catalytic subunit of AMPK) knockout specifically in Tregs on the host's immune microenvironment remains largely unexplored. METHODS: Histological changes in immune organs were assessed using HE staining. The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox (AMPKα1fl/fl) mice and Treg-specific AMPKα1 knockout mice (AMPKα1fl/flFoxp3cre mice). RESULTS: Compared to AMPKα1fl/fl mice, the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significantly reduced. Additionally, while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure, both its size and the ratio of thymus weight to body weight were significantly decreased. The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative (DN) cells. Consequently, the percentage of CD4+ T cells derived from these DN cells also decreased, even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice. Importantly, the proportion of Siglec-F+ CD11b+ eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre mice. Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4+ T cells in peripheral blood, alongside a decrease in the proportion of mature CD8+ T cells. Similarly, the proportion of CD4+ T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice. In contrast, the proportion of neutrophils significantly decreased, while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice. In lymph nodes, the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred, and the lymphoid follicles were missing, a feature not observed in AMPKα1fl/fl mice. Furthermore, the knockout of AMPKα1 in Tregs reduced the CD3+ T cell population, particularly the CD8+ T cell population, in lymph nodes. Although the mature Treg cell population was significantly lower in AMPKα1fl/flFoxp3cre mice, the percentage of CD4+ T cells was markedly increased. In contrast, there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/fl mice. CONCLUSION: The populations of mature Tregs, CD8+ T cells and eosinophils in various immune organs were significantly altered in mice with Treg-specific AMPKα1 knockout, suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261616
This study interrogates the therapeutic efficacy and molecular mechanism of aconitine combined with paeoniflorin in a rat model of knee osteoarthritis (KOA), focusing on the Indian hedgehog (Ihh)-glioma-associated oncogene homolog (Gli) signaling axis. Anterior cruciate ligament transection (ACLT) was performed on male rats, which were then allocated to sham, model, celecoxib (24 mg/kg), and three aconitine-paeoniflorin dose groups (5+50, 10+100, 20+200 μg/kg; n=10 per group). Behavioral tests, hematoxylin-eosin staining, micro-computed tomography, ELISA for matrix metalloproteinase 13 (MMP13) and type II collagen (Col II), immunofluorescence, and qRT-PCR for Ihh, Gli, patched 1 (Ptch1), and MMP13 were conducted. Molecular docking assessed binding affinities. Safety was evaluated via serum aspartate aminotransferase, creatinine, blood urea nitrogen, urinary protein, and histopathology of heart, liver, and kidney. Results demonstrated that the combination significantly elevated mechanical and thermal pain thresholds (P<0.05, 0.01, 0.001), restored cartilage matrix integrity, improved bone microarchitecture, decreased serum MMP13, and increased Col II (P<0.05, 0.01, 0.001). Ihh, Gli, Ptch1, and MMP13 protein and gene expressions were markedly downregulated (P<0.05, 0.01, 0.001). Docking confirmed binding energies ≤−5 kcal/mol for aconitine and paeoniflorin with Ihh, Gli, ADAMTS5, and MMP13. No significant hepatic, renal, or cardiac toxicity was observed. The combination inhibits aberrant Ihh-Gli pathway activation, suppresses cartilage matrix degradation, and offers a safer, multi-target alternative to celecoxib for KOA management.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261612
Critical-sized bone defects (CSBD) remain a clinical bottleneck due to insufficient osteogenic drive and uncontrolled degradation of current grafts. This study evaluates a photocrosslinked hydrogel composed of cuttlebone (CB) and bovine serum albumin (BSA) for repairing 5 mm rat calvarial CSBD. SD rats were randomized into control, positive control (Bio-Oss® Collagen), BSA, 0.5% CB/BSA, 1.5% CB/BSA, and 3.0% CB/BSA groups (n=6). After 8 weeks, micro-CT revealed no new bone in controls, whereas all CB/BSA groups exhibited significant increases in bone volume fraction, bone mineral density, and trabecular thickness (P<0.05), with reduced bone surface-to-volume ratio (P<0.05). Histology confirmed new bone formation in hydrogel groups versus loose fibrous tissue in controls. Immunohistochemistry and immunofluorescence showed elevated COL1A1, PECAM-1, and OCN expression (P<0.05). qRT-PCR and Western blotting demonstrated upregulation of WNT3A, β-catenin, VEGFA, COL1A1, PECAM-1, and OCN (P<0.05). The 3.0% CB/BSA group exhibited the most pronounced osteogenic effect. Blood routine and serum liver/kidney function tests showed no abnormalities, and major organs displayed no inflammation, necrosis, or fibrosis. These findings indicate that CB/BSA photocrosslinked hydrogel promotes bone repair with favorable in vivo safety, likely through activation of the Wnt/β-catenin signaling pathway.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04896-8
Vascular calcification (VC) in type 2 diabetes (T2D) is driven by endothelial-to-mesenchymal transition (EndMT), yet effective therapies remain elusive. Elevated plasma microRNA-32-5p (miR-32) correlates with calcification, but its role in bone marrow mesenchymal stem cell-derived extracellular vesicle (BMSC-EV) therapy is undefined. We characterized BMSC-EVs by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining quantified VC severity. qRT-PCR and Western blotting assessed BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin; immunofluorescence localized VE-cadherin and N-cadherin. In vivo validation used miR-32–/– and ApoE–/– mice. RNA sequencing and bioinformatics explored mechanisms. BMSC-EVs attenuated VC in endothelial cells (ECs) and inhibited EndMT. In vivo, BMSC-EV treatment significantly reduced T2D-associated VC severity. Notably, miR-32 knockout further enhanced the inhibitory effect of BMSC-EVs on VC. Transcriptomic and functional analyses linked the protective effect to MAPK/FoxO signaling modulation, potentially via ferroptosis regulation. These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis, providing a mechanistic foundation for EV-based therapeutics.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04895-9
Spinal cord injury (SCI) remains a global health challenge with limited effective therapies. Exosomes from mesenchymal stem cells (MSCs) show neuroprotective potential, but their efficacy is constrained by insufficient potency and unclear mechanisms. This study engineered hypoxia-conditioned bone marrow MSC (BMSC)-derived exosomes and evaluated their therapeutic effects in in vitro and in vivo SCI models. Hypoxic preconditioning significantly enriched miR-615-3p in BMSC exosomes. In spinal neuron injury models, hypoxic exosomes enhanced cell viability, reduced apoptosis, and ameliorated mitochondria-associated endoplasmic reticulum membrane (MAM) dysfunction. Mechanistically, miR-615-3p directly targeted and suppressed phosphodiesterase 4C (PDE4C), activating the cAMP/PKA pathway, which modulated calcium signaling, attenuated mitochondrial calcium overload, and reduced endoplasmic reticulum stress. In a mouse SCI model, short-term treatment with hypoxic exosomes promoted functional recovery within 14 days post-injury, with improved locomotor performance, reduced lesion volume, attenuated tissue edema, and decreased inflammatory cell infiltration. In vivo, hypoxic exosomes upregulated miR-615-3p and downregulated PDE4C in injured spinal cord tissues. These results demonstrate that hypoxia-conditioned BMSC exosomes exert neuroprotective effects via the miR-615-3p/PDE4C axis, highlighting their potential as a novel therapeutic strategy for SCI by targeting calcium homeostasis and mitochondrial-ER dysfunction. However, long-term efficacy and safety beyond 14 days, as well as validation in larger animal models, remain to be established before clinical translation.
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.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026042
Efficient genome packaging is a critical step in the phage life cycle, directly influencing viral maturation and infectivity. In tailed phages, this process is driven by a packaging motor composed of a portal protein and a terminase complex. The terminase complex usually consists of a large subunit (TerL) and a small subunit (TerS), which cooperate to recognize, cleave, and translocate genomic DNA into the capsid. However, due to the remarkable diversity and complexity of phage packaging systems, the molecular mechanisms governing TerS-mediated DNA recognition remain poorly understood. Here, we report the 3.51 Å cryo-electron microscopy structure of the TerS from the short-tailed cyanophage Pam5, which infects the host Pseudanabaena mucicola Chao 1806. Pam5 TerS assembles into a nonameric ring with a radially symmetric spiral architecture. Biochemical assays show that Pam5 TerS recognizes the genomic DNA via a specific interaction between the N-terminal helix-turn-helix (HTH) domain of TerS and a 21-bp DNA sequence within the terS gene. In contrast, the TerS from another short-tailed cyanophage, Pam1, which infects the same host, binds to DNA in a sequence-independent manner. These findings reveal that cyanophages, even infecting the same host, could adopt two distinct DNA recognition strategies: HTH-mediated sequence-dependent or sequence-independent modes. This work provides structural and mechanistic insights into the diverse DNA-recognition strategies of TerS and advances our understanding of the evolutionary plasticity of viral genome packaging mechanisms.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025253
Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive subtype of renal cell carcinoma and is characterized by poor prognosis and high molecular heterogeneity. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in cancer, yet the functional role of SNHG11 in KIRC remains unclear. In this study, we perform integrated multiomics analysis using data from the TCGA and ICGC cohorts and reveal that SNHG11, a methylation-associated lncRNA, is significantly correlated with poor clinical outcomes. In vitro and in vivo assays demonstrate that SNHG11 promotes tumor proliferation and progression. Mechanistically, SNHG11 enhances oxidative phosphorylation, as evidenced by increased ATP production, disrupted mitochondrial membrane potential, and altered NAD+/NADH ratios. Furthermore, SNHG11 expression is associated with somatic mutation patterns, particularly those involving BAP1 and PBRM1, indicating potential crosstalk between epigenetic regulation and genetic alterations. These findings reveal that SNHG11 is a novel biomarker in KIRC and a potential therapeutic target.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026049
Esophageal squamous cell carcinoma (ESCC) represents a common malignancy of the digestive system. Circular RNAs (circRNAs) are a distinct class of single-stranded non-coding RNAs that are essential in the progression of various tumors given that they can act as microRNA (miRNA) sponges in a manner similar to that of mRNAs. In this study, circ_0006156 is screened to be highly expressed in ESCC tissues through high-throughput sequencing and quantitative real-time polymerase chain reaction. Subsequent in vitro and in vivo experiments are conducted to validate its biological functions. Furthermore, the regulatory relationships among circ_0006156, miR-202-5p, and TGFBR1 are investigated using RNA antisense purification, miRNA sequencing, RNA immunoprecipitation, fluorescence in situ hybridization, dual-luciferase reporter assay, and bioinformatics analyses. The results show significant overexpression of circ_0006156 in ESCC tissues, with relatively shorter overall survival observed in patients with high circ_0006156 expression. circ_0006156 is further identified to directly bind to miR-202-5p. miR-202-5p inhibits the proliferation, migration, and invasion of ESCC cells in vitro and partially rescues the effects induced by circ_0006156. Consistent results are reported by subcutaneous xenograft tumor experiments in nude mice. In addition, circ_0006156 is confirmed to act as an endogenous sponge for miR-202-5p, which results in a relieved suppression of its target gene TGFβR1. In summary, circ_0006156 can regulate TGFβR1 expression by sponging miR-202-5p, which may further activate the TGFβ/Smad pathway and promote ESCC progression. Collectively, circ_0006156 functions as a novel oncogenic RNA in ESCC and may serve as a potential tumor marker.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026043
Pentatrichomonas hominis is a zoonotic protozoan that primarily inhabits the cecum and colon of dogs, with infection rates as high as 47.4%, posing a significant public health risk due to close human contact. Current detection methods, including direct smear microscopy and PCR, have limitations in sensitivity, equipment requirements, and operational complexity. To address the need for a practical on-site detection method, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify specific antigens from P. hominis excretory-secretory (ES) proteins. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was selected as a candidate antigen due to its high immunogenicity and species specificity. The GAPDH gene was cloned and expressed in E. coli, and the recombinant protein was purified. Mouse anti-GAPDH serum was generated, and its reactivity was confirmed by Western blot and indirect ELISA (titer 1:102,400). Immunofluorescence localization showed GAPDH in the cytoplasm of P. hominis trophozoites. Based on this antigen, we developed a colloidal gold immunochromatographic strip for rapid detection of P. hominis in dogs. The strip demonstrated high sensitivity and specificity, providing a practical tool for veterinary diagnosis and epidemiological surveillance. This study is the first to report an immunochromatographic strip for P. hominis detection, offering a rapid, user-friendly alternative to existing methods.
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: 10.12307/2026.21228
BACKGROUND: Vascular injury-related diseases have garnered significant attention in the medical field, and the browning of perivascular adipose tissue is closely linked to these diseases. However, the regulatory mechanisms of specific genes involved in this process remain unclear. OBJECTIVE: To investigate the potential mechanism by which iroquois homeobox 3 regulates the browning of perivascular adipose tissue in vascular injury. METHODS: The perivascular adipose tissue-related single-cell sequencing data matrix GSE275779 was analyzed to investigate the expression levels and functions of iroquois homeobox 3 in various cell subpopulations. In conjunction with adipocyte-related microarray and sequencing data GSE44059, GSE7032, GSE185518, and GSE168387, differentially expressed genes were identified, and the expression level of iroquois homeobox 3 during the differentiation of browning adipocytes was validated. The downstream target genes of iroquois homeobox 3 were screened using the msigdb database and the ChIP-seq database GTRD. By disrupting iroquois homeobox 3 and overexpressing retinol saturase in adipocyte precursor cells, the mRNA and protein expression levels of browning-related genes were detected by qPCR and western blot. RESULTS AND CONCLUSION: Bioinformatics analysis showed that adipocyte characteristic factors such as PR domain containing 16, cell death-inducing DFFA-like effector A, and uncoupling protein 1 were significantly downregulated in perivascular adipose tissue of diabetic patients, and these genes are involved in adipose browning. Combined with high-throughput sequencing data analysis, it was found that iroquois homeobox 3 is highly expressed in brown adipose tissue and participates in brown adipocyte differentiation. Further screening identified retinol saturase as a downstream target gene of iroquois homeobox 3, and its level was differentially expressed during brown adipocyte differentiation. In mature brown adipocytes, knockdown of iroquois homeobox 3 led to decreased expression of retinol saturase and browning-related markers (uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, PR domain containing 16). In the retinol saturase rescue experiment, overexpression of retinol saturase significantly upregulated the protein levels of browning-related markers but did not affect the expression of iroquois homeobox 3. This study preliminarily reveals the potential mechanism by which iroquois homeobox 3 regulates perivascular adipose tissue browning during vascular injury.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21271
BACKGROUND: As the population ages, research on gut microbiota in the elderly is gaining attention. However, bibliometric analysis in this field is still lacking. OBJECTIVE: To comprehensively analyze literature on gut microbiota in older adults from multiple databases, identify current research hotspots, predict future trends, and provide potential directions for subsequent research. METHODS: CNKI was searched using the subject terms “gut microbiota in older adults,” “gut microecology in older adults,” and “intestinal flora in older adults.” The Web of Science database was searched using the search strategy of “TS=(elderly gut microbe OR elderly gut microbiome OR elderly gut microbiota OR elderly intestinal microbiome OR elderly intestinal microbiota).” Bibliometric tools VOSviewer and CiteSpace were employed to systematically analyze publication years, country distribution, research institutions, authors, and keywords in the retrieved literature. RESULTS AND CONCLUSION: A total of 250 and 604 eligible articles were obtained from the CNKI and Web of Science databases, respectively. From 2014 to 2023, the global publication volume in the field of gut microbiota in older adults showed a steady upward trend. Research interest and discussions in this field have increased significantly worldwide, with expanding depth and breadth through interdisciplinary collaboration. Notably, COVID-19, oxidative stress, depression, and cognitive impairment emerged as prominent keywords in the past 2 years. This bibliometric analysis visually demonstrated the research status and development trends in the field of gut microbiota in the elderly over the past decade. The field is currently in a rising phase, and further exploration of the mechanisms of gut microbiota and intervention strategies for related diseases is still needed.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21311
BACKGROUND: Alzheimer’s disease (AD) is a neurodegenerative disorder. Although β-amyloid and Tau proteins are core biomarkers for AD diagnosis, their heterogeneity and diagnostic limitations necessitate the exploration of novel biomarkers for disease diagnosis and treatment. OBJECTIVE: To analyze the interaction between N6-methyladenosine (m6A) epitranscriptomic modifications and ferroptosis genes in AD using machine learning, bioinformatics analysis, and experimental validation, to identify characteristic genes for AD pathogenesis, and to reveal their association with immune microenvironment regulation, thereby providing novel biomarkers for early diagnosis and precise treatment of AD. METHODS: Genomic data of human hippocampal tissues from GSE5281, GSE48350 (training sets), and GSE33000 (validation set) in the GEO database were integrated. Differentially expressed m6A regulators in AD were screened in the training sets, and the correlation between m6A and ferroptosis genes was assessed to identify ferroptosis-related differentially expressed genes associated with m6A. Support vector machine recursive feature elimination combined with Boruta feature selection was used to determine AD characteristic genes. Gene set enrichment analysis was performed to dissect functional modules of characteristic genes. A logistic regression model combined with receiver operating characteristic curves was constructed to evaluate the diagnostic efficacy of characteristic genes in the validation set. Single-sample gene set enrichment analysis was applied to quantify immune cell infiltration levels and analyze their regulatory association with characteristic genes. Transcription factor/miRNA-mRNA regulatory networks were predicted using ENCORI, miRWalk 3.0, and NetworkAnalyst databases. Potential therapeutic compounds were screened via the CTD database. qRT-PCR and western blotting were used to validate characteristic genes in hippocampal tissues of APP/PS1 double-transgenic mice. RESULTS AND CONCLUSION: (1) Two significantly differentially expressed m6A regulators, Wilms tumor 1 associated protein (WTAP) and methyltransferase-like protein 14 (METTL14), were identified, with 16 ferroptosis-related genes associated with them. (2) Machine learning identified five core characteristic genes: fumarate hydratase (FH), aspartate aminotransferase (GOT1), HRas proto-oncogene (HRAS), metallothionein 3 (MT3), and SET domain containing 1B (SETD1B). (3) Characteristic genes were functionally enriched in oxidative phosphorylation, Huntington disease, Parkinson disease, fatty acid degradation and metabolism, and proteasome signaling pathways. (4) The logistic regression diagnostic model achieved area under the curve values of 0.873 and 0.904 in the training and validation sets, respectively, indicating excellent diagnostic efficacy. (5) Immune microenvironment analysis showed that HRAS was significantly correlated with chemokine receptor family and plasmacytoid dendritic cell infiltration levels. (6) A regulatory network comprising 5 mRNAs, 37 miRNAs, and 142 transcription factors was constructed, and 71 potential therapeutic drugs were predicted. (7) Experimental validation showed that mRNA and protein expression of GOT1, HRAS, and SETD1B in the hippocampus of APP/PS1 mice were significantly different (P < 0.05 or P < 0.01), consistent with bioinformatics analysis. (8) The results reveal that FH, GOT1, HRAS, MT3, and SETD1B can serve as characteristic genes for AD; immune infiltration correlation analysis suggests that HRAS may serve as a potential immunotherapeutic marker for AD, providing a theoretical basis for early diagnosis and targeted therapy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21257
BACKGROUND: Chinese herbal compound has a unique curative effect on lumbar disc degeneration. In order to further understand the mechanism of its action, researchers have carried out many animal experiments in vivo, but there is no agreement on the animal model, the way of administration and the choice of observation indicators.
OBJECTIVE: To review the progress in animal experimental studies on the treatment of lumbar disc degeneration with Chinese herbal compounds, focusing on the preparation of animal models of lumbar disc degeneration, the administration methods of Chinese herbal compounds and the evaluation indexes of efficacy, in order to provide a reference for related studies.
METHODS: CNKI, WanFang, VIP, PubMed and Web of Science were retrieved by computer for relevant literature published from database inception to November 2024. The Chinese terms were “Chinese medicine, compound, Chinese medicine, herbal, drug combination, soup, formula, low back pain, degenerative disc disease, disc degeneration, intervertebral disc injury, animal, rat, mouse, rabbit, dog, pig, sheep, monkey, primate, model, modeling, experiment, research, progress, review”; the English terms were “traditional Chinese medicine, Chinese herbal medicine, Chinese medicine formula, herbal formula, intervertebral disc degeneration, degenerative disc disease, disc degeneration, intervertebral disc injury, animal model, animal experiment, preclinical study, rat, mouse, rabbit, sheep, dog, pig, non-human primate, monkey, primate, treatment, therapy, effect, intervention”. A total of 789 relevant articles were retrieved, and 139 articles met the inclusion criteria.
RESULTS AND CONCLUSION: (1) Researchers using Chinese herbal compounds to treat intervertebral disc degeneration preferred rats, gerbils, guinea pigs, mice, or New Zealand rabbits as experimental animals. (2) Various modeling methods for intervertebral disc degeneration have their own advantages and disadvantages; the annulus fibrosus puncture model is the most widely used model in such studies, and combined modeling methods can better simulate the process of intervertebral disc degeneration. (3) The administration routes of Chinese herbal compounds in animal models are consistent with those in humans, with oral administration being the main route. (4) Chinese herbal compounds have good therapeutic effects on intervertebral disc degeneration, often verified by imaging, behavioral, molecular biological, and histological methods.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21300
BACKGROUND: Traditional Chinese Medicine (TCM) has significant potential and benefits in the treatment of intervertebral disc degeneration. However, reviews on the mechanisms by which TCM ameliorates disc degeneration are relatively limited. OBJECTIVE: To review how TCM compounds and their active ingredients improve intervertebral disc degeneration through mechanisms such as anti-inflammation, antioxidative stress, maintenance of extracellular matrix balance and regulation of programmed cell death. METHODS: CNKI, WanFang, PubMed, and Web of Science were retrieved for relevant literature published from January 2001 to June 2025. The Chinese search terms were “Chinese herb, compound, traditional Chinese medicine, herbal medicine, soup, formula, degenerative disc disease, disc degeneration, disc injury, annulus fibrosus, cartilage endplates, nucleus pulposus, research, progress, review, experiment, inflammation, oxidative stress, extracellular matrix, programmed cell death, apoptosis, pyroptosis, ferroptosis, autophagy, immune cells, mechanism”, and English search terms were “Traditional Chinese medicine, herbal medicine, herbal formula, Intervertebral Disc Degeneration, Intervertebral Disc, disc degeneration, nucleus pulposus, annulus fibrosus, cartilage endplate, Oxidative Stress, Extracellular Matrix, Inflammation, Programmed Cell Death, Apoptosis, Pyroptosis, Ferroptosis, Autophagy, review, progress, experiment”. According to inclusion and exclusion criteria, 104 articles were finally included for review. RESULTS AND CONCLUSION: TCM can effectively inhibit the release of inflammatory factors and activation of inflammatory pathways through multiple mechanisms, improving the local inflammatory state of the intervertebral disc, but the specific mechanisms in immune cell-mediated inflammatory responses remain unclear. TCM shows strong multi-target regulatory ability in alleviating oxidative stress in the intervertebral disc, especially in enhancing antioxidant enzyme activity, stabilizing mitochondrial function, and inhibiting reactive oxygen species accumulation. However, systematic comparisons of antioxidant effects of different active ingredients in different disc cell types are lacking, and the crosstalk between related signaling pathways needs further exploration. TCM can effectively alleviate disc structural disruption by regulating extracellular matrix synthesis and degradative enzyme activity. Apoptosis, pyroptosis, ferroptosis, and autophagy collectively participate in the development of intervertebral disc degeneration; they are not isolated but interact through complex signaling networks. Therefore, the multi-target and holistic regulatory advantages of TCM are expected to simultaneously regulate multiple programmed cell death processes, protecting disc cells from multiple levels and delaying degeneration.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21284
BACKGROUND: Spinal cord injury triggers a cascade of neuro-muscular system damage, involving central pattern generator dysfunction and peripheral muscle molecular network disruptions. Exercise can regulate key genes and promote the recovery of spinal cord injury. OBJECTIVE: To identify exercise-regulated key genes through bioinformatics analysis and explore the mechanisms by which exercise intervention facilitates the recovery of spinal cord injury. METHODS: The GSE45550 dataset based on the GPL1355 platform was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes regulated by acute and short-term exercise interventions during the subacute phase of spinal cord injury in rats were identified. Gene Ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Gene Set Enrichment Analysis were performed on these differentially expressed genes, and a protein-protein interaction network was constructed. RESULTS AND CONCLUSION: (1) After acute exercise intervention in the subacute phase of spinal cord injury, 106 genes were upregulated and 97 genes were downregulated in the gastrocnemius muscle, whereas short-term exercise intervention resulted in 138 upregulated and 105 downregulated genes. (2) Gene Ontology analysis showed that acute exercise mainly enriched genes related to chromosome segregation, while short-term exercise mainly promoted signal transduction processes. (3) KEGG analysis indicated that acute exercise was mainly associated with gastric acid secretion and upregulation of motor protein pathways, whereas short-term exercise mainly involved upregulation of neuroactive ligand-receptor interaction and downregulation of some inflammatory signaling pathways. (4) GSEA analysis revealed that acute exercise mainly upregulated cell cycle and DNA separation, while short-term exercise mainly downregulated interleukin-17 signaling and tumor necrosis factor signaling pathways. (5) Protein-protein interaction network showed that acute and short-term exercise interventions formed 2 and 3 central modules, respectively. In summary, acute exercise intervention significantly activates cell proliferation-related pathways (such as cell cycle and mitosis), upregulating pro-proliferative genes like Top2a and Sele; whereas short-term intervention exerts anti-inflammatory effects by downregulating inflammatory pathways such as interleukin-17 and tumor necrosis factor, and downregulating factors like COMP. These findings provide a reference for the molecular mechanism research of spinal cord injury rehabilitation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21413
BACKGROUND: Recently, percutaneous minimally invasive pedicle screw fixation systems have become a popular treatment option for thoracolumbar fractures due to ongoing innovation in orthopedic internal fixation devices. Currently, while many studies compare the effectiveness of open pedicle screw fixation through or across the fractured vertebra, fewer studies compare these two methods when using navigation-assisted percutaneous minimally invasive techniques. OBJECTIVE: To compare the clinical efficacy of percutaneous minimally invasive pedicle screw fixation in the treatment of thoracolumbar fracture through and across the injured vertebra. METHODS: A retrospective analysis was performed on 67 patients with single level thoracolumbar fracture without spinal cord nerve injury who were treated in the Department of Spine Surgery, Affiliated Hospital of Yan'an University from October 2021 to June 2023. All of them were treated with percutaneous pedicle screw fixation with the assistance of computer navigation, and were followed up to 6 months after surgery. The injured vertebrae were divided into transinjured vertebrae group (n=35) and cross-injured vertebrae group (n=32). RESULTS AND CONCLUSION: ① There were no significant differences in preoperative general data between the two groups (P > 0.05), indicating comparability. ② Intragroup comparison: In both groups, the anterior vertebral height ratio, Cobb angle, visual analog scale score, and Oswestry disability index at 7 days and 6 months after surgery were significantly improved compared with preoperative values (P < 0.05). ③ Intergroup comparison: The operation time, intraoperative blood loss, incision length, and intraoperative fluoroscopy times in the cross-injured vertebrae group were significantly less than those in the trans-injured vertebrae group (P < 0.05), while there was no significant difference in hospital stay between the two groups (P > 0.05). At 7 days and 6 months after surgery, there were no significant differences in anterior vertebral height ratio, Cobb angle, visual analog scale score, and Oswestry disability index between the two groups (P > 0.05). ④ It is suggested that for patients with single-level thoracolumbar fractures without spinal cord nerve injury, compared with trans-injured vertebra fixation, percutaneous minimally invasive pedicle screw fixation across the injured vertebra has advantages of shorter operation time, less bleeding, smaller surgical incision, and fewer fluoroscopy times. In the medium-term follow-up period, both trans-injured and cross-injured percutaneous minimally invasive fixation can effectively restore and maintain the height of the injured vertebra, correct kyphotic deformity, rebuild spinal stability, and relieve pain, achieving excellent clinical results. For patients with AO type A thoracolumbar fractures with normal body mass index, without spinal cord nerve injury and posterior ligamentous complex injury, the less traumatic cross-injured vertebra percutaneous pedicle screw fixation is recommended.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21402
BACKGROUND: There are individual differences in the effectiveness of arthroscopic surgery in improving knee osteoarthritis, and subjective scoring scales may be biased in evaluating the clinical efficacy of arthroscopic treatment for knee osteoarthritis. OBJECTIVE: To explore the correlation between gait parameters and joint function recovery in patients with knee osteoarthritis after arthroscopic surgery. METHODS: A total of 98 patients with knee osteoarthritis admitted to Chongqing Armed Police Corps Hospital from October 2023 to October 2024 were selected as the research subjects. According to Lysholm knee function score after 6 months of follow-up, they were divided into the excellent group (n=63) and the fair group (n=35). Clinical data including gender, age, body mass index, disease duration, respiration, heart rate, Kellgren-Lawrence grade, smoking history, drinking history, hypertension history, location of onset, and postoperative complications were collected. The intraoperative and postoperative indicators, as well as the knee joint function scores and gait parameters at different times before and after surgery were compared between the two groups. Multivariate Logistic regression was used to analyze the independent influencing factors of knee joint function recovery. Stratified regression analysis was conducted to explore the impact of different clinical and pathological characteristics after treatment on gait parameters. Generalized estimating equations were used to analyze the differences in gait parameters among patients with different knee joint functions after treatment. Generalized additive models were used to analyze the impact of gait parameters on Lysholm score after treatment. Receiver operating characteristic curves were drawn to analyze the value of gait parameters in judging the recovery of knee joint function after treatment. RESULTS AND CONCLUSION: (1) There were significant differences in age, disease duration, Kellgren-Lawrence grade, and postoperative complications between the excellent and fair groups (P < 0.05). (2) The fair group had longer operation time, more intraoperative blood loss, longer postoperative swelling regression time, and longer rehabilitation time than the excellent group (P < 0.05). (3) After surgery, the fair group had higher Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale scores, and lower Lysholm score, step frequency, and step speed than the excellent group (P < 0.05). (4) Logistic regression analysis showed that age, Kellgren-Lawrence grade, postoperative complications, and postoperative swelling regression time were independent risk factors affecting knee joint function recovery (P < 0.05). (5) Stratified regression analysis showed that age, Kellgren-Lawrence grade, postoperative swelling regression time, and postoperative complications all had negative effects on step frequency and step speed (β < 0, P < 0.05). (6) Generalized estimating equation analysis showed that the degree of knee joint function recovery was associated with gait characteristics (β > 0, P < 0.05). (7) Generalized additive model analysis showed that the effects of step frequency and step speed on Lysholm score after treatment were linear. (8) Receiver operating characteristic curve analysis showed that the combined detection of step frequency and step speed had higher predictive efficacy (area under the curve > 0.85, P < 0.05). (9) These findings suggest that arthroscopic surgery can improve knee joint function in patients with knee osteoarthritis, and dynamic tracking of postoperative gait parameter changes combined with functional scoring scales reveals the association between step frequency, step speed, and knee joint function outcome, further clarifying its clinical predictive value and providing a new quantitative tool for clinical functional assessment to achieve more precise postoperative rehabilitation guidance.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21393
BACKGROUND: The elastic modulus of β-tricalcium phosphate bioceramic rods is close to that of normal bone tissue, and it exhibits excellent biocompatibility and mechanical properties. It can be used as a supporting material inside the femoral head after core decompression. However, there are few biomechanical studies on osteonecrosis of the femoral head and the changes in stress and displacement of the femoral head after ceramic rod implantation. OBJECTIVE: To explore the biomechanical effects of core decompression with ceramic rod implantation in the treatment of osteonecrosis of the femoral head during the peri-collapse stage. METHODS: A total of 21 hips were selected from 19 patients with osteonecrosis of the femoral head implanted with ceramic rods at the peri-collapse stage. Preoperative and postoperative imaging data were obtained, and relevant CT images were loaded in Mimics 21.0 software to construct a three-dimensional model of the femoral head. A global model of the proximal femur that includes cortical and cancellous bone, as well as a model of the proximal cancellous bone of the femur were created. The preoperative MRI image data of the patients were imported, and the necrotic lesion model was made by using the graphic matching technology, which was saved in .stl format. They were transferred to Geomagic 2012 software for smoothing and precise surface processing. Subsequently, the ceramic rod was designed and modeled in SolidWorks 2021 software, and the relevant models were imported for assembly and Boolean operations. After ensuring no interference, ANSYS 2021 software was used to calculate and observe the stress and displacement of the weight-bearing area and necrotic area of the femoral head during single-leg stance and the push-off phase of walking. RESULTS AND CONCLUSION: (1) The area of maximum stress on the femoral head was located in the anterolateral superior part of the necrotic area. During single-leg stance, the stress values in the weight-bearing area and necrotic area were significantly lower postoperatively than preoperatively (P < 0.05), and the femoral head collapse value (displacement of the weight-bearing area) was lower than preoperatively (P < 0.05). (2) During the push-off phase of walking, with the increase in load, the stress values in the weight-bearing area and necrotic area and the femoral head collapse value (displacement of the weight-bearing area) increased, but they were still lower than preoperatively (P < 0.05). (3) It is suggested that core decompression combined with ceramic rod implantation helps to reduce the load on the weight-bearing area of the femoral head, effectively disperse the stress in the weight-bearing area, partially transfer the load to the femoral calcar, improve the local stress concentration, and effectively support the femoral head to prevent further collapse.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21386
BACKGROUND: High tibial osteotomy is an effective treatment for certain patients with knee osteoarthritis; however, traditional T-shaped plates have multiple limitations. OBJECTIVE: To compare the biomechanical performance of titanium alloy porous blocks with that of conventional T-shaped plates and bone grafting schemes in high tibial osteotomy using finite element analysis. METHODS: A computer simulation experiment was conducted, performing three-dimensional finite element analysis on a 55-year-old male patient who underwent high tibial osteotomy. Three different implant geometries were constructed: a conventional T-shaped plate high tibial osteotomy model (Model A), a bone graft–augmented high tibial osteotomy model (Model B), and a titanium alloy porous block–augmented high tibial osteotomy model (Model C). These models were used to evaluate the effects of each implant on total displacement and stress distribution under two loading conditions: standing and initial rising from a seated position. RESULTS AND CONCLUSION: (1) Validation results confirmed that the finite element models were effective. (2) In terms of stability, Model C (titanium alloy porous block–augmented high tibial osteotomy) demonstrated the best reduction in total displacement, with maximum displacements under both standing and rising conditions significantly lower than those of the other two models. (3) Stress analysis revealed that Model C had the lowest T-shaped plate stress levels, (40.9±36.5) MPa (standing) and (66.1±44.7) MPa (rising), reduced by 91.2% and 92.9% compared to Model A; additionally, the average stress at the lateral hinge site was significantly lower than Models A and B, indicating an advantage in reducing lateral hinge fracture risk. Stress distribution at the proximal osteotomy contact surface and hinge site showed that Model C had better stress stimulation effects, promoting bone healing while reducing hinge fracture risk. (4) These findings suggest that the titanium alloy porous block not only enhances initial stability of the surgical area but also optimizes stress transmission pathways and provides a favorable biocompatible environment, offering a new approach to address the limitations of existing plates in mechanical stability and biological fusion, with potential clinical application value.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21370
BACKGROUND: In recent years, metabolic disorders have been confirmed to be closely related to the onset of osteoarthritis, but the causal relationship between plasma metabolites and osteoarthritis has not been systematically elucidated. OBJECTIVE: To explore the causal relationship between 1,400 plasma metabolites and 9 types of osteoarthritis using two-sample Mendelian randomization. METHODS: A genome-wide association study of 1,400 metabolites was used as the exposure. Nine types of arthritis, namely any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, hip osteoarthritis, spinal osteoarthritis, finger osteoarthritis, hand osteoarthritis, and thumb osteoarthritis, were set as the outcomes. Single nucleotide polymorphisms were used as instrumental variables, and sensitive single nucleotide polymorphisms were selected for Mendelian randomization analysis. The inverse variance weighted method was used as the main analysis approach. Meanwhile, four methods, namely MR-Egger, weighted median, simple mode, and weighted mode, were employed for cross-validation. MR-PRESSO, Cochran's Q test, and other methods were used for sensitivity and pleiotropy analyses. The false discovery rate method was used for further correction. RESULTS AND CONCLUSION: Mendelian randomization analysis showed that finger osteoarthritis, hand osteoarthritis, hip osteoarthritis, and spinal osteoarthritis had no results meeting FDR < 0.05. Any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, and thumb osteoarthritis were significantly causally associated with multiple metabolites. Metabolites such as glycine, serine, higenamine, and sulfate were closely related to multiple osteoarthritis types. Compared with some non-weight-bearing joint osteoarthritis (e.g., finger and hand osteoarthritis), plasma metabolites showed stronger sensitivity with weight-bearing joint osteoarthritis (e.g., knee and hip osteoarthritis). This study provides a theoretical basis for metabolic intervention strategies for osteoarthritis in the Chinese population and offers a methodological paradigm for mechanistic research on complex diseases in China.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21317
BACKGROUND: Existing animal models of knee osteoarthritis predominantly focus on mechanical injury factors but fail to simulate and observe the "cold-dampness obstruction" syndrome characteristics in traditional Chinese medicine. OBJECTIVE: To construct a traditional Chinese medicine-Western medicine integrated knee osteoarthritis model for cold-dampness obstruction syndrome and validate its efficacy via a multidimensional assessment. METHODS: Twenty-four male Sprague-Dawley rats (SPF-grade) were randomly divided into sham-operated, model, and cold-dampness obstruction groups. The latter two groups underwent anterior cruciate ligament transection of the right hind knee. The cold-dampness obstruction group received artificial cold-damp environment intervention (temperature 10.5 °C, humidity 90%, 4 h/day, for 4 weeks) starting 14 days post-surgery. The sham-operated group had skin incision and immediate closure. Before modeling and at 1, 2 weeks post-modeling, and 4 weeks after cold-damp intervention, traditional Chinese medicine syndrome scores and CatWalk gait analysis were performed. Right hind knee joint tissues were harvested for histopathological observation and Mankin scoring. RESULTS AND CONCLUSION: (1) Traditional Chinese medicine syndrome scores: The cold-dampness obstruction group showed significant mental fatigue, reduced activity, loose stools, dark purple tongue, dull fur, decreased food intake, and slower weight gain (P < 0.01). (2) CatWalk gait parameters: At 1 week post-modeling, compared with the sham-operated group, the model and cold-dampness obstruction groups showed decreased maximum contact intensity, print length, maximum intensity, average intensity of 15 maximum pixels, and increased swing phase of the right hind paw (all P < 0.01). The cold-dampness obstruction group also showed significantly decreased swing speed (P < 0.05). After 4 weeks in the artificial climate chamber, compared with the sham-operated group, the cold-dampness obstruction group showed significantly decreased maximum contact intensity, maximum intensity, average intensity of 15 maximum pixels (P < 0.01), increased swing phase (P < 0.01), and decreased swing speed (P < 0.05). (3) Histopathology: Mankin scores in the model and cold-dampness obstruction groups were significantly higher than in the sham-operated group (P < 0.01), and the cold-dampness obstruction group had significantly higher scores than the model group (P < 0.01). These results indicate that anterior cruciate ligament transection combined with cold-damp environment can successfully construct a cold-dampness obstruction type early knee osteoarthritis rat model. CatWalk gait parameters and traditional Chinese medicine syndrome scores provide an objective evaluation system for studying the mechanisms of traditional Chinese medicine in knee osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21336
BACKGROUND: High-altitude hypoxia has been reported to damage the male reproductive system, but whether stem cells can protect against male reproductive damage caused by high-altitude hypoxia has not been reported. OBJECTIVE: To investigate the preventive effect of human umbilical cord mesenchymal stem cell transplantation on reproductive damage in hypoxia-exposed male mice. METHODS: Human umbilical cord mesenchymal stem cells were isolated and cultured, and three-lineage differentiation and flow cytometry identification were performed. Twenty-one C57BL/6 male mice were randomly divided into control, hypoxia, and stem cell groups (n=7). The hypoxia and stem cell groups were exposed to a chronic intermittent hypoxia model simulating an altitude of 5,000 m (11.1% oxygen). In the stem cell group, 1×10^6 human umbilical cord mesenchymal stem cells were injected via the tail vein once a week for 6 weeks, while the other groups received PBS. Body mass, food intake, and water intake were monitored. After hypoxia exposure, testicular tissue was analyzed for morphology, ultrastructure, reactive oxygen species levels, and mitochondrial membrane potential; epididymal tissue was analyzed by hematoxylin-eosin staining and sperm motility; and the homing ability of stem cells was observed by DiL fluorescence tracing. RESULTS AND CONCLUSION: Human umbilical cord mesenchymal stem cell transplantation significantly improved water and food intake in hypoxic mice but had no significant effect on body mass. Morphological analysis showed that hypoxia caused edema of the testis and epididymis and shedding of spermatogenic cells, while stem cell transplantation alleviated these structural damages and reversed mitochondrial swelling and atrophy in germ cells. Additionally, stem cell transplantation significantly inhibited hypoxia-induced increase in reactive oxygen species, restored mitochondrial membrane potential, and improved sperm motility. Tracing experiments showed that after entering the mice, stem cells mainly accumulated in lung tissue, with low homing to the testis. In conclusion, human umbilical cord mesenchymal stem cell transplantation can protect the structure and function of germ cell mitochondria, reduce hypoxia-induced testicular and epididymal edema, and thereby restore spermatogenesis and sperm motility.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21360
BACKGROUND: In recent years, the application of kidney organoid technology in acute kidney injury has gradually become a research hotspot. Traditional animal models have species differences from humans, and physiological and pathological processes of their kidneys cannot fully represent the human situation. Kidney organoid technology forms 3D kidney models through stem cell culture, which can simulate the complex structure and function of human kidneys. It has shown great potential in disease modeling and mechanism exploration of acute kidney injury, prediction of drug nephrotoxicity, and exploration of regeneration and repair mechanisms. OBJECTIVE: To summarize the application progress of kidney organoids in acute kidney injury research, providing new technical means and research strategies for the prevention and treatment of acute kidney injury. METHODS: Literature related to organoids and acute kidney injury was searched in CNKI and PubMed databases. Chinese search terms included "acute kidney injury, organoid, pluripotent stem cells, 3D bioprinting, kidney-on-a-chip, regenerative medicine, kidney transplantation"; English search terms included "acute kidney injury, organoid, pluripotent stem cells, 3D bioprinting, kidney-on-a-chip, regenerative medicine, kidney transplantation". All retrieved literature were original research articles and relevant reviews, with the search time limit from database inception to April 2025. Finally, 99 articles were screened for analysis and summary. RESULTS AND CONCLUSION: (1) The cell sources for inducing kidney organoid formation reported in the literature mainly include pluripotent stem cells, embryonic stem cells, and urine-derived stem cells. These induced kidney organoids play important roles in in vitro drug screening, kidney development, and disease modeling. (2) 3D bioprinting and kidney-on-a-chip technology are emerging techniques for constructing kidney organoids. 3D bioprinting can precisely and specifically construct complex multicellular structures, while kidney-on-a-chip technology has characteristics such as high gas permeability, sensitivity, and low cost, which can extend organoid lifespan, increase biocompatibility, and are suitable for preclinical drug development and toxicity screening. (3) The combination of gene editing technology with kidney organoid models brings new perspectives and tools for kidney disease research, drug development, and regenerative medicine. It can construct kidney organoids with specific reporter genes or sensitive indicators, and amplify and classify specific kidney cell types in kidney organoids. (4) Kidney organoids show unique advantages in disease simulation, drug evaluation, and exploration of regenerative therapeutic strategies for acute kidney injury. They can serve as in vitro models to study the toxicity mechanisms of drugs such as cisplatin, doxorubicin, and red yeast rice supplements that cause acute kidney injury, screen high-throughput drugs and therapeutic targets, and also play an important role in the field of renal transplantation regenerative medicine.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21348
BACKGROUND: Platelets are important blood resources, yet in routine blood bank processes they are often filtered out along with white blood cells as medical waste. Optimizing whole blood separation processes to prepare platelet lysate products and exploring their applications in tissue engineering and regenerative medicine is of great value. OBJECTIVE: To optimize whole blood separation to prepare therapeutic-grade platelet lysate and to investigate the protective effect of platelet lysate on hypoxic injury of cardiomyocytes. METHODS: Platelets were isolated from 21 qualified whole blood units under closed blood bag and tubing conditions, and 21 platelet lysates were prepared by freeze-thawing. The mass concentration ranges of platelet-derived growth factor AA, platelet-derived growth factor BB, platelet-derived growth factor AB, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, and transforming growth factor beta 1 in platelet lysates were measured using enzyme-linked immunosorbent assay kits. Bacterial contamination was assessed by colony culture method and mycoplasma contamination by PCR detection kit. A cardiomyocyte hypoxia model was established to evaluate the protective effect of platelet lysate on hypoxic injury. RESULTS AND CONCLUSION: (1) The mass concentration ranges of major growth factors and cytokines in platelet lysates were: platelet-derived growth factor AA 12.86-24.17 μg/L, platelet-derived growth factor BB 0.25-0.32 μg/L, platelet-derived growth factor AB 85.09-114.91 μg/L, vascular endothelial growth factor 10.57-58.37 μg/L, epidermal growth factor 0.43-0.69 μg/L, insulin-like growth factor 1 106-204.9 μg/L, fibroblast growth factor 0.03-0.06 μg/L, and transforming growth factor beta 1 124.17-192.38 μg/L. (2) Colony culture and mycoplasma detection results were negative. (3) Low volume fraction (1%) platelet lysate yielded the highest proliferation efficiency of cardiomyocytes; low volume fraction (1%) platelet lysate stimulated cardiomyocytes to produce high levels of superoxide dismutase and glutathione peroxidase to protect cardiomyocytes. This study established a method for preparing therapeutic-grade platelet lysate by optimizing the whole blood separation process, which can improve the utilization rate of blood resources. Platelet lysate has high levels of major growth factors and can significantly promote the repair of hypoxic injured cardiomyocytes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21344
BACKGROUND: Neural stem cells located in the ventricular zone and subventricular zone are crucial for cortical neurodevelopment and the treatment of neurodegenerative diseases. However, their precise regulatory mechanisms remain incompletely understood. miRNA-9 is one of the most abundantly expressed miRNAs in the vertebrate embryonic and adult brain, playing diverse roles during development. Nevertheless, the role of miR-9 in neural stem cell differentiation remains unclear. OBJECTIVE: To investigate the role of miR-9 in regulating the differentiation of neural stem cells in the ventricular zone and subventricular zone. METHODS: Neural stem cells were isolated from the ventricular zone and subventricular zone of embryonic day 14.5 ICR mice and cultured in proliferation medium for 3-4 days to form neurospheres. Stemness was identified by Pax6/Nestin immunofluorescence double staining. The expression profile of miR-9 was detected by qRT-PCR in telencephalon tissues at embryonic days 12.5, 14.5, 16.5, 18.5 and postnatal days 0, 7, as well as in embryonic day 14.5 neural stem cells cultured in vitro. Neural stem cells were transfected with miR-9 inhibitor or mimic using transfection reagents. After 24 hours, cells were differentiated for 3-4 days (neurons) and 6-8 days (glial cells). The differentiation of each lineage was quantified by immunofluorescence staining for Tuj1 (neuronal marker), myelin basic protein (oligodendrocyte marker), and glial fibrillary acidic protein (astrocyte marker). RESULTS AND CONCLUSION: qRT-PCR results showed that miR-9 was highly expressed in early embryonic telencephalon (E12.5-E14.5) and gradually decreased with development (E16.5 to P7). In E14.5 neural stem cells, miR-9 expression level was close to 90% of the internal reference RNU6B. Functional experiments showed that compared with the control group, the miR-9 inhibition group had decreased proportions of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes, while the proportion of glial fibrillary acidic protein-positive astrocytes increased. Conversely, the miR-9 overexpression group had increased proportions of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes, and decreased proportion of glial fibrillary acidic protein-positive astrocytes, with significant differences (P < 0.001). These results indicate that miR-9 plays a bidirectional regulatory role in neural stem cell differentiation: (1) It participates in the temporal regulation of neurogenesis through developmental stage-specific expression patterns (high early, downregulated later); (2) It maintains the balance of trilineage differentiation by promoting neuronal and oligodendrocyte differentiation while inhibiting astrocyte generation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21407
BACKGROUND: The pathological process of intervertebral disc degeneration is accompanied by angiogenesis-lymphatic imbalance and changes in the immune microenvironment, both of which play important roles in intervertebral disc degeneration. OBJECTIVE: To systematically summarize the roles of angiogenesis-lymphatic imbalance-related cytokines in intervertebral disc degeneration. METHODS: The first author searched relevant literature published between January 2000 and April 2025 in the PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The Chinese search terms included "intervertebral disc degeneration, vascular-lymphatic imbalance, angiogenesis, vascular endothelial growth factor (VEGF), lymphatic vessel, Prox-1, immune microenvironment." A total of 65 articles were ultimately included for review. RESULTS AND CONCLUSION: During intervertebral disc degeneration, the vascular-lymphatic system and immune microenvironment play crucial roles in maintaining disc homeostasis. When disc degeneration occurs, angiogenesis and lymphatic disruption increase inflammatory factors within the disc, leading to enhanced degradation of the extracellular matrix. Concurrently, changes in the immune microenvironment, characterized by increased immune cell infiltration, elevated levels of pro-inflammatory cytokines and chemokines, and activation of local immune responses, modulate vascular and lymphatic vessels, ultimately reducing disc repair capacity and inducing chronic pain, thereby exacerbating the degree of disc degeneration.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21452
BACKGROUND: Tendon injury repair is often compromised by inflammatory cascades and disordered collagen metabolism, leading to scar formation and mechanical deterioration. Curcumin exhibits anti-inflammatory, antioxidant, and pro-repair potential, but its rapid metabolism and low bioavailability limit clinical application. OBJECTIVE: To construct a thermosensitive injectable curcumin-loaded chitosan/sodium β-glycerophosphate hydrogel and evaluate its efficacy in tendon repair. METHODS: (1) Rat tendon stem cells were cultured with different concentrations of curcumin for 24 hours. Cell viability was assessed using the CCK-8 assay, and the 20 µmol/L concentration was selected for subsequent experiments. Rat tendon stem cells were cultured with 0 (control) and 20 µmol/L curcumin, and cell migration was assessed using a wound healing assay. Rat tendon stem cells were cultured in three groups: a control group received no treatment; a model group received tert-butyl hydroperoxide to induce oxidative stress; a curcumin group received tert-butyl hydroperoxide plus 20 µmol/L curcumin. qRT-PCR and western blot were used to detect the expression of matrix metalloproteinase 3, matrix metalloproteinase 13, collagen type I alpha 1 chain, collagen type III alpha 1 chain, Bcl-2, and Bax. (2) Chitosan/sodium β-glycerophosphate thermosensitive injectable hydrogels with or without curcumin (final concentration 20 µmol/L) were prepared. The microstructure and drug release were characterized. Rat tendon stem cells were co-cultured with the hydrogels, and cell compatibility was evaluated by live/dead staining and cytoskeletal staining. (3) Sixty SD rats were randomly divided into five groups: sham surgery (n=12), model (n=12), hydrogel only (n=12), curcumin solution (n=12), and curcumin-loaded hydrogel (n=12). The Achilles tendon rupture model was established, and treatments were injected at the tendon stump, with a second injection after 4 days. At 8 weeks post-surgery, peritendinous adhesion, hematoxylin-eosin staining, Masson staining, immunohistochemistry for cyclooxygenase-2 and collagen type I alpha 1 chain, and biomechanical analysis were performed. RESULTS AND CONCLUSION: (1) Curcumin promoted the migration of rat tendon stem cells. Compared with the model group, the curcumin group showed decreased mRNA and protein expression of matrix metalloproteinase 3, matrix metalloproteinase 13, collagen type III alpha 1 chain, and Bax protein (P < 0.05), and increased expression of collagen type I alpha 1 chain and Bcl-2 protein (P < 0.05). (2) Scanning electron microscopy revealed a typical three-dimensional porous network structure of the hydrogel with uniform pore size and interconnected pores. The curcumin-loaded hydrogel exhibited good sustained release. Live/dead and cytoskeletal staining showed good cytocompatibility. (3) The curcumin-loaded hydrogel group had lower peritendinous adhesion than the model, hydrogel only, and curcumin solution groups. Hematoxylin-eosin and Masson staining showed reduced inflammatory cell infiltration and orderly collagen deposition in the curcumin-loaded hydrogel group. Immunohistochemistry showed lower cyclooxygenase-2 expression and higher collagen type I alpha 1 chain expression in the curcumin-loaded hydrogel group compared with the model and hydrogel only groups (P < 0.05). The maximum tensile stress and elastic modulus were higher in the curcumin-loaded hydrogel group than in the model, hydrogel only, and curcumin solution groups (P < 0.05). In conclusion, the curcumin-loaded chitosan/sodium β-glycerophosphate thermosensitive hydrogel synergistically exerts anti-inflammatory effects and promotes orderly collagen deposition, significantly improving the quality of tendon repair.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21447
BACKGROUND: Neobavaisoflavone could promote bone formation and may be a potential small molecule drug for bone regeneration. The use of 3D printed bone tissue engineering scaffolds as drug delivery carriers for neobavaisoflavone is expected to enhance the potential application of bone regeneration. OBJECTIVE: To explore the effects of polylactic acid/polydopamine/neobavaisoflavone bone scaffold on osteoclast and osteoblast activity. METHODS: (1) Fused deposition modeling technology was used to manufacture a 3D printed polylactic acid scaffold. These polylactic acid scaffolds were immersed in a dopamine solution containing or without neobavaisoflavone to produce polylactic acid/polydopamine/neobavaisoflavone scaffolds and polylactic acid/polydopamine scaffolds, respectively. The surface morphology, surface hardness, and compressive strength of the three groups of scaffolds were characterized, and the drug release properties of the polylactic acid/polydopamine/neobavaisoflavone scaffolds were investigated. (2) Mouse embryonic osteoblast MC3T3-E1 cells were co-cultured with the three groups of scaffolds. CCK-8 assay and live/dead staining were used to evaluate the cytocompatibility of the scaffolds. Transwell assay was used to evaluate the effect of scaffolds on osteoblast migration. Alkaline phosphatase quantitative assay and alizarin red staining were used to evaluate the effect of scaffolds on osteoblast differentiation. RAW264.7 cells were co-cultured with the three groups of scaffolds. After osteoclast induction, tartrate-resistant acid phosphatase staining was used to evaluate the effect of scaffolds on osteoclast differentiation. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that all three groups of scaffolds had three-dimensional structure and regular interconnected porous structure with an average pore size of 400 µm. The surface hardness and compressive strength of polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds were higher than those of polylactic acid scaffolds (P < 0.05). Polylactic acid/polydopamine/neobavaisoflavone scaffolds had good drug release behavior and could continuously release drugs for more than 14 days in vitro. (2) CCK-8 assay and live/dead staining showed that all three groups of scaffolds had good cytocompatibility, and polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds could promote MC3T3-E1 cell proliferation. Transwell assay showed that compared with polylactic acid scaffolds, polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds could promote MC3T3-E1 cell migration. Alkaline phosphatase quantitative assay and alizarin red staining showed that compared with the other two groups, polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds could promote osteogenic differentiation of MC3T3-E1 cells. Tartrate-resistant acid phosphatase staining showed that polylactic acid/polydopamine/neobavaisoflavone scaffolds could inhibit osteoclast differentiation of RAW264.7 cells. (3) These results indicate that polylactic acid/polydopamine/neobavaisoflavone scaffolds have good biosafety and can promote bone regeneration by regulating osteoblast and osteoclast activities.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21499
BACKGROUND: Increasing evidence has demonstrated the crucial role of synovial cell-chondrocyte signaling crosstalk mediated by synovial fluid exosomes in knee osteoarthritis. The signaling interaction between synovial cells and chondrocytes reveals, at the molecular level, the bidirectional regulatory role of synovial fluid exosomes in the progression of knee osteoarthritis. OBJECTIVE: To comprehensively interpret the interactions between synoviocytes and chondrocytes mediated by synovial fluid exosomes from multiple perspectives and levels to provide new insights and directions for research and clinical applications in the related field. METHODS: A literature search was conducted in PubMed for publications from January 2001 to June 2025 using the keywords “osteoarthritis*, exosomes, synovial cells, chondrocytes.” All relevant original studies, reviews, and clinical trials published from January 2001 to June 2025 were included, while irrelevant mechanisms and low-relevance studies were excluded. Finally, 93 articles were selected for comprehensive analysis. RESULTS AND CONCLUSION: During the development and progression of knee osteoarthritis, synovial cells and chondrocytes establish close signal communication via synovial fluid exosomes. This signaling interaction significantly affects the progression of knee osteoarthritis, potentially exacerbating cartilage degeneration and synovial inflammation, while also exerting protective regulatory effects under specific conditions. Therefore, the dual nature of this mechanism highlights the necessity for precise intervention, and targeting key molecules in exosome-mediated intercellular signaling pathways may offer new therapeutic strategies and targets for knee osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21482
BACKGROUND: During the repair process following tendon injury, an excessive inflammatory response can cause tendon cell apoptosis, thereby leading to a reduction in the biomechanical properties of the tendon. Meanwhile, a persistent inflammatory response can also trigger tissue fibrosis and adhesion. Studies have confirmed that interleukin-10 exerts an inflammatory regulatory role in connective tissue cells such as fibroblasts and can block inflammatory responses produced in various models. OBJECTIVE: To explore the effect of interleukin-10 against inflammatory responses following acute tendon injury. METHODS: Forty-two Sprague-Dawley rats were randomly divided into a normal group (n=6), model group (n=12), control group (n=12), and intervention group (n=12). Except for the normal group, the other three groups underwent acute Achilles tendon injury modeling via intra-tendinous injection of type I collagenase solution (the model was successfully established after 3 days). On the day of modeling, the control and intervention groups were subjected to daily injections of PBS and interleukin-10 protein solution, respectively, at the 1 cm points on both sides of the hind limb midline and abdominal midline intersection. Injections were given once daily for 4 consecutive days. On day 3 after successful modeling, ultrasound examination of the Achilles tendon was performed. On days 3 and 7 after successful modeling, tissue samples were collected for hematoxylin-eosin staining to observe pathological changes, immunohistochemical staining to detect phosphorylated nuclear factor kappa B (p-NF-κB) and tumor necrosis factor alpha (TNF-α) protein expression, RT-PCR to detect NF-κB, TNF-α, and cyclooxygenase-2 (COX-2) mRNA expression, and western blot to detect p-NF-κB, TNF-α, and COX-2 protein expression. RESULTS AND CONCLUSION: Ultrasound showed that the model group had blurred tendon boundaries and increased thickness, while the intervention group had clearer boundaries and thickness close to normal. Hematoxylin-eosin staining on day 3 showed that the model and control groups had disordered collagen fibers, massive inflammatory cell infiltration, and round nuclei concentrated; the intervention group had reduced fiber disorder, fewer inflammatory cells, and more elongated spindle-shaped tenocytes. On day 7, the model and control groups showed significantly improved collagen fiber arrangement, reduced inflammatory infiltration, and tenocytes transitioning from round to spindle shape with mostly aligned nuclei; the intervention group showed parallel and orderly collagen fibers approaching normal, further reduced inflammatory infiltration, and mostly elongated spindle-shaped tenocytes. Immunohistochemistry showed that on days 3 and 7, the model group had higher p-NF-κB and TNF-α protein expression than the normal and intervention groups (P < 0.05). RT-PCR showed that on days 3 and 7, the model group had higher NF-κB, TNF-α, and COX-2 mRNA expression than the normal and intervention groups (P < 0.05). Western blot showed that on days 3 and 7, the model group had higher p-NF-κB, TNF-α, and COX-2 protein expression than the normal group (P < 0.05); on day 3, the intervention group had lower p-NF-κB, TNF-α, and COX-2 protein expression than the model group (P < 0.05). These findings indicate that interleukin-10 can alleviate inflammatory responses during acute tendon injury repair.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21480
BACKGROUND: Autophagy and senescence are considered important factors in the pathogenesis of osteoarthritis, but their specific regulatory mechanisms remain unclear. OBJECTIVE: To screen autophagy- and senescence-related genes in osteoarthritis through bioinformatics analysis combined with machine learning methods, providing new molecular targets for early diagnosis and treatment of osteoarthritis. METHODS: Osteoarthritis-related datasets (including GSE51588, GSE169077, and GSE114007) were downloaded from the GEO database. Differential expression analysis, weighted gene co-expression network analysis, and functional enrichment analysis were performed to screen autophagy- and senescence-related genes in osteoarthritis. LASSO regression, random forest (RF), and support vector machine (SVM) were used to further screen potential core genes, and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of core genes. Based on the GSE51588 dataset, the CIBERSORT algorithm was used to analyze the proportions of immune cell types such as T cell subsets, B cells, and macrophages in osteoarthritis and healthy control knee cartilage specimens. The expression of ubiquitin-conjugating enzyme E2I, ribosomal protein S6 kinase 1, interleukin-2 receptor beta chain, YEATS protein family member 4, histone H4 variant, and Toll-like receptor 3 was detected in the external validation set GSE114007. Clinical knee cartilage specimens from 5 osteoarthritis patients and 5 healthy controls were collected, and RT-qPCR was used to detect the mRNA expression of these genes. RESULTS AND CONCLUSION: (1) A total of 26 autophagy- and senescence-related differentially expressed genes were obtained. Functional enrichment analysis showed that these genes were mainly involved in biological processes such as cellular homeostasis, immune regulation, and cell death, and played important roles in multiple signaling pathways. Six key genes were screened by machine learning: ubiquitin-conjugating enzyme E2I, ribosomal protein S6 kinase 1, interleukin-2 receptor beta chain, YEATS protein family member 4, histone H4 variant, and Toll-like receptor 3. The area under the receiver operating characteristic curve (AUC) values of these genes were all greater than 0.8, indicating high diagnostic performance. Immune infiltration analysis showed that the infiltration of plasma cells, resting CD4 memory T cells, resting NK cells, monocytes, M2 macrophages, eosinophils, and neutrophils was significantly decreased in the osteoarthritis group, while the infiltration of follicular helper T cells, gamma delta T cells, activated NK cells, M1 macrophages, and resting dendritic cells was significantly increased. (2) In the external validation set, the expression of ubiquitin-conjugating enzyme E2I, interleukin-2 receptor beta chain, and Toll-like receptor 3 was higher in the osteoarthritis group than in the healthy control group (P < 0.05), while there was no significant difference in the expression of histone H4 variant, YEATS protein family member 4, and ribosomal protein S6 kinase 1 between the two groups (P > 0.05). In clinical samples, the mRNA expression of ribosomal protein S6 kinase 1, interleukin-2 receptor beta chain, YEATS protein family member 4, histone H4 variant, and Toll-like receptor 3 was higher in the osteoarthritis group than in the healthy control group (P < 0.05), while there was no significant difference in the expression of ubiquitin-conjugating enzyme E2I mRNA between the two groups (P > 0.05). (3) These results indicate that Toll-like receptor 3 and interleukin-2 receptor beta chain can serve as key genes for autophagy and senescence in osteoarthritis chondrocytes, and may become diagnostic molecular markers and potential therapeutic targets for osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21545
BACKGROUND: Osteonecrosis of the femoral head is a refractory disorder characterized by osteocyte apoptosis and structural collapse of the femoral head. Its pathogenesis is closely associated with vascular injury, dysregulated bone metabolism, and aberrant mechanical stress. In recent years, animal models have served as indispensable tools for simulating pathological processes, playing an irreplaceable role in elucidating molecular mechanisms of osteonecrosis of the femoral head and evaluating novel interventions. Nevertheless, the standardization of model development and their clinical translational value require systematic investigation. OBJECTIVE: To analyze the research landscape in the field of osteonecrosis of the femoral head using bibliometric approaches, with an emphasis on evaluating the application characteristics, limitations, and future optimization directions of animal models in study design, providing a reference for advancing mechanistic understanding and therapeutic development. METHODS: Literature published between January 2015 and March 2025 was retrieved from the Web of Science Core Collection (SCI-Expanded), China National Knowledge Infrastructure (CNKI), and Wanfang databases. The search strategy for English literature was TS=(osteonecrosis of the femoral head) AND TS=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR "laboratory animal" OR "experiment animal"). For Chinese literature, the search was SU=股骨头坏死 AND SU=鼠+兔+犬+猪+羊+猴+实验动物+动物实验. CiteSpace 6.3.R1 software was used to perform visualization analysis of countries, institutions, authors, keywords, and co-cited references. Trends were summarized based on animal model classification and application characteristics. RESULTS AND CONCLUSION: (1) In English literature, China contributed over 80% of the research (458 articles). Hot topics focused on steroid-induced necrosis mechanisms (e.g., oxidative stress-autophagy axis), stem cell/tissue engineering therapies, and traditional Chinese medicine interventions. The research on animal models of osteonecrosis of the femoral head exhibited a "high output-low collaboration" characteristic. (2) In Chinese literature, the publishing institutions were mainly traditional Chinese medicine-related institutions, and traditional Chinese medicine and steroid-induced osteonecrosis of the femoral head were important research hotspots. (3) Future efforts should deepen cross-species validation platforms, multi-omics integration, and collaborative strategies for the development of Chinese and Western medicine to accelerate clinical translation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21523
BACKGROUND: Recent studies on the pathogenesis of multiple sclerosis suggest that intervening in glial cells may play a key role in reducing relapses and delaying disability progression. Grape seed proanthocyanidin oligomers significantly inhibit demyelination in cuprizone-treated mice. OBJECTIVE: To explore the mechanism by which grape seed proanthocyanidin oligomers protect myelin sheaths through regulating astrocytes. METHODS: (1) Animal experiment: Thirty mice were randomly divided into normal group, CPZ group, and CPZ+oligomeric proanthocyanidin group. The latter two groups were fed a diet containing 0.2% CPZ for 6 weeks to induce demyelination. From the 5th week, the normal and CPZ groups were given ddH2O by gavage, while the CPZ+oligomeric proanthocyanidin group received grape seed proanthocyanidin oligomers [50 mg/(kg·d)] once daily for 2 weeks. Behavioral changes were observed; LFB and oil red staining were used to assess myelin pathology; ELISA detected inflammatory factors in the brain; immunofluorescence staining detected related protein expression. (2) Cell experiment: In vitro, grape seed proanthocyanidin oligomers (30 μg/mL) were used to intervene in an astrocyte inflammation model induced by tumor necrosis factor α, interleukin 1α, and C1q. Conditioned medium was collected and used to culture oligodendrocytes. Cells were divided into normal, model, and model+oligomeric proanthocyanidin groups. L-lactate dehydrogenase and CCK-8 assays were used to detect oligodendrocyte damage and cell activity, and western blot was used to detect apoptosis-related protein expression. RESULTS AND CONCLUSION: (1) Grape seed proanthocyanidin oligomers significantly improved demyelination in CPZ mice, inhibited the expression of pro-inflammatory factors tumor necrosis factor α, interleukin 6, interleukin 1α, and interleukin 17 in the brain, promoted the secretion of anti-inflammatory factor transforming growth factor β, accompanied by astrocyte proliferation in the corpus callosum, significantly reduced the marker C3d of pro-inflammatory astrocytes, and inhibited the phosphorylation of JNK, a signaling molecule related to astrocyte polarization. (2) Compared with the model group, the conditioned medium after intervention with grape seed proanthocyanidin oligomers significantly reduced the apoptosis of oligodendrocytes induced by inflammatory astrocytes, promoted the expression of Bcl-2, and inhibited the expression of Bax and Caspase-3. (3) These results indicate that grape seed proanthocyanidin oligomers can inhibit demyelination in CPZ mice by inhibiting JNK phosphorylation in astrocytes, reducing the polarization of astrocytes to the pro-inflammatory A1 type, thereby inhibiting the apoptosis of oligodendrocytes induced by inflammatory astrocytes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21608
BACKGROUND: At present, there are few longitudinal studies on postmenopausal cognitive impairment, and there is no systematic bibliometric analysis of its development context and hot trends. OBJECTIVE: To systematically integrate the related research on postmenopausal cognitive impairment with the help of bibliometric tools, identify the research trends and hot trends in this field, and promote interdisciplinary cooperation and clinical transformation. METHODS: The Web of Science Core Collection database was retrieved for literature related to postmenopausal cognitive impairment published from January 1, 2005 to March 24, 2025. Visualization analysis was conducted using software such as VOSviewer, the R package “Bibliometrix,” and CiteSpace. RESULTS AND CONCLUSION: A total of 1 452 articles were included, involving 71 countries, 1 830 institutions, 510 journals, and 6 909 authors. The annual publication volume showed a fluctuating upward trend. The United States dominated the field, with Stanford University, University of Pittsburgh, Harvard Medical School, and University of Illinois leading. Menopause-The Journal of the North American Menopause Society published the most articles (78), and JAMA-J Am Med Assoc had the highest co-citation count (3 791). Espeland, Mark A. ranked first with 55 publications, and Shumaker, Sally A. was the most co-cited author (859 times). High-frequency keyword “estrogen” (211 times) and burst keywords “plus progestin” (strength=15.77) and “estrogen replacement therapy” (strength=15.57) indicated that the long-term effects and safety of hormonal interventions remained the core research focus. Keyword clustering revealed four research directions. Future research could focus on constructing a “cross-life cycle-multidimensional” framework, which would help comprehensively understand the mechanisms of hormones on cognitive function and neuropsychiatric status at different life stages. The shift in hot topics from single issues (e.g., magnetic resonance imaging, hormones and cognition) to multiple health issues (psychological, tumor risk, cardiovascular, metabolic diseases, physical activity, etc.) and the non-hormonal turn in intervention strategies reflected the development trend of the discipline.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21546
BACKGROUND: Articular cartilage is primarily composed of collagen. Using collagen as a scaffold material, combined with autologous bone marrow mesenchymal stem cells for in situ repair, has become a new method for treating articular cartilage damage.
OBJECTIVE: To evaluate the effectiveness of collagen combined with fibrin sealant in repairing articular cartilage defects in rabbits.
METHODS: Forty-eight New Zealand rabbits were used. Full-thickness cartilage defects of 4.5 mm in diameter and 3 mm in depth were created on the trochlear surface of the medial femoral condyle of the left hind limbs. The rabbits were randomly divided into four groups: microfracture group (n=12) underwent microfracture surgery. Collagen group (n=12) underwent microfracture surgery followed by injection of domestically produced collagen into the cartilage defect. CartiRegen group (n=12) underwent microfracture surgery followed by injection of a mixture of imported collagen and fibrin sealant into the cartilage defect. Experimental group (n=12) underwent microfracture surgery followed by injection of a mixture of domestically produced collagen and fibrin sealant into the cartilage defect. At 12 and 24 weeks post-surgery, knee joint MRI examinations were performed, and the knee joint cartilage repair tissue was subjected to hematoxylin-eosin, toluidine blue, safranin O-fast green staining, type II collagen immunohistochemical staining, ICRS scoring, and Mankin scoring. The compression modulus and hardness of the repaired cartilage were measured at 24 weeks.
RESULTS AND CONCLUSION: MRI examination showed that at 24 weeks, the microfracture group had almost complete filling of the cartilage defect, but poor integration with surrounding normal cartilage; the collagen group had almost complete filling and basically complete integration with slight differences; the CartiRegen and experimental groups had complete filling and no obvious differences in integration and surface with surrounding healthy cartilage. Histological staining showed that the microfracture group had light and uneven staining with poor cartilage morphology; the collagen group had relatively uniform staining, smooth repair surface, basically integrated with surrounding normal cartilage, but with fissures; the CartiRegen and experimental groups had uniform staining, smooth surface, dense tissue, good integration with surrounding tissue, and good filling. The ICRS and Mankin scores at 24 weeks were lower in the CartiRegen and experimental groups than in the microfracture and collagen groups (P < 0.05). The hardness of the repaired cartilage at 24 weeks was greater in the collagen, CartiRegen, and experimental groups than in the microfracture group (P < 0.05). These results indicate that collagen combined with fibrin sealant and microfracture has good repair effects on cartilage damage.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21612
BACKGROUND: Understanding the characteristics of lung tissue repair and risk factors in patients with chronic obstructive pulmonary disease (COPD) is crucial for improving disease management and enhancing patient quality of life. Existing clinical indicators cannot accurately quantify the tissue repair potential and disease progression risk in patients with a history of frequent hospitalizations. OBJECTIVE: To conduct a risk prediction model analysis of lung tissue repair mechanisms in COPD based on computer simulation and case validation, thereby promoting lung tissue repair/regeneration in COPD patients, reducing the frequency of hospitalizations, and improving quality of life. METHODS: Medical records from 200 patients with COPD hospitalized at Beijing Jingmei Group General Hospital from 2022-10-01 to 2023-10-01 were collected. Patients were grouped based on the number of hospitalizations for COPD within 1 year after discharge: 100 patients with ≥2 hospitalizations were assigned to the frequent hospitalization group, and 100 patients with <2 hospitalizations were assigned to the non-frequent hospitalization group. General clinical data, pulmonary function, blood gas analysis, and hematological indicators were compared between the two groups. Variables with P < 0.05 were included in a multivariate logistic regression model to identify risk factors for rehospitalization within 1 year. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive efficacy of the clinical risk factor model. RESULTS AND CONCLUSION: (1) Pulmonary function: There were significant differences between the two groups in FEV1% predicted, FVC, FVC% predicted, FEV1/FVC, residual volume/total lung capacity ratio, diffusing capacity of the lung for carbon monoxide (DLCO), and DLCO/alveolar volume (P < 0.05). (2) Blood gas analysis: Significant differences were found in oxygen partial pressure, carbon dioxide partial pressure, oxygen saturation, and respiratory failure type (P < 0.05). (3) Hematological indicators: Significant differences were observed in absolute neutrophil count, D-dimer, absolute lymphocyte count, neutrophil percentage, and red blood cell distribution width (RDW) (P < 0.05), while no significant differences were found in eosinophil percentage, fibrinogen, and absolute eosinophil count (P > 0.05). (4) Logistic regression analysis showed that FEV1% predicted (OR=1.01, 95%CI: 1.004-1.017, P=0.011), DLCO (OR=2.28, 95%CI: 1.270-3.025, P=0.004), type I respiratory failure (OR=3.15, 95%CI: 2.414-5.947, P=0.001), type II respiratory failure (OR=7.03, 95%CI: 1.688-8.604, P=0.001), and RDW (OR=1.50, 95%CI: 0.65-3.44, P < 0.0001) were risk factors for frequent hospitalizations in COPD patients. (5) ROC curve analysis showed that when FEV1% predicted was below 52.9%, DLCO below 4 mmol/(min·kPa), presence of type I respiratory failure, or RDW above 14.5%, the risk of frequent hospitalizations increased. (6) The logistic regression model and ROC curve analysis indicated that severely impaired diffusion capacity, combined respiratory failure, and elevated RDW are major risk factors for frequent hospitalizations in COPD patients. Early identification and intervention of these factors are important for improving lung tissue repair potential, predicting disease progression risk, and enhancing quality of life.
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.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21563
BACKGROUND: Lumbar disc herniation is a prevalent spinal degenerative disorder in clinical practice. Traditional treatment predominantly relies on surgical intervention; however, the phenomenon of spontaneous resorption in lumbar disc herniation offers a novel non-surgical approach. OBJECTIVE: To investigate the efficacy of a comprehensive non-surgical treatment regimen in promoting the spontaneous resorption of a severely herniated L5/S1 disc through a two-year follow-up. METHODS: A patient with severe L5/S1 disc herniation was treated with a comprehensive non-surgical regimen including non-steroidal anti-inflammatory drugs, physical therapy, and exercise rehabilitation, and followed for two years. During follow-up, pain symptoms were closely monitored, and serial MRI examinations dynamically recorded the evolution of the herniation. Additionally, an extensive literature review was conducted to explore the underlying mechanisms of spontaneous resorption. RESULTS AND CONCLUSION: After two years of comprehensive non-surgical treatment, the patient's pain symptoms significantly alleviated, visual analog scale scores markedly decreased, and MRI clearly showed gradual resorption of the herniation, indicating the effectiveness of this therapy in promoting spontaneous resorption. Spontaneous resorption is accomplished by the synergistic action of multiple biological processes including inflammatory response activation, neovascularization, macrophage infiltration (M1/M2 polarization regulation), and matrix degradation. Key predictors of resorption potential include herniation characteristics, MRI rim enhancement, and posterior longitudinal ligament integrity. Future applications of single-cell sequencing, multimodal imaging, and deep learning technologies may elucidate molecular mechanisms, enable early prediction, and assist precise clinical treatment. In summary, this comprehensive non-surgical treatment protocol provides a reliable basis for the treatment of lumbar disc herniation, multi-mechanism synergy clarifies the resorption principle, key predictive indicators facilitate personalized treatment planning, and advanced technology applications point the way toward precision biological therapy and improved clinical outcomes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21582
BACKGROUND: Early synovial inflammation plays a crucial role in the onset and progression of knee osteoarthritis and has become a significant focus for research and intervention in joint diseases. Electroacupuncture, as a common physical intervention, lacks systematic molecular-level elucidation of its mechanism on the synovium. Combining transcriptomic technology to analyze the gene expression profile of synovial tissue can help reveal key signaling pathways and targets regulated by electroacupuncture, providing theoretical basis and data support for early intervention in osteoarthritis.
OBJECTIVE: To investigate the effect of electroacupuncture on early synovial inflammation in a rat model of knee osteoarthritis based on transcriptomic sequencing technology.
METHODS: Twenty-four 3-month-old male Sprague-Dawley rats were randomly divided into control, model, and electroacupuncture groups (n=8 per group). The model and electroacupuncture groups underwent anterior cruciate ligament transection to induce knee osteoarthritis, while the control group did not. Four weeks after modeling, the electroacupuncture group received electroacupuncture at bilateral "Zusanli" (ST36), "Xuehai" (SP10), "Taixi" (KI3), and "Yanglingquan" (GB34) with dense-disperse waves of 3 Hz/15 Hz, current intensity 1 mA, 30 minutes per session, once daily, 5 days per week, for 2 weeks. After intervention, left knee synovium was collected for mRNA sequencing, and right knee joints were subjected to safranin O-fast green staining and Mankin's scoring.
RESULTS AND CONCLUSION: (1) Compared with the control group, the model group showed rough cartilage surface and disordered synovial cell arrangement, with increased Mankin's score (P < 0.001). Compared with the model group, the electroacupuncture group showed smoother cartilage surface, reduced inflammatory infiltration in synovial tissue, and decreased Mankin's score (P < 0.05). (2) There were 29 genes upregulated in the model group and downregulated in the electroacupuncture group, and 19 genes downregulated in the model group and upregulated in the electroacupuncture group. (3) Gene Ontology analysis showed that these differentially expressed genes were mainly enriched in MHC protein complex binding, protein homodimerization activity, and BH3 domain binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed enrichment in cell adhesion molecules, phosphatidylinositol 3-kinase-protein kinase B signaling pathway, nuclear factor κB signaling pathway, and peroxisome proliferator-activated receptor signaling pathway. (4) Compared with the control group, the model group showed significantly increased mRNA expression of Myh9, Hmox1, and S100a8 (P < 0.001, P < 0.001, P < 0.001), and significantly decreased mRNA expression of Rack1 and Ddit3 (P < 0.01, P < 0.001). Compared with the model group, the electroacupuncture group showed significantly decreased mRNA expression of Myh9, Hmox1, and S100a8 (P < 0.05, P < 0.001, P < 0.001), and significantly increased Ddit3 mRNA expression (P < 0.001), while Rack1 mRNA expression showed an increasing trend but without significant difference (P > 0.05). Real-time quantitative PCR results were basically consistent with gene sequencing results. These findings indicate that electroacupuncture can significantly alleviate early synovial inflammation in knee osteoarthritis rats, possibly by inhibiting the expression of Myh9, Hmox1, and S100a8, and promoting the expression of Rack1 and Ddit3 in synovial tissue.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21566
BACKGROUND: Osteoarthritis is closely related to aging and characterized by degeneration of articular cartilage, subchondral bone sclerosis, and low-grade inflammatory responses. Aging and injury are significant triggers for inflammatory factors that mediate joint pathological changes. Cobimetinib, a MEK1 inhibitor, has an unclear effect on the inflammatory senescence of chondrocytes. OBJECTIVE: To compare the effects of cobimetinib and the classic anti-aging drug combination of dasatinib and quercetin (D+Q) in inhibiting inflammatory senescence of chondrocytes, and to explore its potential application in the treatment of osteoarthritis. METHODS: Primary chondrocytes were isolated and cultured, and cell viability was detected by CCK-8 assay. Cells were divided into control group, model group, D+Q group, and cobimetinib group. Except for the control group, cells in the other three groups were induced with interleukin-1β to establish an inflammatory senescence model, and then treated with cobimetinib or D+Q combination. Senescence phenotype was observed by β-galactosidase staining. The activation of MEK-ERK1/2 pathway was detected by real-time quantitative PCR, western blot, and immunofluorescence. The expression levels of senescence markers (P16, P21, P53) and senescence-associated secretory phenotype factors (inducible nitric oxide synthase, cyclooxygenase-2, chemokine ligand 3, interleukin-6) were measured, and the changes in extracellular matrix synthesis and degradation-related molecules (COL2A1, matrix metalloproteinase 13, matrix metalloproteinase 3) were evaluated. RESULTS AND CONCLUSION: Both cobimetinib and D+Q effectively inhibited the activation of MEK-ERK1/2 pathway, alleviated the senescence phenotype of chondrocytes, significantly downregulated the expression of P16, P21, and P53, reduced the levels of senescence-associated secretory phenotype factors, restored COL2A1 expression, and inhibited the expression of matrix metalloproteinase 13 and matrix metalloproteinase 3. These results indicate that cobimetinib effectively alleviates interleukin-1β-induced inflammatory senescence of chondrocytes by inhibiting the MEK-ERK1/2 pathway, and has a similar anti-aging effect to the D+Q combination, while showing greater potential in promoting matrix synthesis and inhibiting degradation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21058
BACKGROUND: Hemiplegia, a prevalent stroke-related condition, is often studied for motor dysfunction; however, spasticity remains under-researched. Abnormal muscle tone significantly hinders hemiplegic patients' walking recovery. OBJECTIVE: To determine whether early suspension-protected training with a personal assistant machine for stroke patients enhances walking ability and prevents muscle spasms. METHODS: Thirty-two early-stage stroke patients from Shenzhen University General Hospital and the China Rehabilitation Research Center were randomly assigned to the experimental group (n=16) and the control group (n=16). Both groups underwent 4 weeks of gait training under the suspension protection system for 30 minutes daily, 5 days a week. The experimental group used the personal assistant machine during training. Three-dimensional gait analysis (using the Cortex motion capture system), Brunnstrom staging, Fugl-Meyer Assessment for lower limb motor function, Fugl-Meyer balance function, and the modified Ashworth Scale were evaluated within 1 week before the intervention and after 4 weeks of intervention. RESULTS AND CONCLUSION: After the 4-week intervention, all outcome measures showed significant changes in each group. The experimental group had a small but significant increase in the modified Ashworth Scale score (P < 0.05, d=|0.15|), while the control group had a large significant increase (P < 0.05, d=|1.48|). The experimental group demonstrated greater improvements in walking speed (16.5 to 38.44 cm/s, P < 0.05, d=|4.01|), step frequency (46.44 to 64.94 steps/min, P < 0.05, d=|2.32|), stride length (15.50 to 29.81 cm, P < 0.05, d=|3.44|), and peak hip and knee flexion (d=|1.82| to |2.17|). After treatment, the experimental group showed significantly greater improvements than the control group in walking speed (38.44 vs. 26.63 cm/s, P < 0.05, d=|2.75|), stride length, peak hip and knee flexion (d=|1.31| to |1.45|), step frequency (64.94 vs. 59.38 steps/min, P < 0.05, d=|0.85|), and a reduced support phase (bilateral: 24.31% vs. 28.38%, P < 0.05, d=|0.88|; non-paretic: 66.19% vs. 70.13%, P < 0.05, d=|0.94|). For early hemiplegia, personal assistant machine-assisted gait training under the suspension protection system helps establish a correct gait pattern, prevents muscle spasms, and improves motor function.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025029
Intervertebral disc degeneration (IVDD) is the principal cause of low back pain, with current therapies limited to symptomatic relief. This study investigates the role of circ_0000389 in IVDD pathogenesis. Bioinformatic analysis of the GSE67566 dataset identified circ_0000389 as differentially expressed. RT-qPCR revealed significant downregulation of circ_0000389 in degenerating nucleus pulposus (NP) tissues. Functional assays demonstrated that circ_0000389 overexpression promotes nucleus pulposus cell (NPC) proliferation and inhibits extracellular matrix (ECM) catabolism. Mechanistically, dual-luciferase reporter and RNA immunoprecipitation assays confirmed that circ_0000389 directly sponges miR-346, and miR-346 directly targets KLF7. miR-346 overexpression reversed the protective effects of circ_0000389, while KLF7 overexpression reversed the effects of miR-346. These findings establish the circ_0000389/miR-346/KLF7 axis as a critical regulator of IVDD progression, providing a potential therapeutic target.