Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Objective: To evaluate the effect of traditional Chinese medicine (TCM) on children's emotional face expression analysis and parental emotional expression. Methods: A randomized controlled trial was conducted with 120 children aged 6-12 years, divided into TCM intervention and control groups. Emotional face expression analysis was performed using facial expression recognition software, and parental emotional expression was assessed via questionnaires. Results: The TCM group showed significant improvements in emotional face expression recognition accuracy and parental emotional expression scores compared to controls (p<0.05). Conclusion: TCM intervention may enhance children's emotional expression and parental emotional communication, suggesting potential benefits for emotional development.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzad002
The order Acipenseriformes, which includes sturgeons and paddlefishes, represents “living fossils” with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.
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/s13287-026-04921-w
Background Lung ischemia–reperfusion injury (IRI) is a major contributor to primary graft dysfunction (PGD) after lung transplantation. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising therapeutic agents in inflammatory diseases by ameliorating tissue damage and promoting repair. However, the anti-inflammatory efficacy of these approaches and the underlying mechanisms in lung ischemia–reperfusion injury remain incompletely understood. Methods The protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) against lung ischemia–reperfusion injury were evaluated using two delivery approaches, inhalation and intravenous injection. Both in vivo and in vitro models were employed to assess the biological activity of MSC-EVs and to elucidate the underlying molecular mechanisms. In addition, a rat orthotopic lung transplantation (OLT) model was established to further examine the translational relevance of MSC-EVs. Results MSC–EVs treatment significantly ameliorated lung IRI, with inhalation showing superior efficacy over intravenous delivery. Mechanistically, miR-22-3p within MSC-EVs targeted macrophage NLRP3, suppressing activation of the NLRP3/Caspase-1/IL-1β pathway and promoting M2 polarization. The protective efficacy was confirmed in a clinically relevant rat OLT model, underscoring their translational potential
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04549-2
Adipose-derived stem cells (ADSCs) are a specific type of mesenchymal stem cells (MSCs) obtained easily from adipose tissue (AT). Compared with MSCs, ADSCs are easier to obtain, have fewer ethical issues, and have a higher proliferative capacity, which makes them a promising type of stem cell in regenerative medicine. ADSCs possess impressive capabilities in cell regeneration as well as differentiation, making them promising candidates for injury repair, tissue regeneration and alleviation of inflamed tissues. At present, most clinical studies on ADSCs focus on the treatment of wounds, multiple sclerosis, soft tissue trauma, aging, diabetes, Parkinson’s disease, bone and cartilage regeneration, stroke, and spinal cord injury, while its clinical applications in the gastrointestinal tract are relatively few. Therefore, this review summarizes the findings of preclinical experiments, clinical trials, and areas that may require further development of ADSCs in the treatment of digestive disorders, including inflammatory bowel disease (IBD), colorectal cancer (CRC), colorectal fibrosis, hepatocellular carcinoma, hepatic fibrosis, gastric cancer (GC), gastrostomy closure and radiation-induced proctitis. The review is concluded by discussing the goals for improvement and future directions for ADSCs before large-scale clinical application.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04851-z
Background Bronchopulmonary dysplasia (BPD) is a chronic lung disease driven by inflammation and oxidative stress. Mesenchymal stem cells (MSCs) have shown protective effects against hyperoxic lung injury. However, few studies have thoroughly examined the significantly differentially expressed genes (DEGs) in the lungs before and after MSC treatment. In this study, we analyzed the significant DEGs in lung tissues during both in vivo and vitro umbilical cord-derived mesenchymal stem cells (UCMSCs)-mediated repair of hyperoxic lung injury and investigated their potential mechanisms of action. Methods Neonatal rats were exposed to hyperoxia and subsequently treated with UCMSCs. Inflammatory responses were quantified via ELISA and RT‒qPCR, while Western blotting (WB) and immunohistochemistry (IHC) were used to examine NLRP3 inflammasome and IL-1β expression. Transcriptomic analysis of UCMSC-mediated lung repair revealed 46 DEGs, which were validated by RT‒qPCR, and WB verified the significant differential expression of ALDH1A2. In RLE-6TN cells, Aldh1a2 expression was reduced during MSC-mediated repair of H2O2-induced oxidative stress injury. Functional evaluations were performed. WB further analyzed NLRP3 inflammasome and IL-1β expression in these processes. A recombinant adenoviral overexpression vector was intratracheally administered to hyperoxia-exposed neonatal rats. Arterial blood gas and RT‒qPCR were performed, and ELISA, WB, and IHC were used to evaluate the impact of Aldh1a2 overexpression on lung inflammation and oxidative stress, focusing on the NLRP3 inflammasome. Results UCMSCs ameliorated hyperoxia-induced alveolar simplification and microvessel loss, reduced inflammation and oxidative stress injury, and inhibited the expression of the NLRP3 inflammasome. RT‒qPCR and WB analyses revealed significant differential expression of Aldh1a2 in UCMSC-treated hyperoxia-induced lung injury. UCMSCs also mitigated H2O2-induced oxidative stress injury in RLE-6TN cells. Inhibition of Aldh1a2 expression exacerbated oxidative stress, upregulated NLRP3 inflammasome and IL-1β expression, and impaired the reparative effects of UCMSCs. Conversely, Aldh1a2 overexpression or UCMSC intervention ameliorated hyperoxia-induced alveolar simplification and microvascular abnormalities, suppressed inflammation, and enhanced lung ventilation and angiogenesis. These findings indicated that Aldh1a2 overexpression inhibits NLRP3 inflammasome activation and IL-1β release. Conclusions Aldh1a2 was significantly differentially expressed in UCMSC-mediated repair of hyperoxic lung injury, and its overexpression ameliorates BPD by inhibiting NLRP3 inflammasome activation, suggesting a novel therapeutic target for BPD.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04701-y
Background This study systematically evaluated the immunomodulatory function of PD-L1-positive mesenchymal stem cells (PD-L1(+) MSCs) using single-cell RNA sequencing (scRNA-seq) and investigated their roles in suppressing inflammation and regulating pathological bone formation in curdlan-induced SKG ankylosing spondylitis (AS) mouse models. Methods scRNA-seq identified MSC subpopulations with high immunomodulatory capacity and key biomarker PD-L1 for subpopulation classification. In vitro co-culture experiments were conducted to evaluate the effects of MSC subpopulations on T-cell proliferation and TNF-α levels. In vivo experiments were performed in forty-eight SKG mouse models to analyze the effects of MSC subpopulations on joint inflammation scores, T-cell subset proportions, inflammatory cytokines, histopathology, and pathological bone formation. Results scRNA-seq revealed significant heterogeneity in MSCs under inflammatory stimulation, with the immunomodulatory subpopulation exhibiting high expression of PD-L1 and IDO. In vitro experiments demonstrated that PD-L1(+) MSCs significantly suppressed T-cell proliferation and reduced TNF-α levels. Joint redness and swelling scores showed that the PD-L1(+) MSC group exhibited the most significant improvement in arthritis, while the IL-17Ai, PD-L1(-) MSC, and MSC groups also effectively reduced inflammation, with significantly lower scores than the model control(MC) group. Histological analysis revealed severe inflammatory cell infiltration in the MC group, while the IL-17Ai, PD-L1(+) MSC, and MSC groups exhibited reduced infiltration. Immunohistochemical analysis further confirmed these findings, with PD-L1(+) MSCs exhibiting a significant reduction in TNF-α and IL-17A-positive cells (P < 0.0001 and P < 0.01, respectively). PD-L1(+) MSCs regulated immune responses by reducing Th17 cell proportions, increasing Th2 and Treg cell proportions, and significantly lowering pro-inflammatory cytokines IFN-γ, IL-17A, and TNF-α. MicroCT analysis indicated that the PD-L1(+) MSC, MSC, and IL-17Ai group effectively suppressed pathological bone formation.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03898-8
Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription (P < 0.0001) and inhibited the proliferation (P = 0.0065) of hepatic progenitor cells by suppressing the mTOR signalling pathway and activating the apoptosis pathway. Furthermore, knocking down NPM1 in hepatic progenitor cells resulted in more apoptotic cells (7.33 ± 0.09% vs. 3.76 ± 0.13%, P < 0.0001) but fewer apoptotic cells in the presence of NSC348884 (47.57 ± 0.49% vs. 63.40 ± 0.05%, P = 0.0008) than in the control cells, suggesting that low-NPM1-expressing cells are more resistant to NSC348884. In addition, NSC348884 induced the apoptosis of BEL-7402 cells with an IC50 of 2.77 μmol/L via the downregulation of the IL-6R and mTOR signalling pathways and inhibited the growth of BEL-7402 cells in a subcutaneous xenograft tumour model (P = 0.0457). Conclusions Targeting NPM1 inhibits proliferation and induces apoptosis in hepatic progenitor cells and BEL-7402 cells, thus serving as a potential therapy for cHCC-CCA.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03945-4
Background Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. Methods To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. Results Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. Conclusion Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03624-w
Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04111-6
Background hucMSC-exosomes can be engineered to strengthen their therapeutic potential, and the present study aimed to explore whether hypoxic preconditioning can enhance the angiogenic potential of hucMSC-exosomes in an experimental model of POF. Methods Primary hucMSCs and ROMECs were isolated from fresh tissue samples and assessed through a series of experiments. Exosomes were isolated from hucMSCs under normoxic or hypoxic conditions (norm-Exos and hypo-Exos, respectively) and then characterized using classic experimental methods. Based on a series of angiogenesis-related assays, we found that hypo-Exos significantly promoted ROMEC proliferation, migration, and tube formation and increased angiogenesis-promoting molecules in vitro. Histology, immunohistochemistry, and immunofluorescence experiments in a rat model of POF demonstrated that hypoxia pretreatment strengthens the therapeutic angiogenic effect of hucMSC-exosomes in vivo. Subsequently, high-throughput miRNA sequencing, qRT-PCR analysis, and western blotting were employed to identify the potential molecular mechanism. Results We found that hypo-Exos enhance endothelial function and angiogenesis via the transfer of miR-205-5p in vitro and in vivo. Finally, based on the results of bioinformatics analysis, dual luciferase reporter assays, and gain- and loss-of-function studies, we found evidence indicating that exosomal miR-205-5p enhances angiogenesis by targeting the PTEN/PI3K/AKT/mTOR signalling pathway. These results indicated for the first time that exosomes derived from hypoxia-conditioned hucMSCs strongly enhance angiogenesis via the transfer of miR-205-5p by targeting the PTEN/PI3K/AKT/mTOR signalling pathway. Conclusions Our findings provide a theoretical basis and demonstrate the potential application of a novel cell-free approach with stem cell-derived products in the treatment of POF.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026002
The newly discovered midnolin-proteasome pathway is a unique ubiquitin-independent mechanism for degrading nuclear proteins, which is crucial for maintaining cellular protein homeostasis. The Catch domain of midnolin is essential for substrate recognition and binding, yet the underlying mechanism for its broad substrate specificity remains elusive. Transcription factor IRF4, essential for the functions of B and T cells, is a substrate of midnolin. This study presents comprehensive biochemical and structural analyses of the human midnolin Catch domain in complexes with both wild-type and mutant IRF4 peptides. The crystal structure of the Catch-IRF4 complex reveals that the Catch domain creates a substrate-binding groove at the interface of the Catch1 and Catch2 subdomains, recognizing and binding to the 215-QVTGTFYAC-223 sequence motif of IRF4. The binding motif of IRF4 forms a β-strand that is embedded into the substrate-binding groove, resulting in an antiparallel five-stranded β-sheet. The interactions between the IRF4 peptide and the Catch domain are predominantly hydrophobic and exhibit high spatial complementarity. Additionally, the biochemical, modeling and structural data indicate that the V2 and A8 positions of the IRF4 sequence motif can be substituted with other hydrophobic or small polar residues (G/A/V/L/I/M/P/F/Y/C/S/T), but not with large polar and charged residues (D/N/E/Q/H/K/R). The G4 position can be replaced by Ser, while the F6 position can be substituted with Tyr. These results suggest that the Catch domain can recognize and bind to a variety of substrates containing the sequence motif x[G/A/V/L/I/M/P/F/Y/C/S/T]x[G/S]x[F/Y]x[G/A/V/L/I/M/P/F/Y/C/S/T]x or briefly the G/SxF/Y motif (where x represents polar residues) located in an unstructured or loop region on the protein surface, and the hydrophobic interactions and spatial complementarity between the binding motifs of substrates and the Catch domain govern the substrate specificity. Collectively, these findings elucidate the molecular basis for midnolin’s broad substrate specificity.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026018
Doxorubicin (DOX) remains a cornerstone chemotherapeutic agent for malignancies, yet its clinical utility is severely limited by dose-dependent cardiotoxicity, which can lead to progressive left ventricular dysfunction and heart failure. Pleiotrophin (PTN), a heparin-binding growth factor with diverse physiological functions, regulates glucose and lipid metabolism and promotes oxidative energy pathways. However, whether PTN exerts protective effects against DOX-induced cardiotoxicity (DIC) remains unclear. In this study, we establish cellular and animal models of DIC. DOX administration induces pronounced myocardial injury in both models, characterized by impaired ventricular contractility, increased fibrotic remodeling, and reduced cell viability. Concurrently, PTN protein expression is significantly downregulated in cardiomyocytes under DOX treatment. Overexpression of PTN substantially alleviates these pathological changes. In vitro, PTN reduces mitochondrial oxidative stress and apoptosis while restoring energy production and cell viability. In vivo, PTN improves mitochondrial ultrastructure, decreases cardiomyocyte apoptosis, and enhances cardiac function. Mechanistically, PTN directly binds to SIRT1 and activates AMPK phosphorylation at Thr172, triggering a downstream cascade through the AMPK-PGC1α axis that reprograms mitochondrial energy metabolism and attenuates cardiotoxicity. In conclusion, the PTN-SIRT1 axis protects against DIC by reducing oxidative stress and promoting mitochondrial energy homeostasis via the AMPK/PGC1α pathway, highlighting its potential as a novel therapeutic target for preventing chemotherapy-related cardiac injury.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025100
Sulfasalazine (SAS), a clinically utilized anti-inflammatory drug, has been shown to induce ferroptosis by inhibiting system Xc− activity, thereby causing cellular glutathione depletion. Recently, protein disulfide isomerase (PDI) was shown to be an upstream mediator of the oxidative cell death (oxytosis/ferroptosis) induced by glutamate, erastin, RSL3 and SAS. The present study aims to further characterize the detailed biochemical and cellular mechanisms of SAS-induced ferroptosis in two cell lines, i.e., H9C2 rat cardiomyocytes and BRL-3A rat hepatocytes, with a focus on elucidating the critical role of PDI in mediating SAS-induced toxicity. We find that SAS can induce ferroptosis in H9C2 and BRL-3A cells, which is accompanied by a sequential increase in the buildup of cellular nitric oxide (NO), reactive oxygen species (ROS) and lipid-ROS. SAS activates PDI-mediated dimerization of inducible NO synthase (iNOS) and cellular accumulation of NO, and these effects are followed by ROS and lipid-ROS accumulation. Furthermore, SAS markedly upregulates the iNOS protein levels in these cells. Knockdown of PDI or pharmacological inhibition of PDI catalytic activity effectively suppresses SAS-induced iNOS dimerization, abrogates SAS-induced accumulation of NO, ROS and lipid-ROS, and prevents ferroptosis. On the other hand, PDI activation through the use of TrxR1 inhibitors sensitizes these cells to SAS-induced ferroptosis. These findings provide further experimental support for a pivotal role of PDI in SAS-induced cytotoxicity through the activation of the PDI-NOS-NO axis, which then leads to the accumulation of cellular ROS and lipid-ROS and ultimately the induction of oxidative cell death.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025097
Some structured RNAs, such as riboswitches and aptamers, can bind to their cognate ligands and have been used in biosensors and gene expression control elements. However, current methods for detecting ligand binding to structured RNAs are either severely limited or inconvenient. In this study, we design a multibase pair bridge to integrate a hammerhead ribozyme into structured RNAs to detect ligand binding events. The experimental results demonstrate that the length of the bridge has a significant effect on the cleavage of the ribozyme; optimal cleavage can be achieved with three to six base pairs in the bridge. The dissociation constant (KD) values obtained through this method are in agreement with those determined by in-line probing techniques, and 1 pmol of allosteric ribozyme RNA is sufficient for measurement. We apply this method to evaluate the binding affinity of the riboswitch candidate Motif_9307. Our findings indicate that this motif has no binding affinity for S-adenosylmethionine or several other tested ligands, which is consistent with the results of the in-line probing experiments. Notably, our method reveals an increase in cleavage activity when yeast extract is added as a mixture of ligands, suggesting that the ligand of Motif_9307 is present in the extract. In conclusion, we develop an alternative approach for measuring ligand binding events associated with riboswitch candidates and aptamers.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
This study elucidates the mechanisms by which cancer-associated fibroblast (CAF)-derived platelet-derived growth factor C (PDGFC) promotes the progression of lung adenocarcinoma (LUAD) and explores the impact of PDGFC on immune regulation within the tumor microenvironment (TME). Our results show that there is higher expression of PDGFC in CAFs than in nontumor tissue fibroblasts (NFs) and that higher expression of PDGFC is correlated with poor prognosis in LUAD patients. Furthermore, CAF-derived PDGFC promotes epithelial-mesenchymal transition (EMT) in cancer cells as well as matrix metalloproteinase 2 (MMP2) expression through the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Moreover, our study demonstrates that CAF-derived PDGFC is essential for the activation and infiltration of fibroblasts in the TME, as well as the inflammatory infiltration of different immune cell types and the immunosuppressive conditions within the TME. In particular, PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, which can lead to reciprocally positive feedback to accelerate malignant tumor progression. This discovery provides a novel TME-targeted strategy for LUAD treatment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025014
Ferroptosis is a novel form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxides. Recent research has suggested that ferroptosis in osteoblasts contributes to steroid-induced osteonecrosis of the femoral head (SONFH). However, the relationship between ferroptosis and SONFH remains unclear. In this study, in vitro experiments show that dexamethasone (Dex) treatment reduces the expressions of key ferroptosis regulators, SLC7A11 and GPX4, in MC3T3-E1 cells. This reduction leads to a decrease in intracellular glutathione (GSH) levels, accompanied by elevated levels of total iron, malondialdehyde (MDA), and reactive oxygen species (ROS). Importantly, the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively reverses Dex-induced ferroptosis in MC3T3-E1 cells. Furthermore, RNA-seq analysis reveals that the long noncoding RNA (lncRNA) XR_877193.1 is significantly upregulated in Dex-treated MC3T3-E1 cells. Functional studies demonstrate that the knockdown of lncRNA XR_877193.1 promotes osteogenic differentiation by inhibiting Dex-induced ferroptosis in MC3T3-E1 cells, whereas its overexpression exacerbates cell death via ferroptosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis reveals that the differentially expressed lncRNA XR_877193.1 is enriched in ferroptosis-related pathways, including the PI3K/AKT signaling pathway. Moreover, PI3K/AKT inhibitors reverse ferroptosis in MC3T3-E1 cells inhibited by lncRNA XR_877193.1 knockdown. Collectively, our findings indicate that lncRNA XR_877193.1 knockdown exerts anti-ferroptosis effects by stimulating the PI3K/AKT signaling pathway, suggesting a promising therapeutic strategy for attenuating SONFH.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025199
Pregnancy induces profound physiological adaptations to meet the dynamic nutritional demands of fetal development, including a deliberate reduction in maternal insulin sensitivity to ensure fetal glucose availability. However, excessive insulin resistance may precipitate gestational diabetes mellitus (GDM), increasing the risk of both obstetric complications and long-term metabolic disorders in mothers and offspring. Although the role of adipose tissue in pregnancy-associated metabolic adaptation has been extensively studied, the contribution of skeletal muscle remains poorly understood. Here, we systematically characterize pregnancy-induced molecular and metabolic changes in maternal skeletal muscle through multi-omics profiling. We use transcriptomic, metabolomic, computational single-cell deconvolution, and qPCR validation in an established C57BL/6J mouse pregnancy model (8-week-old females). Pregnancy triggers remarkable skeletal muscle remodelling, featuring histological reorganization with myofiber depletion and expanded endothelial compartments. Concurrent metabolic disturbances include insulin resistance, dysregulated TCA cycle activity, and impaired ubiquinone biosynthesis. This study represents a multi-omics-based systematic elucidation of pregnancy-induced maternal skeletal muscle adaptations. Our findings demonstrate that pregnancy induces profound structural reorganization and metabolic reprogramming in maternal skeletal muscle, characterized by prioritized fetal nutrient provision at the expense of maternal tissue utilization. These observations not only reveal previously unrecognized mechanisms of pregnancy-specific metabolic regulation but also, more importantly, establish a critical theoretical foundation for developing skeletal muscle-targeted intervention strategies to prevent gestational diabetes mellitus.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025136
Tumor cells exhibit a notable ability to adapt to constantly changing microenvironments and possess distinct metabolic traits during metastasis. This study aims to establish a melanoma lung metastasis model in mice to elucidate the metabolic mechanisms involved in early-stage metastasis prior to treatment. The male C57BL/6 mice are divided into five groups based on time intervals of 6, 24, 72, and 120 h post-injection (SKCM-M groups) of melanoma cells, as well as a normal control group (NOR group). Our results demonstrate that platelet activation mainly occurs in the initial phases of metastasis to help tumor cells survive. NMR-based metabolomics analysis of mouse lung tissues identifies distinct metabolites and pathways associated with early-stage metastasis, revealing significant alterations in energy and amino acid metabolism during tumor progression. Further analysis indicates that methylxanthine and allantoin could serve as potential biomarkers for monitoring the early progression of tumor metastasis in cancer patients, providing novel insights into early diagnostic strategies for lung metastasis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025118
Cervical cancer represents a significant global health concern affecting women. The global cancer burden data published by the World Health Organization’s International Agency for Research on Cancer (IARC) indicated that the incidence and mortality of cervical cancer were the fourth most common malignancy in females worldwide in 2022 [1]. DNA methylation is recognized as a pivotal epigenetic mechanism for gene silencing, which may accumulate with disease severity [2]. Hypermethylation has been discovered in several tumor suppressor gene (TSG) promoters in human cancers, and further understanding of gene silencing mechanisms has led more studies to consider epigenetic disruption as an important mechanism leading to the silencing of tumor suppressor genes in tumor development [3]. Recent studies have reported that methylation of the zinc finger protein 154 (ZNF154) gene plays an oncogenic role in the development of several cancers [4]. ZNF154 has been shown to inhibit tumor cell proliferation in nasopharyngeal carcinoma by altering the expression of E-cadherin through the Wnt/β-catenin pathway, thereby inhibiting epithelial-to-mesenchymal transition (EMT) [5]. He et al. [6] demonstrated that ZNF154 could transcriptionally regulate the expressions of tumor suppressor genes involved in the cell cycle, the p53 signaling pathway, and the Wnt/β-catenin signaling pathway in esophageal squamous cell carcinoma. Thus, ZNF154 can be considered a novel cancer biomarker of clinical significance. However, the role of ZNF154 in cervical cancer remains unclear. In the present study, we analyzed ZNF154 expression and its potential biological functions and molecular mechanisms in cervical cancer. ZNF154 was found to be downregulated by promoter methylation in cervical cancer tissue. Its overexpression in cervical cancer cells inhibited cell proliferation and migration. Mechanistically, ZNF154 inhibits the Wnt/β-catenin signaling pathway by directly targeting and positively modulating Nemo-like kinase (NLK) activity. Collectively, our findings indicate the crucial role of ZNF154 in the proliferation and migration of cervical cancer cells, indicating that ZNF154 may serve as a promising target for future therapeutic development.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024078
Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like (Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p (Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024073
Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, the CHIKV distribution has undergone significant changes worldwide, from the original tropics and subtropics regions to temperate regions, which has attracted global attention. However, the interactions between CHIKV and its host remain insufficiently understood, which dampens the need for the development of an anti-CHIKV strategy. In this study, on the basis of the optimal overexpression of non-structural protein 4 (nsP4), we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway. Specifically, the scaffold protein receptor for activated C kinase 1 (RACK1) is identified as a novel host interactor and regulator of CHIKV nsP4. The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4, which is caused by the promotion of degradation but not the inhibition of nsP4 translation. Furthermore, the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132, suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway. This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4, which could be a potential target for developing drugs against CHIKV.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024085
Despite the tremendous progress in cancer research over the past few decades, effective therapeutic strategies are still urgently needed. Accumulating evidence suggests that immune checkpoints are the cause of tumor immune escape. PD-1/PD-L1 are among them. Posttranslational modification is the most critical step for protein function, and the regulation of PD-L1 by small molecules through posttranslational modification is highly valuable. In this review, we discuss the mechanisms of tumor cell immune escape and several posttranslational modifications associated with PD-L1 and describe examples in which small molecules can regulate PD-L1 through posttranslational modifications. Herein, we propose that the use of small molecule compounds that act by inhibiting PD-L1 through posttranslational modifications is a promising therapeutic approach with the potential to improve clinical outcomes for cancer patients.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025095
Alzheimer’s disease (AD) is the most common neurodegenerative disease that usually begins with short-term memory loss, gradually progresses to cognitive dysfunction and causes loss of body function and eventual death. Mutations in the APP gene encoding the Aβ precursor protein (APP) are known to cause early-onset AD and suggest that Aβ is a major factor in AD development. Enzyme complexes, such as α-, β- and γ-secretases, catalyze various cleavage pathways to produce a variety of Aβ isoforms of different lengths. These Aβ peptides have proven toxic to the brain and accumulate in AD to form cerebral plaques. The main isoform of Aβ present in these plaques is the 42 amino acid variant known as Aβ42. A previous study revealed that changes in the stiffness of the extracellular matrix (ECM) can induce remodeling of the cytoskeleton of neurons in the brain tissues of AD patients, leading to changes in the morphology and function of neurons. ECM stiffness is unique to each specific tissue, and resident cells have developed to function optimally in microenvironments with specific ECMs. Brain tissues are reported to have a Young’s modulus of elasticity between 0.1 and 16 kPa. In patients with AD, a decrease in the elasticity of brain tissues was detected. Interestingly, the ECM is known to play an important role in cytoskeleton remodeling and neuronal function, and a stiff ECM has been reported to promote actin polymerization and stress fiber formation, whereas a soft ECM triggers actin depolymerization. However, it remains uncertain whether alterations in ECM stiffness in the AD brain contribute to Aβ-induced toxicity, particularly considering that Aβ is recognized to cause neuronal toxicity by disrupting the actin cytoskeleton, which leads to subsequent synaptic and dendritic abnormities. As such, the present study aimed to investigate the effects of substrate stiffness on Aβ-induced toxicity to the neuronal network in cultured neurons. Hippocampal neurons cultured on soft and stiff substrates were assessed for cell viability by MTT assay. When the neuronal cultures were exposed to 1 μM Aβ42 for 48 h, there was a significant decrease in the viability of the cells cultured on the stiff substrates, but there was no significant effect on the viability of the neuronal cultured on the soft substrates. In addition, the influence of Aβ42 on the number of synapses within the cultured neuronal network was analyzed using confocal immunofluorescence imaging. This analysis revealed that Aβ42 exposure induced a decrease in synaptic formation in cultured neurons, which was dependent on substrate stiffness. To evaluate the effect of substrate stiffness on Aβ42-induced toxicity to synaptic transmission in the cultured neuronal network, spontaneous Ca2+ oscillations were examined in neurons cultured on substrates with different stiffness treated with Aβ42. The percentage of neurons with spontaneous Ca2+ oscillations was significantly greater in neurons cultured on stiff substrates than in those cultured on soft substrates. After Aβ42 exposure, the percentage of neurons with spontaneous Ca2+ oscillations was significantly decreased in neurons cultured on the stiff substrates. Exposure to Aβ42 only slightly influenced the percentage of spontaneous Ca2+ oscillations in neurons cultured on the soft substrate. The amplitude and frequency of spontaneous Ca2+ oscillations were significantly greater in neurons cultured on the stiff substrates than in those cultured on the soft substrates. After exposure to Aβ42, the amplitude and frequency of spontaneous Ca2+ oscillations were significantly reduced in neurons cultured on stiff substrates. However, exposure to Aβ42 had only a weak influence on the amplitude and frequency of spontaneous Ca2+ oscillations in neurons cultured on soft substrates. To further investigate the effects of substrate stiffness on synapse function following exposure to Aβ42, spontaneous postsynaptic currents were recorded in DIV14-16 neurons cultured on stiff and soft substrates. The percentage of neurons with spontaneous postsynaptic currents was considerably greater in neurons cultured on the stiff substrates than in those cultured on soft substrates.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025090
Ovarian aging is a natural process characterized by a decline in both the quantity and quality of oocytes, which subsequently leads to diminished fertility, particularly in women over the age of 35. Given the societal trend toward postponing childbirth, it is imperative to understand the molecular mechanisms that underpin ovarian aging to address infertility issues. Melatonin (MT) is recognized for its therapeutic potential in mitigating ovarian aging; however, the specific epigenetic mechanisms involved, particularly concerning m6A methylation, remain inadequately defined. Our investigation demonstrates that MT mitigates ovarian aging in murine models, significantly decreasing m6A methylation levels. In vitro analyses of ovarian granulosa (KGN) cells reveals a marked increase in YTHDF2 expression, with differentially methylated genes being notably enriched in the polyubiquitination pathway. Further examination shows that YTHDF2 enhances the expression of the E3 ligase UBE3C by modulating the m6A methylation of UBE3C mRNA, thereby reducing the expression of the P53 senescence factor and alleviating the effects of ovarian aging.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025038
Hepatocellular carcinoma (HCC) is a highly fatal form of malignancy that seriously threatens patient survival. The global 5-year survival rate for HCC patients ranges from 15% to 19%, and nearly 80% of patients are diagnosed at an advanced stage. Therefore, exploring the mechanism of HCC development and identifying biomarkers and therapeutic targets for HCC are vital. MicroRNAs (miRNAs), a class of noncoding single-stranded RNAs, are 20–24 nucleotides (nt) long. They play pivotal roles in modulating the progression of diverse diseases. The specific role of miR-32-5p in the development of HCC remains unclear. In this study, qRT-PCR is utilized to precisely determine the downregulated expression levels of miR-32-5p in HCC. Subsequently, functional analysis reveals the suppressive role of miR-32-5p in modulating the proliferative and migratory capabilities of HCC cells. Glycogen synthase kinase 3β (GSK3β) has emerged as a potential target of miR-32-5p, which is confirmed through a dual-luciferase reporter assay. Notably, the expression of GSK3β in HCC tissue specimens is negatively correlated with the abundance of miR-32-5p, and patients with high GSK3β expression have shorter survival time. Furthermore, the targeted downregulation of GSK3β remarkably impedes the proliferation and migration of tumor cells. This study suggests that miR-32-5p inhibits the proliferation and migration of HCC through regulating the GSK3β/NF-κB signaling pathway. Therefore, this study reveals that miR-32-5p exerts its suppressive effect on HCC progression, suggesting that it is a promising target for both diagnostic and targeted therapeutic interventions against HCC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025017
Studies of cell-to-cell activities in the tumor microenvironment (TME) have identified multiple potential targets for oncotherapy. The interplay between tumor cells and neighboring cancer-associated fibroblasts (CAFs) persists in all stages of tumor progression. In this study, we reveal that exosomes from breast cancer cells can be endocytosed into fibroblasts and transform normal fibroblasts (NFs) into CAFs and that the ability of exosomes from highly metastatic breast cancer cells is greater than that of those from poorly metastatic breast cancer cells. Further investigation reveals that exosomes from highly metastatic breast cancer cells contain much more miR-105-5p than those from poorly metastatic breast cells do and that exosomal miR-105-5p facilitates the transformation of NFs to CAFs. A detailed study reveals that RBMY1A1-dependent sorting of miR-105-5p into fibroblasts and subsequent internalization of miR-105-5p promote the transformation of NFs to CAFs by downregulating LATS2 expression and activating NF-κB signaling, which concurrently facilitates the EMT of breast cancer cells. Thus, our results indicate that exosomal miR-105-5p may be a potential target for novel therapeutic strategies to prevent the coevolution of breast cancer cells and CAFs.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025015
Graphene and its derivatives exhibit excellent electrical and mechanical properties, including a high specific surface area, excellent electron mobility, and good biocompatibility, which make them ideal materials for fabricating biosensor devices. Nevertheless, sensors based on pure graphene sensors still have certain limitations. For example, the number of dangling chemical bonds on the graphene surface is insufficient, which restricts the chemisorption of target molecules on the graphene surface. Additionally, graphene tends to stack and self-polymerize due to the presence of strong π-π interactions, van der Waals forces, and high surface energy, which leads to limitations in its semiconductor applications. The incorporation of other nanomaterials (e.g., metals, metal oxides, and conductive polymers) into graphene sheets has been demonstrated to prevent graphene agglomeration and improve the nanostructure. Conductive polymers have been the subject of considerable interest within the context of electronic device manufacturing and the development of electrochemical sensors. This is due to a number of factors, including their low cost, simple preparation, high electrical conductivity, and high compatibility with modern electronic devices. Polypyrrole (PPY), a widely used conductive polymer, has attracted attention, particularly in electrode modification. PPY exhibits excellent electrical conductivity, redox reversibility, biocompatibility, and environmental stability while also offering low production costs, making it an attractive option for use as a conductive polymer. Concurrently, the distinctive structural characteristics of graphene and its oxides render them prospective conductive fillers for conductive polymers. Consequently, the incorporation of graphene into polymers can compensate for their inherent limitations and enhance the long-term stability of sensing materials. The combination of graphene and conducting polymers represents a powerful means of preparing modified electrodes with good electrochemical properties, which have been successfully applied to the electrochemical detection of various biomolecules. For example, Oliveira et al. developed an electrochemical gene sensor based on PPY and graphene quantum dots for the detection of the PML/RARα fusion gene in childhood acute promyelocytic leukemia. As a graphene derivative, reduced graphene oxide (rGO) is similar to graphene in numerous aspects, including favourable electrical conductivity, flexibility, low cytotoxicity, hydrophilicity, a substantial surface-area-to-volume ratio, and elevated chemical resistance. These attributes render rGO an exemplary matrix for nanocomposites. Owing to the presence of hydrophilic and reactive functional groups, rGO is ideal for use in biosensors. The hydrophilic nature of rGO is instrumental in the assembly of biosensors, enabling the fabrication of sensing platforms through techniques such as drop-casting, spin-coating, ink-jet printing, and processing of electrode materials. In the present study, a “sandwich” DNA hybridisation strategy was employed to construct an electrochemical DNA sensor based on PPY-rGO composite nanomaterials. PPY-rGO nanocomplexes were initially prepared by electrochemical deposition and subsequently modified on the surface of a screen-printed carbon electrode (SPCE) to increase the conductivity of the electrode, with SARS-CoV-2 serving as the target. The PPY-rGO nanocomplexes possess a substantial specific surface area and excellent conductivity, in addition to providing many attachment sites for the subsequent electrodeposition of AuNPs by cyclic voltammetry (CV). This enables the immobilization of a greater number of single-stranded DNA (ssDNA) probes, thereby enhancing the sensitivity and specificity of the sensor for the detection of target molecules. To further improve the specificity of detection, two DNA probes were designed on the basis of a sandwich hybridization strategy. One is a specific capture DNA (CDNA) with a sulfhydryl tag, and the other is a signal DNA (SDNA) with a biotin moiety, which can bind to horseradish peroxidase-streptavidin biofunctionalized gold nanoparticles (SA-HRP-AuNPs). Hybridization of the CDNA, target DNA (tDNA), and SDNA on the electrode surface formed a sandwich structure, whereby the SA-HRP-AuNPs bound to the biotin moiety. The detection of tDNA sequences was achieved via differential pulse voltammetry (DPV), which measures the current change of the sensor in hydrogen peroxide (H2O2) and hydroquinone (HQ) as the solvent electrochemical test solution. Electrochemical characterization and sensor performance testing were performed via a convenient electrochemical workstation and PSTrace software from PalmSens (Houten, Netherlands). SPCE electrodes were
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024096
Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In this study, we aim to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results show that 218 genes are differentially expressed in placentas from preeclamptic pregnancies. Notably, KEGG pathway analysis reveals significant enrichment of genes related to autophagy-related signaling pathways, including the PI3K-Akt signaling pathway, the AMPK signaling pathway, and the mTOR signaling pathway. Additionally, our findings indicate an increase in autophagy in placentas from pregnancies complicated by preeclampsia as well as in trophoblasts subjected to hypoxic conditions. Next, we examine the impact of 3-methyladenine (3-MA), a targeted inhibitor of autophagy, on the progression of PE. The administration of 3-MA profoundly alleviates the severity of PE-like symptoms in rats subjected to reduced uterine perfusion pressure (RUPP). The findings from our study suggest that inhibiting autophagy may serve as a promising approach for adjuvant chemotherapy for PE.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024216
The persistent global burden of hepatitis B virus (HBV) infection has prompted ongoing investigations into host determinants of viral control. In this study, we investigate the regulatory influence of the host gene cleavage stimulation factor subunit 2 (CSTF2) on HBV replication dynamics. We demonstrate differential CSTF2 expression across the spectrum of HBV infection phases, with upregulated expression noted during the immune-reactive and inactive carrier states compared with the immune-tolerant phase. Notably, dose-responsive attenuation of HBV DNA, as well as surface and core protein levels, is observed subsequent to CSTF2 overexpression, whereas HBV RNA levels remain unaffected. Upon HBV transfection, a notable alteration in CSTF2 subcellular localization is discerned, suggesting active relocalization to the cytoplasm, potentially mediated through interaction with the HBV posttranscriptional regulatory element (PRE). This interaction appears to impede the nuclear export of HBV RNA. Additionally, distinct antiviral efficacies are attributed to the functional domains of the CSTF2 protein, indicating a multifaceted host defense mechanism. These insights increase the understanding of host-virus interplay and identify CSTF2 as a candidate for antiviral therapeutic strategies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024181
MicroRNAs (miRNAs) have emerged as essential regulators that play important roles in the development of multiple systems. Recent studies have identified significant roles for miRNAs in the progression of cardiac hypertrophy. This study aims to investigate the effects of miR-133b-3p on angiotensin II (Ang II)-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Our experimental results reveal that miR-133b-3p expression is significantly decreased in both animal and cell models of cardiac hypertrophy induced by Ang II. Overexpression of miR-133b-3p reverses the hypertrophic manifestations and apoptosis induced by Ang II. Through bioinformatics analysis and dual-luciferase reporter assays, CDIP1 (cell death inducing p53 target 1) is identified as a direct target of miR-133b-3p, and the overexpression of miR-133b-3p reduces CDIP1 expression. Additionally, CDIP1 silencing suppresses cardiomyocyte hypertrophy and apoptosis induced by Ang II. In summary, these results suggest that miR-133b-3p may serve as a potential diagnostic marker for cardiac hypertrophy and that the upregulation of miR-133b-3p inhibits cardiac hypertrophy by targeting CDIP1.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024212
It is unclear what part KLF7 plays in cervical cancer. In this study, immunohistochemical and bioinformatics analyses reveal that KLF7 expression is lower in normal cervical tissues than in cervical cancer tissues, and the high level of KLF7 transcripts in cervical cancer tissues is negatively correlated with patients’ overall and disease-free survival. In addition, KLF7 overexpression facilitates the proliferation, migration, and invasion of cervical cells, reduces PFKL expression, and increases the expressions of KLF4, Nanog, OCT4, CD44, SOX2, and ACADL. Additionally, knocking out the Exon 2 of KLF7 in HeLa cells results in a decrease in the total expression of KLF7 but an increase in the nuclear expression of KLF7, an increase in the capacity for proliferation, migration, invasion, and oncogenicity, and an increase in the density and ridge density of mitochondria. Consistent with these findings, RNA-seq analysis shows that knocking out the Exon 2 of KLF7 facilitates the expression of gene sets associated with cancer compared with that in wild-type HeLa cells. Moreover, the administration of alpha-lipoic acid (ALA) leads to a reduction in KLF7 expression in cells and tumor tissues, a suppression of the proliferation, migration, and invasion of HeLa and SiHa cells, and an increase in the carcinogenic potential of HeLa cells, while KLF7 overexpression shows the opposite effect on the expressions of ACADL and PFKL in HeLa and SiHa cells. In conclusion, KLF7 promotes the development of cervical cancer, and ALA can downregulate KLF7 expression and play a positive role in cervical cancer treatment.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025167
Axenfeld-Rieger syndrome (ARS) is a rare genetic disorder characterized by anterior segment dysgenesis and systemic features. PITX2 variants are a major cause. In this study, we recruited four unrelated Chinese families with ARS and performed Sanger sequencing of PITX2. We identified four heterozygous variants: c.118delA (p.Arg40Glyfs*115), c.211G>T (p.Glu71X), c.253-1G>T, and c.663_670dupGACTCCTC (p.Pro224Argfs*18). These variants co-segregated with the phenotype in an autosomal dominant pattern, with two arising de novo. All variants were absent from ExAC and gnomAD, indicating rarity. Our findings expand the mutation spectrum of PITX2 and provide insights into the molecular mechanisms of ARS.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025096
Ferroptosis, a novel form of regulated necrosis, has drawn the attention of the scientific community. Nevertheless, few studies have focused on the impact of ferroptosis on MC3T3-E1 cells in the context of steroid-induced osteonecrosis of the femoral head (SONFH). In this study, we explore the relationship between the degree of ferroptosis induced by dexamethasone (Dex) and the expression of silent information regulatory protein 1 (Sirt1). The results indicate that the ferroptosis level induced by Dex is mediated by the downregulation of Sirt1. Overexpression of Sirt1 increases the levels of the ferroptosis-related proteins SLC7A11 and GPX4 in MC3T3-E1 cells following Dex exposure. Moreover, the effect of Dex on Sirt1 expression is regulated by hypermethylation of the Sirt1 promoter, which is catalyzed by DNA methyltransferase 3a (DNMT3a). In summary, this study reveals that Dex can trigger ferroptosis by promoting DNMT3a-mediated DNA methylation and downregulating Sirt1 expression. Our findings provide an additional new mechanism for Dex-induced ferroptosis in MC3T3-E1 cells.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024047
The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase complex in which the ubiquitin-like (UBL) domains of SHARPIN and HOIL-1L interact with HOIP to determine the structural stability of LUBAC. The interactions between subunits within LUBAC have been a topic of extensive research. However, the impact of the LTM motif on the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP remains unclear. Here, we discover that the absence of the LTM motif in the AlphaFold2-predicted LUBAC structure alters the HOIP-UBA structure. We employ GeoPPI to calculate the changes in binding free energy (ΔG) caused by single-point mutations between subunits, simulating their protein-protein interactions. The results reveal that the presence of the LTM motif decreases the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP, leading to a decrease in the structural stability of LUBAC. Furthermore, using the AlphaFold2-predicted results, we find that HOIP (629‒695) and HOIP-UBA bind to both sides of HOIL-1L-UBL, respectively. The experiments of Gromacs molecular dynamics simulations, SPR and ITC demonstrate that the elongated domain formed by HOIP (629‒695) and HOIP-UBA, hereafter referred to as the HOIP (466‒695) structure, interacts with HOIL-1L-UBL to form a structurally stable complex. These findings illustrate the collaborative interaction between HOIP-UBA and HOIP (629‒695) with HOIL-1L-UBL, which influences the structural stability of LUBAC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024146
Eukaryotic gene expression is regulated at multiple levels, aiding in maintaining normal phenotypes and environmental adaptability. Transcriptional regulation complexity has been extensively studied using high-throughput sequencing, and previous studies have shown that different transcript isoforms can be produced through complex regulatory mechanisms via large-scale RNA sequencing. Additionally, translational regulation, which significantly influences gene expression, is controlled by complex mechanisms [1]. The untranslated regions (UTRs) of eukaryotic mRNA, encompassing the 5′ UTR, 3′ UTR and polyadenylation tail (polyA), are pivotal for translational regulation, with distinct cis-regulatory elements in the 5′ UTR and 3′ UTR of various transcript isoforms, leading to substantial variations in translational regulation across transcripts. To shed light on translational regulation, previous studies have performed isolation of ribosome-associated poly-adenylated RNAs (i.e., translatome) and deep sequencing for mRNA translation [2]. Polysome profiling is the most common method used to study translatome, which can enable the isolation of full-length translated mRNAs, thereby facilitating the identification of UTRs, assessment of selective translation, and comprehension of the regulatory mechanisms underlying gene expression [2]. Drosophila embryonic development progresses very rapidly and requires precise regulation of the transcription and translation of a large number of genes to ensure normal gene expression. Although Drosophila has been extensively studied as a model organism, the specific interplay between transcription and translation during embryonic development stages is not yet fully understood. To investigate the dynamic regulation of gene expression during Drosophila embryogenesis, we conducted transcriptome and translatome co-profiling on early (0‒4 h) embryos and S2R+ cells, a cell line derived from late embryonic stages of Drosophila melanogaster [3], to compare the differences in translational regulation at the gene and transcript isoform levels. S2R+ cell culture and early (0–4 h) embryo collection were performed (see Supplementary Methods) to compare transcriptome and translatome profiling, as shown in Supplementary Figure S1. Cytosolic RNA and ribosome-associated RNA were isolated from embryos [4] and S2R+ cells, which were used for constructing RNA-Seq libraries. Four libraries were generated for RNA-seq (see Supplementary Methods), consisting of two cytosolic RNA libraries and two ribosome-associated RNA libraries (Supplementary Figure S1A,B). The strand-specific RNA-seq libraries were prepared using the Illumina TruSeq Stranded mRNA Sample Preparation Kit (Illumina, San Diego, USA). The library was sequenced on the Illumina HiSeq X Ten System. We employed Trimmomatic [5] to remove low-quality reads, which resulted in approximately 89 million, 76 million, 72 million, and 56 million clean reads for the transcriptome and translatome of the early embryos and S2R+ cells, respectively. These reads were then mapped to the Drosophila genome (UCSC dm6) using HISAT2 [6]. The unique mapped reads ratio ranges from 94% to 85% and reads mapped to rRNA were less than 6% (Supplementary Table S1), indicating the high quality of the four RNA-seq libraries. Using StringTie [7], 33,470 transcripts were assembled for four mapping sequencing libraries, which revealed an average of 1.9 transcribed transcripts and 1.8 translated transcripts per gene (Supplementary Table S1), suggesting the usage of transcript isoforms widely existed in both transcription and translation of Drosophila embryos. To explore the divergence of the transcriptome during Drosophila development, we compared the transcriptome of the early embryos and S2R+ cells to identify genes with |log2(fold change)| ≥1, FPKM ≥1 in at least one condition, and adjusted P value ≤0.001. In total, we identified 2267 differentially expressed genes (DEGs) from 8815 genes. Among these DEGs, 2147 genes showed higher expression levels in the embryos, while 120 genes showed higher expression levels in S2R+ cells (Figure 1A and Supplementary Figure S2A). To investigate the underlying functional mechanism, we performed enrichment analysis to identify DEG-enriched pathways (Supplementary Table S2). Interestingly, the top 10 enriched pathways are related to morphogenesis an
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024147
The subcellular localization of RNA is critical to a variety of physiological and pathological processes. Dissecting the spatiotemporal regulation of the transcriptome is key to understanding cell function and fate. However, it remains challenging to effectively enrich and catalogue RNAs from various subcellular structures using traditional approaches. In recent years, proximity labeling has emerged as an alternative strategy for efficient isolation and purification of RNA from these intricate subcellular compartments. This review focuses on examining RNA-related proximity labeling tools and exploring their application in elucidating the spatiotemporal regulation of RNA at the subcellular level.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024062
Ubiquitin-conjugation enzyme E2C (UBE2C) is a crucial component of the ubiquitin-proteasome system that is involved in numerous cancers. In this study, we find that UBE2C expression is significantly increased in mouse embryos, a critical stage during skeletal muscle development. We further investigate the function of UBE2C in myogenesis. Knockdown of UBE2C inhibits C2C12 cell differentiation and decreases the expressions of MyoG and MyHC, while overexpression of UBE2C promotes C2C12 cell differentiation. Additionally, knockdown of UBE2C, specifically in the tibialis anterior muscle (TA), severely impedes muscle regeneration in vivo. Mechanistically, we show that UBE2C knockdown reduces the level of phosphorylated protein kinase B (p-Akt) and promotes the degradation of Akt. These findings suggest that UBE2C plays a critical role in myoblast differentiation and muscle regeneration and that UBE2C regulates myogenesis through the Akt signaling pathway.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261620
This bibliometric investigation systematically maps the research landscape of traditional Chinese medicine (TCM) interventions targeting mitochondrial reactive oxygen species (mtROS) from database inception to March 31, 2026. A total of 1,026 Chinese and 649 English articles were retrieved from CNKI, Wanfang, VIP, and Web of Science Core Collection. CiteSpace, VOSviewer, and Bibliometrix were employed to analyze annual publication output, countries, institutions, authors, journals, and keywords, including co-occurrence clustering and burst detection. Results demonstrate sustained growth in annual publications, with China dominating the field, though domestic and international collaboration networks remain fragmented. Core research institutions include Heilongjiang University of Chinese Medicine, Henan University of Chinese Medicine, and Guangxi University of Chinese Medicine. The most productive journals are Chinese Journal of Experimental Traditional Medical Formulae and Journal of Ethnopharmacology. Top Chinese keywords are oxidative stress, mitochondria, TCM, Chinese herbal medicine, and mechanisms of action; top English keywords are oxidative stress, apoptosis, activation, TCM, and reactive oxygen species. Keyword burst analysis reveals a research frontier transition from basic antioxidant mechanisms toward network pharmacology, molecular docking, and ferroptosis. These findings provide data-driven guidance for subsequent mechanistic studies and research planning, highlighting the need for strengthened cross-disciplinary cooperation.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261617
This study systematically compared the pharmacokinetic behavior and tissue distribution of tetrahydropalmatine (THP) following intragastric (ig) and intraperitoneal (ip) administration in a rat model of neuropathic pain, and evaluated analgesic efficacy against acute thermal pain in mice using the hot-plate test. A rapid, sensitive LC-MS/MS method was validated for THP quantification in plasma and tissues (heart, liver, brain, lung, kidney), with linearity from 0.5 to 1250.0 ng/mL (r = 0.9993) and acceptable precision, accuracy, and matrix effects. Non-compartmental analysis using WinNonlin 7.0 revealed that ip administration achieved faster absorption and higher bioavailability than ig. At 4 mg/kg, ip administration yielded a tmax of 0.21 ± 0.08 h, comparable to ig (0.25 ± 0.00 h), but significantly greater AUC0–t. Tissue distribution showed widespread THP exposure, with ip producing higher concentrations in liver, kidney, and plasma at multiple time points; liver and kidney were primary enrichment organs, with notable brain exposure. In the hot-plate test, both routes significantly prolonged licking latency, but ip administration produced superior analgesia. At 4 and 20 mg/kg, ip significantly increased latency at 0.5 and 1.0 h (P < 0.05), whereas ig required 2 h (4 mg/kg) or 1 h (20 mg/kg) to achieve significance (P < 0.05), indicating faster onset for ip. The study confirms that ip administration offers faster absorption, higher bioavailability, and more rapid tissue distribution, with pharmacodynamic responses consistent with pharmacokinetic exposure. These findings provide a pharmacokinetic and pharmacodynamic basis for clinical route selection and dose optimization of THP.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04919-4
Lung cancer remains the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of diagnoses. Lung cancer stem-like cells (LCSCs) drive metastasis, recurrence, and therapeutic failure, yet effective targeting strategies remain elusive. Oxysterol-binding protein-like 2 (OSBPL2/ORP2) is a lipid transport protein that localizes to lipid droplets (LDs) and regulates cholesterol homeostasis, but its role in lung cancer stemness has not been defined. Here, we demonstrate that OSBPL2 reduces cellular cholesterol content, as quantified by HPLC-MS, and inhibits lipid droplet accumulation in lung cancer cells. OSBPL2-mediated lipid transportation significantly suppressed tumor sphere formation, stemness marker expression (ALDH1A1, CD133, Nanog), and in vivo tumorigenesis and metastasis. In peritoneal carcinomatosis models using BALB/c mice (n=10 per group) injected with L-Osbpl2 or L-Vector transduced LLC cells (5×10^6 cells/100µL), OSBPL2 overexpression reduced metastatic tumor burden. Clinical specimen analysis revealed that OSBPL2 represses LCSC marker expression and its level negatively correlates with tumor stage progression and lymph node metastasis. These findings establish OSBPL2 as a critical regulator of lung cancer stemness through lipid metabolic reprogramming, offering a potential therapeutic target for aggressive NSCLC.
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/s13287-026-04921-w
Lung ischemia-reperfusion injury (IRI) remains the principal driver of primary graft dysfunction (PGD) following transplantation, with no approved pharmacological prophylaxis. This study evaluated mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) delivered by inhalation versus intravenous injection in murine hilar clamp and rat orthotopic lung transplantation (OLT) models. Inhalation achieved superior attenuation of pulmonary injury relative to systemic administration. Mechanistically, MSC-EV-encapsulated miR-22-3p was delivered to alveolar macrophages, where it targeted NLRP3 and suppressed the ASC/Caspase-1/IL-1β axis, reducing pyroptosis and promoting M2 polarization. These effects lowered cytokine-driven damage and enhanced tissue repair. Efficacy was confirmed in a clinically relevant rat OLT model, supporting translational potential for PGD prevention. The findings establish a pathway-specific, cell-free therapeutic strategy with a favorable route-dependent efficacy profile.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026018
Doxorubicin (DOX) remains a cornerstone chemotherapeutic agent for malignancies, yet its clinical utility is severely limited by dose-dependent cardiotoxicity, which can lead to progressive left ventricular dysfunction and heart failure. Pleiotrophin (PTN), a heparin-binding growth factor with diverse physiological functions, regulates glucose and lipid metabolism and promotes oxidative energy pathways. However, whether PTN exerts protective effects against DOX-induced cardiotoxicity (DIC) remains unclear. In this study, we establish cellular and animal models of DIC. DOX administration induces pronounced myocardial injury in both models, characterized by impaired ventricular contractility, increased fibrotic remodeling, and reduced cell viability. Concurrently, PTN protein expression is significantly downregulated in cardiomyocytes under DOX treatment. Overexpression of PTN substantially alleviates these pathological changes. In vitro, PTN reduces mitochondrial oxidative stress and apoptosis while restoring energy production and cell viability. In vivo, PTN improves mitochondrial ultrastructure, decreases cardiomyocyte apoptosis, and enhances cardiac function. Mechanistically, PTN directly binds to SIRT1 and activates AMPK phosphorylation at Thr172, triggering a downstream cascade through the AMPK-PGC1α axis that reprograms mitochondrial energy metabolism and attenuates cardiotoxicity. In conclusion, the PTN-SIRT1 axis protects against DIC by reducing oxidative stress and promoting mitochondrial energy homeostasis via the AMPK/PGC1α pathway, highlighting its potential as a novel therapeutic target for preventing chemotherapy-related cardiac injury.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026002
The newly discovered midnolin-proteasome pathway is a unique ubiquitin-independent mechanism for degrading nuclear proteins, which is crucial for maintaining cellular protein homeostasis. The Catch domain of midnolin is essential for substrate recognition and binding, yet the underlying mechanism for its broad substrate specificity remains elusive. Transcription factor IRF4, essential for the functions of B and T cells, is a substrate of midnolin. This study presents comprehensive biochemical and structural analyses of the human midnolin Catch domain in complexes with both wild-type and mutant IRF4 peptides. The crystal structure of the Catch-IRF4 complex reveals that the Catch domain creates a substrate-binding groove at the interface of the Catch1 and Catch2 subdomains, recognizing and binding to the 215-QVTGTFYAC-223 sequence motif of IRF4. The binding motif of IRF4 forms a β-strand that is embedded into the substrate-binding groove, resulting in an antiparallel five-stranded β-sheet. The interactions between the IRF4 peptide and the Catch domain are predominantly hydrophobic and exhibit high spatial complementarity. Additionally, the biochemical, modeling and structural data indicate that the V2 and A8 positions of the IRF4 sequence motif can be substituted with other hydrophobic or small polar residues (G/A/V/L/I/M/P/F/Y/C/S/T), but not with large polar and charged residues (D/N/E/Q/H/K/R). The G4 position can be replaced by Ser, while the F6 position can be substituted with Tyr. These results suggest that the Catch domain can recognize and bind to a variety of substrates containing the sequence motif x[G/A/V/L/I/M/P/F/Y/C/S/T]x[G/S]x[F/Y]x[G/A/V/L/I/M/P/F/Y/C/S/T]x or briefly the G/SxF/Y motif (where x represents polar residues) located in an unstructured or loop region on the protein surface, and the hydrophobic interactions and spatial complementarity between the binding motifs of substrates and the Catch domain govern the substrate specificity. Collectively, these findings elucidate the molecular basis for midnolin’s broad substrate specificity.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21246
BACKGROUND: Fibrosis results from dysregulated tissue healing, characterized by abnormal proliferation of fibroblasts and excessive deposition of extracellular matrix, affecting nearly all organs including liver, kidney, heart, lung, and skin. OBJECTIVE: To summarize fibrosis-related diseases such as liver, kidney, cardiac, and pulmonary fibrosis, focusing on the major abnormal cells, signaling pathways, and therapeutic approaches. METHODS: PubMed and CNKI were searched using English terms "fibrosis, fibroblasts, fibrotic organs, extracellular matrix, tissue repair, inflammatory response" and Chinese equivalents. After screening according to inclusion and exclusion criteria, 200 articles were included for review. RESULTS AND CONCLUSION: Key abnormal cells in fibrosis include immune cells (macrophages, neutrophils, lymphocytes), fibroblasts, epithelial cells, and endothelial cells, with fibroblasts playing a central role. Major abnormal pathways include TGF-β, Wnt/β-catenin, Notch, TLR4/MyD88/NF-κB, and Hippo/YAP signaling, whose dysregulation drives fibrosis. Epigenetic modifications (DNA methylation, histone modification, non-coding RNA regulation) modulate fibrosis progression. Anti-fibrotic therapies include pharmacological, cellular, and gene-based approaches, targeting signaling pathways to inhibit persistent fibroblast activation or modulating extracellular matrix deposition to alleviate fibrosis and improve organ function.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21203
BACKGROUND: Bisphosphonates, as the core drugs of anti-bone resorption therapy, are widely used in the treatment of metabolic bone diseases. However, long-term use can cause the complications of bisphosphonate related osteonecrosis of the jaw. The traditional pathogenesis focuses on the inhibitory effect of bisphosphonates on osteoclasts, but it is difficult to fully explain the pathological development of osteonecrosis. Compared with the relatively mature osteoclast research, there are fewer reports on the effects of bisphosphonates on the biological characteristics and functions of osteoblast-related cells, and there are differences between some reports. This difference may be due to the experimental system, drug concentration and cell source, highlighting the necessity of conducting systematic and standardized research.
OBJECTIVE: To investigate the effect of the third-generation bisphosphonate-zoledronic acid commonly used in clinical practice on the healing of tooth extraction sockets and the proliferation, migration and osteogenic differentiation of bone marrow mesenchymal stem cells derived from the jaw in mice.
METHODS: Sixteen male C57BL/6J mice were randomly divided into control and experimental groups. The experimental group received intraperitoneal injection of zoledronic acid combined with subcutaneous injection of dexamethasone, while the control group received an equal volume of PBS. After 2 weeks of injection, the left maxillary first molars of all mice were extracted, and after another 2 weeks of injection, the mice were sacrificed. The healing of extraction sockets was evaluated by gross observation, Micro CT imaging and three-dimensional reconstruction, and hematoxylin-eosin staining. Jaw bone marrow mesenchymal stem cells were isolated and cultured from both groups. After normal culture and osteogenic induction, cell proliferation, migration, and osteogenic differentiation were assessed by CCK-8 assay, qPCR, Western blot, alkaline phosphatase staining, and alizarin red staining.
RESULTS AND CONCLUSION: Compared with the control group, the experimental group showed poor healing of extraction sockets with more inflammatory cell infiltration. The proliferation and migration abilities of jaw bone marrow mesenchymal stem cells were significantly inhibited in the experimental group (P < 0.05). Alkaline phosphatase staining was weaker, calcium nodule formation was reduced, and the expression of osteogenic markers (alkaline phosphatase, integrin-binding sialoprotein, collagen type I alpha 1 chain, Runt-related transcription factor 2) was downregulated in the experimental group (P < 0.05). These results indicate that zoledronic acid can adversely affect extraction socket healing, possibly by inhibiting the proliferation, migration, and osteogenic differentiation of jaw bone marrow mesenchymal stem cells.
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: 10.12307/2026.21233
BACKGROUND: Gushukang Granule is a Chinese herbal compound preparation, commonly used clinically for the treatment of osteoporosis and other bone-related diseases. However, its role in the regulation of muscle metabolism is not clear. OBJECTIVE: To investigate the inhibitory effect of Gushukang Granule-containing serum on dexamethasone-induced C2C12 muscle atrophy. METHODS: (1) In vivo experiment: Thirty-six 3-month-old female Sprague-Dawley rats were randomly divided into model group, blank group and Gushukang group, with 12 rats in each group. The rats in the model group were given 2.5 mg/kg dexamethasone by intragastric administration, once a day, for 1 week, followed by normal feeding for 3 weeks; the Gushukang group was given 0.48 g/kg Gushukang Granule suspension by gavage after modeling, once a day, for 3 weeks; the blank group was not modeled and given equal volume of distilled water by gavage, once a day, for 4 weeks. Two hours after the last administration, left femur and gastrocnemius muscle specimens were taken for hematoxylin-eosin staining, and RNA was extracted from right gastrocnemius and femur tissues; real-time fluorescence quantitative PCR was used to detect mRNA expression levels of mitochondrial function, autophagy and inflammation-related genes. (2) In vitro experiment: C2C12 cells were cultured and induced to differentiate into myotubes with 2% horse serum. Differentiated myotubes were divided into control group, model group and Gushukang-containing serum group. Muscle atrophy model was constructed by incubating with 4 µmol/L dexamethasone for 48 h, and the Gushukang group was treated with 10% Gushukang-containing serum for 24 h after dexamethasone treatment for 24 h. CCK-8 was used to detect cell viability, flow cytometry to detect reactive oxygen species levels, transmission electron microscopy to observe ultrastructural changes, and western blot to detect expression levels of mitochondrial function-related proteins, autophagy-related proteins and antioxidant-related proteins. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining showed that compared with the model group, the muscle fiber structure of rats in the Gushukang group recovered better; real-time fluorescence quantitative PCR further verified that Gushukang Granule up-regulated mitochondrial function and autophagy-related genes, supporting its multi-target mechanism to alleviate muscle atrophy. (2) Flow cytometry and CCK-8 results showed that after dexamethasone treatment, reactive oxygen species levels in C2C12 cells were significantly increased (P < 0.05), and cell viability was significantly decreased (P < 0.05); transmission electron microscopy revealed that dexamethasone induced ultrastructural disorder, reduced number of organelles, atrophic and blurred mitochondria, accompanied by a large number of autophagosomes and cytoplasmic vacuoles; western blot results showed that after dexamethasone treatment, the expression of mitochondrial function-related proteins translocase of outer mitochondrial membrane 20 and heat shock protein 60 was significantly decreased, autophagy-related proteins LC3 and Beclin-1 were abnormally expressed (P < 0.05), and silent information regulator 1 expression was significantly decreased (P < 0.05), suggesting that dexamethasone disrupted mitochondrial homeostasis and inhibited autophagy. After treatment with Gushukang Granule-containing serum, reactive oxygen species levels were significantly decreased (P < 0.05), cell viability was significantly increased (P < 0.05); transmission electron microscopy showed that ultrastructure was improved and mitochondrial morphology was relatively restored; western blot results showed that the expression of translocase of outer mitochondrial membrane 20, heat shock protein 60, and silent information regulator 1 was significantly up-regulated (P < 0.05), and LC3 and Beclin-1 expression returned to normal levels (P < 0.05), indicating that Gushukang Granule-containing serum played a positive role in improving mitochondrial function, reducing oxidative stress, and regulating autophagy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21272
BACKGROUND: Patients with cervical spondylosis often exhibit varying kinematic abnormalities due to degenerative structural changes and biomechanical imbalances in the cervical spine. Although previous studies have compared specific kinematic parameters between healthy individuals and cervical spondylosis patients, research on coupled motions and their associated ratios remains limited. OBJECTIVE: To investigate changes in kinematic parameters in cervical spondylosis patients before and after Feng's spinal manipulation therapy. METHODS: Thirty patients with cervical spondylosis and 30 healthy controls were enrolled. Participants completed three standardized motion tasks: lateral flexion, flexion-extension, and axial rotation. Three-dimensional cervical spine kinematics were quantified using stereophotogrammetry upon admission and discharge. The following kinematic parameters were analyzed: primary range of motion, coupled motion range, coupled motion patterns, motion symmetry, motion smoothness, and motion velocity. RESULTS AND CONCLUSION: Compared with healthy controls, patients with cervical spondylosis showed significantly reduced maximal angles in lateral flexion, flexion-extension, and axial rotation (P < 0.05), and significantly increased ratios of coupled flexion-extension during lateral flexion, coupled rotation during lateral flexion, coupled lateral flexion during extension, and coupled lateral flexion during rotation (P < 0.05). After treatment, patients showed significant improvements in visual analog scale score and cervical dysfunction index (P < 0.05). Significant differences were found in maximal lateral flexion angle, lateral flexion symmetry, maximum and average lateral flexion velocity, maximal flexion-extension angle, maximum and average flexion-extension velocity, maximal rotation angle, rotation symmetry, maximum rotation velocity, and average left rotation velocity before and after treatment (P < 0.05). No significant differences were observed in coupled motion patterns before and after treatment (P > 0.05). Significant differences were found in the ratios of coupled flexion-extension during right lateral flexion, coupled rotation during lateral flexion, coupled flexion-extension during right rotation, and coupled lateral flexion during rotation before and after treatment (P < 0.05). In conclusion, patients with cervical spondylosis exhibit increased ratios of some coupled motions relative to primary motions. Feng's spinal manipulation can significantly improve clinical symptoms and effectively restore cervical motor function.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21270
BACKGROUND: Conventional observational studies are inadequate to reveal the potential causal relationship of biomarkers in burns patients. Mendelian randomization, leveraging genetic variation as an instrumental variable to mimic the advantages of randomized controlled trials, has emerged as a crucial tool for dissecting causal associations in complex diseases. OBJECTIVE: To explore the relationship of burn injury with 41 inflammatory cytokines and 35 blood and urinary biomarkers using Mendelian Randomization. METHODS: (1) Burn-related data of genome-wide association studies were obtained from the IEU open GWAS project database, constructed by The University of Bristol, UK, including 218 131 samples and 16 380 465 single nucleotide polymorphisms were included in the study. (2) Data for 41 types of inflammatory cytokines were derived from a study involving 8 293 participants in the Finnish Young Cardiovascular Risk Study database, which is constructed by the Research Centre for Applied and Preventive Cardiovascular Medicine, University of Turku. (3) Data for 35 types of blood and urinary biomarkers were derived from a study involving 363 228 participants from the UK Biobank, which is a large biomedical database project jointly initiated by the UK government, the Wellcome Trust, and the Medical Research Council of the UK. Single nucleotide polymorphisms were employed as instrumental variables, and analyses were conducted using inverse variance weighting, MR Egger, weighted median, and weighted mode methods. Cochrane's Q test was used to identify heterogeneity, and MR Egger intercept test, MR-PRESSO test, and leave-one-out analysis were used to assess the reliability of exposure-outcome associations. RESULTS AND CONCLUSION: Burn injury reduced levels of interleukin-9 (OR=0.97; 95%CI, 0.949 to 0.997; P=0.030) and testosterone (OR=0.997; 95%CI, 0.995 to 0.999; P=0.025), with no heterogeneity or horizontal pleiotropy, demonstrating robustness. The Mendelian randomization analysis indicates that burn injury leads to decreased levels of interleukin-9 and testosterone, suggesting that increasing these levels may aid in tissue repair and improve protein breakdown rate after burn.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21306
OBJECTIVE: Non-invasive brain stimulation has been shown to improve restricted, repetitive behaviors and social deficits in children with autism; however, the efficacy of different stimulation protocols varies. This study systematically evaluated the efficacy of non-invasive brain stimulation on core symptoms in children with autism and compared the efficacy of different stimulation protocols. METHODS: Comprehensive electronic searches were conducted across CNKI, VIP, WanFang, CBM, PubMed, Embase, Cochrane Library, and Web of Science from database inception through March 2025 to identify randomized controlled trials evaluating non-invasive brain stimulation protocols targeting core symptoms in children with autism spectrum disorder. Two independent reviewers performed dual-phase screening, data extraction, and methodological quality assessment using the Cochrane Risk of Bias Tool version 2.0. Both conventional and network meta-analyses were implemented through Revman 5.4 and Stata 17.0. RESULTS: A total of 27 studies were finally included for review, involving 10 stimulation protocols of non-invasive brain stimulation and including 1 701 children with autism. (1) The results of conventional Meta-analysis showed that non-invasive brain stimulation was more effective than conventional rehabilitation in lowering the scores of Childhood Autism Rating Scale, Autism Behavior Checklist, Autism Treatment Evaluation Checklist, and Repetitive Behavior Scale-Revised. (2) The network meta-analysis showed that compared with conventional rehabilitation, high-frequency repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex [MD=-6.00, 95%CI(-8.68, -3.33), P < 0.05, SUCRA=89.5%] was most effective in improving Childhood Autism Rating Scale scores, while high-frequency repetitive transcranial magnetic stimulation over Broca's area [MD=-15.11, 95%CI(-18.28, -11.95), P < 0.05, SUCRA=91.1%] was most effective in improving Autism Behavior Checklist scores. CONCLUSION: Current evidence indicates that high-frequency repetitive transcranial magnetic stimulation is most effective in improving core symptoms in children with autism. Due to the dual limitations of methodological heterogeneity and limited sample size in the included studies, large-sample, methodologically rigorous randomized controlled trials are urgently needed to further verify the reliability of these conclusions.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21291
BACKGROUND: ABL1 is involved in the regulation of multiple cellular processes, yet its functions within the cardiovascular system remains largely unexplored. In particular, its role in cardiac ischemia/reperfusion injury and necroptosis has not been reported. OBJECTIVE: To investigate the role of ABL1 in cardiac ischemia/reperfusion injury and myocardial necroptosis, as well as the underlying molecular mechanisms. METHODS: (1) Animal experiment: C57BL/6J mice were randomly divided into four groups: sham surgery group, ischemia/reperfusion group, ABL1 knockdown + ischemia/reperfusion group, and ABL1 negative control + ischemia/reperfusion group. Lentiviral vectors targeting ABL1 were injected in situ into the myocardium. One week later, ischemia/reperfusion injury was induced by ligation of the left anterior descending coronary artery followed by reperfusion. ABL1 protein expression, cardiac function, myocardial fibrosis, and cardiomyocyte surface area were assessed. (2) Cell experiment: H9c2 cells were divided into four groups: negative control cell line + PBS, ABL1 knockdown cell line + PBS, negative control cell line + H2O2 500 µmol/L, and ABL1 knockdown cell line + H2O2 500 µmol/L. Additionally, H9c2 cells were divided into five groups: negative control cell line + PBS, negative control cell line + H2O2 500 µmol/L, ABL1 knockdown cell line + H2O2 500 µmol/L, ABL1 knockdown cell line + Parkin overexpression adenovirus + H2O2 500 µmol/L, and ABL1 knockdown cell line + Parkin negative control adenovirus + H2O2 500 µmol/L. Cell viability, necroptosis, reactive oxygen species levels, and mitochondrial membrane potential were measured. Expression of ABL1, Parkin, and cyclophilin D was detected, and the interaction between ABL1 and Parkin was examined. RESULTS AND CONCLUSION: (1) ABL1 protein expression was significantly downregulated in the mouse cardiac ischemia/reperfusion model. (2) Knockdown of ABL1 exacerbated ischemia/reperfusion-induced cardiac dysfunction, as evidenced by decreased left ventricular ejection fraction and fractional shortening, and increased left ventricular end-systolic and end-diastolic diameters. (3) Knockdown of ABL1 promoted ischemia/reperfusion-induced myocardial fibrosis and aggravated ventricular remodeling. (4) ABL1 protein expression was significantly downregulated in the cardiomyocyte oxidative stress model. (5) Knockdown of ABL1 exacerbated oxidative stress-induced cell viability loss, necroptosis, and reactive oxygen species accumulation. (6) ABL1 regulated mitochondrial membrane permeability, modulated the expression of Parkin and cyclophilin D, and regulated cellular oxidative stress levels by targeting Parkin. (7) These results indicate that ABL1 expression is significantly downregulated in both in vivo ischemia/reperfusion and in vitro oxidative stress models, and knockdown of ABL1 aggravates cardiac ischemia/reperfusion injury and cardiomyocyte oxidative stress injury, acting through the Parkin-CypD pathway.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21289
BACKGROUND: The pathogenesis of ulcerative colitis is highly complex, necessitating the development of models that more closely mimic human physiological and pathological responses to study the mechanisms underlying its onset and progression. OBJECTIVE: To establish a mouse ulcerative colitis organoid model. METHODS: Colon organoids of C57BL/6J mice were extracted, cultured and passaged in vitro. Colon organoids from mice after three generations of passage were taken and incubated in lipopolysaccharide at varying concentrations [0 (control), 150, 175, 200, 225, 250, 275, 300, 325, and 350 μg/mL] to induce inflammation for 24 hours. The morphology of mouse colon organoids was observed under a microscope, and changes in proliferation viability were assessed using the cell counting kit-8 assay. After 24 hours of incubation with 0, 225, 250, 275 μg/mL lipopolysaccharide, the levels of tumor necrosis factor α, interleukin-6, interleukin-9, and interleukin-10 were measured by ELISA. After 24 hours of incubation with 0 and 275 μg/mL lipopolysaccharide, the expression of occludin and zonula occludens-1 was detected by immunofluorescence staining, and the mRNA expression of tumor necrosis factor α, interleukin-6, interleukin-9, occludin, and zonula occludens-1 was detected by q-PCR. RESULTS AND CONCLUSION: (1) Under the microscope, colon organoids in the 150-275 μg/mL lipopolysaccharide group showed varying degrees of swelling, while those in the 300-350 μg/mL lipopolysaccharide group had inhibited growth and swelling. CCK-8 assay showed that 150-350 μg/mL lipopolysaccharide reduced the proliferation viability of mouse colon organoids, with 225-350 μg/mL having a more pronounced effect. Based on cell morphology and proliferation viability results, 225, 250, and 275 μg/mL lipopolysaccharide were selected for ELISA. (2) Compared with the control group, the levels of interleukin-6 and tumor necrosis factor α were increased in the 225, 250, and 275 μg/mL lipopolysaccharide groups (P < 0.05), and the level of interleukin-9 was increased in the 275 μg/mL lipopolysaccharide group (P < 0.05). (3) Immunofluorescence staining showed that compared with the control group, the expression of occludin and zonula occludens-1 was decreased in the 275 μg/mL lipopolysaccharide group. q-PCR detection showed that compared with the control group, the mRNA expression of interleukin-6 and tumor necrosis factor α was increased (P < 0.05), occludin mRNA expression was decreased (P < 0.05), and there was no significant difference in the expression of interleukin-9 and zonula occludens-1 (P > 0.05). (4) These results indicate that an in vitro mouse ulcerative colitis model based on organoids was successfully constructed, providing a powerful tool for studying the mechanisms of ulcerative colitis and screening effective drugs.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21416
BACKGROUND: Non-infectious poor wound healing following lumbar surgery is a significant clinical complication that prolongs hospitalization and increases the risk of reoperation. However, its predictive indicators remain unclear. Based on the hypothesis that paraspinal muscle degeneration may impede tissue repair by altering the local microenvironment, this study aimed to investigate the predictive value of preoperative paraspinal muscle fatty infiltration for non-infectious poor wound healing and its association with osteoporosis. OBJECTIVE: To quantify the degree of paraspinal muscle fatty infiltration using preoperative MRI and evaluate its predictive value for non-infectious poor wound healing after lumbar surgery. METHODS: A retrospective analysis was conducted on medical records of 4,368 patients who underwent traditional open posterior lumbar surgery at Third Affiliated Hospital of Guangzhou University of Chinese Medicine between 2019 and 2024. We screened 190 patients with a postoperative hospital stay of 15 days or longer. Based on postoperative wound healing and infection indicators, 41 patients with non-infectious poor healing were selected as the poor healing group. From the remaining 4,178 patients, 40 patients with good healing were selected as the good healing group. The poor healing group was further subdivided into osteoporosis and non-osteoporosis subgroups. Preoperative lumbar MRI images were collected, and Image J software was used to measure the cross-sectional area of the psoas major muscle and the percentage of fat infiltration in the erector spinae and multifidus muscles. RESULTS AND CONCLUSION: (1) There were no significant differences in gender, age, or diabetes between the poor healing and good healing groups (P > 0.05). (2) The functional cross-sectional area and fat infiltration percentage of the psoas major, erector spinae, and multifidus muscles were significantly different between the two groups (P < 0.05). (3) Logistic regression analysis showed that fat infiltration percentage was an independent risk factor for poor wound healing. (4) Receiver operating characteristic curve analysis showed that fat infiltration percentage had high predictive value for poor wound healing (area under the curve > 0.7). (5) One-way ANOVA indicated that osteoporosis was a risk factor for fat infiltration in the L4 multifidus muscle (P < 0.05). (6) The results indicate that paraspinal muscle fat infiltration percentage is an important predictor of non-infectious poor wound healing after traditional open posterior lumbar surgery, providing clinical reference. Osteoporosis was also confirmed as a risk factor for L4 multifidus fat infiltration, but due to the small subgroup sample size, whether osteoporosis affects non-infectious poor healing after lumbar surgery requires further clinical trials.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21315
BACKGROUND: Studies have confirmed that A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8) plays a regulatory role in fibrosis, so it is of great clinical significance to explore the mechanism of ADAMTS8 in hypertrophic scars. OBJECTIVE: To investigate the regulatory effect of ADAMTS8 on hypertrophic scars. METHODS: (1) Immunohistochemical staining was used to detect the expression of type I collagen, type III collagen, alpha-smooth muscle actin and ADAMTS8 in normal human skin and hypertrophic scar tissues. Western blot was used to detect ADAMTS8 protein expression in normal skin and hypertrophic scar tissues. With hypertrophic scar as positive sample and normal skin as negative sample, receiver operating characteristic curve was drawn to analyze the ability of ADAMTS8 to predict and distinguish normal skin from hypertrophic scar. (2) STRING 12.0 platform was used to construct a protein-protein interaction network for ADAMTS8, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the obtained targets. (3) Fibroblasts from human hypertrophic scar tissue were isolated and cultured. The 3rd to 6th generation fibroblasts were divided into three groups: control group (routine culture), Ad-NC group (transfected with empty adenovirus), and Ad-ADAMTS8 group (transfected with adenovirus overexpressing ADAMTS8). CCK-8 assay and EdU staining were used to detect cell proliferation activity, and flow cytometry and TUNEL staining were used to detect cell apoptosis. RESULTS AND CONCLUSION: (1) Immunohistochemical staining showed that the expression of type I collagen, type III collagen and alpha-smooth muscle actin in hypertrophic scars was higher than that in normal skin (P < 0.001), while ADAMTS8 expression was lower than that in normal skin (P < 0.001). Western blot showed that ADAMTS8 protein expression in hypertrophic scars was lower than that in normal skin (P < 0.001). Receiver operating characteristic curve showed that the area under the curve of ADAMTS8 predicting hypertrophic scar was 0.86, indicating that ADAMTS8 has good ability to distinguish hypertrophic scar from normal skin. (2) The top 41 genes were screened through STRING database. KEGG enrichment showed that ADAMTS8 was mainly involved in extracellular matrix receptor interaction, phosphatidylinositol-3-kinase-protein kinase B signaling pathway, efferocytosis and other biological processes and key mechanisms. GO enrichment showed that ADAMTS8 was involved in apoptosis-related pathway enrichment, including negative regulation of fibroblast growth factor receptor signaling pathway, fibroblast growth factor binding, negative regulation of apoptosis and apoptotic process. (3) CCK-8 assay and EdU staining showed that overexpression of ADAMTS8 inhibited the proliferation of hypertrophic scar fibroblasts; flow cytometry and TUNEL staining showed that overexpression of ADAMTS8 promoted apoptosis of hypertrophic scar fibroblasts. (4) These results indicate that ADAMTS8 expression is decreased in human hypertrophic scars, and overexpression of ADAMTS8 can inhibit proliferation and promote apoptosis of hypertrophic scar fibroblasts.
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: 10.12307/2026.21348
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: 10.12307/2026.21333
BACKGROUND: Periprostatic adipose tissue is the white visceral adipose tissue that is closest to the prostate, which is part of the prostate cancer tumor microenvironment and plays a key role in the occurrence and progression of prostate cancer. OBJECTIVE: To investigate the ability of adipose-derived stem cells derived from periprostatic adipose tissue to form three-dimensional cell sheets. METHODS: Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy. Adipose-derived stem cell suspensions were prepared using a combination of enzymatic digestion and mechanical dissection. Adipose-derived stem cell proliferation was assessed using a CCK-8 assay. Expression of stem cell-associated antigens CD34/CD44/CD45/CD90/CD105 was determined by flow cytometry. Multidirectional differentiation potential of the stem cells was assessed using osteogenic/adipogenic/chondrogenic differentiation assays. Adipose-derived stem cells were cultured for three weeks in low-glucose DMEM containing 100 μg/mL vitamin C and 10% fetal bovine serum to construct cell sheets, followed by histological analysis and scanning electron microscopy. RESULTS AND CONCLUSION: Adipose-derived stem cells from periprostatic adipose tissue exhibited a long spindle or fusiform shape, aligned growth, and consistent morphology. Primary culture reached 95% confluence at 9-10 days with good cell viability, and no obvious senescence was observed up to passage 15. Flow cytometry showed expression rates of CD44, CD90, and CD105 at 98.24%, 84.99%, and 89.14%, respectively, while CD34 and CD45 were expressed at 0.64% and 1.02%. After 3 weeks of osteogenic, adipogenic, and chondrogenic induction, the cells could differentiate into osteoblasts, adipocytes, and chondrocytes. After continuous culture for 3 weeks, the cells formed a three-dimensional cell sheet with a smooth surface and uniform texture, rich in extracellular matrix components such as fibronectin and type I collagen. Scanning electron microscopy revealed a flat surface with aligned long spindle-shaped cells and abundant extracellular matrix deposition between cells. This study successfully isolated adipose-derived stem cells from periprostatic adipose tissue of prostate cancer patients and constructed a three-dimensional cell sheet by stimulating extracellular matrix secretion with vitamin C over 3 weeks of continuous culture.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21331
BACKGROUND: Age-related degeneration is closely associated with bone metabolic imbalance. In the jaw, this manifests as alveolar bone resorption, tooth loosening, and even loss. Impaired osteogenic differentiation potential of senescent jaw bone marrow mesenchymal stem cells is a critical factor hindering jaw bone regeneration. Quercetin, a natural flavonoid compound, exhibits antioxidant, anti-inflammatory, and cell differentiation-regulating properties, yet effect and mechanism of quercetin in osteogenic differentiation of senescent jaw bone marrow mesenchymal stem cells remain unclear. OBJECTIVE: To investigate the effects of quercetin on the proliferation, migration, osteogenic differentiation, and senescence of aged jaw bone marrow mesenchymal stem cells. METHODS: Jaw bone marrow mesenchymal stem cells were isolated from the mandibles of 10 8-week-old SD rats and cultured using a combination of bone marrow flushing and bone slice digestion. Jaw bone marrow mesenchymal stem cells were subcultured to the third and seventh passages, serving as the young and senescent groups, respectively. The quercetin group was treated with quercetin based on the senescent group. CCK-8 assay was used to detect the effects of 0.01, 0.1, 1, 10, 100 μmol/L quercetin on proliferation of senescent jaw bone marrow mesenchymal stem cells, and the optimal concentration was selected. Cell scratch assay was used to observe cell migration ability. RT-qPCR and western blot were used to detect the expression of senescence markers. β-galactosidase staining was used to observe the proportion of positive cells. After 7 days of osteogenic induction, RT-qPCR and western blot were used to detect the expression of osteogenic markers. After 14 days of osteogenic induction, alkaline phosphatase staining was performed. After 21 days of osteogenic induction, alizarin red staining was performed. Western blot was used to detect the expression of phosphorylated protein kinase B, protein kinase B, phosphorylated mammalian target of rapamycin, and mammalian target of rapamycin. RESULTS AND CONCLUSION: Compared with the young group, the proliferation ability of the senescent group decreased. Compared with the senescent group, 1 μmol/L quercetin significantly promoted the proliferation of senescent jaw bone marrow mesenchymal stem cells (P < 0.01). Compared with the senescent group, the migration ability of senescent jaw bone marrow mesenchymal stem cells in the quercetin group was improved, the proportion of β-galactosidase positive cells was significantly reduced, and the mRNA and protein expression of senescence-related P16, P53, and P21 were decreased (P < 0.05). After osteogenic induction, compared with the senescent group, the quercetin group showed increased calcium nodule formation, alkaline phosphatase staining area, and mRNA and protein expression of alkaline phosphatase, osteopontin, and Runt-related transcription factor 2 (P < 0.05). Compared with the senescent group, the phosphorylation levels of protein kinase B and mammalian target of rapamycin in the quercetin group were significantly reduced (P < 0.05). These results indicate that quercetin can inhibit senescence of jaw bone marrow mesenchymal stem cells caused by multiple passages and promote osteogenic differentiation by regulating the protein kinase B/mammalian target of rapamycin signaling pathway.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21474
BACKGROUND: The tendon suturing technique for the hand has been continuously innovated with the development of biomechanics, minimally invasive techniques, and regenerative medicine. Over the past two decades, research has focused on optimizing traditional suturing techniques and the application of new repair materials, improving the effectiveness of tendon repair and the level of functional recovery in the hand. OBJECTIVE: To assess the global research status and development trends of hand tendon repair techniques over the past two decades through bibliometric analysis, identify research hotspots and their evolution. METHODS: Relevant literature was selected from the Web of Science database from 2005 to 2024, and bibliometric methods were employed for analysis. Data were organized using Microsoft Excel and analyzed for publication trends using the R language Bibliometrix package. VOSviewer was used to visualize keyword co-occurrence and collaboration networks, while CiteSpace was utilized to identify research hotspots and their temporal evolution. RESULTS AND CONCLUSION: Over the past two decades, research in the field of tendon suturing has shown a fluctuating growth trend. The United States, China, and Europe are the main contributing countries, with the United States occupying a central position in the global research network. Research on flexor tendon repair mainly focuses on biomechanics and the development of new repair materials, while extensor tendon research emphasizes postoperative functional recovery and complex injury repair. In recent years, biomaterials and regenerative medicine have gradually become research hotspots, promoting the application of precision medicine in tendon repair. In the future, interdisciplinary collaboration and the combination of advanced materials will further optimize hand tendon repair techniques.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21387
BACKGROUND: The magnetic field mitochondrial regulation technology has been proven to enhance skeletal muscle function. Low-load blood flow restriction training can effectively induce adaptive growth of muscle strength through metabolic emergency mechanisms. Currently, both technologies have become hotspots in the application and research of skeletal muscle function improvement and treatment. However, the differences in their effects on muscle strength enhancement and whether their combined application can produce a synergistic effect remain unclear. OBJECTIVE: To observe the differences in the effects of low-frequency pulsed magnetic stimulation (1.5 mT, 3 300 Hz) and low-load blood flow restriction training on muscle strength enhancement and the impact of their combined intervention on lower limb muscle strength. METHODS: Fifty-six healthy subjects were recruited and randomly divided into magnetic stimulation group (high-load squat training + magnetic stimulation), blood flow restriction group (low-load blood flow restriction squat training), combined group (low-load blood flow restriction squat training + magnetic stimulation), and control group (high-load squat training). The trial lasted 4 weeks, with training three times per week, and low-frequency pulsed magnetic stimulation (1.5 mT, 3 300 Hz) was administered every 48 hours. After the trial, changes in maximal strength, explosive power, and strength endurance of the lower limb muscles were observed among groups. RESULTS AND CONCLUSION: Fifty subjects completed the trial and were included in the analysis. ① After 4 weeks of intervention, the maximal strength, explosive power, and strength endurance of the lower limbs in the magnetic stimulation, blood flow restriction, and combined groups significantly increased. ② In terms of maximal strength increase, blood flow restriction was superior to magnetic field mitochondrial regulation technology; low-load blood flow restriction also enhanced distal muscle strength, while magnetic field mitochondrial regulation technology had the advantage of improving maximal strength without fatigue accumulation. ③ In terms of explosive power increase, both technologies had similar effects; magnetic stimulation was more advantageous for explosive power in single-joint movements, while low-load blood flow restriction training was more advantageous for explosive power in multi-joint coordinated movements. ④ In terms of strength endurance increase, magnetic stimulation technology, due to its mitochondrial function regulation, effectively improved muscle fatigue resistance. The results suggest that the combined application of magnetic stimulation and low-load blood flow restriction can produce synergistic effects on maximal strength, explosive power, and strength endurance of the lower limbs. This technical approach may provide a novel and efficient auxiliary training protocol for lower limb muscle strength enhancement in postoperative rehabilitation and sports injury patients who cannot undergo high-intensity resistance training.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21491
BACKGROUND: Lentiviral vector (LV)-mediated autologous hematopoietic stem cell gene therapy is expected to be a novel curative treatment for β-thalassemia. The LV serves as a core agent of gene therapy, directly influencing future clinical efficacy and treatment costs. Therefore, the primary task is to develop high-performance lentiviral vectors. OBJECTIVE: To explore the feasibility of an ex vivo gene therapy and assess the activity and functionality of the β-globin-LV in thalassemic mice. METHODS: A novel lentiviral vector, HS40-LV, carrying the human β-globin gene cassette, was constructed. 7.5 Gy-conditioned Hbbth3/+ mice were subjected to HS40-LV-modified hematopoietic stem cell transplantation. Normal mice and untreated thalassemic mice served as controls. Peripheral blood samples were collected from mice at 2, 4, 6, 8, and 10 months post-treatment. The integrated proviral DNA in the individual sample was detected by using qPCR. The proportion of red blood cells expressing human β-globin was detected by fluorescence-activated cell sorting. Fresh whole blood was collected for blood smears, which were used for Giemsa staining, reticulocyte staining, and fully automated blood cell analysis. At 10 months post-treatment, the liver, spleen, and bone marrow tissues were sampled from all three groups to prepare single-cell suspensions and extract genomic DNA for qPCR detection of vector marking; flow cytometry was used to detect cells expressing transgenic β-globin; portions of spleen and liver were subjected to hematoxylin-eosin staining and Prussian blue staining. RESULTS AND CONCLUSION: (1) The HS40-LV vector achieved a transduction efficiency of 50% in hematopoietic stem cells. (2) During the 10-month follow-up, the proportion of vector-marked cells and β-globin-positive red blood cells in peripheral blood of treated mice steadily increased, reaching an average of 50% vector marking and 70% β-globin-positive red blood cells at 10 months post-transplantation. (3) Biological distribution of the lentiviral vector and expression of transgenic β-globin were also detected in liver, spleen, and bone marrow hematopoietic tissues. (4) Gene therapy corrected hematological parameters in thalassemic mice, such as significant reductions in poikilocytes, reticulocytes, and cell fragments, and a significant increase in overall hemoglobin levels. (5) Histopathological improvements were also observed, with significant reductions in iron deposition in spleen and liver, and improved extramedullary hematopoiesis. These results indicate that the novel HS40-LV vector achieved stable expression in vivo, and modified cells corrected some symptoms in thalassemic mice.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21484
BACKGROUND: In sarcopenic osteoporosis, muscle loss and osteoporosis often coexist, leading to a significant increase in the risk of falls and fractures. Gushukang Granules are clinically used for the treatment of osteoporosis; however, the mechanism of action on myogenic and osteogenic factors in muscle and bone remains unclear.
OBJECTIVE: To investigate the effects of Gushukang Granules on myogenic and osteogenic factors in the muscles and bones of rats.
METHODS: Thirty-six healthy Sprague-Dawley rats were randomly divided into control, model, and Gushukang groups (n=12 per group). Osteoporosis was induced in the latter two groups by ovariectomy. Four weeks after surgery, the Gushukang group received 1.05 mL/kg Gushukang Granules solution by gavage, while the other groups received an equal volume of saline, once daily for 12 weeks. General conditions were observed. Hematoxylin-eosin staining was used to assess morphological changes in muscle and bone tissues. RT-qPCR was performed to detect mRNA expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) in muscle, and osteocalcin (OCN) and insulin-like growth factor 1 (IGF-1) in bone. Immunohistochemistry was used to observe the expression of IL-6, TNF-alpha, IGF-1, and OCN in muscle and bone tissues. Western blot was used to detect protein expression levels of these factors.
RESULTS AND CONCLUSION: Compared with the control group, the model group exhibited typical sarcopenic osteoporosis phenotype: muscle fibers were sparse, disordered, and atrophic; bone trabeculae were reduced, sparse, and disconnected. mRNA and protein expression of IL-6 and TNF-alpha were significantly increased (P < 0.01), while IGF-1 and OCN were significantly decreased (P < 0.01). Compared with the model group, the Gushukang group showed significant improvement: muscle fiber arrangement became more orderly with interstitial fibrosis; bone trabeculae increased and connectivity improved (though still loose). IL-6 and TNF-alpha expression were significantly decreased (P < 0.01), while IGF-1 and OCN were significantly increased (P < 0.01). Western blot results were consistent with immunohistochemistry. These findings suggest that Gushukang Granules can improve muscle atrophy and bone trabecular thinning in ovariectomized rats by downregulating the abnormal high expression of IL-6 and TNF-alpha, and upregulating IGF-1 and OCN, possibly through regulating muscle-bone crosstalk signaling pathways and balancing inflammatory and growth factor levels, providing experimental support for the clinical treatment of sarcopenic osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21475
BACKGROUND: The pathogenesis of steroid-induced osteonecrosis of the femoral head remains unclear; however, it is closely associated with mitochondrial damage in osteoblasts. OBJECTIVE: To explore the impact of dexamethasone on mitochondrial dysfunction in osteoblasts following steroid-induced osteonecrosis of the femoral head and to analyze its regulatory roles in osteoblast apoptosis and autophagy. METHODS: MC3T3-E1 cells were cultured in vitro and divided into control group (no treatment) and dexamethasone group (1 μmol/L dexamethasone treatment for 24 hours). Osteoblast differentiation capacity was assessed by alizarin red staining and qRT-PCR. Mitochondrial morphology was examined using transmission electron microscopy, MitoTracker Red fluorescence staining, and flow cytometry. Mitochondrial membrane potential and energy metabolism were evaluated by JC-1 fluorescence staining and ATP content detection. Mitochondrial superoxide levels were measured using MitoSOX fluorescence probe and flow cytometry. Intracellular total reactive oxygen species and glutathione content were also measured to assess oxidative stress status. Additionally, Western blot and qRT-PCR were used to detect the expression of apoptosis-related proteins (Bax, Bcl-2) and autophagy markers (LC3B, p62), flow cytometry was used to analyze apoptosis rate, and autophagy flux was observed via mRFP-GFP-LC3 adenovirus transfection combined with confocal microscopy. RESULTS AND CONCLUSION: Compared with the control group, the dexamethasone group showed significantly reduced osteogenic differentiation capacity of MC3T3-E1 cells, abnormal mitochondrial structure (swelling, cristae disruption), decreased mitochondrial membrane potential, reduced ATP synthesis, increased mitochondrial superoxide and total reactive oxygen species levels, and increased glutathione consumption (P < 0.05). The dexamethasone group showed significantly upregulated pro-apoptotic protein Bax (P < 0.01), significantly downregulated anti-apoptotic protein Bcl-2 (P < 0.01), increased LC3B-II/I ratio (P < 0.01), and decreased p62 levels (P < 0.01); dexamethasone treatment significantly increased the apoptosis rate (P < 0.01). mRFP-GFP-LC3 adenovirus tracing revealed increased formation of autophagosomes and autolysosomes. These results indicate that dexamethasone induces mitochondrial dysfunction and oxidative stress, synergistically regulating apoptosis and autophagy in MC3T3-E1 cells, thereby impairing bone formation and repair function. This mechanism may be a key pathological basis for the pathogenesis of steroid-induced osteonecrosis of the femoral head.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21540
BACKGROUND: The bone marrow serves not only as a primary hematopoietic organ but also as an essential component of bone tissue. The bone marrow microenvironment is a critical niche for maintaining hematopoietic stem cell function, while the hematopoietic process itself can regulate bone remodeling and maintain bone mass stability. The precise synergistic interaction between the skeletal and hematopoietic systems maintains the health of both blood and bone, yet a systematic summary of these interactions is lacking. OBJECTIVE: To systematically review the research progress on the interactions between the skeletal and hematopoietic systems, aiming to provide a reference for their mutual regulation and to explore potential therapeutic targets for blood diseases such as anemia and leukemia, and bone diseases such as osteoporosis and osteoarthritis. METHODS: A search of CNKI, Wanfang, and PubMed databases was conducted for literature published from January 2000 to July 2025 using keywords including 'bone mass regulation', 'hematopoietic function', 'bone marrow microenvironment', and 'bone and blood axis'. A total of 115 articles were included for analysis. RESULTS AND CONCLUSION: (1) The bidirectional regulatory network of the 'bone-blood axis' in the bone marrow microenvironment and its core mechanisms were systematically elaborated. (2) The bone marrow microenvironment, as a dynamic system composed of multiple cellular and non-cellular components, precisely regulates the quiescence, self-renewal, and differentiation of hematopoietic stem cells through core signaling pathways such as Wnt/β-catenin, Notch, RANK/RANKL/OPG, and Hippo-YAP, while also receiving reverse regulation from the hematopoietic system. (3) This bidirectional dialogue also dominates bone remodeling, with immune cells (e.g., macrophages and T lymphocytes) serving as key bridges connecting the skeletal and hematopoietic systems by secreting specific factors. (4) Imbalance in this dialogue network is an important pathological basis for the occurrence of cross-system diseases such as osteoporosis, myelofibrosis, and leukemia. (5) This article provides a new perspective for understanding the bone marrow microenvironment through the framework of the 'bone-blood axis', revealing the co-pathogenesis of blood and bone diseases. Targeting key signaling nodes of this axis or utilizing synergistic intervention strategies (e.g., denosumab, enasidenib) may open new avenues for integrated treatment of cross-system diseases in the future.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21531
BACKGROUND: The pathogenesis of coronary heart disease is complex. A single omics approach is limited in elucidating its biological pathways, whereas multi-omics integration helps reveal molecular interaction networks across different levels, addressing the limitations of single-omics methods. OBJECTIVE: To investigate the pathological mechanisms of coronary heart disease in a mouse model using proteomics and metabolomics. METHODS: Healthy SPF-grade 8-week-old male C57BL/6 mice were randomly divided into a sham operation group and a model group. The mouse model of coronary heart disease was established by ligation of the left anterior descending coronary artery, while the sham operation group underwent threading without ligation. At 28 days post-surgery, cardiac function was assessed by echocardiography, and myocardial infarct size was evaluated by TTC staining. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to screen differentially expressed proteins and metabolites between groups, followed by integrated omics analysis. RESULTS AND CONCLUSION: Compared with the sham group, the model group exhibited reduced cardiac function, with significantly decreased left ventricular ejection fraction and left ventricular fractional shortening (P < 0.05), and significantly increased myocardial infarct size (P < 0.01). Proteomics identified 420 differentially expressed proteins, including 282 upregulated (e.g., Serum amyloid A protein, protein kinase D) and 138 downregulated (e.g., Protein YIPF5, E3 ubiquitin-protein ligase). KEGG pathway enrichment revealed involvement in ATP-dependent chromatin remodeling and renin-angiotensin system pathways. Metabolomics identified 155 differential metabolites, including 56 upregulated (e.g., Thromboxane, Tromethamine) and 99 downregulated (e.g., N-Acetyl-D-Tryptophan, D-Xylulose 5-Phosphate). KEGG analysis linked these to purine metabolism and glycerophospholipid metabolism. Integrated analysis found correlations between 26 differentially expressed proteins and 16 differential metabolites, involving proteins such as ATP1A3 and Hexokinase, and metabolites such as Cytochalasin B and Gluconasturtiin. CONCLUSION: The pathological mechanisms of coronary heart disease are closely related to disturbances in energy metabolism networks, activation of inflammatory-coagulation cascades, and dysregulation of ion homeostasis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21526
BACKGROUND: Magnetic mitochondrial calcium regulation technology, as a non-invasive method for promoting skeletal muscle function, has been effectively demonstrated in improving muscle function and enhancing metabolic sensitivity. Existing studies have shown that this technology has significant physiological promoting effects on adults, the elderly, and postoperative rehabilitation populations, but its intervention effects on skeletal muscle function and body composition in adolescents aged 12-13 years remain unclear. OBJECTIVE: To investigate the sensitivity of skeletal muscle function and body composition to magnetic stimulation in adolescents aged 12-13 years by evaluating these parameters. METHODS: A total of 34 junior high school students from Liaoning Experimental School were recruited and randomly divided into a control group and an experimental group. The control group maintained routine campus activities without a specific physical training program. The experimental group additionally received low-frequency pulsed magnetic field intervention twice a week (stimulation duration 10 min, magnetic field intensity 1.5 mT, frequency 3300 Hz, with an interval of 72 h between interventions) for 4 consecutive weeks. Before (pre-test) and after (post-test) the intervention, changes in maximum strength, explosive power, endurance quality, and body composition indicators of the intervention site were observed. RESULTS AND CONCLUSION: After 4 weeks of 8 sessions of low-frequency pulsed magnetic field stimulation, the participants' explosive power, aerobic endurance, muscle isometric endurance, and body composition indicators were significantly improved, indicating that adolescents aged 12-13 years have good magnetic calcium-regulated stimulation sensitivity for the above skeletal muscle functions and body composition. In terms of maximum strength improvement, the effect was not significant, and their muscle magnetic sensitivity was lower than that of adults, but it had certain advantages in maintaining maximum strength under long-term sedentary conditions. The results indicate that magnetic calcium-regulated mitochondrial technology, as a novel passive, non-invasive skeletal muscle function promotion technique, can be attempted as a new intervention means to improve adolescent physical health.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21539
BACKGROUND: Calcium sulfate bone graft materials have good biocompatibility but lack antibacterial properties, potentially leading to infections. Magnesium oxide has antibacterial effects and can promote bone regeneration and angiogenesis. OBJECTIVE: To develop novel calcium sulfate-magnesium oxide bone graft materials with antibacterial properties and the ability to promote bone regeneration, and to systematically evaluate its antibacterial capabilities, cytocompatibility, and osteogenic and angiogenic potential. METHODS: (1) α-Calcium sulfate hemihydrate was synthesized by a hydrothermal method. α-Calcium sulfate hemihydrate was mixed with magnesium oxide at mass ratios of 2.5%, 7.5%, 15%, and 25%, and distilled water was added to form calcium sulfate-magnesium oxide composites, denoted as CS-2.5MgO, CS-7.5MgO, CS-15MgO, and CS-25MgO. The surface morphology, compressive strength, in vitro degradation, and H2O2 production in PBS were characterized. (2) Escherichia coli (or Staphylococcus aureus) suspensions were co-cultured with the five groups of materials, and antibacterial properties were evaluated by agar plate coating and inhibition zone tests. (3) MC3T3 cells were co-cultured with material extracts, and cytocompatibility was assessed by CCK-8 and live/dead staining. After osteogenic induction, alkaline phosphatase staining and alizarin red staining were used to evaluate osteogenic mineralization, and Western blot detected RUNX2 and WNT3a protein expression. (4) Human umbilical vein endothelial cells were co-cultured with material extracts, and angiogenic potential was evaluated by Matrigel tube formation assay, and Western blot detected endothelial nitric oxide synthase protein expression. (5) α-Calcium sulfate hemihydrate, CS-2.5MgO, CS-7.5MgO, CS-15MgO, and CS-25MgO loaded with Staphylococcus aureus were implanted into muscle incisions of SD rats. At 1, 3, and 7 days postoperatively, materials and adjacent muscle tissues were rinsed, and the rinse fluid was collected for colony counting by agar plate coating. Hematoxylin-eosin staining was used to observe inflammatory cell infiltration in surrounding muscle tissues. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that α-calcium sulfate hemihydrate mostly exhibited short rod-like crystals with a few long strip crystals and smooth surfaces; in the composites, magnesium oxide particle aggregates were distributed on crystal surfaces and between crystals, with density increasing with magnesium oxide ratio. Compared with α-calcium sulfate hemihydrate, the compressive strength and degradation rate of the composites decreased, while H2O2 production in PBS increased. Agar plate coating and inhibition zone tests showed that the composites had excellent antibacterial properties, which increased with magnesium oxide ratio. CCK-8 and live/dead staining showed that α-calcium sulfate hemihydrate, CS-2.5MgO, and CS-7.5MgO had good cytocompatibility. Alkaline phosphatase staining, alizarin red staining, and Western blot showed that CS-2.5MgO enhanced osteogenic mineralization. Matrigel tube formation and Western blot showed that CS-7.5MgO had the strongest angiogenic ability. (2) Rinse fluid agar plate coating showed that the composites had good in vivo antibacterial properties compared with α-calcium sulfate hemihydrate, increasing with magnesium oxide ratio. Hematoxylin-eosin staining showed that inflammatory cell infiltration and exudation in muscle tissues were significantly reduced in all composite groups compared with α-calcium sulfate hemihydrate group. (3) These results indicate that calcium sulfate-magnesium oxide composites have good cytocompatibility and antibacterial properties, and can effectively promote osteogenesis and angiogenesis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21593
BACKGROUND: Intervertebral disc degeneration is a core pathological mechanism of discogenic diseases, characterized by an imbalance in extracellular matrix metabolism. Tissue inhibitors of metalloproteinases, as endogenous antagonists of matrix metalloproteinases, play a crucial role in regulating extracellular matrix homeostasis, but the specific functions of subtypes, signaling pathway interactions, and epigenetic regulatory mechanisms have not been systematically clarified. OBJECTIVE: To review the expression changes, functional heterogeneity, and regulatory networks of tissue inhibitors of metalloproteinases in intervertebral disc degeneration, focusing on the molecular mechanisms and signaling pathways in oxidative stress, mechanical load, and inflammatory microenvironment, and to evaluate the translational potential of gene therapy strategies based on tissue inhibitors of metalloproteinases. METHODS: The first author searched PubMed, Web of Science, Embase, CNKI, Wanfang and other databases from inception to March 2025. Chinese search terms included '椎间盘退变，椎间盘退行性变，椎间盘退化，金属蛋白酶类组织抑制剂，信号通路', and English search terms included 'Tissue Inhibitor of Metalloproteinases, Tissue Inhibitor of Metalloproteinase, TIMPs, Intervertebral disc degeneration, Disc degeneration, Degenerative Disc Disease, Degenerative Intervertebral Discs'. Finally, 76 eligible articles were included for review. RESULTS AND CONCLUSION: (1) Subtype functions of tissue inhibitors of metalloproteinases: TIMP1 exhibits dual regulation (early protection/late depletion); TIMP2 maintains extracellular matrix homeostasis by inhibiting matrix metalloproteinase activity, and its abnormal expression can activate pro-apoptotic signaling pathways (e.g., miR-185-5p/MMP2 axis and inflammatory factor-mediated MMP/TIMP imbalance); TIMP3 exerts multi-dimensional protective effects by inhibiting matrix metalloproteinase activity, tumor necrosis factor-alpha converting enzyme/tumor necrosis factor-alpha axis, and angiogenesis; TIMP4 is regulated by miR-155-5p/fibroblast growth factor 2 and participates in extracellular matrix homeostasis. (2) Epigenetic reprogramming mechanisms: Abnormal mechanical stress degrades TIMP3 mRNA through the WTAP/YTHDF2-m6A axis, while miR-222 targets TIMP3 to synergistically accelerate extracellular matrix degradation. (3) Multi-modal therapeutic strategies: Photobiomodulation (wavelength-specific regulation of TIMP/MMP), stem cell exosomes (miR-199a/GREM1 axis), and irisin intervention can remodel matrix metabolic balance. This review summarizes the theoretical framework of 'functional network imbalance of tissue inhibitors of metalloproteinases', revealing its multi-level regulatory characteristics as a core driver of intervertebral disc degeneration, and providing a theoretical basis for developing precise therapies targeting epigenetic modifications and mechano-biological coupling interventions.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21581
BACKGROUND: In recent years, magnetic stimulation therapy can activate the classical transient receptor potential channel 1, triggering the calcium-mitochondrial axis to enhance myogenesis and mitochondrial biogenesis in vivo, thereby recapitulating physiological adaptations related to exercise-induced metabolic responses. As an emerging technique for promoting muscle function, magnetic stimulation has gained widespread attention and validation in the rehabilitation of muscular diseases due to its advantages of being non-invasive, passive, and safe. However, there is a lack of clinical studies on the therapeutic efficacy of this technique in the treatment of disuse-induced muscle atrophy. OBJECTIVE: To investigate the therapeutic effect of exercise therapy combined with magnetic stimulation on the recovery of muscle strength and locomotor ability in patients with disuse-induced muscle atrophy of the lower limbs. METHODS: Sixteen patients with lower limb disuse muscle atrophy caused by prolonged bed rest after unilateral Achilles tendon rupture surgery were recruited and randomly divided into control group and experimental group, 8 cases in each group. The control group received traditional exercise rehabilitation therapy, including joint range of motion training, muscle strength training, and soft tissue stretching training, 3 times a week. The experimental group additionally received medical magnetic physical factor stimulation (intensity 1.5 mT, frequency 3 300 Hz, 48 h per session, 10 min each time) on this basis, with a total trial duration of 4 weeks. All subjects underwent maximum voluntary contraction (MVC) test of the lower limbs and gait speed measurements including Timed Up and Go test (TUG), 5-times sit-to-stand test (5STS), and 6 m normal walking speed test before and after intervention. RESULTS AND CONCLUSION: After 4 weeks of intervention, all 16 subjects completed the trial. In the experimental group, the maximum voluntary contraction of the affected lower limb (P=0.001) and the difference rate of MVC between affected and healthy sides (P=0.001) significantly decreased, and the improvements were superior to those in the control group. In terms of gait speed indicators, the experimental group showed significant improvements in TUG (P=0.038), 6 m normal walking speed (P=0.025), and 5STS (P=0.050) compared with baseline. Between-group comparison revealed that the experimental group had significantly greater improvements in MVC of the affected leg (P=0.003), difference rate of MVC between affected and healthy sides (P=0.004), TUG (P=0.019), and 6 m normal walking speed (P=0.011) than the control group. These data confirm that after 4 weeks of low-frequency pulsed magnetic field (1.5 mT, 3 300 Hz) combined with exercise therapy, patients with disuse muscle atrophy after Achilles tendon rupture showed significantly better improvements in MVC of the affected and healthy legs, TUG, and 6 m normal walking speed than the control group, demonstrating that magnetic stimulation combined with exercise therapy has an auxiliary synergistic effect on isometric muscle strength and lower limb motor function. Therefore, magnetic stimulation combined with exercise therapy can be used as a new means for rehabilitation of disuse muscle atrophy.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04919-4
Lung cancer is the first leading cause of cancer death worldwide. Oxysterol-binding protein-like 2 (OSBPL2) is a lipid transport protein regulating cholesterol homeostasis. Here, we clarified the previously unreported role of OSBPL2 in lung cancer stemness properties. We observed that OSBPL2 reduced cholesterol content by HPLC-MS. It inhibited the accumulation of lipid droplets (LDs) in lung cancer. OSBPL2-mediated lipid transportation significantly suppressed tumor sphere formation, stemness markers expression and in vivo tumorigenesis and tumor metastasis. In clinical specimens, we also demonstrated that OSBPL2 repressed the expression of Lung cancer stem-like cells (LCSCs) markers-ALDH1A1, CD133 and Nanog. The level of OSBPL2 was negatively correlated with malignant of lung cancer, such as tumor stage progression and lymph node metastasis. Taken together, these findings illustrated that OSBPL2-mediated lipid transportation inhibited the stemness and aggressiveness of lung cancer cells. OSBPL2 was a potential therapeutic target to develop novel cancer-preventive compound.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05049-7
Dental-derived stromal cells (DSCs), including periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), stem cells from the apical papilla (SCAP), and stem cells from human exfoliated deciduous teeth (SHED), are accessible and expandable candidates for oral and craniofacial regeneration. Their therapeutic performance remains inconsistent because conventionally expanded cells are poorly adapted to in vivo mechanical cues. This review presents mechanical preconditioning as a mechanomedicine-guided strategy for ex vivo functional priming of DSCs. It summarizes DSC responses to tensile and compressive forces, fluid shear stress, hydrostatic pressure, matrix stiffness, and surface topography, and discusses principal mechanotransduction pathways. Representative quantitative loading windows are outlined to support subtype-specific and indication-specific preconditioning design. Key translational barriers include stromal cell heterogeneity, donor variability, senescence, uncertain persistence of mechanically induced states, safety concerns, and the lack of standardized manufacturing workflows. Clinical translation will require a shift from descriptive mechanobiology toward parameter-defined, indication-specific, and good manufacturing practice-compatible preconditioning strategies for DSC-based regeneration.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026045
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the discovery of novel therapeutic agents. Here, we report a natural small molecule, 2-dihydroailanthone (2-DAIL), as a promising candidate for CRC treatment. First, our results demonstrate that 2-DAIL exhibits significant anti-CRC activity in vitro and in vivo. Then, we find that 2-DAIL directly binds to integrin alpha-3 (ITGA3) revealed by stable isotope labeling by amino acids in cell culture coupled with thermal proteome profiling (SILAC-TPP). Additionally, the RNA sequencing data obtained from CRC cells and tumor tissues suggest that 2-DAIL blocks the PI3K/AKT signaling pathway mediated by ITGA3 inhibition. Collectively, 2-DAIL exerts its anti-CRC effects, at least partially, by binding to and inhibiting the function of ITGA3, thereby blocking the activation of the PI3K/AKT signaling pathway, which leads to CRC cell growth inhibition. Our study provides a promising drug candidate for the treatment of CRC and suggests the potential of 2-DAIL in treating other diseases linked to ITGA3 dysfunction.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026021
Macrophages play a pivotal role in bone regeneration, making their polarization a key target for immune regulation and therapeutic intervention. Modulating macrophage polarization represents a promising strategy for enhancing bone repair. Luteolin, a plant-derived flavonoid with well-documented anti-inflammatory properties, has been explored for its role in bone repair. However, its specific effects on macrophage polarization in bone repair remain unclear. This study investigates the role of luteolin in macrophage polarization and its underlying mechanisms. Our findings demonstrate that luteolin promotes M2 polarization while suppressing M1 polarization, as indicated by a reduction in the expression of pro-inflammatory markers, including IL-6 and iNOS, and an increase in the expression of anti-inflammatory factors, such as CD206, IL-10, and TGF-β. Mechanistically, luteolin inhibits STING oligomerization, thereby suppressing the STING-TBK1 pathway and mitigating downstream inflammatory responses. In vivo, in a mouse tibial bone defect model, luteolin effectively alleviates inflammation, facilitates angiogenesis, enhances collagen deposition, and improves bone density. Collectively, these findings highlight the potential of luteolin as a therapeutic agent for bone repair by modulating macrophage polarization and inhibiting STING-TBK1 signaling.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026020
The insulin receptor (IR) is central to the regulation of glucose and lipid metabolism. Although insulin is its primary ligand, insulin-like growth factors I and II (IGF-I and IGF-II) also engage IR, albeit with reduced affinity. The structural basis of cooperative ligand binding, however, has remained poorly understood. Here, we report cryo-Electron Microscopy (cryo-EM) structures of IR in complex with insulin, IGF-I, and IGF-II, revealing that all three ligands engage the receptor at overlapping binding sites and can induce a conserved T-shaped quaternary assembly involving four ligand molecules at site 1/1′ and site 2/2′. Despite this shared overall architecture, distinct ligand-specific conformational changes are observed. Notably, IGF-I and IGF-II adopt different binding sequence at site 1 and site 2 compared to insulin, suggesting unique interaction dynamics. These structural insights highlight divergent mechanisms of ligand recognition and cooperative binding, providing a deeper understanding of hormone-induced conformational modulation of the IR.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with late-stage 5-year survival rates below 50%. Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) drive progression, yet the molecular mediators of CAF-tumor crosstalk are incompletely defined. This study identifies platelet-derived growth factor C (PDGFC) as a critical CAF-secreted factor that promotes epithelial-mesenchymal transition (EMT) and immunosuppression in LUAD. Analysis of patient specimens revealed elevated PDGFC expression in CAFs relative to nontumor tissue fibroblasts (NFs), and high PDGFC levels correlated with poor prognosis. Mechanistically, CAF-derived PDGFC activates the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in cancer cells, inducing EMT and matrix metalloproteinase 2 (MMP2) expression. PDGFC also stimulates PDGFRA expression in both tumor cells and fibroblasts, establishing a reciprocal positive feedback loop that accelerates fibrotic TME remodeling and malignant progression. Immunologically, PDGFC promotes infiltration and polarization of immunosuppressive cell populations, including CD4+ Treg cells, M2 macrophages, and N2 neutrophils, while restraining immunocompetent NK cells. Immunoinhibitors TGFB1, CSF1R, PD-L1, PD-L2, KDR, IL10RB, and HAVCR2 may synergize with PDGFC in modulating immunosuppression. These findings position PDGFC as a diagnostic indicator and potential immunotherapy target for LUAD, offering a novel TME-targeted therapeutic strategy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025095
Alzheimer's disease (AD) is characterized by progressive cognitive decline, with amyloid-beta (Aβ) peptides, particularly Aβ42, playing a central role in neurotoxicity. The extracellular matrix (ECM) stiffness of brain tissue, typically 0.1–16 kPa, is altered in AD patients, but its contribution to Aβ42-induced toxicity remains unclear. This study investigated the effects of substrate stiffness on Aβ42 toxicity in cultured hippocampal neurons. Neurons were cultured on soft and stiff polyacrylamide (PA) gel substrates and exposed to 1 μM Aβ42 for 48 h. Cell viability, synaptic formation, spontaneous Ca2+ oscillations, and spontaneous excitatory/inhibitory postsynaptic currents (sEPSCs/sIPSCs) were assessed. Results showed that Aβ42 significantly reduced viability on stiff substrates but not on soft substrates. Synaptic formation decreased in a stiffness-dependent manner. The percentage of neurons with spontaneous Ca2+ oscillations was significantly greater on stiff substrates than on soft substrates following Aβ42 exposure. Electrophysiological recordings revealed that Aβ42 altered the percentage of neurons with sEPSCs and sIPSCs, as well as their amplitudes and frequencies, with differential effects based on substrate stiffness. These findings demonstrate that ECM stiffness modulates Aβ42-induced neurotoxicity, with stiff substrates exacerbating toxic effects on neuronal network activity. This suggests that ECM stiffness is a critical factor in AD pathogenesis and may inform therapeutic strategies targeting the mechanical microenvironment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025100
Sulfasalazine (SAS), a clinically utilized anti-inflammatory drug, induces ferroptosis by inhibiting system Xc− and depleting glutathione. This study characterizes the biochemical and cellular mechanisms of SAS-induced ferroptosis in H9C2 rat cardiomyocytes and BRL-3A rat hepatocytes, focusing on protein disulfide isomerase (PDI). SAS induced ferroptosis with sequential increases in cellular nitric oxide (NO), reactive oxygen species (ROS), and lipid-ROS. SAS activated PDI-mediated dimerization of inducible NO synthase (iNOS) and NO accumulation, followed by ROS and lipid-ROS buildup. SAS also upregulated iNOS protein levels. PDI knockdown or pharmacological inhibition suppressed iNOS dimerization, abrogated NO, ROS, and lipid-ROS accumulation, and prevented ferroptosis. Conversely, PDI activation via TrxR1 inhibitors sensitized cells to SAS-induced ferroptosis. These findings support a pivotal role of the PDI-NOS-NO axis in SAS-induced cytotoxicity, leading to oxidative cell death. The study provides mechanistic insights and suggests strategies for sensitizing cancer cells to SAS-induced ferroptosis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025097
Structured RNAs such as riboswitches and aptamers bind cognate ligands and serve as biosensors and gene-control elements, yet existing methods for detecting ligand-binding events are limited or inconvenient. This study designs a multibase pair bridge to integrate a hammerhead ribozyme into structured RNAs, enabling ligand-binding detection via modulation of ribozyme cleavage. Bridge length critically affects cleavage: optimal activity occurs with three to six base pairs. Dissociation constants (KD) obtained by this method agree with in-line probing values, and 1 pmol of allosteric ribozyme RNA suffices for measurement. Applied to riboswitch candidate Motif_9307, the assay revealed no binding affinity for S-adenosylmethionine or several other tested ligands, consistent with in-line probing. Notably, cleavage activity increased upon addition of yeast extract as a ligand mixture, indicating the presence of the Motif_9307 ligand in the extract. This approach provides an alternative method for measuring ligand-binding events associated with riboswitch candidates and aptamers.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025096
Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive bone disorder driven by prolonged glucocorticoid exposure, with limited therapeutic options. Ferroptosis, a regulated form of necrosis, has emerged as a potential contributor to SONFH pathogenesis, yet its mechanistic link to osteoblast dysfunction remains poorly defined. This study investigates the relationship between dexamethasone (Dex)-induced ferroptosis and silent information regulator 1 (Sirt1) in MC3T3-E1 osteoblastic cells. Dex treatment downregulated Sirt1 expression and increased ferroptosis markers, while Sirt1 overexpression elevated the ferroptosis-related proteins SLC7A11 and GPX4 following Dex exposure. Mechanistically, Dex promoted hypermethylation of the Sirt1 promoter via DNA methyltransferase 3a (DNMT3a), leading to Sirt1 suppression. These findings establish a novel epigenetic axis—DNMT3a-mediated Sirt1 promoter hypermethylation—that drives Dex-induced ferroptosis in osteoblasts. The study was conducted exclusively in vitro, and the pathophysiological relevance requires validation in animal models. Nevertheless, this work provides a foundation for understanding the epigenetic regulation of osteoblast ferroptosis and suggests potential therapeutic avenues for preventing SONFH.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025021
Homocysteine (Hcy) is an independent risk factor for atherosclerosis, and defective macrophage autophagy accelerates plaque formation. Pyruvate dehydrogenase (PDH), a key component of the PDH complex, links energy metabolism to autophagy, but its role in Hcy-induced atherosclerosis remains undefined. Proteomic profiling of Hcy-treated macrophages identified 748 upregulated and 760 downregulated proteins, with KEGG enrichment in amino acid biosynthesis, carbon metabolism, and glycolysis/gluconeogenesis. In ApoE–/– mice, Hcy treatment markedly reduced PDH expression and activity, leading to impaired autophagy. PDH activation restored autophagy by promoting assembly of the ULK1-FIP200-Atg13 complex via modulation of AMPK/mTOR signaling. These findings suggest that PDH activation may serve as a therapeutic strategy for Hcy-induced atherosclerosis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025126
Ventricular arrhythmias (VAs) are the predominant cause of mortality following myocardial infarction (MI), driven by electrophysiological remodeling including dysregulated calcium cycling. Prior work demonstrated that CDR1as knockdown ameliorates arrhythmias by modulating Nav1.5 and Kir6.2 channels post-MI. This study investigates the role of CDR1as in calcium channel remodeling after ischemic arrhythmia. MI was induced in mice by left anterior descending coronary artery ligation, and patch-clamp techniques measured Ca current (ICaL) in isolated ventricular cardiomyocytes. Cav1.2 expression was significantly decreased in the infarct border zone at 12 h post-MI. CDR1as knockdown via AAV9-CDR1as-shRNA administration enhanced cardiac function and restored both ICaL density and Cav1.2 expression in MI model mice. The data suggest that MI alters cardiac calcium expression and increases vulnerability to VAs, and that targeting the CDR1as pathway to modulate calcium channels may be a viable antiarrhythmic strategy post-MI. Notably, CDR1as did not significantly affect RyR2 protein, though it regulated SERCA2a expression. The study hypothesizes that CDR1as may regulate Cav1.2 via mRNA methylation or by acting as an endogenous inhibitor of Cav1.2. These findings reveal an unprecedented role for CDR1as in post-MI arrhythmias and support further investigation into its therapeutic potential.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025143
Vascular calcification (VC) is an independent risk factor for cardiovascular morbidity and mortality, characterized by hydroxyapatite deposition in arterial walls, leading to increased stiffness, decreased compliance, and plaque rupture. No clinically acknowledged therapy reverses VC. Dihydrocapsaicin (DHC), the primary pungent capsaicinoid in chili peppers, exhibits analgesic, anticancer, anti-inflammatory, antioxidant, and anti-obesity properties. Using the Comparative Toxicogenomics Database, we identified 20 experimental target genes of DHC, including ATF4, CASP3, CASP4, CASP7, CAT, CDKN1A, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP2E1, DDIT3, EIF2S1, ERN1, HSPA5, IGF1, MAP1LC3A, MAPK1, MAPK3, and TP53. Chemical-phenotype analysis revealed associations with apoptotic processes and autophagy. In a human vascular smooth muscle cell (hVSMC) calcification model induced by 1.2 μL of 100 mM CaCl2 in α-MEM basal medium, co-treatment with DHC (0.5, 2, or 8 μL of 4 mM solution) for 3–6 h significantly inhibited calcium deposition, as quantified by Alizarin Red staining and ImageJ analysis. These findings suggest that DHC modulates VC through mechanisms involving cell death, endoplasmic reticulum stress, and calcium signaling, highlighting its potential as a therapeutic agent for VC.