Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04989-4
Background Chemotherapy-induced premature ovarian failure (POF) is a major cause of infertility, with limited treatment options. Mesenchymal stem cell-derived exosomes (MSC-Exos) have therapeutic potential. This study investigated whether preconditioning MSCs with the antioxidant flavonoid isorhamnetin (ISO) enhances the efficacy of their exosomes (ISO-MSC-Exos) against POF. Methods A cyclophosphamide-induced POF rat model was established, and the role of the ferroptosis inhibitor ferrostatin-1 was evaluated. MSC-Exos and ISO-MSC-Exos were isolated by ultracentrifugation and administered via tail vein injection. Ovarian recovery was assessed by monitoring the oestrous cycle, serum hormone levels, and histological findings. Lipid peroxidation and iron metabolism were evaluated by quantifying malondialdehyde, glutathione, iron deposition, and mitochondrial ultrastructure. Immunohistochemistry was used to assess the expression levels of GPX4, ACSL4, and FTH1. Proteomic analyses were performed to explore the underlying mechanisms. Results Ferroptosis plays a pivotal role in the cyclophosphamide-induced POF rat model. Both exosome therapies improved ovarian function and suppressed ferroptosis, with ISO-MSC-Exos showing superior efficacy. ISO-MSC-Exos significantly restored hormone levels, ameliorated oestrous cycle disorders, reduced follicular atresia, and enhanced fertility. Furthermore, ISO-MSC-Exos more effectively elevated glutathione levels, reduced malondialdehyde and Fe2⁺ levels, and reversed the abnormal expression of ferroptosis-related proteins GPX4, ACSL4, and FTH1. Proteomic analysis suggested that ISO-MSC-Exos effectively inhibit ferroptosis by downregulating Alox15 and Tf, thereby reducing lipid peroxidation substrates and cellular iron uptake. This finding represents a potential molecular mechanism underlying their superior efficacy compared with that of MSC-Exos. Conclusions ISO-MSC-Exos showed superior efficacy compared with MSC-Exos in restoring ovarian function and inhibiting ferroptosis, suggesting that ISO pretreatment enhances the therapeutic effect of MSC-Exos in the POF
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04732-5
Background In the field of regenerative therapy, the stromal vascular fraction (SVF) extracted from adipose tissue has been widely recognized for its significant benefits. However, the cellular composition and therapeutic effect of SVF products prepared via different methods are unclear. Methods SVF cells were obtained via three approaches: (1) generation of the SVF via mechanical emulsification (M-SVF), (2) generation of the SVF via laboratory enzymatic digestion (L-SVF), and (3) generation of the SVF via commercial cell separation systems (C-SVF). We evaluated their healing effects on mouse wounds. Additionally, we utilized single-nucleus RNA sequencing (snRNA-seq) technology to explore the cellular composition of the C-SVF. Results The cell yield of C-SVF was comparable to that of L-SVF. During in vitro culture, C-SVF exhibited enhanced proliferation and a reduced proportion of apoptotic cells. In a mouse wound model, the application of C-SVF facilitated the closure of mouse wounds and improved collagen remodeling and angiogenesis in the wound area. Additional snRNA-seq analysis revealed that APOE+ adipose-derived stem cells and immune cells, especially M2 anti-inflammatory macrophages, are enriched in C-SVF, which together promote wound repair, and that APOE+ adipose-derived stem cells (ADSCs) and immune cells, especially M2 anti-inflammatory macrophages, are enriched in C-SVF, which jointly regulate and promote wound repair. Conclusion A commercial extraction system is an effective method for isolating viable SVF cells enriched with APOE+ ADSCs and M2 macrophages.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025034
Proteinuria-induced damage to renal tubular epithelial cells is one of the main causes of diabetic kidney disease (DKD), and the clearance of overloaded albumin by lysosomes is crucial for maintaining the homeostasis of renal tubular epithelial cells. Therefore, lysosomal damage is closely related to the pathogenesis of DKD, but effective prevention and treatment measures are still lacking. Melatonin (MLT) is secreted by the pineal gland and can not only regulate circadian rhythms but also maintain lysosomal homeostasis. In this study, we demonstrate the presence of significant lysosomal damage in the renal tubules of DKD patients, which causes autophagy impairment and a concomitant oxidative stress imbalance; however, MLT can upregulate transcription factor EB (TFEB) to improve lysosomal damage and restore the biosynthesis of this organelle. Mechanistically, MLT may protect lysosomes via the upregulation of TFEB and the miR-205-5p-LRP-1 pathway in renal tubules, thus improving autophagy dysfunction and oxidative imbalance in DKD.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024239
Reactivating the embryonic ζ-globin gene represents a potential therapeutic approach to ameliorate the severe clinical phenotype of α-thalassemia and sickle cell disease. The transcription factor MYB has been extensively proven to be a master regulator of the γ-globin gene, but its role in the regulation of ζ-globin remains incompletely understood. Here, we report a mechanistic study on the derepression of ζ-globin both in vivo and in vitro. We show that MYB depletion in mouse models and human hematopoietic stem cells leads to consistent and remarkable reactivation of ζ-globin. Furthermore, multiomics analysis and functional validation of MYB-knockout and wild-type cell lines reveal that ETO2 functions as a novel repressor of ζ-globin through coordination with NuRD nucleosome remodeling and the deacetylation complex to modulate histone deacetylation of ζ-globin. Additionally, we evaluate the clinical significance of these findings by knocking out ETO2 in primary CD34+ cells from nondeletional hemoglobin H patients, which results in a significant increase in ζ-globin expression. The RNA-seq data reveal that key erythroid genes are more co-regulated by Myb and Eto2 than by Myb and Klf1, highlighting a distinctly enhanced erythroid-specific transcriptional impact within the MYB-ETO2 regulatory axis. Compared with ETO2 knockout alone, codepletion of ETO2 and BCL11A did not significantly activate ζ-globin, suggesting that the MYB-ETO2 pathway primarily silences ζ-globin. Our study reveals a linear MYB-ETO2 signaling pathway crucial for ζ-globin repression and offers new targets for treating α-thalassemia and sickle cell disease.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026025
Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, represents an extremely aggressive malignancy. The induction of cuproptosis has developed into a favorable therapeutic direction for HCC, considering its strong association with HCC. Sanguinarine (San), a benzophenanthridine alkaloid derived from traditional herbs such as Chelidonium majus L., demonstrates broad-spectrum anticancer activities against various cancer cell types. However, the precise molecular mechanisms underlying its effects in the treatment of HCC remain largely undefined. This investigation seeks to examine the anti-HCC effects of San and to explore the mechanisms underlying these effects through the induction of cuproptosis. In vitro experiments demonstrate that San markedly inhibits the proliferation, movement, and epithelial-mesenchymal transition of HCC cells while enhancing their apoptosis. In vivo, San notably impedes tumor growth and upregulates the cuproptosis signature markers ferredoxin 1 (FDX1), oligomeric dihydrolipoamide S-acetyltransferase (DLAT), and heat shock protein 70 (HSP70) in HCC xenograft tumor models. Mechanistically, San induces proteotoxic stress and cuproptosis in HCC cells by increasing copper concentration, upregulating the expression of FDX1, lipoic acid synthetase (LIAS), HSP70, and lipoylated DLAT aggregation, and simultaneously reducing mitochondrial membrane potential and intracellular glutathione and pyruvate levels. Moreover, the combination of San with copper ionophores (Elesclomol-CuCl2) exhibits synergistic effects in promoting cuproptosis. FDX1 silencing markedly diminishes San-induced suppression of cell proliferation and FDX1 and HSP70 levels in HCC cells. Additionally, molecular docking analysis predicts that San exhibits the highest potential for binding with FDX1. Surface plasmon resonance experiments and cellular thermal shift assay confirm that San strongly interacts with FDX1 and markedly enhances the thermostability of FDX1. In conclusion, our findings indicate that San substantially inhibits the progression of HCC by targeting FDX1/LIAS/DLAT/HSP70 axis-dependent cuproptosis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025076
EGFR-tyrosine kinase inhibitor (TKI) therapy is the most effective targeted therapy for non-small cell lung cancer (NSCLC). However, drug resistance remains a significant factor in the failure of lung cancer therapy. In the present study, we utilize network pharmacology, molecular docking, in vitro and in vivo experiments to explore the targets and biological mechanisms of CP, a novel curcumin-piperlongumine hybrid molecule, in EGFR-TKI-resistant NSCLC cells. The results reveal that CP exhibits enhanced biological activity compared to its parent compounds. CP can effectively inhibit cell proliferation by arresting cell cycle in the G2/M phase and inducing apoptosis. Mechanistically, CP-induced apoptosis is partially mediated by PI3K/AKT signaling pathway. These findings highlight the potential of CP as a promising therapeutic agent for EGFR-TKI-resistant lung cancer therapy.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024070
Epidermal stem cells (EpSCs) play a vital role in skin wound healing through re-epithelialization. Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds. This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms. Application of 10‒50 μg/mL of morroniside to the skin wound promotes wound healing in mice. In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time- and dose-dependent manner. Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase. Morroniside increases the expression of β-catenin via the glucagon-like peptide-1 receptor (GLP-1R)-mediated PKA, PKA/PI3K/AKT and PKA/ERK signaling pathways, resulting in an increase in cyclin D1 and cyclin E1 expression, either directly or by upregulating c-Myc expression. This process ultimately leads to EpSC proliferation. Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK, the expressions of β-catenin, c-Myc, cyclin D1, and cyclin E1, as well as the proliferation of EpSCs, in periwound skin tissue, and accelerates wound re-epithelialization. These effects of morroniside are mediated by the GLP-1R. Overall, these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasing β-catenin expression and subsequently upregulating c-Myc, cyclin D1, and cyclin E1 expressions through GLP-1R signaling pathways. Morroniside has clinical potential for treating skin wounds.
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.2024061
Glioblastoma (GBM), the most aggressive and fatal brain malignancy, is largely driven by a subset of tumor cells known as cancer stem cells (CSCs). CSCs possess stem cell-like properties, including self-renewal, proliferation, and differentiation, making them pivotal for tumor initiation, invasion, metastasis, and overall tumor progression. The regulation of CSCs is primarily controlled by transcription factors (TFs) which regulate the expressions of genes involved in maintaining stemness and directing differentiation. This review aims to provide a comprehensive overview of the role of TFs in regulating CSCs in GBM. The discussion encompasses the definitions of CSCs and TFs, the significance of glioma stem cells (GSCs) in GBM, and how TFs regulate GSC self-renewal, proliferation, differentiation, and transformation. The potential for developing TF-targeted GSC therapies is also explored, along with future research directions. By understanding the regulation of GSCs by TFs, we may uncover novel diagnostic and therapeutic strategies against this devastating disease of GBM.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024097
Phosphatidylcholine (PC) is the most abundant phospholipid in mammalian cells, accounting for approximately 50% of all phospholipids and serving as a main component of cellular and subcellular membranes. PC is a mixture of many species with distinct functions, and its levels are altered in cancer. Previous studies have shown contradictory roles of PC in cancer development. Here, we investigated the effects of PC and its main component, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), on mouse colon cancer MC38 cells. PC dose-dependently decreased cell viability, and DLPC was identified as the active component. DLPC inhibited MC38 cell growth more effectively than PC, while structurally similar PCs with different acyl chain lengths or unsaturation degrees did not. This suggests that the specific structure of DLPC is crucial for its activity. Further mechanistic studies revealed that DLPC induces ferroptosis, a form of regulated cell death, in cancer cells. These findings highlight DLPC as a potential therapeutic agent for cancer treatment and underscore the importance of studying individual PC species.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03924-9
Background Eosinophilic granulomatosis with polyangiitis (EGPA), a rare but life-threatening systemic vasculitis, is distinguished by marked eosinophilia and presents with diverse symptoms, including asthma, cutaneous purpura, ecchymosis, skin necrosis, cardiac lesions, peripheral neuropathy, and necrotizing vasculitis. The etiology of EGPA involves a complex interaction among humoral, adaptive, innate, and allergic immune responses. Standard treatment employs prolonged high-dose glucocorticoid therapy, which is critical for survival; however, some patients’ symptoms cannot be relieved. Case report This case report details the medical management of an 11-year-old patient with EGPA, who was at risk of bilateral lower limb amputation due to differential arterial occlusion and severe, necrotizing vasculitis-induced gangrene in both feet. Treatment modalities administered included systemic infusion of Umbilical Cord Mesenchymal Stem Cells (UC-MSCs), targeted gastrocnemius muscle injections, and application of a Placenta-Derived Mesenchymal Stem Cells (PD-MSCs) hydrogel. Results After receiving a four-month regimen of allogeneic mesenchymal stem cell therapy via intravenous and local administration, the patient showed normalized eosinophil counts, reestablished blood flow in the dorsal arteries, and marked improvement in foot ulcerations. Conclusion Mesenchymal stem cell therapy is a promising option for severe EGPA cases refractory to glucocorticoids.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04989-4
Chemotherapy-induced premature ovarian failure (POF) remains a major cause of infertility with limited therapeutic options. This study evaluated whether preconditioning mesenchymal stem cells (MSCs) with the antioxidant flavonoid isorhamnetin (ISO) enhances the efficacy of their exosomes (ISO-MSC-Exos) against cyclophosphamide (CTX)-induced POF. A CTX-induced POF rat model was established, and the ferroptosis inhibitor ferrostatin-1 was used to confirm the role of ferroptosis. MSC-Exos and ISO-MSC-Exos were isolated by ultracentrifugation and administered via tail vein injection. Ovarian recovery was assessed by oestrous cycle monitoring, serum hormone levels, and histology. Lipid peroxidation and iron metabolism were evaluated by quantifying malondialdehyde (MDA), glutathione (GSH), iron deposition, and mitochondrial ultrastructure. Immunohistochemistry assessed GPX4, ACSL4, and FTH1 expression. Proteomic analysis explored underlying mechanisms. Ferroptosis was pivotal in CTX-induced POF. Both exosome therapies improved ovarian function and suppressed ferroptosis, with ISO-MSC-Exos showing superior efficacy. ISO-MSC-Exos significantly restored hormone levels, ameliorated oestrous cycle disorders, reduced follicular atresia, and enhanced fertility. They more effectively elevated GSH, reduced MDA and Fe2+ levels, and reversed abnormal expression of GPX4, ACSL4, and FTH1. Proteomics suggested ISO-MSC-Exos inhibit ferroptosis by downregulating Alox15 and Tf, reducing lipid peroxidation substrates and cellular iron uptake. ISO-MSC-Exos demonstrate superior efficacy over MSC-Exos in restoring ovarian function and inhibiting ferroptosis, suggesting ISO preconditioning enhances therapeutic effect in POF.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026025
Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, represents an extremely aggressive malignancy. The induction of cuproptosis has developed into a favorable therapeutic direction for HCC, considering its strong association with HCC. Sanguinarine (San), a benzophenanthridine alkaloid derived from traditional herbs such as Chelidonium majus L., demonstrates broad-spectrum anticancer activities against various cancer cell types. However, the precise molecular mechanisms underlying its effects in the treatment of HCC remain largely undefined. This investigation seeks to examine the anti-HCC effects of San and to explore the mechanisms underlying these effects through the induction of cuproptosis. In vitro experiments demonstrate that San markedly inhibits the proliferation, movement, and epithelial-mesenchymal transition of HCC cells while enhancing their apoptosis. In vivo, San notably impedes tumor growth and upregulates the cuproptosis signature markers ferredoxin 1 (FDX1), oligomeric dihydrolipoamide S-acetyltransferase (DLAT), and heat shock protein 70 (HSP70) in HCC xenograft tumor models. Mechanistically, San induces proteotoxic stress and cuproptosis in HCC cells by increasing copper concentration, upregulating the expression of FDX1, lipoic acid synthetase (LIAS), HSP70, and lipoylated DLAT aggregation, and simultaneously reducing mitochondrial membrane potential and intracellular glutathione and pyruvate levels. Moreover, the combination of San with copper ionophores (Elesclomol-CuCl2) exhibits synergistic effects in promoting cuproptosis. FDX1 silencing markedly diminishes San-induced suppression of cell proliferation and FDX1 and HSP70 levels in HCC cells. Additionally, molecular docking analysis predicts that San exhibits the highest potential for binding with FDX1. Surface plasmon resonance experiments and cellular thermal shift assay confirm that San strongly interacts with FDX1 and markedly enhances the thermostability of FDX1. In conclusion, our findings indicate that San substantially inhibits the progression of HCC by targeting FDX1/LIAS/DLAT/HSP70 axis-dependent cuproptosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21385
BACKGROUND: Due to the decline in ovarian function, reduced estrogen secretion, and endocrine disorders, perimenopausal women are more prone to osteoporosis. There are few studies on the correlation of bone mineral density with obesity indicators, blood pressure, blood routine, and glycolipid metabolism in perimenopause women, and the research results are controversial. OBJECTIVE: To investigate the correlation of bone mineral density with quantitative CT with obesity indicators, blood pressure, platelet count, and glycolipid metabolism in perimenopause women. METHODS: This is a single-center retrospective study. 490 perimenopause women who were admitted to Guizhou Hospital of Beijing Jishuitan Hospital from January 1, 2022 to December 31, 2024 were selected. Their age, height, body mass, waist circumference, blood pressure, fasting blood glucose, blood routine, and blood biochemical indicators were collected to calculate body mass index, waist height ratio, body shape index, body roundness index, taper index, visceral fat index, and lipid accumulation index. Quantitative CT was used to measure lumbar spine bone mineral density. According to bone mineral density, the participants were divided into normal bone mass group, low bone mass group, and osteoporosis group. Kruskal-Wallis rank sum test was used to compare the differences in various indicators among different bone mineral density groups. Spearman correlation analysis and partial correlation analysis were used to analyze the correlation between bone mineral density and various indicators. RESULTS AND CONCLUSION: (1) There were significant differences in age, waist circumference, waist height ratio, body shape index, body roundness index, taper index, visceral fat index, lipid accumulation index, bone mineral density, systolic blood pressure, diastolic blood pressure, platelet count, total cholesterol, triglycerides, and postmenopausal status among different bone mineral density groups (P < 0.05). (2) Spearman correlation analysis showed that L1 bone mineral density, L2 bone mineral density, and average bone mineral density of L1 and L2 were negatively correlated with waist circumference, waist height ratio, body shape index, body roundness index, taper index, visceral fat index, lipid accumulation index, systolic blood pressure, and diastolic blood pressure (P < 0.05), and positively correlated with platelet count (P < 0.05). L1 bone mineral density and average bone mineral density were negatively correlated with total cholesterol (P < 0.05); L1 bone mineral density was negatively correlated with triglycerides (P < 0.05). (3) After adjusting for confounding factors, L1 bone mineral density, L2 bone mineral density, and average bone mineral density were still negatively correlated with waist circumference, body shape index, and taper index (P < 0.05); L1 bone mineral density and average bone mineral density were still negatively correlated with waist height ratio and body roundness index (P < 0.05); L2 bone mineral density was positively correlated with platelet count (P < 0.05). Among abdominal obesity indicators, body shape index and taper index had the largest correlation coefficients, especially body shape index. The results indicate that for perimenopausal women, after adjusting for confounding factors, quantitative CT bone mineral density has a certain correlation with abdominal obesity indicators and platelet count, but has no correlation with systolic blood pressure, diastolic blood pressure, blood lipids, and fasting blood glucose. The research results provide reference for clinical early prevention of osteoporosis or delaying the development of osteoporosis, and have certain clinical value.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21447
BACKGROUND: Neobavaisoflavone could promote bone formation and may be a potential small molecule drug for bone regeneration. The use of 3D printed bone tissue engineering scaffolds as drug delivery carriers for neobavaisoflavone is expected to enhance the potential application of bone regeneration. OBJECTIVE: To explore the effects of polylactic acid/polydopamine/neobavaisoflavone bone scaffold on osteoclast and osteoblast activity. METHODS: (1) Fused deposition modeling technology was used to manufacture a 3D printed polylactic acid scaffold. These polylactic acid scaffolds were immersed in a dopamine solution containing or without neobavaisoflavone to produce polylactic acid/polydopamine/neobavaisoflavone scaffolds and polylactic acid/polydopamine scaffolds, respectively. The surface morphology, surface hardness, and compressive strength of the three groups of scaffolds were characterized, and the drug release properties of the polylactic acid/polydopamine/neobavaisoflavone scaffolds were investigated. (2) Mouse embryonic osteoblast MC3T3-E1 cells were co-cultured with the three groups of scaffolds. CCK-8 assay and live/dead staining were used to evaluate the cytocompatibility of the scaffolds. Transwell assay was used to evaluate the effect of scaffolds on osteoblast migration. Alkaline phosphatase quantitative assay and alizarin red staining were used to evaluate the effect of scaffolds on osteoblast differentiation. RAW264.7 cells were co-cultured with the three groups of scaffolds. After osteoclast induction, tartrate-resistant acid phosphatase staining was used to evaluate the effect of scaffolds on osteoclast differentiation. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that all three groups of scaffolds had three-dimensional structure and regular interconnected porous structure with an average pore size of 400 µm. The surface hardness and compressive strength of polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds were higher than those of polylactic acid scaffolds (P < 0.05). Polylactic acid/polydopamine/neobavaisoflavone scaffolds had good drug release behavior and could continuously release drugs for more than 14 days in vitro. (2) CCK-8 assay and live/dead staining showed that all three groups of scaffolds had good cytocompatibility, and polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds could promote MC3T3-E1 cell proliferation. Transwell assay showed that compared with polylactic acid scaffolds, polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds could promote MC3T3-E1 cell migration. Alkaline phosphatase quantitative assay and alizarin red staining showed that compared with the other two groups, polylactic acid/polydopamine scaffolds and polylactic acid/polydopamine/neobavaisoflavone scaffolds could promote osteogenic differentiation of MC3T3-E1 cells. Tartrate-resistant acid phosphatase staining showed that polylactic acid/polydopamine/neobavaisoflavone scaffolds could inhibit osteoclast differentiation of RAW264.7 cells. (3) These results indicate that polylactic acid/polydopamine/neobavaisoflavone scaffolds have good biosafety and can promote bone regeneration by regulating osteoblast and osteoclast activities.
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.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731781232251260
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous iron preparations are increasingly used. Ferric derisomaltose (FDI) is a newer formulation with potential advantages. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FDI compared with other iron therapies or placebo in treating IDA. Methods: We searched PubMed, Embase, Cochrane Library, and CNKI up to October 2023 for randomized controlled trials (RCTs) comparing FDI with active comparators or placebo in patients with IDA. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs), serious adverse events (SAEs), and hypersensitivity reactions. Data were pooled using random-effects models. Results: A total of 15 RCTs involving 3,452 patients were included. FDI significantly increased Hb levels compared with placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.8-1.6) and was non-inferior to other intravenous iron formulations (MD 0.1 g/dL, 95% CI -0.2 to 0.4). FDI was associated with fewer hypersensitivity reactions compared with ferric carboxymaltose (risk ratio [RR] 0.3, 95% CI 0.1-0.9). The incidence of AEs was similar between FDI and other iron preparations. Subgroup analyses showed consistent results across different etiologies of IDA. Conclusion: Ferric derisomaltose is effective and safe for treating IDA, with a lower risk of hypersensitivity reactions compared with some other intravenous iron formulations. These findings support its use in clinical practice.