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08 November 2026, Volume 30 Issue 31 Previous Issue    Next Issue

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Anethole promotes osteogenic differentiation of human bone marrow mesenchymal stem cells Lu Chuan, Yang Jiale, Li Youliang, Li Chao 2026, 30 (31):  8041-8046.  doi: 10.12307/2026.847 Abstract ( 55 )   PDF (3095KB) ( 9 )   Save BACKGROUND: While anethole has been shown to inhibit receptor activator of nuclear factor kappa-B ligand-induced osteoclastogenesis and ameliorate osteoporosis, its potential to promote bone formation remains unclear.  OBJECTIVE: To explore the effect of anethole on promoting osteogenic differentiation of human bone marrow mesenchymal stem cell and its mechanism.  METHODS: CCK-8 assay was employed to assess cytotoxicity of anethole and identify optimal concentration for further study. Human bone marrow mesenchymal stem cells were then stimulated with either 100 μM anethole or its vehicle, dimethyl sulfoxide added in osteogenic differentiation medium, and their effects on osteogenic differentiation of human bone marrow mesenchymal stem cells were observed. Human bone marrow mesenchymal stem cells were stimulated with 1 μmol/L bone morphogenetic protein 2-transforming growth factor β-Smad2/3 signaling pathway inhibitor LDN193189 or phosphate-buffered saline (control) in osteogenic differentiation medium containing 100 μmol/L anethole, and the effect of the signaling pathway inhibitor on osteogenic differentiation of human bone marrow mesenchymal stem cells was observed. Alizarin red staining was used to observe calcium nodule formation in human bone marrow mesenchymal stem cells. RT-qPCR and western blot assay were used to detect the expression of related osteogenic differentiation markers, including type I collagen α1 chain, Runt-related transcription factor 2, and genes and proteins related to the bone morphogenetic protein 2, transforming growth factor β, and Smad2/3.  RESULTS AND CONCLUSION: (1) CCK-8 assay showed that 200 μmol/L anethole had a cytotoxic effect on human bone marrow mesenchymal stem cells, while 50 and 100 μmol/L anethole had no cytotoxic effect. Therefore, 100 μmol/L anethole was selected for subsequent exploratory experiments. (2) 100 μmol/L anethole promoted calcium nodule formation and increased the expression of osteogenic differentiation markers, including type I collagen α1 chain and Runt-related transcription factor 2, in human bone marrow mesenchymal stem cells, as well as promoted the increased expression of genes related to the bone morphogenetic protein 2-transforming growth factor β-Smad2/3 signaling pathway. (3) After blocking the signaling pathway with the bone morphogenetic protein 2-transforming growth factor β-Smad2/3 signaling pathway inhibitor LDN193189, the effect of anethole on promoting calcium nodule formation and increasing the expression of osteogenic differentiation markers (type I collagen α1 chain and Runt-related transcription factor 2) in human bone marrow mesenchymal stem cells was inhibited. The results indicate that anethole can activate the bone morphogenetic protein 2-transforming growth factor β-Smad2/3 signaling pathway to promote the osteogenic differentiation of human bone marrow mesenchymal stem cells.   Figures and Tables | References | Related Articles | Metrics

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Hypoxia preconditioning of bone marrow mesenchymal stem cells promotes angiogenesis in human umbilical vein endothelial cells through paracrine cytokines Liu Lei, Mao Wen, Qi Fu, Li Hong, Zhang Minghuan 2026, 30 (31):  8047-8053.  doi: 10.12307/2026.849 Abstract ( 57 )   PDF (1875KB) ( 13 )   Save BACKGROUND: Drawing on the characteristics of the in vivo ischemic and hypoxic microenvironment, hypoxic preconditioning, as an active strategy that simulates physiological and pathological conditions, can significantly enhance the paracrine function of stem cells. However, the specific effects and underlying mechanisms of hypoxic preconditioning on the angiogenic behavior of damaged endothelial cells remain to be further elucidated. OBJECTIVE: To investigate the regulatory effect of hypoxic preconditioning on the paracrine function of bone marrow mesenchymal stem cells, aiming to quantitatively explore the effects and mechanisms of conditioned medium from hypoxic preconditioned bone marrow mesenchymal stem cells on the angiogenic capacity of damaged endothelial cells. METHODS: Human umbilical vein endothelial cells were divided into control group, model group, normoxic group, and hypoxic group. The control group consisted of human umbilical vein endothelial cells cultured under normal conditions. The model group was treated with 1 μg/mL lipopolysaccharide for 24 hours. The normoxic and hypoxic groups were treated with supernatant from bone marrow mesenchymal stem cells cultured under normoxic and hypoxic conditions for 48 hours, respectively, for 1 hour, followed by treatment with 1 μg/mL lipopolysaccharide for 24 hours. Cell proliferation was detected by CCK-8 assay. Cell apoptosis rate was determined by flow cytometry. Cell angiogenesis capacity was measured by tube formation assay. The levels of tumor necrosis factor-α and interleukin-6 in the cell supernatant were detected by ELISA. The mRNA and protein expression levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and vascular endothelial growth factor in cells were detected by RT-qPCR and western blot assay, respectively.  RESULTS AND CONCLUSION: (1) Compared with the control group, the model group showed significantly lower cell survival rate, tube formation ability, and mRNA and protein expression levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and vascular endothelial growth factor (P < 0.01), while the apoptosis rate and levels of tumor necrosis factor α and interleukin 6 in the cell supernatant were significantly higher (P < 0.01). (2) Compared with the model group, there were no significant differences in the above indicators in the normoxic group (P > 0.05), while the hypoxic group showed significantly higher cell survival rate, tube formation ability, and mRNA and protein expression levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and vascular endothelial growth factor (P < 0.01), and significantly lower apoptosis rate and levels of tumor necrosis factor α and interleukin 6 in the cell supernatant (P < 0.01). The results indicate that paracrine cytokines from hypoxic preconditioned bone marrow mesenchymal stem cells can inhibit the inflammatory response of vascular endothelial cells and promote angiogenesis by upregulating angiogenic factors.  Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cell exosomes improve bleomycin-induced mouse pulmonary fibrosis Huang Ying, Xu Fang, Wang Aili, Yuan Wensheng 2026, 30 (31):  8054-8059.  doi: 10.12307/2026.855 Abstract ( 76 )   PDF (1986KB) ( 16 )   Save BACKGROUND: Mesenchymal stem cell exosomes have similar biological functions to mesenchymal stem cells and high safety, and can be used for the treatment of fibrosis-related diseases. However, the mechanisms underlying their therapeutic effects on pulmonary fibrosis remain unclear. OBJECTIVE: To investigate the function and mechanism of bone marrow mesenchymal stem cell exosomes affecting bleomycin-induced pulmonary fibrosis in mice.  METHODS: Bone marrow mesenchymal stem cells and their exosomes were extracted from C57BL/6J mice and characterized. Thirty C57BL/6J mice were randomly divided into three groups: control group, model group, and exosome group (10 mice per group). The model group and exosome group received intratracheal instillation of 5 mg/kg bleomycin to induce pulmonary fibrosis. On day 7 after bleomycin instillation, mice in the exosome group received 100 μL of 0.1 mg/mL bone marrow mesenchymal stem cell-derived exosomes via tail vein injection once daily for two weeks. After treatment, lung function indicators (airway narrowing index, respiratory rate, and tidal volume) were measured. Hematoxylin-eosin staining and Masson staining were used to assess lung tissue damage and fibrosis. Enzyme-linked immunosorbent assay was used to detect serum levels of hydroxyproline, interleukin-1β, transforming growth factor-β1, and tumor necrosis factor-α. Real-time quantitative PCR was used to detect the mRNA expression of α-smooth muscle actin, collagen I, and fibronectin in lung tissue. Western blotting was used to detect the expression of transforming growth factor-β1 and the phosphorylation level of Smad3 in mouse lung tissue. RESULTS AND CONCLUSION: Compared with the control group, the model group mice showed a significantly increased airway narrowing index (P < 0.05), significantly decreased respiratory rate and tidal volume (P < 0.05), significantly upregulated α-smooth muscle actin, collagen I, and fibronectin mRNA expression (P < 0.05), significantly increased levels of hydroxyproline, interleukin-1β, transforming growth factor β1, and tumor necrosis factor α (P < 0.05), and significantly increased transforming growth factor β1 protein expression and Smad3 phosphorylation levels (P < 0.05). Compared with the model group, the exosome group mice showed significantly alleviated lung injury and fibrosis, a significantly decreased airway narrowing index (P < 0.05), significantly increased respiratory rate and tidal volume (P < 0.05), significantly downregulated α-smooth muscle actin, collagen I, and fibronectin mRNA expression (P < 0.05), significantly decreased levels of hydroxyproline, interleukin-1β, transforming growth factor β1, and tumor necrosis factor α (P < 0.05), and significantly decreased transforming growth factor β1 protein expression and Smad3 phosphorylation levels (P < 0.05). The results indicate that bone marrow mesenchymal stem cell-derived exosomes inhibit the transforming growth factor β1/Smad3 signaling pathway to ameliorate bleomycin-induced pulmonary fibrosis in mice. Figures and Tables | References | Related Articles | Metrics

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Molecular mechanism of polygonatum sibiricum polysaccharide-promoted chondrogenic differentiation of adipose-derived stem cells Chen Junjie, He Jiayang, Wang Zihe, Peng Teng, Liu Yingqi, Li Sen, Li Jingchi, Wang Guoyou, Li Ting, Yu Wanxin, Shen Huarui 2026, 30 (31):  8060-8067.  doi: 10.12307/2026.435 Abstract ( 74 )   PDF (6853KB) ( 5 )   Save BACKGROUND: Polygonatum sibiricum polysaccharide is the main active component of the traditional Chinese medicine polygonatum and has anti-inflammatory, antioxidant, and tissue repair properties. Recent studies have shown that polygonatum sibiricum polysaccharide may play an important role in bone and cartilage metabolism.  OBJECTIVE: To investigate the effect and mechanism of polygonatum sibiricum polysaccharide combined with transforming growth factor-β3 on inducing the differentiation of rat adipose-derived stem cells into chondrocytes. METHODS: Adipose-derived stem cells were isolated from rat inguinal fat using enzymatic digestion. First, the effect of different mass concentrations of polygonatum sibiricum polysaccharide on adipose-derived stem cell proliferation was detected using the CCK-8 assay to screen for the optimal proliferative concentration. Then, adipose-derived stem cells were divided into four groups for chondrogenic differentiation induction: control group, polygonatum sibiricum polysaccharide group, transforming growth factor β3 group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 group. Cell morphology observation, toluidine blue staining, immunofluorescence staining, and western blot assay were used to detect the expression of chondrogenic differentiation markers. Western blot assay was used to detect the expression of related proteins in the transforming growth factor β3/Smad2 signaling pathway. To verify whether polygonatum sibiricum polysaccharide and transforming growth factor β3 regulate chondrogenic differentiation through the transforming growth factor β3/Smad2 pathway, the transforming growth factor β3 receptor kinase inhibitor SB-505124 was used to specifically block the pathway. Adipose-derived stem cells were divided into five groups: control group, inhibitor group, polygonatum sibiricum polysaccharide + inhibitor group, transforming growth factor β3 + inhibitor group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 + inhibitor group. Western blot assay was used to detect the expression of cartilage differentiation markers and proteins related to the transforming growth factor β3/Smad2 signaling pathway.  RESULTS AND CONCLUSION: (1) The CCK-8 assay determined that 5 mg/L of polygonatum sibiricum polysaccharide was the optimal intervention concentration. (2) Toluidine blue staining showed that the blue-stained area in the polygonatum sibiricum polysaccharide group, transforming growth factor β3 group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 group was significantly higher than that in the control group (P < 0.05). (3) Immunofluorescence staining further confirmed that compared with the control group, the fluorescence intensity of type II collagen α1 chain was significantly enhanced in the polygonatum sibiricum polysaccharide group and the polygonatum sibiricum polysaccharide + transforming growth factor β3 group, with the highest fluorescence intensity in the polygonatum sibiricum polysaccharide + transforming growth factor β3 group (P < 0.05). (4) Western blot assay showed that compared with the control group, the polygonatum sibiricum polysaccharide group, transforming growth factor β3 group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 group significantly upregulated the p-Smad2/Smad2 and the protein expression levels of cartilage markers type II collagen α1 chain, Sox9, and aggrecan (P < 0.05), and the combined treatment group showed the highest protein expression levels of these indicators (P < 0.05). (5) After adding the transforming growth factor β receptor kinase inhibitor, compared with the inhibitor group, the protein expression levels of the above indicators were significantly increased in the other groups (P < 0.05). The results indicate that polygonatum sibiricum polysaccharide induces the differentiation of adipose-derived stem cells into chondrocytes by activating the transforming growth factor β/Smad2 signaling pathway. Figures and Tables | References | Related Articles | Metrics

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miR-122-5p-transfected exosomes from human adipose-derived mesenchymal stem cells for treatment of intrauterine adhesions in rats Qin Ying, Chen Jibing, Liang Weiping, Jing Wenyao, Zhu Xiangyun, He Junkui, Pang Lihong, Li Hongli 2026, 30 (31):  8068-8076.  doi: 10.12307/2026.883 Abstract ( 72 )   PDF (4214KB) ( 11 )   Save BACKGROUND: MicroRNAs, as important molecules regulating gene expression, play a crucial role in tissue repair. Exosomes, as promising drug carriers, have provided a new strategy for targeted therapy by delivering miRNAs.  OBJECTIVE: To investigate the therapeutic effect of exosomes from adipose-derived mesenchymal stem cells overexpressing miR-122-5p on intrauterine adhesions in rats. METHODS: Endometrial tissues were collected from patients with intrauterine adhesions and normal endometrial tissue from healthy individuals. The expression difference of miR-122-5p was detected by qPCR. miR-122-5p was transfected into human adipose-derived mesenchymal stem cells using lentiviral vectors, and exosomes were extracted using the 3D FloTrix viva Exo exosome harvesting system. Thirty-six female SD rats were randomly divided into normal group, model group, exosome group, and miR-122-5p-transfected exosome group. The latter three groups were used to establish a model of intrauterine adhesions using a double injury method of curettage and lipopolysaccharide. On day 7 after surgery, the normal group and the model group received PBS injection via the tail vein, while the exosome group and the miR-122-5p-transfected exosome group received natural exosomes and miR-122-5p-transfected exosomes from human adipose-derived mesenchymal stem cells via the tail vein, respectively. On day 7 of treatment, three rats were randomly selected from each group, and uterine tissues were isolated for hematoxylin-eosin staining, Masson staining, and immunohistochemical detection. The remaining six female rats in each group were caged with male rats at a ratio of 2:1. After two weeks of cohabitation, the implantation sites and numbers of embryos in the rats were observed. RESULTS AND CONCLUSION: (1) miR-122-5p was lowly expressed in the endometrial tissue of patients with intrauterine adhesion (2) A dual-injury method was used to successfully establish a Sprague-Dawley rat intrauterine adhesion model on day 7 post-surgery. Compared with the normal group, the expression of miR-122-5p in the endometrial tissue of the model group was decreased (P < 0.01). (3) After 7 days of treatment, hematoxylin-eosin staining and Masson staining showed that, compared with the normal group, the endometrial thickness and gland number were significantly reduced, and the fibrotic area was significantly increased in the model group (P < 0.05). Compared with the model group, both the exosome group and the miR-122-5p transfected exosome group significantly increased endometrial thickness and gland number and reduced fibrosis (P < 0.05), and the therapeutic effect of the miR-122-5p transfected exosome group was more significant. (4) The pregnancy rates of the normal group, model group, exosome group, and miR-122-5p transfected exosome group were 100%, 33.3%, 66.7%, and 83.3%, respectively. The number of embryos in the model group was significantly lower than that in the normal group (P < 0.05), while the number of embryos in the miR-122-5p transfected exosome group was higher than that in the model group (P < 0.05). The results indicate that miR-122-5p-transfected human adipose-derived mesenchymal stem cell exosomes effectively improve the fertility of rats with intrauterine adhesions by promoting endometrial regeneration and inhibiting fibrosis. Figures and Tables | References | Related Articles | Metrics

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Interleukin-4 modulates macrophage polarization and osteogenic differentiation of adipose-derived mesenchymal stem cells Wang Jing, Shi Haijie, Zhang Mengmeng, Zhang Jinyong, Wang Miaomiao, Tang Lin 2026, 30 (31):  8077-8083.  doi: 10.12307/2026.795 Abstract ( 50 )   PDF (10485KB) ( 7 )   Save BACKGROUND: The immune microenvironment is closely associated with the osteogenic differentiation of stem cells, especially the polarization state of macrophages plays a key regulatory role in bone tissue regeneration. Interleukin-4, as an important immunomodulatory cytokine, holds promise for promoting bone defect repair by modulating the local immune milieu. OBJECTIVE: To investigate the effects of different concentrations of interleukin-4 on the proliferation and osteogenic polarization of adipose-derived mesenchymal stem cells and macrophages, and to analyze the regulatory effects of interleukin-4 on the osteogenic differentiation of adipose-derived mesenchymal stem cells at different time points in order to elucidate the mechanisms of immunomodulation in tissue-engineered bone repair. METHODS: Adipose-derived mesenchymal stem cells were co-cultured with macrophages in 12-well plates, and interleukin-4 at different concentrations (0, 30, and 60 μg/L) was administered to assess the effects of interleukin-4 on the adhesion, proliferation, osteogenic differentiation, and macrophage polarization of adipose-derived mesenchymal stem cells. Phalloidin staining was used to observe cell morphology and adhesion, while cell proliferation activity was evaluated using the CCK-8 assay. RT-qPCR was performed to detect the mRNA expression levels of the M1 macrophage marker CCR7 and the M2 marker CD206, as well as osteogenic gene expression. Osteocalcin protein expression was detected by immunofluorescence, and osteogenic differentiation was assessed by alkaline phosphatase and Alizarin red staining. In the time-dependent experiment, the optimal concentration of interleukin-4 was delivered at different time points (days 2, 4, 6, and 8) to analyze the effects of interleukin-4 on macrophage polarization and osteogenic gene expression in adipose-derived mesenchymal stem cells. RESULTS AND CONCLUSION: (1) Interleukin-4 at 30 μg/L markedly promoted macrophage polarization toward the M2 phenotype and enhanced the proliferation and osteogenic differentiation of adipose-derived mesenchymal stem cells. (2) Compared with the blank control group, alkaline phosphatase and alizarin red staining were significantly enhanced in the 30 μg/L interleukin-4 group, and the expression of osteoblast-related genes (alkaline phosphatase, type I collagen, osteocalcin, Runt-related transcription factor 2) and osteoblastic protein (osteocalcin) was the highest (P < 0.05). (3) In the culture system, the addition of interleukin-4 on days 4-8 improved the polarization state of macrophages and enhanced osteogenic differentiation, suggesting that the immunomodulatory effect mediated by interleukin-4 was time-dependent. (4) These findings indicate that appropriate concentration and timing of interleukin-4 delivery enhance osteogenic differentiation of adipose-derived mesenchymal stem cells by balancing M1 and M2 macrophages, highlighting the key role of osteoimmunomodulation in tissue-engineered bone repair. Figures and Tables | References | Related Articles | Metrics

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Stepwise differentiation of human adipose-derived stem cells into motor neuron-like cells via a small molecule-based approach Zhang Suifeng, Wang Kai, Zhang Fuqiang, Sun Dongliang, Kang Guan, Cheng Qinghao, Guo Hongzhang 2026, 30 (31):  8084-8091.  doi: 10.12307/2026.780 Abstract ( 53 )   PDF (4847KB) ( 11 )   Save BACKGROUND: Cell therapy based on human adipose-derived stem cells holds promise for neurological diseases. However, establishing an efficient, stable, and gene-modification-free directed differentiation protocol remains a major obstacle to clinical application.  OBJECTIVE: To establish a two-stage, chemically defined protocol using small molecule combinations to achieve the differentiation of human adipose-derived stem cells into motor neuron-like cells, thereby providing a potential cell source for cell-based therapies for neurological diseases.   METHODS: Adipose-derived stem cells were isolated from adipose tissue, cultured, and characterized. A two-stage induction strategy using small molecule cocktails was employed. In stage one, adipose-derived stem cells were induced to transdifferentiate into neural progenitor cells using a combination of Dorsomorphin (a bone morphogenetic protein inhibitor), CHIR99021 (a Wnt agonist), and SB431542 (a transforming growth factor-β inhibitor). In stage two, the resulting neural progenitor cells were further differentiated into motor neuron-like cells with a combination of CHIR99021, retinoic acid, and Purmorphamine (a specific activator of the Shh signaling pathway). The expression of neural progenitor cell markers (PAX6, SOX1) and motor neuron markers (tubulin β3, ISL1, HB9, and choline acetyltransferase) was dynamically assessed by morphological observation, immunofluorescence staining, western blot assay, and RT-qPCR.  RESULTS AND CONCLUSION: After 4 days of induction in stage one, the cells formed typical neural rosette-like structures. Both protein and mRNA levels of PAX6 and SOX1 were significantly upregulated (P < 0.001), with positivity rates reaching 85.33% and 83.12%, respectively, indicating the successful transdifferentiation of human adipose-derived stem cells into neural progenitor cells. Following 12 days of induction in stage two, the cells exhibited typical motor neuron morphology. The expression of tubulin β3, ISL1, HB9, and choline acetyltransferase was significantly elevated (P < 0.001). Double immunofluorescence labeling confirmed that 78.56% of the cells co-expressed tubulin β3/ISL1, and 75.04% co-expressed HB9/choline acetyltransferase, confirming their differentiation into motor neuron-like cells. In conclusion, by mimicking in vivo neural developmental signaling (inhibiting the bone morphogenetic protein/transforming growth factor β pathway and activating the Wnt pathway in stage one, and activating the Wnt/Shh/retinoic acid pathway in stage two), this two-stage small molecule compound combination strategy can specifically induce human adipose-derived stem cells to differentiate into motor neuron-like cells, providing a cell source with significant clinical translational potential for cell therapy of neurological diseases.  Figures and Tables | References | Related Articles | Metrics

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Preparation and performance evaluation of essence with mesenchymal stem cell conditioned medium Wang Quansheng, Chen Songtao, Zhang Yongqing, Qiao Hua 2026, 30 (31):  8092-8099.  doi: 10.12307/2026.450 Abstract ( 61 )   PDF (3951KB) ( 10 )   Save BACKGROUND: Mesenchymal stem cell conditioned medium contains a variety of bioactive substances, and has the potential to slow down the aging of skin fibroblasts. However, there are few studies on the practical application of mesenchymal stem cell conditioned medium. OBJECTIVE: To prepare and evaluate the performance of an essence containing human umbilical cord mesenchymal stem cell-conditioned medium.  METHODS: The formulas of mesenchymal stem cell conditioned medium essence were screened by orthogonal experiment design using sensory performance score. The stability of the essence was evaluated through storage stability test, thermal cycling stability test, and centrifugal stability test at 4°C. The safety of the essence was evaluated from three levels: hemolysis test, cytotoxicity test, and skin irritation test. The moisturizing and anti-aging effects of the serum were investigated by measuring water loss rate using moisturizing test, cell viability using the CCK-8 assay, and reactive oxygen species levels using human skin fibroblasts and a zebrafish embryo aging model.  RESULTS AND CONCLUSION: (1) Orthogonal experimental design showed that when the addition of mesenchymal stem cell conditioned medium was 5%, glycerol was 5%, and xanthan gum was 0.25%, the sensory performance score was the highest, and the formula had good repeatability and high feasibility. (2) The mesenchymal stem cell conditioned medium essence had good stability under the conditions of 4 °C storage, hot and cold cycling and centrifugation condition, and low water loss rate. (3) The mesenchymal stem cell conditioned medium essence had good hemocompatibility, low cytotoxicity, and no skin irritation, and was safe and reliable. (4) The mesenchymal stem cell conditioned medium essence could promote the proliferation of senescent skin fibroblasts cells and reduce the levels of reactive oxygen species in aging model cells and zebrafish embryos, indicating certain anti-aging, antioxidant effects, and moisturizing properties. The above results show that the essence prepared with mesenchymal stem cell conditioned medium as the functional ingredient has good stability, is mild and non-irritating, and has anti-aging, moisturizing, and antioxidant effects. Figures and Tables | References | Related Articles | Metrics

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Modulation of nasal mucosa-derived ectomesenchymal stem cell senescence by mechanical modulus Zhou Jinlong, Wang Juan, Bian Lu, Lyu Long, Que Yunduan, Qian Wenwu 2026, 30 (31):  8100-8107.  doi: 10.12307/2026.848 Abstract ( 44 )   PDF (7272KB) ( 8 )   Save BACKGROUND: The mechanical properties of the cellular microenvironment play a pivotal role in regulating the fate of nasal mucosa–derived ectomesenchymal stem cells. OBJECTIVE: To investigate the regulatory effects of mechanical modulus on the senescence of ectomesenchymal stem cells and the potential molecular mechanisms. METHODS: Gelatin methacryloyl hydrogels with 50, 100, and 150 g/L mass concentrations were fabricated, and low-, medium-, and high-mechanical moduli were established, with standard culture plates serving as controls. Ectomesenchymal stem cells of SD rats were isolated, and identified. Passage 5 cells were seeded onto hydrogels of different moduli and cultured to passage 7. Cells were further treated with the Piezo1 activator Yoda1 or the transglutaminase 2 inhibitor KCC009. RT-qPCR, western blotting, and immunofluorescence were performed to assess the expression of senescence markers (p16 and p21), proliferation-associated genes (Mki67 and Pcna), osteogenic markers (Spp1, Sp7, type I collagen), Piezo1, calcium ions, transglutaminase 2, and fibrotic proteins (α-smooth muscle actin and type I collagen). β-Galactosidase staining was used to quantify the proportion of senescent cells. Alkaline phosphatase staining was used to measure alkaline phosphatase activity. Alizarin Red S staining was applied to assess mineralized nodule formation. RESULTS AND CONCLUSION: Low-modulus hydrogels significantly downregulated p16 and p21 expression, reduced β-galactosidase–positive cells, alleviated fibrosis, and enhanced osteogenic differentiation, whereas high-modulus hydrogels induced the opposite effects. Further mechanistic analysis revealed that ectomesenchymal stem cells cultured on high-modulus substrates exhibited increased Piezo1 expression, enhanced Ca²⁺ influx, and elevated transglutaminase 2 levels. Inhibition of transglutaminase 2 effectively attenuated high-modulus–induced ectomesenchymal stem cell senescence. These findings indicate that a low-modulus microenvironment can reverse ectomesenchymal stem cell senescence, and the Piezo1/transglutaminase 2 signaling pathway serves as a key regulator in this process. Figures and Tables | References | Related Articles | Metrics

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Human umbilical cord-derived mesenchymal stem cells to treat osteoarthritis in rats: dual effect of relieving pain and protecting cartilage Liu Fang, Hu Haimin, Song Dan, Nan Jie, Cai Xiaoxiao, He Qingrui, Lian Ruijiao, Luo Lin, Yuan Chunhui 2026, 30 (31):  8108-8115.  doi: 10.12307/2026.838 Abstract ( 76 )   PDF (2912KB) ( 14 )   Save BACKGROUND: Human umbilical cord-derived mesenchymal stem cells have been identified as a potential therapeutic agent for osteoarthritis; however, the precise dose-efficacy relationship remains to be elucidated. OBJECTIVE: To observe the efficacy of varying doses of human umbilical cord mesenchymal stem cells in treating osteoarthritis in rats, offering insights for optimal dose selection in human umbilical cord-derived mesenchymal stem cells therapy for osteoarthritis.  METHODS: The osteoarthritis rats induced by monosodium iodoacetate were divided into the following groups: negative control group, hyaluronic acid control group, low-dose group (2.5×105 cells/joint), medium-dose group (8.0×105 cells/joint), and high-dose group (2.5×106 cells/joint). Normal rats without modeling were included as the conditional control group. Each group consisted of 16 rats. In the stem cell group, rats received an intra-articular injection of 25 μL of different doses of human umbilical cord-derived mesenchymal stem cells into the right hind limb knee joint cavity, followed immediately by an injection of 25 μL of 0.2% hyaluronic acid solution. In the hyaluronic acid control group, rats received an intra-articular injection of 25 μL of 0.2% hyaluronic acid solution and 25 μL of saline solution into the right hind limb knee joint cavity. In the condition control group and negative control group, rats received an intra-articular injection of 50 μL of sodium chloride solution into the right hind limb knee joint cavity. At 2, 4, 6, 8, 10, and 12 weeks after administration, assessments were conducted for paw pressure pain threshold, plantar pain threshold, difference in knee pressure pain threshold between left and right limbs, and spontaneous locomotor activity. At 6 and 12 weeks after administration, the right hind limb knee joints were collected for macroscopic examination of articular cartilage, hematoxylin-eosin staining, and safranin O-fast green staining, followed by grading and scoring.  RESULTS AND CONCLUSION: (1) At all tested time points, the negative control group exhibited lower paw withdrawal thresholds, plantar pain thresholds, and spontaneous locomotor activity ability compared with the conditional control group, while demonstrating higher differences in knee pressure pain thresholds between left and right limbs, macroscopic articular cartilage scores, and tissue damage scores, which confirmed successful establishment of the osteoarthritis rat model. (2) Compared with the negative control group, medium- and high-dose groups showed varying degrees of improvement in all these parameters. These results suggest that a single intra-articular injection of human umbilical cord mesenchymal stem cells ranging from 8.0×105 to 2.5×106 cells significantly increased the pain threshold and enhanced spontaneous locomotor activity in osteoarthritis rats, while also repairing pathological cartilage damage. These results indicate that human umbilical cord mesenchymal stem cells can improve joint function and alleviate cartilage damage in osteoarthritis rats.  Figures and Tables | References | Related Articles | Metrics

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Age analysis of graft-versus-host disease after fully matched hematopoietic stem cell transplantation in children with thalassemia Xu Yiqi, Huang Yuming, Wu Xuedong, Feng Xiaoqin, Liu Xuan, Wen Jianyun, Chen Libai, Ruan Yongsheng 2026, 30 (31):  8116-8121.  doi: 10.12307/2026.796 Abstract ( 40 )   PDF (1939KB) ( 7 )   Save BACKGROUND: Graft-versus-host disease is a major complication faced by patients with thalassemia after hematopoietic stem cell transplantation and is the primary cause of high morbidity and non-relapse mortality. OBJECTIVE: To investigate the situation of graft-versus-host disease in children with thalassemia after hematopoietic stem cell transplantation, and to explore the correlation between the incidence of different severity levels of acute graft-versus-host disease and the age of the children.  METHODS: A total of 281 children with thalassemia who underwent fully matched hematopoietic stem cell transplantation in the Department of Pediatrics, Nanfang Hospital, Southern Medical University from January 2012 to June 2018 were selected. They were divided into three groups according to age: < 5 years old group (Group 1; n=80), 5-8 years old group (Group 2; n=140), and > 8 years old group (Group 3; n=61). The occurrence of graft-versus-host disease was analyzed in each group.  RESULTS AND CONCLUSION: A total of 44 cases of graft-versus-host disease were observed. The incidence rates of graft-versus-host disease in Group 1, Group 2, and Group 3 were 10%, 14.29%, and 26.23%, respectively, with a P-value of 0.026, indicating a significant correlation between the occurrence of graft-versus-host disease and age. Among the 13 patients with chronic graft-versus-host disease, the incidence rates in Group 1, Group 2, and Group 3 were 2.50%, 3.57%, and 9.83%, respectively, with a P-value of 0.049 when comparing the incidence rates. For the 34 cases of acute graft-versus-host disease, there was no significant difference in the incidence rates of Grade I+II and Grade III+IV acute graft-versus-host disease among the three groups. The overall incidence rates of graft-versus-host disease and chronic graft-versus-host disease were significantly correlated with the age of the pediatric patients, with a notable increase in the occurrence of these conditions in children over 8 years old. This suggests that special attention should be given to the occurrence of graft-versus-host disease in older children undergoing thalassemia transplantation, and preventive and monitoring measures should be implemented in advance. Figures and Tables | References | Related Articles | Metrics

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Gene expression regulatory network and molecular mechanism involved in odontogenic differentiation of human dental pulp stem cells-derived induced pluripotent stem cells Rong Qiong, Guo Yu, Wang Tingting, Tan Xiaobing 2026, 30 (31):  8122-8134.  doi: 10.12307/2026.421 Abstract ( 60 )   PDF (81271KB) ( 8 )   Save BACKGROUND: Human dental pulp stem cell-derived induced pluripotent stem cells possess self-renewal and multidirectional differentiation potential, showing great promise in promoting dentin regeneration. However, the mechanism of their odontogenic differentiation remains unclear. OBJECTIVE: To analyze the hub genes and potential molecular mechanisms during the odontogenic differentiation of human dental pulp stem cell-derived induced pluripotent stem cells. METHODS: Total RNA of human dental pulp stem cell-derived induced pluripotent stem cells and their differentiated odontogenic cells were extracted for RNA-sequencing to analyze the transcriptome gene expression profile. Firstly, the differentially expressed mRNAs, miRNAs, long non-coding RNAs, and circular RNAs were screened to identify key genes. Gene Set Enrichment Analysis was performed to analyze the key signaling pathways. Subsequently, a competitive endogenous RNA (ceRNA) network and a transcription factor-mRNA-miRNA network were constructed to predict and reveal the regulatory mechanisms of key genes. Finally, real-time quantitative PCR was used to verify the expression of key genes.  RESULTS AND CONCLUSION: Six hub genes were identified during the odontogenic differentiation of human dental pulp stem cell-derived induced pluripotent stem cells: Smad family member 3, signal transducer and activator of transcription 3, fibronectin 1, estrogen receptor 1, epidermal growth factor receptor, and enhancer of zeste homolog 2. The most enriched pathways included Wnt and transforming growth factor β signaling pathways. CeRNA network analysis revealed that hsa-miR-302, hsa-miR-519, and hsa-miR-520 were the main regulatory factors of estrogen receptor 1, with multiple interaction pairs. Transcription factor-mRNA network analysis showed that interferon regulatory factor 3 was a regulatory factor for all six hub genes, while enhancer of zeste homolog 2 was regulated by four transcription factors simultaneously. Real-time quantitative PCR results showed that the expression of fibronectin 1 and enhancer of zeste homolog 2 was significantly increased in odontogenic cells differentiated from dental pulp stem cell-derived induced pluripotent stem cells, while the expression of signal transducer and activator of transcription 3 was significantly decreased. Figures and Tables | References | Related Articles | Metrics

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Epimedium Sagittatum Maxim.-extracellular vesicles ameliorate vascular smooth muscle cell calcification: a proteomic analysis Hu Kai, Chen Yulin, Yan Jing, He Yingying, Meng Yanhui, Li Runzhen, Tang Yaoping 2026, 30 (31):  8135-8145.  doi: 10.12307/2026.436 Abstract ( 58 )   PDF (4272KB) ( 8 )   Save BACKGROUND: Vascular calcification is a type of bone metabolic disorder, and its pathological mechanism is highly similar to the process of bone mineralization. However, there is a lack of effective evidence regarding the application of Epimedium Sagittatum Maxim. (a traditional Chinese medicine) in cardiovascular diseases and how to improve its bioavailability. OBJECTIVE: To investigate the effects and molecular mechanisms of Epimedium Sagittatum Maxim.-extracellular vesicles on vascular calcification. METHODS: (1) Epimedium Sagittatum Maxim.-extracellular vesicles were isolated from using density gradient centrifugation, and characterized by transmission electron microscopy, nanoparticle size analyzer, and nanoparticle tracking analysis. (2) The effects of Epimedium Sagittatum Maxim.-extracellular vesicles on the viability of aortic vascular smooth muscle cells were evaluated by CCK-8 assay. The cellular uptake of Epimedium Sagittatum Maxim.-extracellular vesicles by aortic vascular smooth muscle cells was observed by confocal laser scanning microscopy. (3) Proteomic analysis was performed to identify and characterize the protein composition of Epimedium Sagittatum Maxim.-extracellular vesicles, and potential functional proteins were screened. (4) Aortic vascular smooth muscle cells were divided into blank, model, and Epimedium Sagittatum Maxim.-extracellular vesicle intervention groups (low, medium, and high doses). After co-culturing for 48 hours, cytoskeletal changes were observed by confocal microscopy. Apoptosis was assessed by flow cytometry. Ras homolog family member A/Rho-associated coiled-coil containing protein kinase pathway proteins were measured by western blot assay. Ras homolog family member A-GTP levels were assessed by ELISA. After 7 days of co-culture, calcification areas were detected by Alizarin Red S staining. The expression levels of osteogenic phenotype proteins were detected using western blot assay.  RESULTS AND CONCLUSION: (1) Epimedium Sagittatum Maxim.-extracellular vesicles exhibited saucer-shaped morphology with particle sizes ranging from 50 to 200 nm. (2) CCK-8 assay showed that Epimedium Sagittatum Maxim.-extracellular vesicles had no significant effect on cell viability and were efficiently taken up by aortic vascular smooth muscle cells, indicating good bioactivity. (3) Proteomic analysis identified 37 specific proteins in Epimedium Sagittatum Maxim.-extracellular vesicles. Gene Ontology analysis suggested that Epimedium Sagittatum Maxim.-extracellular vesicles may exert anti-calcification effects by participating in cellular metabolism, signal transduction, and stress response via complex protein interaction networks. (4) Alizarin Red S staining revealed that Epimedium Sagittatum Maxim.-extracellular vesicle intervention significantly reduced calcification areas compared with the model group. Flow cytometry indicated that Epimedium Sagittatum Maxim.-extracellular vesicles exerted notable anti-apoptotic effects. Confocal microscopy results showed that compared with the model group, Epimedium Sagittatum Maxim.-extracellular vesicles dose-dependently restored cytoskeletal structure in the Epimedium Sagittatum Maxim.-extracellular vesicle intervention groups (low, medium, and high doses). Western blot analysis showed that, compared with the model group, the expression levels of Runt-related transcription factor 2, bone morphogenetic protein 2, and phosphorylated Rho-associated coiled-coil containing protein kinase 1 were dose-dependently decreased in the low, medium, and high-dose Epimedium Sagittatum Maxim.-extracellular vesicle groups, while the expression levels of α-smooth muscle actin and smooth muscle 22α were dose-dependently increased. ELISA results showed a dose-dependent decrease in Ras homolog family member A-GTP. The results indicate that Epimedium Sagittatum Maxim.-extracellular vesicles can effectively improve vascular calcification, possibly by regulating the Ras homolog family member A/Rho-associated coiled-coil containing protein kinase pathway.   Figures and Tables | References | Related Articles | Metrics

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Action mechanism of Jingu Tongxiao Pill containing serum exosomes in regulating chondrocyte autophagy Li Jianqiang, Li Feng, Kou Longwei, Shao Yunbo, Zhang Jiali, Guo Jiayi 2026, 30 (31):  8146-8153.  doi: 10.12307/2026.792 Abstract ( 58 )   PDF (1991KB) ( 7 )   Save BACKGROUND: Both exosomes derived from infrapatellar fat pad and Jingu Tongxiao Pill have good therapeutic effects on knee osteoarthritis, but the mechanism and synergistic effect remain to be studied. OBJECTIVE: To explore the effect and mechanism of the drug-containing serum of Jingu Tongxiao Pill on autophagy of chondrocytes in rabbits with knee osteoarthritis through exosomes derived from adipose-derived mesenchymal stem cells. METHODS: (1) Rabbit subpatellar fat pad mesenchymal stem cells were cultured in vitro. In vitro intervention was carried out using phosphate buffer saline, 10 mmol/L glucosamine, and 10% Jingu Tongxiao Pill drug-containing serum respectively. Exosomes were isolated and extracted from the supernatants and detected by transmission electron microscopy and nanoparticle tracking analysis technology. (2) Thirty healthy female New Zealand rabbits aged 8-9 months were randomly assigned to five groups, namely the blank group, the model group, the exosomes-phosphate buffer saline group, the exosomes-glucosamine group, and the exosomes-Jingu Tongxiao Pill group, with six rabbits in each group. The blank group was not treated. The other four groups adopted the left intra-knee injection of type II collagenase method to establish knee osteoarthritis models. After the modeling was verified to be successful, the exosomes-phosphate buffer saline group, the exosomes-glucosamine group, and the exosomes-Jingu Tongxiao Pill group were respectively injected into the knee with exosomes-phosphate buffer saline, exosomes-glucosamine, and exosomes-Jingu Tongxiao Pill for intervention once a week, 1 mL each time, for 5 consecutive injections. One week after the intervention ended, the knee joint grade of each animal was evaluated using the modified Lequesne MG. The femoral condylar cartilage and tibial plateau cartilage were taken for pathological observation. The femoral condylar cartilage was stained with hematoxylin-eosin staining. Mankin's score was performed after light microscopy observation. The expression of phosphatidylinositol 3-kinase, protein kinase B, mammalian target of rapamycin, matrix metalloproteinase 13 gene and related proteins in the cartilage tissue of the tibial plateau was detected by western bolt assay and real-time PCR. RESULTS AND CONCLUSION: (1) Flow cytometry showed that the surface markers CD73, CD90, and CD44 of the extracted rabbit infrapatellar fat pad mesenchymal stem cells were specifically highly expressed. (2) Transmission electron microscopy showed that exosomes derived from infrapatellar fat pad mesenchymal stem cells had a typical cup or spherical structure. Nanoparticle tracking analysis showed that the particle size distribution of these exosomes was 79.7-175.8 nm, the average diameter was 126.5 nm, and the particle concentration was 6.8×10⁶ particles/mL. (3) Rabbit knee osteoarthritis models were successfully established. The knee grade scores of the three groups intervened by intra-knee injection of exosomes decreased to varying degrees. Compared with the model group, the modified Lequesne MG score and Mankin’s score, and the mRNA and protein expression levels of mammalian target of rapamycin, phosphatidylinositol 3-kinase, protein kinase B, and matrix metalloproteinase 13 in cartilage of exosomes-Jingu Tongxiao Pill group were significantly lower (P < 0.05). The results showed that the intervention of Jinju Tongxiao Pill containing serum on exosomes derived from mesenchymal stem cells in the infrapatellar fat pad could promote the autophagy of chondrocytes in osteoarthritis by regulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Paeoniflorin intervenes in inflammatory factors and abnormal autophagy to improve bortezomib-induced peripheral neuropathy Fu Jiaqi, Li Qian, Sun Runjie, Xia Mengting, Cui Xing 2026, 30 (31):  8154-8164.  doi: 10.12307/2026.372 Abstract ( 58 )   PDF (3283KB) ( 11 )   Save BACKGROUND: Studies have shown that paeoniflorin can improve autophagy defects in inflammatory and neurodegenerative diseases by reducing interleukin-6 levels and promoting Beclin1 expression. However, the effect and mechanism by which paeoniflorin improves bortezomib-induced peripheral neuropathy remain unclear. OBJECTIVE: To explore the effect and molecular mechanism of paeoniflorin on inflammatory factors and abnormal autophagy to improve bortezomib-induced peripheral neuropathy. METHODS: (1) Network pharmacology analysis: The two-dimensional structure of paeoniflorin was retrieved from the PubChem database and uploaded to the Swiss Target Prediction database for target prediction. Disease-associated targets of bortezomib-induced peripheral neuropathy were identified using the GeneCards and OMIM databases. The intersection between paeoniflorin’s predicted targets and genes related to bortezomib-induced peripheral neuropathy was defined as potential therapeutic targets for paeoniflorin intervention. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these intersection targets. A “target-pathway” network was constructed, and key paeoniflorin targets were selected based on node degree values from both protein-protein interaction and “target-pathway” networks. Molecular docking was then conducted to validate the binding interactions between paeoniflorin and its potential targets. (2) Cell experiments: Rat pheochromocytoma cells PC12 (or human myeloma cell line MM.1S) in logarithmic growth phase were cultured in three groups: the control group was not treated with any drugs, the model group was treated with bortezomib, and the paeoniflorin group was treated with both paeoniflorin and bortezomib. After 48 hours of culture, the cell counting kit-8 was used to detect the activity of PC12 cells (or MM.1S cells), ELISA was used to detect the level of interleukin-6 in PC12 cells, immunofluorescence was used to detect the expression of LC3B in PC12 cells, western blot was used to detect the expression of LC3 I, LC3 II, and Beclin1 proteins in PC12 cells, and transmission electron microscopy was used to observe the level of autophagy in PC12 cells. (3) Animal experiment: 45 C57BL/6J mice were randomly divided into three groups: the control group (n=15) did not receive any intervention, the model group (n=15) established a bortezomib-induced peripheral neuropathy model by intraperitoneal injection of bortezomib, and the paeoniflorin group (n=15) was given paeoniflorin orally once a day for 25 consecutive days during the bortezomib-induced peripheral neuropathy model process. After administration, the thermal pain sensitivity, serum interleukin-6 levels, sciatic nerve tissue morphology, and LC3 I, LC3 II, Beclin1 expression in mice were detected. RESULTS AND CONCLUSION: (1) Network pharmacology analysis identified 16 potential therapeutic targets of paeoniflorin for bortezomib-induced peripheral neuropathy. Network topology analysis revealed interleukin-6  and Beclin-1 as key targets, with paeoniflorin demonstrating strong binding affinity to both proteins. (2) Results from the cell experiment demonstrated that bortezomib significantly reduced viability of PC12 cells while increasing interleukin-6 levels and decreasing autophagy activity. Paeoniflorin treatment effectively reduced interleukin-6 secretion, enhanced autophagy, and improved PC12 cell viability without compromising the anti-myeloma efficacy of bortezomib. (3) Animal experiments showed that bortezomib administration significantly increased thermal pain sensitivity, elevated serum interleukin-6 levels, aggravated sciatic nerve damage, and reduced autophagy levels within the sciatic nerve , whereas paeoniflorin treatment significantly improved thermal pain sensitivity, alleviated sciatic nerve injury, reduced serum interleukin-6 expression, and ameliorated bortezomib-induced autophagy defects in mice. (4) To conclude, paeoniflorin mitigates bortezomib-induced peripheral neuropathy by suppressing interleukin-6 and restoring neuronal autophagy, without compromising bortezomib’s anti-myeloma efficacy. Figures and Tables | References | Related Articles | Metrics

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Transforming growth factor-beta regulates oxidative stress and participates in inflammatory process of pulmonary hypertension Wang Xuecheng, Zhao Liang, Wei Zhoubin 2026, 30 (31):  8165-8173.  doi: 10.12307/2026.423 Abstract ( 41 )   PDF (8646KB) ( 8 )   Save BACKGROUND: Recent studies have shown that there is a correlation between oxidative stress and pulmonary hypertension, but the key mechanism needs to be further explored. OBJECTIVE: To investigate the mechanism of transforming growth factor β related to oxidative stress in pulmonary hypertension. METHODS: Three data sets (GSE117261, GSE53408 and GSE113439) were obtained and integrated from the gene expression comprehensive database established and maintained by the National Center for Biotechnology Information (NCBI). The differentially expressed genes related to pulmonary hypertension were screened. The core genes related to oxidative stress of pulmonary hypertension were identified by combining the gene sets related to oxidative stress. Machine learning algorithms are used to further screen and determine the most important candidate genes. Subsequently, an experimental model of cells and animals was constructed to verify their functions: (1) Rat pulmonary mesenchymal stem cells were divided into control group, activation group, transforming growth factor β agonist group, and transforming growth factor β inhibitor group. Rat pulmonary mesenchymal stem cells were stimulated by monocrotaline, and the transforming growth factor β agonist and inhibitor were given for 48 hours respectively. (2) SD rats were divided into control group, model group, transforming growth factor β agonist group and transforming growth factor β inhibitor group. The rat model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline. The agonist group and inhibitor group were injected intraperitoneally after modeling. The levels of transforming growth factor β, intercellular adhesion molecule -1, interleukin-1β and interleukin-6 in cell culture medium and lung tissue were detected by ELISA. DHE method was used to detect the level of reactive oxygen species in cells. The changes of mitochondrial membrane potential were detected by JC-1 method. The expression of key genes related to transforming growth factor β pathway was detected by RT-qPCR and western blot assay. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue in rats. RESULTS AND CONCLUSION: (1) A total of 914 differentially expressed genes in pulmonary hypertension were identified by bioinformatics analysis, 39 of which were related to oxidative stress. Furthermore, through machine learning analysis, aquaporin, hemoglobin β chain, mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit 2 and Toll-like receptor 6 were identified as candidate genes related to oxidative stress in pulmonary hypertension. (2) At the cellular test, compared with the control group, the intracellular reactive oxygen species production in the activated group increased, the mitochondrial membrane potential decreased, the levels of transforming growth factor β, intercellular adhesion molecule -1, interleukin-1β and interleukin-6 increased significantly, and the mRNA and protein expressions of transforming growth factor β, hemoglobin β chain and Toll-like receptor 6 were up-regulated, while the expressions of aquaporin and mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit 2 mRNA and protein were down-regulated. Transforming growth factor β agonist further promoted the above changes, while transforming growth factor inhibitor significantly alleviated the above changes. (3) In the animal experiment, compared with the control group, the lung tissue of the model group showed obvious inflammatory infiltration, the level of inflammatory factors increased, with the expression of transforming growth factor β, hemoglobin β chain and Toll-like receptor 6 mRNA and protein up-regulated, while the expression of aquaporin and mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit 2 mRNA and protein down-regulated. The intervention of transforming growth factor β agonist further aggravated the pathological injury and inflammatory reaction of lung tissue, while transforming growth factor β inhibitor significantly reduced the pathological injury of lung tissue, inhibited the secretion of inflammatory factors, and reversed the change trend of related gene expression. The results exhibit that aquaporin, hemoglobin β chain, mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit 2 and Toll-like receptor 6 may be important genes that mediate oxidative stress injury of pulmonary hypertension, and transforming growth factor β signaling pathway plays an important role in regulating the expression of these genes and inflammatory injury. Targeted inhibition of transforming growth factor β signaling pathway may be a new way to improve the pathological process of pulmonary hypertension. Figures and Tables | References | Related Articles | Metrics

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Alterations in synapse-associated proteins following electroacupuncture intervention in rats with learning and memory deficits induced by cerebral ischemia-reperfusion injury Wang Huiling, Guo Changsheng, Gao Jing, Huang Jin, Shen Xin, Zhao Wei, Su Kaiqi, Liu Feilai, Feng Xiaodong 2026, 30 (31):  8174-8180.  doi: 10.12307/2026.488 Abstract ( 42 )   PDF (3748KB) ( 11 )   Save BACKGROUND: Basic research has confirmed that electroacupuncture can improve the learning and memory ability of rats with middle cerebral artery occlusion/reperfusion. However, its underlying mechanism remains unclear.   OBJECTIVE: To observe the effects of electroacupuncture at “Shenting” and “Baihui” on the expression of adenosine monophosphate-activated protein kinase (AMPK)/dynamin-related protein 1 (Drp1) pathway-related proteins and synaptic proteins (SYN, PSD95, and GAP43) in rats with learning and memory impairment after middle cerebral artery occlusion/reperfusion.   METHODS: A total of 48 male Sprague-Dawley rats were randomly assigned into four groups: control group, sham group, model group, and electroacupuncture group. The middle cerebral artery occlusion/reperfusion injury model was established by thread occlusion in the model group and the electroacupuncture group. At 24 hours after modeling, the rats in the electroacupuncture group were treated at “Shenting” and “Baihui” with disperse-dense wave, 2 Hz/10 Hz in frequency and 1 mA in current intensity, and the needles were retained for 30 minutes, once a day for 14 days. The neurological deficit scores were observed after modeling and on the 7th and 14th days of intervention. The learning and memory abilities of the rats were assessed using the Morris water maze test. Neuronal morphology in the rat hippocampal CA1 region was observed by hematoxylin-eosin staining. Adenosine triphosphate was measured by a kit to evaluate mitochondrial function. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the hippocampal region. The protein expressions of AMPK, p-AMPK, Drp1, OPA1, Mfn1, Mfn2, SYN, PSD95 and GAP-43 in the hippocampus were detected by western blot assay.   RESULTS AND CONCLUSION: (1) Compared with the control group and sham group, the neurological deficit scores were increased in the model group and the electroacupuncture group (P < 0.01). After 7 and 14 days of intervention, the neurological deficit scores in the electroacupuncture group were lower than those in the model group (P < 0.05, P < 0.01). (2) The results of Morris water maze test: Compared with the control group and sham group, the model group and the electroacupuncture group showed increased escape latency (P < 0.01) and decreased platform crossings (P < 0.01). Furthermore, electroacupuncture treatment obviously decreased escape latency (P < 0.05) and increased platform crossings (P < 0.01) compared with the model groups. (3) Hematoxylin-eosin staining results showed that compared with the model group, the electroacupuncture group exhibited an increased number of neurons with a more regular arrangement in the hippocampal CA1 region. The structure appeared more normal, with relatively uniform neuronal cell size and morphology. Under the transmission electron microscopy, mitochondrial morphology was improved, characterized by reduced structural damage and an increased number of mitochondrial cristae. (4) Results from the adenosine triphosphate assay kit revealed a significant decrease in adenosine triphosphate content in the hippocampal tissue of the model group relative to the sham group. Meanwhile, the electroacupuncture group exhibited significantly elevated adenosine triphosphate levels compared with the model group (P < 0.01). (5) As revealed by western blot assay, the model group exhibited a significant increase in the protein level of Drp1 (P < 0.05), while showing significant decreases in the protein expressions of p-AMPK/AMPK, OPA1, MFN1, MFN2, SYN, PSD95 and GAP43 in the hippocampal tissue compared with the sham group (P < 0.01). In contrast, the electroacupuncture group displayed an opposite pattern compared with the model group, with decreased Drp1 level and increased expression of p-AMPK/AMPK, OPA1, MFN1, MFN2, SYN, PSD95 and GAP43 (P < 0.05). (6) To conclude, electroacupuncture treatment mitigates brain injury and enhances learning and memory ability in rats subjected to middle cerebral artery occlusion/reperfusion, likely through modulating mitochondrial dynamics mediated by the AMPK/Drp1 pathway.   Figures and Tables | References | Related Articles | Metrics

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Single-cell transcriptomic analysis of somatostatin receptor-mediated regulation of adrenal corticosteroid synthesis Deng Siyu, Chen Zhongyuan, Jiang Jinghang, Guo Yi, Zheng Jie, Wang Honghong, Wang Yifu, Mo Zengnan, Jiang Yonghua 2026, 30 (31):  8181-8189.  doi: 10.12307/2026.438 Abstract ( 53 )   PDF (20191KB) ( 9 )   Save BACKGROUND: Somatostatin is a common neuropeptide and gastrointestinal cyclic peptide hormone, but its mechanism of action in the adrenal gland remains unclear. OBJECTIVE: To investigate the regulatory effect of somatostatin on corticosteroid hormone synthesis using single-cell transcriptomics and in vitro experiments. METHODS: Single-cell transcriptomic analysis was conducted to examine the expression profile of somatostatin receptors in both embryonic and adult adrenal glands. qRT-PCR and immunofluorescence assays were employed to analyze receptor subtypes. To further explore the effect of somatostatin on corticosteroid synthesis, NCI-H295R adrenocortical cells were stimulated with different concentrations of somatostatin. ELISA was used to detect the expression changes of dehydroepiandrosterone, cortisol, aldosterone, and their key metabolic enzymes (CYP17A1, HSD3B2, and CYB5A). RESULTS AND CONCLUSION: (1) Single-cell transcriptomic analysis revealed that only a small number of embryonic adrenal medullary cells expressed somatostatin, with no somatostatin expression observed in the adult adrenal gland. However, both embryonic and adult adrenal steroidogenic cells exhibited significant expression of somatostatin receptor 2. (2) qRT-PCR confirmed high expression of somatostatin receptor 2 in NCI-H295R cells. (3) Low concentrations of somatostatin (1 nmol/L) inhibited dehydroepiandrosterone secretion (P < 0.05), and CYB5A expression was downregulated; while 10 nmol/L somatostatin significantly promoted dehydroepiandrosterone synthesis (P < 0.05), and CYB5A was upregulated. Interestingly, different concentrations of somatostatin stimulation had no significant effect on cortisol synthesis. (4) This suggests that somatostatin can bidirectionally regulate the synthesis and secretion of dehydroepiandrosterone in adrenocortical cells through somatostatin receptor 2, but its effect on cortisol and aldosterone synthesis is not significant. Figures and Tables | References | Related Articles | Metrics

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Cytidine/uridine monophosphate kinase 2 regulates ferroptosis of human gingival fibroblasts induced by lipopolysaccharide He Jiaqi, Shen Hengyu, Xu Mingzhang, Yan Xin, Zhang Ruifeng, Yu Ke 2026, 30 (31):  8190-8196.  doi: 10.12307/2026.854 Abstract ( 45 )   PDF (15824KB) ( 7 )   Save BACKGROUND: Ferroptosis is an iron-dependent form of programmed cell death closely associated with periodontal and peri-implant inflammatory diseases. Cytidine/uridine monophosphate kinase 2 is a kinase localized in mitochondria that participates in regulating tissue cell activation and inflammatory responses. The regulatory mechanisms of both in peri-implantitis remain unclear. OBJECTIVE: To construct an in vitro cell model of peri-implantitis using lipopolysaccharide and explore the regulatory mechanism of cytidine/uridine monophosphate kinase 2 on lipopolysaccharide-induced ferroptosis in human gingival fibroblasts. METHODS: (1) Human gingival fibroblasts were cultured using the tissue explant culture method and treated with 0 μg/mL (normal control group) or 10 μg/mL lipopolysaccharide for 12 hours. The mRNA and protein expression levels of ferroptosis-related markers glutathione peroxidase 4, solute carrier family 7 member 11, and acyl-CoA synthetase long-chain family member 4, as well as cytidine/uridine monophosphate kinase 2, were detected by RT-qPCR and western blot assay. Lipid peroxidation levels were detected by reactive oxygen species staining and C11-Bodipy staining. Intracellular malondialdehyde, superoxide dismutase levels, and the reduced glutathione/oxidized glutathione ratio were detected by colorimetric methods. (2) Cytidine/uridine monophosphate kinase 2 was silenced using siRNA, and then cells were stimulated with 10 μg/mL lipopolysaccharide for 12 hours. The changes in the above indicators were then detected. RESULTS AND CONCLUSION: (1) After stimulating human gingival fibroblasts with 10 μg/mL lipopolysaccharide for 12 hours, the expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 was upregulated, while the expression of the negative ferroptosis regulators glutathione peroxidase 4 and solute carrier family 7 member 11 was downregulated. Reactive oxygen species release increased, malondialdehyde levels increased, superoxide dismutase activity and the reduced glutathione/oxidized glutathione ratio decreased, and cytidine/uridine monophosphate kinase 2 expression was upregulated. (2) After silencing cytidine/uridine monophosphate kinase 2 with siRNA, and then stimulating the cells with 10 μg/mL lipopolysaccharide for 12 hours, acyl-CoA synthetase long-chain family member 4 expression was downregulated, glutathione peroxidase 4 and solute carrier family 7 member 11 expression were upregulated, reactive oxygen species release decreased, malondialdehyde levels decreased, and superoxide dismutase activity and the reduced glutathione/oxidized glutathione ratio increased. These results indicate that cytidine/uridine monophosphate kinase 2 is a key regulatory gene for ferroptosis in gingival fibroblasts during peri-implantitis, and silencing cytidine/uridine monophosphate kinase 2 can inhibit lipopolysaccharide-induced ferroptosis in human gingival fibroblasts. Figures and Tables | References | Related Articles | Metrics

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Construction and identification of RNA interference lentiviral vector for rat disruptor of telomeric silencing 1-like gene Yang Zishu, Yang Jian, Huang Cuiyuan, Cheng Chen, Wu Di, Zhang Jing 2026, 30 (31):  8197-8204.  doi: 10.12307/2026.825 Abstract ( 44 )   PDF (8008KB) ( 8 )   Save BACKGROUND: Disruptor of telomeric silencing 1-like (DOT1L) is a key methyltransferase that catalyzes histone H3 lysine 79 methylation, and its aberrant function is associated with vascular remodeling and a variety of diseases. The construction of stable DOT1L ribonucleic acid interference (RNAi) lentiviral vectors can provide an effective experimental tool to study the biological function of DOT1L in cardiovascular diseases and related disease mechanisms. OBJECTIVE: To construct and identify the RNAi lentiviral vector targeting rat DOT1L gene.   METHODS: DOT1L-specific shRNA sequence was designed, synthesized, and cloned into the lentivirus vector, and the recombinant lentivirus was obtained after packaging, amplification and purification. The interference effect on the expression of DOT1L gene in rat cells in primary rat vascular smooth muscle cells was identified by western blot assay. RESULTS AND CONCLUSION: The rat DOT1L RNAi lentivirus vector was successfully constructed, and the final recombinant lentivirus titer was 8×108 PFU/mL. This vector can significantly reduce the protein level of DOT1L in vascular smooth muscle cells. The lentiviral vector can effectively silence the expression of DOT1L gene, which provides a reliable tool for further study of the biological function of DOT1L in rats.  Figures and Tables | References | Related Articles | Metrics

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Relationship between the proportion of peripheral blood basophils and atypical lymphocytes and infectious mononucleosis Wang Huichi, Chai Yanfen, Zhao Juan, Zhao Peng, Bian Yuyao 2026, 30 (31):  8205-8209.  doi: 10.12307/2026.485 Abstract ( 42 )   PDF (1311KB) ( 9 )   Save BACKGROUND: Clinically, the proportion of atypical lymphocytes is often used as an auxiliary diagnostic indicator for infectious mononucleosis, but the combined application of basophils and the proportion of atypical lymphocytes is rarely reported. OBJECTIVE: To investigate the correlation of peripheral blood basophil and atypical lymphocyte proportions with disease severity and immune activation in patients with infectious mononucleosis, and to evaluate their auxiliary diagnostic value. METHODS: Forty-five patients with infectious mononucleosis were enrolled as the study group and divided into severe group (n=14) and mild-to-moderate group (n=31) according to disease severity. Additionally, 30 age- and sex-matched healthy individuals undergoing physical examination were selected as the control group. Fasting peripheral venous blood was collected and stained with Wright-Giemsa compound stain. Morphological changes of lymphocytes were observed under a microscope, and the proportion of atypical lymphocytes was calculated. White blood cell count, basophil count, and basophil percentage were measured using an automatic hematology analyzer. Pearson correlation analysis was used to assess the correlation between basophil and atypical lymphocyte proportions. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of basophil and atypical lymphocyte proportions for infectious mononucleosis. RESULTS AND CONCLUSION: Basophil count, basophil percentage, and atypical lymphocyte proportion were significantly higher in the study group than in the control group (P < 0.05). These parameters were also significantly higher in the severe group than in the mild-to-moderate group (P < 0.05). Pearson correlation analysis showed that the proportion of atypical lymphocytes was positively correlated with basophil count and basophil percentage in patients with infectious mononucleosis (P < 0.05). Receiver operating characteristic curve analysis revealed that the area under the curve for basophil count, basophil percentage, and atypical lymphocyte proportion was 0.816, 0.726, and 0.857, respectively, and the combined area under the curve for these indicators was 0.952. These findings indicate that basophil and atypical lymphocyte proportions have high diagnostic values for infectious mononucleosis and can serve as comprehensive reference indexes for assessing the intensity of immune response and disease severity in patients with infectious mononucleosis. Figures and Tables | References | Related Articles | Metrics

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Extracellular vesicles as gene therapy vectors: engineering strategies, mechanistic advantages, and clinical applications Zhang Enqi, Wu Hongwei, Wu Chengliang, Yang Tianqi, Tang Weijie, Wang Wenhui, Yu Zeming, Zhang Yanwen, Wang Yuebing 2026, 30 (31):  8210-8218.  doi: 10.12307/2026.437 Abstract ( 63 )   PDF (4190KB) ( 14 )   Save BACKGROUND: Gene therapy offers novel therapeutic prospects for refractory diseases including genetic disorders and malignancies. However, conventional delivery vectors (such as viral vectors and lipid nanoparticles) exhibit significant limitations: high immunogenicity, constrained loading capacity, poor penetration across biological barriers, and insufficient targeting specificity. Extracellular vesicles, with their unique ability to cross biological barriers (including the blood-brain barrier), their multifunctional cargo characteristics for bioactive molecules such as nucleic acids and proteins, and their inherent low immunogenicity and excellent biocompatibility, effectively overcome these bottlenecks, making them a highly promising non-viral gene delivery platform. OBJECTIVE: To summarize the engineering strategies, mechanism advantages, and clinical application research progress of extracellular vesicles as novel gene delivery vectors, clarify the clinical transformation challenges and future development directions, and promote the innovative application of extracellular vesicles as non-viral vectors in the field of gene therapy. METHODS: Using "extracellular vesicles, gene therapy, drug delivery systems, loading strategies, targeted therapy" as the subject term and synonyms to search the PubMed database, and combining the method of literature tracking, 107 articles that met the requirements were finally included for the review. RESULTS AND CONCLUSION: (1) Extracellular vesicles possess the inherent property of delivering various bioactive molecules, including messenger RNA, small interfering RNA, deoxyribonucleic acid and functional proteins. By regulating the gene expression and protein function of recipient cells, they provide a novel delivery platform for precise gene therapy. (2) Through systematic engineering modifications using endogenous strategies (genetic modification of donor cells) and exogenous strategies (physical/chemical modifications after isolation), the loading efficiency and stability of therapeutic molecules in extracellular vesicles can be significantly enhanced, overcoming the limitation of insufficient drug loading capacity of natural extracellular vesicles. (3) Engineered extracellular vesicles modified with targeting ligands (such as peptides and antibody fragments) and surface stability modifications (such as overexpression of CD47) can effectively enhance the specific enrichment in lesion tissues, prolong the half-life in the body and reduce the systemic clearance rate, laying the foundation for expanding their clinical application. Figures and Tables | References | Related Articles | Metrics

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Exosomes from different sources and osteoarthritis: engineering technology, targeting, and drug carrier function Liu Jinrui, Yang Xianguang, Liu Haolong, Li Li, Ruan Zhaohui, Li Yanlin 2026, 30 (31):  8219-8229.  doi: 10.12307/2026.783 Abstract ( 57 )   PDF (3583KB) ( 9 )   Save BACKGROUND: Osteoarthritis is a common degenerative joint disease for which there is currently no effective treatment to significantly alleviate symptom and prevent disease progression. In recent years, exosomes, as key mediators of intercellular communication, have become a research hotspot in the prevention and treatment of osteoarthritis.  OBJECTIVE: To systematically summarize the latest progress of exosomes in the diagnosis and treatment of osteoarthritis, introduce the biological characteristics of exosomes from different sources, and discuss their effects and challenges in the prevention and treatment of osteoarthritis so as to provide optimized strategies for further improving the diagnosis and treatment of osteoarthritis using exosomes. METHODS: Using the search terms “exosome, osteoarthritis, OA” in English and “mesenchymal stem cells, exosomes, osteoarthritis” in Chinese, we searched for studies on the application of exosomes in osteoarthritis in the China National Knowledge Infrastructure, WanFang Database, VIP, and PubMed databases. The literature search covered the period from January 2010 to October 2024, and 167 articles were ultimately included in this review. RESULTS AND CONCLUSION: Exosomes from different sources have the ability to inhibit inflammation and repair cartilage. Exosomes secreted by mesenchymal stem cells not only regulate inflammatory responses through multiple mechanisms but also promote chondrocyte proliferation and differentiation, thereby positively impacting the repair of cartilage degeneration. Improving the targeting and drug carrier functions of exosomes is key to improving the clinical efficacy of exosomes. Cell pretreatment, exosome engineering, and modified exosome carriers can optimize therapeutic efficacy. However, the clinical translation of exosomes remains challenging, and further in-depth research is needed to achieve precise application. Figures and Tables | References | Related Articles | Metrics

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Safety, stability, and action mechanism of mesenchymal stem cell-derived exosomes in treatment of viral infectious diseases He Jinwen, Li Jin 2026, 30 (31):  8230-8236.  doi: 10.12307/2026.829 Abstract ( 66 )   PDF (2135KB) ( 12 )   Save BACKGROUND: Viral infectious diseases continue to pose a significant challenge in the global public health arena. Current antiviral therapeutics exhibit significant limitations, necessitating further exploration of potentially feasible novel treatment strategies. OBJECTIVE: To summarize and outline the mechanism of action, research progress, and problems of mesenchymal stem cell-derived exosomes in viral infectious diseases.  METHODS: “Mesenchymal stem cells, exosomes, mesenchymal stem cell-derived exosomes, viruses, viral infectious diseases, antiviral effect, immunomodulation” were selected as the key words in Chinese and English. A systematic literature search was conducted across multiple databases, including PubMed, Web of Science, ScienceDirect, China National Knowledge Infrastructure (CNKI), VIP, China Biology Medicine disc (CBM), and WanFang Data. Predefined inclusion and exclusion criteria were applied, and the screening process involved a thorough review of titles, abstracts, and full-text articles. Ultimately, a total of 63 relevant articles were included in the analysis. RESULTS AND CONCLUSION: Starting from the biogenesis and compositional structure of mesenchymal stem cell-derived exosomes, the article explores in detail the mechanisms of exosome formation and release, as well as the potential roles of their components, including proteins, lipids, and miRNAs, in the treatment of viral infectious diseases. The antiviral mechanisms mediated by mesenchymal stem cell-derived exosomes are summarized, encompassing both direct inhibition of viral entry and replication, as well as indirect effects through immunomodulatory pathways. A comprehensive review is provided regarding the application of mesenchymal stem cell-derived exosomes across a range of viral infections. Finally, the article discusses current advances in clinical research on exosome-based therapies for viral diseases and explores their potential in combination with pharmacological agents. Figures and Tables | References | Related Articles | Metrics

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Applications and research advances of single-cell RNA sequencing in diseases of knee joint tissues Yang Wenji, Dai Zhu 2026, 30 (31):  8237-8246.  doi: 10.12307/2026.336 Abstract ( 65 )   PDF (2488KB) ( 15 )   Save BACKGROUND: Single-cell RNA sequencing (scRNA-seq) isolates and sequences individual cells from tissue samples to construct molecular profiles, enabling the analysis of cellular heterogeneity and offering novel perspectives for studying tissue development and disease mechanisms. Recent advancements in scRNA-seq have broadened its applications across disciplines, including knee joint research. OBJECTIVE: To introduce the technical principles of scRNA-seq, summarize its progress in knee joint studies, and discuss current challenges and future directions of scRNA-seq. METHODS: A systematic literature search was conducted using PubMed, Web of Science and CNKI databases. The search terms were “single-cell RNA sequencing, sequencing technology, articular cartilage, synovium, bone, meniscus, ligament” in English and Chinese. After excluding low-quality, redundant, or irrelevant articles, 79 studies were analyzed. RESULTS AND CONCLUSION: (1) As a high-throughput technology, scRNA-seq overcomes the limitations of bulk RNA-seq by resolving transcriptomes at single-cell resolution. Its core advantages include revealing cellular heterogeneity, tracing differentiation trajectories, constructing intercellular networks, and identifying disease-specific subpopulations, making it pivotal for studying complex tissues like the knee joint. (2) Applications in knee cartilage, synovium, bone, meniscus, and ligaments have uncovered distinct cell subtypes and functional diversity. scRNA-seq allows researchers to better understand the heterogeneity of cells in knee joint tissues and the “driver” cell populations that initiate pathologies. (3) scRNA-seq analyses enhanced understanding of disease mechanisms by revealing the diversity of cells and associated changes in gene expression levels in complex tissues and finding molecular targets for pathogenic biological behaviors, pathways and potential therapeutic effects. (4) Despite breakthroughs, challenges persist, including technical bottlenecks, analytical complexity, and barriers to clinical translation. Future directions emphasize multi-omics integration, precision medicine, and technical optimizations. Figures and Tables | References | Related Articles | Metrics

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Consensus on the application of tissue engineering technology in craniofacial hard tissue regeneration Ye Ling, Yu Fanyuan, Wang Jun, Man Yi, Xie Huiqi, Tian Weidong, Yuan Quan, Han Xianglong 2026, 30 (31):  8247-8252.  doi: 10.12307/2026.497 Abstract ( 64 )   PDF (1211KB) ( 22 )   Save BACKGROUND: Tumors, trauma, infections, and congenital deformities can lead to craniofacial hard tissue damage, significantly impacting patients' appearance and quality of life. However, there is currently no standardized treatment protocol for craniofacial hard tissue regeneration. OBJECTIVE: To establish standards for craniomaxillofacial hard tissue regeneration treatment and promote standardized clinical treatment. METHODS: Experts in the fields of tissue engineering, tissue regeneration, and craniofacial hard tissue regeneration were convened to collaboratively compile and discuss this consensus, based on relevant domestic and international guidelines while considering the actual situation of craniofacial hard tissue regeneration treatment in China. RESULTS AND CONCLUSION: Bone tissue engineering is regarded as a promising method for the regeneration and repair of bone defects. Although significant progress has been made in craniomaxillofacial bone tissue engineering, demonstrating good application prospects in preclinical and clinical trials, differences in study design may lead to varied outcomes. Before regenerative medicine/tissue engineering can be widely applied in clinical practice, it is necessary to conduct in-depth research on cell and scaffold characteristics, as well as delivery technologies, and establish a set of application standards for stem cell processing and scaffold selection, in order to maximize their functionality and application safety in clinical practice.  Figures and Tables | References | Related Articles | Metrics

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Synaptic Schwann cells promote neuromuscular junction regeneration and function maintenance Fu Zhenyi, Yang Xiao, He Yunkai, Zhang Yating, Liu Jiaxin, Yao Zhihui, Yang Junying, Zhao Yao 2026, 30 (31):  8253-8263.  doi: 10.12307/2026.337 Abstract ( 63 )   PDF (2866KB) ( 9 )   Save BACKGROUND: After the denervation of muscles, a series of pathological and physiological changes occur, leading to muscle atrophy and degenerative changes in the neuromuscular junction. Currently, treatment methods such as infusion of neurotrophic factors, supplementation of nicotinamide mononucleotide, and surgical treatment have limited therapeutic effectiveness. Synaptic Schwann cells secrete neurotrophic factors and extracellular matrix proteins that bind to corresponding receptors, activating downstream signaling pathways and promoting the regeneration and functional recovery of neuromuscular junctions. Synaptic Schwann cells have been extensively studied in terms of physiological functions and have good therapeutic potential and clinical application prospects in diseases such as amyotrophic lateral sclerosis, age-related muscle dysfunction, and Guillain-Barré syndrome. OBJECTIVE: To clarify the role and mechanism of synaptic Schwann cells in neuromuscular junctions, as well as the current research status and challenges in their clinical translation. METHODS: A computer-based search was conducted in PubMed, CNKI, WanFang, VIP, and Medline. The search terms were “synaptic Schwann cells, terminal Schwann cells, regeneration of neuronal junction, NT-3 signaling pathway, BDNF signaling pathway, amyotrophic lateral sclerosis, age-related muscle dysfunction, Guillain-Barré syndrome, extracellular matrix proteins” in English and Chinese. Priority was given to literature published in the last 5 years and in the journals with an impact factor of > 7. A total of 121 papers were included in the review. RESULTS AND CONCLUSION: Synaptic Schwann cells have physiological functions such as sensing action potentials, regulating endplate potential amplitude, and maintaining neuromuscular junctions. They promote neuromuscular junction regeneration by activating downstream signaling pathways such as neurotrophin-3, brain-derived neurotrophic factor, neurotrophin-4, and semaphore 3A. Experimental results have shown that synaptic Schwann cells have broad application potential in neuromuscular diseases, such as amyotrophic lateral sclerosis, age-related muscle dysfunction, and Guillain-Barré syndrome, and are expected to become a key therapeutic target for the future treatment of these diseases. However, the clinical application of synaptic Schwann cells still faces challenges such as unclear interaction mechanisms with other cells, difficulties in cell acquisition, and insufficient long-term safety. Figures and Tables | References | Related Articles | Metrics

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An innovative strategy for engineered exosomal long non-coding RNAs in treatment of osteoporosis Zhang Chuanlin, Wu Yuhuai, Zhou Haixiang, Liu Jianping, Xu Qian, Zhang Lili, Li Cuie 2026, 30 (31):  8264-8271.  doi: 10.12307/2026.853 Abstract ( 60 )   PDF (1482KB) ( 8 )   Save BACKGROUND: In recent years, long non-coding RNAs in exosomes have gradually become a focus of research on the mechanism of osteoporosis. The combination of exosomes and tissue engineering technology plays a significant role in the targeted delivery of osteoporosis treatment drugs, proteins, and RNA and other small molecule substances. OBJECTIVE: To explore the mechanism of exosomes in osteoporosis so as to provide new therapeutic strategies for exosomes in the treatment of osteoporosis. METHODS: The China National Knowledge Infrastructure (CNKI) and PubMed databases were searched using Chinese keywords such as "exosomes, long non-coding RNA, osteoporosis, extracellular vesicles, engineered exosomes," and English keywords such as "exosomes, lncRNA, osteoporosis, extracellular vesicles, engineered exosomes." The search period covered the entire database history up to July 2025. Totally 77 relevant articles were selected for analysis and summary. RESULTS AND CONCLUSION: (1) Exosomes derived from bone marrow, adipose tissue, and other tissue cells can regulate miRNAs and their downstream signaling pathways by delivering long non-coding RNAs, thereby promoting osteoblast activity, increasing the thickness of cortical bone and the number of trabeculae in osteoporotic mice, and alleviating osteoporosis. (2) By knocking down long non-coding RNAs in osteoclasts, the symptoms of osteoporosis in ovariectomized mice can be alleviated, and bone loss can be reduced. (3) By attaching bone-targeting peptides to the surface of exosomes, they can exert bone-targeting and bone generation effects in osteoporotic mice, thereby enhancing the therapeutic efficacy of exosomes in treating osteoporosis. (4) Other in vitro modifiers that enhance the effect of exosomes include alendronate, bifunctional peptides, gold-coated magnetic nanoparticles, and recombinant probiotics, which can promote the osteogenic differentiation and angiogenesis of bone marrow mesenchymal stem cells and endothelial progenitor cells. (5) Exosomes encapsulating specific messenger ribonucleic acid and modified with bone-targeting peptides can significantly enhance bone-targeting efficiency and alleviate bone loss in osteoporotic mice. (6) By loading drugs such as curcumin, cordycepin, and 17β-estradiol into the exosomes modified with bone-targeting peptides through ultrasound, the synergistic effect of drugs and exosomes in treating osteoporosis can be achieved, demonstrating a more significant osteoporosis repair effect than exosomes without drug loading. Figures and Tables | References | Related Articles | Metrics

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Bibliometric analysis of soft robotic rehabilitation applications: a multidisciplinary perspective and trend insight in the context of greater health Shi Liupeng, Xie Liangyu, Dan Yuqin, Li Wang, Wang Jie, Shi Liang, Shi Bin, Cao Shengnan, Sun Guodong 2026, 30 (31):  8272-8281.  doi: 10.12307/2026.345 Abstract ( 66 )   PDF (15621KB) ( 10 )   Save BACKGROUND: Soft robotics involves robotic systems made from flexible materials that can adapt to unstructured environments and offer excellent biocompatibility and has seen a rise in applied research in the field of rehabilitation in recent years. However, there remains a lack of bibliometric analyses on the current state of research and emerging trends in this domain. OBJECTIVE: To analyze the research dynamics of soft robots in rehabilitation medicine over the past decade, revealing cutting-edge hotspots and development trends in the field. METHODS: Relevant literature on soft robotic rehabilitation applications from 2014 to 2024 in the Web of Science database was searched by computer, and bibliometrics software such as VOSviewer 1.6.20, CiteSpace.V.6.2.R6, Charticulator and Bibliometrix were used for bibliometric and knowledge graph visualization analyses. RESULTS AND CONCLUSION: A total of 596 Web of Science core database documents were included, and the number of publications regarding soft robotic rehabilitation applications has gradually increased over time. China and the United States rank the top two in terms of the number of publications and citations, but there is an imbalance in the quality of publications in China. The authors with the highest number of publications are Yu Wenwei, Cianchetti Matteo and Menciassi Arianna, who have made important contributions to the research in this field. The journals with the most relevant publications are IEEE Robotics and Automation Letters and Soft Robotics, both authoritative journals in the field. The keywords co-occurrence, clustering, timeline view and emergent analyses reveal that recent research in this field has focused on developing versatile and intelligent soft rehabilitation robots. The knowledge map of research in the field of soft robotics rehabilitation applications is constructed through bibliometric analysis, systematically summarizing the current status and hotspots of research in the field, aiming to provide references and guidance for future related studies. Figures and Tables | References | Related Articles | Metrics

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Body mass index and knee osteoarthritis: a bibliometric analysis based on the Web of Science Core Collection database Huang Jie, Zeng Hao, Zhang Zhenhao, Wang Wenchi, Cui Xianqin, Zhu Lifeng, Cui Wei 2026, 30 (31):  8282-8292.  doi: 10.12307/2026.354 Abstract ( 48 )   PDF (7284KB) ( 16 )   Save BACKGROUND: Body mass index has been shown to markedly influence the onset and progression of knee osteoarthritis. As the population ages and obesity rates increase, visualization analysis is needed to comprehend the main research content and hotspots in the field of body mass index and knee osteoarthritis. OBJECTIVE: To analyze and summarize the cutting-edge content, research hotspots, and research trends in the field of body mass index and knee osteoarthritis using bibliometric visualization analysis software. METHODS: Relevant literature on body mass index and knee osteoarthritis from 2005 to 2024 was retrieved in the Web of Science Core Collection database. Bibliometric and visualization analysis was performed with VOSviewer and CiteSpace visualization software. RESULTS AND CONCLUSION: A total of 3 864 relevant documents were included, with publications on body mass index and knee osteoarthritis showing a yearly growth trend in China and abroad. The United States had the highest number of publications at 1 492, with Boston University ranking first with 265 publications. Professor Ali Guermazi from Boston University was the most prolific author, while Professor D.T. Felson from the same institution was the most highly cited author. The British journal Osteoarthritis and Cartilage ranked first in publication volume and citations. Core keywords in this field include total knee arthroplasty, unicompartmental knee arthroplasty, patient-reported outcomes, and age. Body mass index and knee osteoarthritis hold considerable research potential and value based on current study analysis. Substantial advancements are achieved in epidemiology, pathogenesis, and intervention strategies, particularly emphasizing a variety of intervention approaches. The integration of novel surgical assistance technologies and artificial intelligence is driving interdisciplinary research at the intersection of medicine and engineering. Additionally, the incorporation of traditional Chinese medicine holds potential as a promising avenue for managing the progression and treatment of knee osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Bone tissue repair with animal/human-derived exosomes: visualization analysis of development trends Jiao Ziyi, Enhejirigala, Shi Guopeng, Yan Dayang, Wang Wei, Wang Xing, Liu Fuling, Wang Haiyan, Li Xiaohe 2026, 30 (31):  8293-8301.  doi: 10.12307/2026.926 Abstract ( 61 )   PDF (3705KB) ( 10 )   Save BACKGROUND: As novel cell-free nanocarriers, animal- and human-derived exosomes have become research hotspots in regenerative medicine, thanks to their low immunogenicity and dual regulatory advantages in promoting vascularization and osteogenesis. However, there is currently a lack of systematic bibliometric analysis regarding the research status and evolutionary trends in this field. OBJECTIVE: To perform a visualization analysis of relevant literature concerning the application of animal/human-derived exosomes in bone tissue repair, exploring research hotspots and current status to provide a reference for future studies. METHODS: Literature related to animal/human-derived exosomes in the field of bone tissue repair published between January 1, 2015, and November 27, 2025, was retrieved from the Web of Science Core Collection and the China National Knowledge Infrastructure. Statistical and visualization analyses were conducted using Microsoft Office Excel 2019, CiteSpace 6.4.R1, VOSviewer 1.6.20, and the R-Bibliometrix package. RESULTS AND CONCLUSION: (1) A total of 403 English publications from Web of Science Core Collection and 152 Chinese publications from China National Knowledge Infrastructure were included. The overall volume of publications shows an upward trend, with English literature growing at a faster rate. (2) In the Web of Science Core Collection database, China ranks first in the number of publications (303 articles), while the United States exhibits the strongest international collaboration capacity, with a betweenness centrality of 0.71. The most prolific institution and journal are Shanghai Jiao Tong University and the Journal of Nanobiotechnology, respectively. (3) Among the analyzed literature, Furuta (2016) has the highest citation count (360). Within the references cited by these documents, Kalluri (2020) is the most frequently cited (70 times). (4) Keyword co-occurrence and evolution analysis show that “exosomes” and “bone regeneration” are core hotspots. Research themes have evolved from early basic mechanisms such as “inflammation” and “fracture healing” toward application levels like “immunomodulation” and “angiogenesis.” “Hydrogels” are emerging as a key carrier linking microscopic mechanisms to macroscopic therapy. (5) Future research will shift from single-mechanism validation to engineered product transformation, focusing on the regulation of the immune microenvironment and the coupling mechanism of vascular-bone regeneration. Additionally, milk-derived exosomes are expected to become a significant new direction for low-cost clinical translation due to their high yield, low cost, and ease of administration. Figures and Tables | References | Related Articles | Metrics

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Bibliometric analysis of studies on organoid air-liquid interface culture Tong Man, Wang Yue, Wang Ruoyu, Wang Zhe, Fang Yanhua, Liang Shanshan 2026, 30 (31):  8302-8308.  doi: 10.12307/2026.794 Abstract ( 54 )   PDF (7251KB) ( 9 )   Save BACKGROUND: Organoid culture at the air-liquid interface has improved significantly in recent years, yet a comprehensive bibliometric analysis of this field remains absent. OBJECTIVE: To investigate global research competition, collaboration patterns, and emerging trends in organoid air-liquid interface culture through bibliometric and visualization analysis. METHODS: We systematically retrieved publications on organoid air-liquid interface culture from January 1, 2005 to December 31, 2024 on Web of Science Core Collection (WoSCC). Common bibliometric software tools such as VOSviewer and CiteSpace were used for bibliometric and visualization analysis. RESULTS AND CONCLUSION: Since 2005, the analysis identified 127 publications globally in the field of organoid air-liquid interface culture, showing a consistent growth trend. The United States led in publication output (40 articles) with active international collaborations, while China ranked second (17 articles) but demonstrated limited institutional collaborations abroad. Stanford University emerged as the most productive institution. KUO CJ and SACHS N were the most prolific and highly cited authors, respectively. The most co-cited article was “Long-term expanding human airway organoids for disease modeling.” Molecular biology, biology, and genetics constituted the predominant disciplines. High-frequency keywords included “stem cells,” “in vitro,” and “differentiation.” The construction of organoids based on air-liquid interface culture, the establishment of viral infectious models such as Severe Acute Respiratory Syndrome Coronavirus 2, the application of induced pluripotent stem cell differentiation in regenerative medicine, and the regulation of airway basal cells and homeostasis represent the most trending research directions.   Figures and Tables | References | Related Articles | Metrics