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08 November 2025, Volume 29 Issue 31 Previous Issue    Next Issue

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Calcined deer antler slices promote proliferation of bone marrow mesenchymal stem cells Shao Xuekun, Shi Dianhua, Ding Zhiping, Qiu Zhuoya, Wang Ping, Wang Yi, Wang Cheng, Ding Xiaoyan, Sun Tiefeng 2025, 29 (31):  6601-6608.  doi: 10.12307/2025.673 Abstract ( 115 )   PDF (3987KB) ( 90 )   Save BACKGROUND: Through scientific research addressing the effect of calcined deer antler slices on promoting the proliferation of bone marrow mesenchymal stem cells, it aims to provide empirical support for the integration and innovation of traditional Chinese medicine and modern regenerative medicine, and promote the widespread application of traditional Chinese medicine in the treatment of skeletal system diseases. OBJECTIVE: To investigate the effect of calcined deer antler slices on bone marrow mesenchymal stem cell proliferation.  METHODS: Different calcination samples were prepared by wrapping deer antler slices with materials such as clay, yellow clay, and salted yellow clay, resulting in seven different samples (clay-cotton cloth, yellow clay-cotton cloth, salted yellow clay-cotton cloth, yellow clay-tin foil, salted yellow clay-tin foil, yellow clay-honey roasted, salted yellow clay-honey roasted antler slices). Water-soluble extract content in deer antler slices was determined before and after calcination. CCK-8 assay was used to evaluate the effects of different aqueous extracts of calcined antler slices on the proliferation activity of bone marrow mesenchymal stem cells. RESULTS AND CONCLUSION: (1) Calcination significantly increased the water-soluble extract content of deer antler slices, with the highest content observed in samples treated with yellow clay and honey. (2) Calcined deer antler slices significantly promoted bone marrow mesenchymal stem cell proliferation, among which the yellow clay-honey roasted deer antler slices have the most significant effect on promoting the proliferation of bone marrow mesenchymal stem cells. Figures and Tables | References | Related Articles | Metrics

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Extraction and subculture of neural stem cells from mouse embryonic spinal cord: comparison and analysis on advantages and disadvantages of three commonly used digestive enzymes Luo Dan, Ge Zhilin, Hou Yonghui, Wang Wanshun, Zhan Jiheng, Hou Yu, Lin Dingkun, Chen Shudong 2025, 29 (31):  6609-6615.  doi: 10.12307/2025.540 Abstract ( 75 )   PDF (3464KB) ( 138 )   Save BACKGROUND: In the research and application of neural stem cells, cell culture and passage are key links, which directly affect the quality of cells and experimental results. It is of great significance to find the most suitable digestive enzymes that can maintain the biological characteristics of embryonic mouse spinal cord neural stem cells and enhance their passage efficiency.  OBJECTIVE: To explore the most suitable digestive enzyme for passage of neural stem cells from the spinal cord of embryonic mice. METHODS: Microscopic dissection was used to isolate and extract spinal cord tissue from E14 d embryonic mice, which was cultured in DMEM/F12 serum-free medium containing epidermal growth factor, basic fibroblast growth factor, and B27. After spherulation, Nestin and Sox2 immunofluorescence identification was performed. During neural stem cell passage and culture, single-cell suspensions were prepared using trypsin, papain, and TrypLETM Express enzyme digestion combined with blow molding. The cell dispersion and spheroidization were observed, and passage 3 cells were stained with propidium iodide to detect cell death. Cell proliferation was detected by counting the total number of cells. Immunofluorescence staining, western blot assay and RT-PCR were used to detect the expression of Olig2, Tuj1, GFAP, and NeuN at the protein and mRNA levels and to identify cell differentiation.  RESULTS AND CONCLUSION: After 72 hours of culture, E14 d embryonic mouse spinal cord tissue cells could form suspended neurospheres, which could be passaged after 5-7 days. Compared with trypsin and papain, TrypLETM Express enzyme combined with blow beating method was used for passage. The cell dispersion rate was high, the activity was good, and more NeuN- and Tuj1-positive neurons differentiated. This study optimized the culture and passaging process of neural stem cells, laying a foundation for further research on stem cell transplantation therapy for spinal cord diseases. Figures and Tables | References | Related Articles | Metrics

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Comparison of biological characteristics of mouse bone marrow mesenchymal stem cells after interference and overexpression of telomere Cajal body protein-1 Lin Shuqian, Zhao Xilong, Gao Jing, Pan Xinghua, Li Zian, Ruan Guangping 2025, 29 (31):  6616-6624.  doi: 10.12307/2025.686 Abstract ( 57 )   PDF (3917KB) ( 96 )   Save BACKGROUND: With the increase of age, the function of bone marrow-derived mesenchymal stem cells is gradually reduced, and delaying the aging of bone marrow-derived mesenchymal stem cells itself has become an important topic.  OBJECTIVE: To explore ways to delay the aging of bone marrow-derived mesenchymal stem cells by changing the expression of telomerase Cajal body protein 1 (TCAB1) gene.  METHODS: Mouse bone marrow-derived mesenchymal stem cells were cultured by cell adhesion method. TCAB1 gene in bone marrow-derived mesenchymal stem cells was overexpressed and interfered by recombinant lentivirus technique. The expression of aging related genes P16, P21, P53, and P27 was detected by qPCR. The relative length of telomeres was detected by qPCR. The expression of aging proteins P16, P21, P53, and P27 was detected by western blot assay. Cell proliferation was detected by CCK-8 assay. Annexin V-PE/7-AAD apoptosis kit was used to detect the degree of cell apoptosis.  RESULTS AND CONCLUSION: Bone marrow-derived mesenchymal stem cell lines overexpressing TCAB1 gene had decreased expression of senescence related genes and proteins, increased Telomere relative length, stronger cell proliferation, less apoptosis, and a youthful state. The expression of age-related genes and proteins in bone marrow mesenchymal stem cells interfering with TCAB1 gene increased, and the relative telomere length decreased; cell proliferation ability was weak; cell apoptosis was more, and cells showed senescence. These results indicate that increasing the expression of TCAB1 in an appropriate range can delay the rate of cell senescence. Figures and Tables | References | Related Articles | Metrics

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Effect of human umbilical cord mesenchymal stem cells co-culture combined with ginsenoside Rg1 on heart failure cell model Ren Shutong, Hao Miao, Liu Yue, Hou Ping, Quan Juanhua 2025, 29 (31):  6625-6633.  doi: 10.12307/2025.556 Abstract ( 74 )   PDF (2035KB) ( 95 )   Save BACKGROUND: How to improve the expansion of cells, reduce cell loss, increase homing rate and reduce apoptosis is the main problem in the preclinical research of human umbilical cord mesenchymal stem cells. Ginsenoside Rg1 can promote the proliferation and differentiation of mesenchymal stem cells in different microenvironments in vitro or in vivo, which may be a candidate drug to improve the efficiency of human umbilical cord mesenchymal stem cell transplantation.  OBJECTIVE: To investigate the effect of human umbilical cord mesenchymal stem cells co-culture combined with ginsenoside Rg1 on pentobarbital sodium induced heart failure cell model.  METHODS: H9C2 cells were divided into five groups: Control group, pentobarbital sodium group, human umbilical cord mesenchymal stem cell group, ginsenoside Rg1 group, and human umbilical cord mesenchymal stem cell + ginsenoside Rg1 group. H9C2 cells in the control group were cultured in normal DMEM for 24 hours. H9C2 cells in the other groups were cultured in DMEM containing 0.8% pentobarbital sodium for 7 minutes to establish a heart failure cell model. After modeling, above models were treated with human umbilical cord mesenchymal stem cells, ginsenoside Rg1, or their combination. CCK-8 assay and EdU staining were used to detect cell proliferation. TUNEL assay was used to detect cell apoptosis. Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities were detected according to kit instructions. The mRNA levels of tumor necrosis factor α, interleukin 1β, and interleukin 6 in the supernatant were determined by ELISA. The mRNA levels of tumor necrosis factor α, interleukin 1β, interleukin 6, Bax, and Bcl2 in the cells were determined by RT-qPCR. The protein levels of Bax, Bcl2, Toll-like receptor 4, p65, and p-p65 were determined by western blot assay.   RESULTS AND CONCLUSION: (1) Compared with the pentobarbital sodium group, H9C2 cell viability and EdU positive rate were increased; TUNEL positive rate and Bax mRNA and protein expression were decreased, and Bcl-2 mRNA and protein expression were increased; Na+-K+ -ATPase activity decreased; Ca2+-Mg2+-ATPase activity increased; tumor necrosis factor α, interleukin-1β, and interleukin-6 levels decreased in H9C2 cell supernatant, and tumor necrosis factor α, interleukin-1β, and interleukin-6 mRNA expression decreased in H9C2 cells; the expression of toll-like receptor 4 and P-P65 protein decreased with significant difference in human umbilical cord mesenchymal stem cell group, ginsenoside Rg1 group and human umbilical cord mesenchymal stem cell + ginsenoside Rg1 group (P < 0.05). (2) Compared with human umbilical cord mesenchymal stem cell group and ginsenoside Rg1 group, the above indexes in human umbilical cord mesenchymal stem cells + ginsenoside Rg1 group were further improved (P < 0.05). The results showed that human umbilical cord mesenchymal stem cells combined with ginsenoside Rg1 promoted the viability of heart failure cells induced by pentobarbital sodium and inhibited inflammation mediated by the Toll-like receptor 4/nuclear factor κB pathway. Figures and Tables | References | Related Articles | Metrics

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Exosomes derived from human umbilical cord mesenchymal stem cells in treatment of osteoporotic femoral fractures in SD rats Bu Xianmin, Liang Di, Zhang Bin, Xu Yingjie, Ding Hao, Wu Bin, Tian Ronghua 2025, 29 (31):  6634-6641.  doi: 10.12307/2025.538 Abstract ( 134 )   PDF (2566KB) ( 75 )   Save BACKGROUND: Exosomes derived from human umbilical cord mesenchymal stem cells are widely used for bone repair and reconstruction, significantly enhancing osteogenesis and promoting angiogenesis. OBJECTIVE: To explore the mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells in the treatment of osteoporotic fractures. METHODS: Human umbilical cord mesenchymal stem cells were extracted using tissue block culture method. Exosomes derived from human umbilical cord mesenchymal stem cells were extracted using ultracentrifugation method for identification. Thirty 12-week-old female SD rats were randomly divided into sham-operated group (n=6) and ovariectomized group (n=24). Osteoporosis model was established by castration in the ovariectomized group. 12 weeks after modeling, 6 rats in the ovariectomized group and 6 rats in the sham-operated group were randomly selected for Micro-CT and hematoxylin-eosin staining to verify the models. After verification, the remaining 18 rats in the ovariectomized group were randomly assigned to three groups to establish osteoporotic fracture models. The fracture end was separately injected with PBS (PBS group), exosomes at 1.5×1011 particles/mL (low-concentration exosome group), and 3×1011 particles/mL (high-concentration exosome group). Four weeks after operation, fracture healing and bone angiogenesis were evaluated by imaging and histological observations. RESULTS AND CONCLUSION: (1) In the gross specimens, compared with the PBS group, the exosome group had faster fracture healing and more callus formation. (2) The X-ray score of fracture healing in the exosome group was significantly higher than that in the PBS group, and the difference was significant (P < 0.05). (3) Micro-CT three-dimensional imaging: Compared with the PBS group, the fracture healing in the exosome group was accelerated and the callus formation was significantly increased; the bone volume fraction in the exosome group was significantly higher than that in the PBS group, and the difference was significant (P < 0.01). (4) Hematoxylin-eosin staining and Masson’s trichrome staining showed that bone trabeculae and the new bone tissue in the exosome group were more than those in the PBS group. (5) Immunohistochemical staining showed that the expression of CD31 and osteocalcin in the exosome group was significantly higher than that in the PBS group. The high-concentration exosome group had a higher density of new blood vessels, more callus formation, and faster fracture healing than the low-concentration exosome group, showing a concentration-dependent manner. The results show that exosomes derived from human umbilical cord mesenchymal stem cells can promote the repair of osteoporotic fracture by enhancing the angiogenesis and osteogenesis. The mechanism may be related to the increased expression of CD31 and osteocalcin. Figures and Tables | References | Related Articles | Metrics

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Human umbilical cord-derived mesenchymal stem cells thwart pyroptosis of lung tissue cells in septic mice He Changliang, Wang Yan, Luo Ling, Liu Jian 2025, 29 (31):  6642-6648.  doi: 10.12307/2025.547 Abstract ( 73 )   PDF (2088KB) ( 119 )   Save BACKGROUND: Acute lung injury is a common severe complication in sepsis patients, with a complex pathogenesis, for which there is currently no effective pharmacological treatment. The therapeutic mechanism by which human umbilical cord-derived mesenchymal stem cells improve sepsis-induced acute lung injury through the inhibition of excessive cellular pyroptosis is increasingly receiving attention. OBJECTIVE: To investigate the effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on cellular pyroptosis in lung tissues of mice with sepsis-induced acute lung injury. METHODS: Totally 48 male Balb/c mice were randomly divided into sham, model, and treatment groups (n=16 per group). The model and treatment groups underwent cecum ligation and puncture to establish a sepsis-induced acute lung injury model, while the sham group underwent laparotomy without further procedures. The treatment group received a tail vein injection of 200 μL of human umbilical cord-derived mesenchymal stem cell suspension (5×105 cells) 6 hours after the procedure, while the model and sham groups received 200 μL of saline 6 hours after the surgery. Twenty-eight hours post-procedure, five mice from each group were randomly selected for tail vein injection of Evans blue dye to assess pulmonary vascular permeability. The remaining mice from each group had their bronchoalveolar lavage fluid and lung tissues collected for ELISA to measure levels of interleukin-1β and interleukin-18, cell counts, and macrophage numbers in the bronchoalveolar lavage fluid. Hematoxylin and eosin staining was used to observe the pathological morphology of lung tissue. TUNEL staining was used to assess cellular pyroptosis. RT-PCR and western blot analyses were conducted to measure mRNA and protein expression levels of Toll-like receptor 4, GSDMD, and Caspase-11 in lung tissues. RESULTS AND CONCLUSION: Compared to the model group, the treatment group showed a significant decrease in pulmonary vascular permeability at 28 hours post-procedure (P < 0.05), reduced levels of interleukin-1β and interleukin-18 in bronchoalveolar lavage fluid (P < 0.05), and lower cell and macrophage counts (P < 0.05). Lung injury severity was reduced, with a decreased pyroptosis index (P < 0.05) and significantly lower levels of Toll-like receptor 4, GSDMD, GSDMD-N, and Caspase-11 mRNA and protein expression in lung tissues (P < 0.05). These results suggest that human umbilical cord-derived mesenchymal stem cells may improve the severity of sepsis-induced lung injury to some extent by inhibiting the activation of the Toll-like receptor 4/Caspase-11/GSDMD signaling pathway and reducing cellular pyroptosis in lung tissues.  Figures and Tables | References | Related Articles | Metrics

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Effects of platelet-derived growth factor-DD on proliferation and multilineage differentiation of human tendon-derived stem cells Wen Huawei, Zhang Qingsong, Tang Ming, Li Yanan, Tan Hongfei, Fang Yushun 2025, 29 (31):  6649-6655.  doi: 10.12307/2025.537 Abstract ( 111 )   PDF (1703KB) ( 64 )   Save BACKGROUND: Chronic rotator cuff injury is often companied by tendon degeneration and impaired function of tendon-derived stem cells. As am important cytokine, platelet-derived growth factor-DD has a regulatory effect on the proliferation and differentiation of tendon-derived stem cells.  OBJECTIVE: To investigate the effect of platelet-derived growth factor-DD on the proliferation and multilineage differentiation of tendon-derived stem cells in human chronic rotator cuff injury.  METHODS: Tendon-derived stem cells were isolated from human chronic rotator cuff injury tissue and cultured in vitro. Immunofluorescence staining was used to observe the cytoskeletal morphology of tendon-derived stem cells. Flow cytometry was used to identify the phenotype of tendon-derived stem cells. Tendon-derived stem cells were divided into two groups. The control group did not receive any intervention. The platelet-derived growth factor-DD group was treated with 5 μg/mL platelet-derived growth factor-DD. The effect of platelet-derived growth factor-DD on the proliferation and multilineage differentiation of tendon-derived stem cells was evaluated by cell proliferation assay and three-lineage differentiation assay.  RESULTS AND CONCLUSION: (1) The number of EdU-positive cells in the platelet-derived growth factor-DD group was significantly increased compared with the control group (P < 0.05). Tendon-derived stem cells entered the rapid proliferation phase earlier, and the cell growth was logarithmic. (2) The positive areas of Oil Red O staining, Alcian Blue staining, and Alizarin Red staining in the platelet-derived growth factor-DD group were significantly larger than those in the control group (P < 0.05). (3) The above results show that platelet-derived growth factor-DD significantly promotes the proliferation and adipogenic, osteogenic, and chondrogenic differentiation of tendon-derived stem cells.  Figures and Tables | References | Related Articles | Metrics

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Extraction and culture of enteric glial cells from C57BL/6 newborn neonatal mice Zhao Nan, Ding Yong, Xiu Hang, Liu Pengfei, Liang Guogang 2025, 29 (31):  6656-6660.  doi: 10.12307/2025.546 Abstract ( 110 )   PDF (1105KB) ( 70 )   Save BACKGROUND: The pathogenesis of inflammatory bowel disease involves inflammation, immune activation, visceral hypersensitivity, and dysbiosis of the gut microbiota. Inflammation promotes the release of inflammatory mediators by immune cells, damaging the enteric nervous system. Enteric glial cells are an important component of the intestinal nervous system and are excellent cells for studying intestinal neuroinflammation. Primary enteric glial cells play a crucial role in exploring cell therapies for intestinal nervous system diseases. Currently, the methods for obtaining these cells are mostly cumbersome. Therefore, finding a convenient and fast method for extracting this cell is crucial.  OBJECTIVE: To establish a method for optimizing the isolation, culture, and identification of mouse enteric glial cells.  METHODS: 0-7-day-old C57BL/6 neonatal mice were euthanized by excessive inhalation of isoflurane. After soaking in 75% alcohol for disinfection, the duodenum (1 cm below the pylorus to 1 cm above the Qu's ligament) was removed by laparotomy at the midline of the abdomen. A 1 mL syringe was filled with DPBS and the intestinal contents were repeatedly rinsed until the intestine became translucent, and the mesentery and blood vessels were peeled off. The duodenum was cut to a size of 1 mm and digested in 0.25% EDTA trypsin for 20 minutes. Then an equal amount of DMEM/F12 complete culture medium was added to terminate digestion. The liquid was filtered through a 100 μm cell filter, centrifuged, and the cells were resuspended in 1 mL of DMEM/F12 complete culture medium. When the cell adhesion growth density reached 80%, cells were digested for subculture. When cells were cultured to the third generation, glial fibrillary acid protein labeled with enteric glial cells was used for identification by immunofluorescence method. RESULTS AND CONCLUSION: The isolated and cultured cells were full of colloids, with protrusions extending outward and passable. Glial fibrillary acid protein staining was positive. This method can successfully isolate and culture enteric glial cells and is easy to operate, providing a stable model for the study of the pathophysiology of the enteric nervous system. Figures and Tables | References | Related Articles | Metrics

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Effect of fibronectin on differentiation of human neural stem cells into oligodendrocyte precursor cells Wang Zhaoyan, Wang Qian, Liu Weipeng, Yang Hui, Luan Zuo, Qu Suqing 2025, 29 (31):  6661-6666.  doi: 10.12307/2025.693 Abstract ( 65 )   PDF (2015KB) ( 54 )   Save BACKGROUND: Oligodendrocyte precursor cells are seed cells for the treatment of white matter damage diseases. Establishing an efficient and stable in vitro differentiation method is an important prerequisite for clinical translational research.  OBJECTIVE: To investigate the effect of fibronectin on biological characteristics such as proliferation, migration, and differentiation of oligodendrocyte precursor cells derived from human neural stem cells. METHODS: Human neural stem cells cultured in suspension were digested into single cells using Accutase. The expression of specific markers Nestin, Sox2, Vimentin, CD133, and Musashi was detected by flow cytometry. The single cells of human neural stem cells were resuspended in oligodendrocyte precursor cell medium and seeded in six-well plates coated with different concentrations of fibronectin (0, 1, 2.5, 5, and 10 μg/mL). Accutase digestion was performed after 7 days of culture. Cells were counted by trypan staining. Fibronectin-coated group with the strongest amplification ability and the oligodendrocyte precursor cells without fibronectin-coated group were selected for further tests. The migration ability of the two groups of cells was detected by Transwell. Flow cytometry was used to detect the expression of Olig2, Sox10, and PDGFR-α. Oligodendrocyte precursor cells were induced to differentiate into oligodendrocytes for 3 weeks, and the expression of Galc in differentiated cells was detected by immunofluorescence staining.  RESULTS AND CONCLUSION: (1) Human neural stem cells grew in suspension spheres. Flow cytometry showed that human neural stem cells highly expressed Nestin, Sox2, Vimentin, CD133, and Musashi. (2) The cell bodies of oligodendrocyte precursor cells induced by human neural stem cells were round or oval, with strong refractive nature and bipolar or tertiary protrusions. Compared with the 0 μg/mL fibronectin coating group, there was a significant difference in the amplification ability of oligodendrocyte precursor cells in the 2.5, 5, and 10 μg/mL fibronectin coating groups (P < 0.05). The amplification ability of oligodendrocyte precursor cells was the strongest when the fibronectin concentration was 10 μg/mL. (3) Flow cytometry results showed that the oligodendrocyte precursor cell markers Olig2, Sox10, and PDGFR-α were highly expressed in the 0 and 10 μg/mL fibronectin coating groups, and there was no significant difference between the two groups (P > 0.05). (4) Transwell chamber assay results showed that compared with the 0 μg/mL fibronectin-coated group, the migration ability of oligodendrocyte precursor cells in the 10 μg/mL fibronectin-coated group was increased (P < 0.01). (5) After 3 weeks of differentiation into oligodendrocytes, oligodendrocyte precursor cells showed complex morphology with multiple branches, grids or membrane sheets. Immunofluorescence staining results showed that there was no statistical difference in the Galc positive rate of oligodendrocytes between the two groups (P > 0.05). These findings indicate that when the concentration of fibronectin coated well plate is 10 μg/mL, the proliferation and migration of oligodendrocyte precursor cells are the strongest, but it does not affect the expression of oligodendrocyte precursor cells-specific markers Olig2, Sox10, and PDGFR-α and their differentiation into oligodendrocytes.  Figures and Tables | References | Related Articles | Metrics

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Nuclear factor I-C regulates differentiation of human stem cells from apical papilla Wu Yue, Zhu Yongna, Ge Xiang, Liu Fan, He Zeyu, Liu Xi 2025, 29 (31):  6667-6673.  doi: 10.12307/2025.649 Abstract ( 44 )   PDF (2470KB) ( 102 )   Save BACKGROUND: Overexpression of the nuclear factor I-C gene in vitro promotes the differentiation of human stem cells from apical papilla, as does the activation of the Wnt/β-catenin signaling pathway. Moreover, nuclear factor I-C regulates the Wnt/β-catenin pathway in mesenchymal stem cells. However, whether nuclear factor I-C can affect cell differentiation by activating the Wnt/β-catenin pathway in human stem cells from apical papilla has not been reported. OBJECTIVE: To investigate the role of nuclear factor I-C in the Wnt/β-catenin signaling pathway in regulating the differentiation of human stem cells from apical papilla.   METHODS: Human stem cells from apical papilla were cultured by the slide-covered tissue block method and lentiviral transfection overexpressing the nuclear factor I-C gene. (1) A control group, an empty viral vector group, and an overexpressed nuclear factor I-C gene group were set up. The expression of β-Catenin, LRP5, and TCF7L2 was detected by Western blotting. (2) The control group, empty viral vector group, overexpressed nuclear factor I-C gene group, and overexpressed nuclear factor I-C gene+DKK-1 (Wnt pathway inhibitor) group were set up. Alkaline phosphatase staining and activity quantification were performed after 7 days of osteogenic induction. qPCR and Western blotting were performed to detect the expression of Runt-related transcription factor 2, dentin salivary phosphoprotein, osteocalcin mRNA, and protein after 14 days of osteogenic induction. Alizarin Red staining was used to observe the formation of mineralized nodules.  RESULTS AND CONCLUSION: (1) Compared with the control and empty viral vector groups, the expression of Wnt/β-Catenin pathway-related proteins β-Catenin, LRP5, and TCF7L2 in human apical dentin papilla stem cells was significantly increased in the overexpressed nuclear factor I-C gene group (P < 0.01). (2) Compared with the control and empty viral vector groups, the expression of alkaline phosphatase and osteocalcin in human apical dentin papilla stem cells was significantly increased (P < 0.01); the expression levels of Runt-related transcription factor 2, dentin salivary phosphoprotein, osteocalcin mRNA and protein were significantly higher (P < 0.01), and the number of mineralized nodules was significantly increased (P < 0.01) in the overexpressed nuclear factor I-C gene group. (3) Compared with the overexpressed nuclear factor I-C gene group, the alkaline phosphatase activity and the expression of Runt-related transcription factor 2, dentin salivary phosphoprotein, osteocalcin mRNA and protein expression levels were significantly down-regulated (P < 0.05), and the number of mineralized nodules was significantly reduced (P < 0.05) in human stem cells from apical papilla of the overexpressed nuclear factor I-C gene+DKK-1 group. The results show that nuclear factor I-C can activate the Wnt/β-catenin signaling pathway in human stem cells from apical papilla and mediate the osteogenic/odontogenic differentiation of human stem cells from apical papilla. Figures and Tables | References | Related Articles | Metrics

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Inhibitory effects of sinomenine hydrochloride in T-cell acute lymphoblastic leukemia CEM cells and transcriptomic analysis Kang Linzhi, Liu Zhenshuai, Wei Jiaxu, Chang Na, Zhu Dacheng 2025, 29 (31):  6674-6680.  doi: 10.12307/2025.661 Abstract ( 61 )   PDF (2701KB) ( 107 )   Save BACKGROUND: Sinomenine hydrochloride has anti-tumor effects, but it is rarely reported in T-cell acute lymphoblastic leukemia.  OBJECTIVE: To investigate the inhibitory effect of sinomenine hydrochloride on CEM cells in acute T lymphoblastic leukemia.  METHODS: Different concentrations (0.5, 1, 2 and 4 mmol/L) of sinomenine hydrochloride were used to act on CEM cells. CCK-8 assay was used to detect the inhibition rate of cell proliferation and calculate the IC50. Inverted microscope and Giemsa staining were used to observe the changes of CEM cells. The RNA sequencing was performed to analyze the differential gene expression and biological information. Combined with transcriptome sequencing analysis results, flow cytometry was used to detect the apoptosis rate of CEM cells after treatment with of different concentrations (1, 2, and 4 mmol/L) of sinomenine hydrochloride. Western blot assay was used to detect the expression of Bcl-2, Bax, and Caspase-9 proteins in CEM cells after treatment with of different concentrations (1, 2, and 4 mmol/L) of sinomenine hydrochloride.   RESULTS AND CONCLUSION: (1) Sinomenine hydrochloride inhibited the growth of CEM cells in dose and time-dependent manner. (2) After dosing, the number of CEM cells decreased and pyknosis appeared. (3) RNA sequencing revealed 53 differential expressed genes. Gene Ontology was significantly enriched in cellular process, cellular anatomical entities, and binding. Signaling pathway analysis related to tumor was apoptosis. (4) Sinomenine hydrochloride induced the apoptosis of CEM cell in a concentration-dependent manner. (5) Sinomenine hydrochloride could promote the expressions of Bax and Caspase-9, but restrain the expression of Bcl-2 in CEM cells. Therefore, sinomenine hydrochloride can induce apoptosis in CEM cells and suppress cell proliferation, maybe via up-regulation of the protein levels of Bax and caspase-9 and down-regulation of the protein level of Bcl-2.  Figures and Tables | References | Related Articles | Metrics

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Significance of interleukin-18 expression in bone marrow and peripheral blood of rats exposed to hypoxia Li Jinjie, Xiao Jingxue, Li Nan, Song Zhen, Zhou Yanyun, Ma Jie 2025, 29 (31):  6681-6687.  doi: 10.12307/2025.557 Abstract ( 73 )   PDF (1327KB) ( 69 )   Save BACKGROUND: The level of peripheral erythrocytes in rats is significantly increased under hypoxia exposure, and the proliferation of nucleated erythrocytes in the bone marrow may be one of the direct causes of the increase in peripheral erythrocytes. Previous studies have focused on the effects of factors such as erythropoietin and hypoxia-inducible factor, but little research has been done on related factors such as inflammation and immunity. OBJECTIVE: To study the expression of interleukin-18 in bone marrow nucleated erythrocytes, bone marrow supernatant and peripheral blood of rats after hypoxia exposure, and to explore the possible role of interleukin-18 in the pathogenesis of chronic mountain sickness.  METHODS: Sixteen healthy male SD rats were randomly divided into two groups: the experimental group was kept in a hypobaric oxygen chamber at a simulated altitude of 5 000 m for 28 days, and the control group was kept in a laboratory at an altitude of 2 260 m for 28 days. The blood routine tests of the two groups of rats were performed. The proportion of CD71+ nucleated erythrocytes in the bone marrow of the two groups of rats was determined by flow cytometry. The expressions of interleukin 18 mRNA and protein in CD71+ nucleated erythrocytes in the bone marrow of the two groups of rats were determined by RT-qPCR and western blot assay. The expressions of interleukin 18 protein in the sternum of the two groups of rats were determined by immunofluorescence. The levels of interleukin 18 in the peripheral blood and bone marrow supernatant of the two groups of rats were determined by ELISA.  RESULTS AND CONCLUSION: (1) The indexes of erythrocyte count, hemoglobin, hematocrit, and mean hemoglobin content in peripheral blood of the experimental group were higher than those of the control group (P < 0.05). (2) The proportion in bone marrow CD71+ erythroblasts was significantly higher in the experimental group than that in the control group (P < 0.05). (3) RT-qPCR results showed that the expression of interleukin 18 mRNA in CD71+ nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group (P < 0.05). (4) Western blot assay results showed that the expression of interleukin 18 protein in CD71+ nucleated erythrocytes in the bone marrow of rats in the experimental group was significantly higher than that in the control group (P < 0.05). (5) The immunofluorescence results showed that the expression of interleukin 18 protein in the sternum of rats in the experimental group was significantly higher than that in the control group (P < 0.05). (6) ELISA results exhibited that the level of interleukin 18 in the serum of rats of the experimental group was higher than that in the control group (P < 0.05), but the level of interleukin 18 in the bone marrow supernatant of rats in the experimental group was lower than that in the control group (P < 0.05). The results indicate that the increased expression of interleukin 18 in bone marrow CD71+ erythroblasts and peripheral blood of rats under hypobaric hypoxia may be involved in the proliferation of erythroblasts in bone marrow. Figures and Tables | References | Related Articles | Metrics

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Lycium barbarum polysaccharide intervenes in SH-SY5Y cell injury induced by beta-amyloid protein 1-42: protective effect of mitochondrial autophagy Su Qin, Jia Siwei, Guo Minfang, Meng Tao, Li Yanbing, Mu Bingtao, Song Lijuan, Ma Cungen, Yu Jiezhong 2025, 29 (31):  6688-6696.  doi: 10.12307/2025.545 Abstract ( 86 )   PDF (2062KB) ( 158 )   Save BACKGROUND: Neurodegenerative diseases are closely related to the imbalance of mitochondrial autophagy regulation. Previous studies by the research group have shown that lycium barbarum polysaccharide has neuroprotective effects, but whether it can improve the damage of SH-SY5Y cells induced by β-amyloid protein 1-42 by regulating mitochondrial autophagy is still unclear.  OBJECTIVE: To explore the protective effect and mechanism of Lycium barbarum polysaccharide on SH-SY5Y cells induced by β-amyloid protein 1-42.   METHODS: An Alzheimer's disease cell model was established by inducing SH-SY5Y cells with β-amyloid protein 1-42, and then intervening with Lycium barbarum polysaccharide. SH-SY5Y cells were divided into three groups: control group, β-amyloid protein 1-42 group (20 μmol/L β-amyloid protein 1-42 for 24 hours), and Lycium barbarum polysaccharide group (1 g/L Lycium barbarum polysaccharide was added 1 hour in advance to form a protective effect, and then 20 μmol/L β-amyloid protein 1-42 was added to intervene with Lycium barbarum polysaccharide for 24 hours). CCK8 assay was used to detect cell viability. Mitochondrial membrane potential was detected by JC-1. TUNEL staining was used to detect cell apoptosis. Immunofluorescence and western blot assay were used to detect the expression of synaptic, apoptosis, and mitophagy-related indicators.   RESULTS AND CONCLUSION: (1) Compared with the control group, the cell viability of the β-amyloid protein 1-42 group decreased (P < 0.05); cell apoptosis rate increased (P < 0.05); mitochondrial membrane potential decreased (P < 0.05); the expressions of pro-apoptotic proteins Bax and Caspase3 increased (P < 0.05); the expression of anti-apoptotic protein Bcl-2 decreased (P < 0.05); the expression levels of synaptic-related proteins Syn and PSD-95 decreased (P < 0.05); the expression levels of mitochondrial autophagy-related proteins Pink1, LC3A/B, Parkin, and Beclin-1 decreased (P < 0.05); and the expression of P62 increased (P < 0.05). (2) Compared with the β-amyloid protein 1-42 group, the cell viability in the Lycium barbarum polysaccharide group was increased (P < 0.05); the apoptosis rate was decreased (P < 0.05); the mitochondrial membrane potential was increased (P < 0.05); the expression levels of Bax and Caspase3 were decreased (P < 0.05); the expression of Bcl-2 was increased (P < 0.05); the expressions of Syn and PSD-95 were increased (P < 0.05); the expression levels of Pink1, LC3A/B, Parkin, and Beclin-1 were increased (P < 0.05), and the expression of P62 was decreased (P < 0.05). These findings indicate that Lycium barbarum polysaccharide may inhibit β-amyloid protein 1-42-induced damage to SH-SY5Y cells by regulating mitophagy, reduce cell apoptosis, and increase neuronal synaptic plasticity.  Figures and Tables | References | Related Articles | Metrics

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Bioinformatics identification and validation of mitochondrial genes related to acute myocardial infarction Tian Yushi, Fu Qiang, Li Ji 2025, 29 (31):  6697-6707.  doi: 10.12307/2025.614 Abstract ( 383 )   PDF (5058KB) ( 197 )   Save BACKGROUND: Mitochondria are of great significance in the injury and repair of acute myocardial infarction, so it is of great clinical significance to explore the pathogenesis and progression of acute myocardial infarction based on mitochondrial genes.  OBJECTIVE: To explore whether mitochondrial genes can be used as reliable biomarkers to assess the progression of acute myocardial infarction.  METHODS: The acute myocardial infarction dataset was downloaded from the Gene Expression Omnibus GSE66360 and GSE12288, and the human mitochondrial gene set was obtained from the mitochondrial protein database. Differential gene analysis and weighted correlation network analysis were performed on the acute myocardial infarction dataset GSE66360, and the genes were obtained for protein-protein interaction analysis, gene ontology, and kyoto encyclopedia of genes genomes analysis. The intersection genes were intersected with human mitochondrial genes to obtain differential mitochondrial genes. Gene set enrichment analysis and immune infiltration analysis were performed on differential mitochondrial genes. Receiver operating characteristic curve analysis was performed in the external dataset GSE12288 to verify the expression characteristics of the differential mitochondrial genes.  RESULTS AND CONCLUSION: (1) A total of 548 differential genes were obtained for acute myocardial infarction. Differential gene analysis and weighted gene co-expression network analysis showed that the Blue module contained the most genes (4 992). There were 116 intersecting genes, among which tumor necrosis factor, interleukin-1B, interleukin-6, Toll-like receptor 4, and interleukin-10 were the core genes. (2) Gene ontology analysis showed that the biological process mainly involved inflammatory response, positive regulation of tumor necrosis factor production, cell surface receptor signaling pathway. Cell composition mainly involved tertiary granular membrane, plasma membrane outer layer, plasma membrane, etc. Molecular function mainly involved immunoglobulin G binding, transmembrane signal receptor activity, chemokine activity, etc. Kyoto encyclopedia of genes genomes analysis showed that these genes were mainly involved in tumor necrosis factor, interleukin-17, and nuclear factor kappa-light-chain-enhancer of activated B cell pathways. (3) A total of eight differential mitochondrial genes were obtained, and four characteristic genes were screened after least absolute shrinkage and selection operator and proportional hazards model analysis, including phorbol-12-myristate-13-acetate-induced protein1, BCL2 related protein A1, solute carrier family 25 member 37, and deoxyribonucleic acid polymerase beta, and corresponded to tumor protein 53, oxidative phosphorylation, sulfur metabolism, and glycerol phospholipid metabolism pathways, respectively. (4) Receiver operating characteristic curve analysis showed that the four characteristic genes were all of diagnostic significance, and were negatively correlated with resting dendritic cells and naïve B cells. (5) These results suggest that the expression characteristics of phorbol-12-myristate-13-acetate-induced protein1, BCL2 related protein A1, solute carrier family 25 member 37, and deoxyribonucleic acid polymerase beta can be used as potential biomarkers to predict mitochondrial function in acute myocardial infarction, which can further improve the accuracy of prediction of acute myocardial infarction. Figures and Tables | References | Related Articles | Metrics

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Biological mechanism of mitophagy in idiopathic pulmonary fibrosis Xie Yizi, Lin Xueying, Zhang Xinxin, Huang Xiufang, Zhan Shaofeng, Jiang Yong, Cai Yan 2025, 29 (31):  6708-6716.  doi: 10.12307/2025.672 Abstract ( 105 )   PDF (5585KB) ( 268 )   Save BACKGROUND: Mitophagy is closely associated with the development of idiopathic pulmonary fibrosis, but its mechanism remains unclear.  OBJECTIVE: To investigate the biological mechanism of mitophagy in idiopathic pulmonary fibrosis and provide ideas for the risk prediction of idiopathic pulmonary fibrosis and subtype differentiation.   METHODS: The mitophagy-related genes in idiopathic pulmonary fibrosis were obtained through GEO and Reactome Pathway databases. The mitophagy-related characteristic genes in idiopathic pulmonary fibrosis were screened based on intergroup differences and random forest model. GO functional enrichment analysis and KEGG, Reactome with WIKI pathway enrichment analyses were performed by g:Profiler database. Mitophagy subtypes in idiopathic pulmonary fibrosis were distinguished by consensus clustering method and immune infiltration analysis was performed. The mitophagy-related key gene was screened. Finally, the predictive value of mitophagy-related key gene for the risk of idiopathic pulmonary fibrosis was quantified by alignment diagram and the correlation between mitophagy-related key gene and clinical characteristics of idiopathic pulmonary fibrosis was explored.  RESULTS AND CONCLUSION: (1) A total of 13 genes related to mitophagy in idiopathic pulmonary fibrosis were identified and 5 characteristic genes were screened, containing PINK1, RPS27A, SRC, HIF1A, and CDH6. (2) GO analysis was mainly involved in ubiquitin protein ligase binding, and cellular response to hypoxia. Pathway enrichment analysis was mainly involved in PINK1-PRKN mediated mitophagy, NOTCH signaling pathway, signaling by EGFR and angiogenesis. (3) HIF1A had significant expression differences between subtypes, which might serve as a key gene for the differentiation of mitophagy subtypes of idiopathic pulmonary fibrosis. (4) Immune infiltration analysis suggested that myeloid-derived suppressor cell, neutrophil and type 1 T helper cell might have infiltration differences between subtypes, while HIF1A was positively correlated with multiple immune cells. (5) Alignment diagram suggested that the risk of idiopathic pulmonary fibrosis might be predicted by the expression level of HIF1A. (6) Clinical characteristics analysis indicated patients with high expression of HIF1A might have poorer lung function and more severe fibrosis. It is concluded that PINK1, RPS27A, SRC, HIF1A, and CDH6 may influence the development of idiopathic pulmonary fibrosis through mitophagy, in which HIF1A may serve as a key gene for risk prediction with clinical subtype differentiation and HIF1A is strongly associated with the lung function of patients.  Figures and Tables | References | Related Articles | Metrics

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Development of patch clamp technology in the past 10 years: visual analysis based on CiteSpace and VOSviewer Guo Haizhen, Cong Zidong, Zhao Yuke, Li Xiaofeng, Yu Lu, Qian Shule, Wang Runying, Du Wuxun 2025, 29 (31):  6717-6726.  doi: 10.12307/2025.615 Abstract ( 263 )   PDF (5182KB) ( 168 )   Save BACKGROUND: Patch clamp technique has been developed for more than 40 years as the “gold standard” for the study of ion channels. However, the research content of scientific research institutions is relatively independent, and the existing research results are not systematically summarized, which leads to the phenomenon of high repeatability and weak innovation in the existing research. Therefore, it is urgent to make a comprehensive review of patch clamp technology to clarify the current research status, hot spots, and future development direction. OBJECTIVE: To summarize the research status and development trend of patch clamp technique in recent 10 years. METHODS: Publications on patch clamp technology from 2013 to 2023 were collected using the Web of Science core collection database. CiteSpace and VOSviewer software were used to quantify the number of publications and analyze the network of literature entries, including countries, institutions, journals, authors, keywords, highly cited literature, and co-cited references. RESULTS AND CONCLUSION: (1) In recent 10 years, the research in the field of patch clamp technology has gradually entered a stage of stable development. (2) China and the United States are the leading countries in this regard. The Chinese Academy of Sciences is an institution with core influence. Journal of Neuroscience is the main publication. Park, Won Sun team (Jeonbuk National University) and Chu, Li team (Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease) have made outstanding contributions in this field, but there is less collaboration and communication between the teams and no network cooperation model has been formed. (3) Patch clamp technology is mainly used in the electrophysiological characteristics of the nervous system and the pathological mechanism of the disease, which is the focus of researchers’ continuous attention. (4) In the study of electrophysiological characteristics of cardiovascular system and its pathological mechanism, the electrophysiological characteristics of primary cardiomyocytes and induced pluripotent stem cell-derived cardiomyocytes and the pathological mechanism of atrial fibrillation, cardiotoxicity, sudden cardiac death, hypertension and other cardiovascular diseases have been the focus of research in recent years. (5) In the application of patch clamp technology combined with other biotechnology, it will be an important research direction to focus on the cross fusion with optogenetics, two-photon calcium imaging and other technologies. (6) In the research of drug screening and identification of therapeutic targets, especially the research of patch clamp technology and traditional Chinese medicine compound, it will become a great help in the future research of component traditional Chinese medicine.  Figures and Tables | References | Related Articles | Metrics

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Optimal parameters for physical interventions in bone marrow mesenchymal stem cell differentiation Liu Xun, Ouyang Hougan, Pan Rongbin, Wang Zi, Yang Fen, Tian Jiaxuan 2025, 29 (31):  6727-6732.  doi: 10.12307/2025.622 Abstract ( 72 )   PDF (1227KB) ( 60 )   Save BACKGROUND: In recent years, it has been found that physical interventions play a significant role in influencing proliferation, differentiation, and migration of bone marrow mesenchymal stem cells. However, the current physical intervention still exists such as basic research data to be strengthened, unified parameter standards need to be further improved and other shortcomings.  OBJECTIVE: To review the effects of physical interventions on the differentiation of bone marrow mesenchymal stem cells.  METHODS: PubMed and CNKI databases were searched for relevant articles using “bone marrow mesenchymal stem cells (BMSC), bone marrow stromal cells, osteogenesis differentiation, chondrocytes differentiation, electrical stimulation, mechanical stimulation, hypoxia, electromagnetic fields, low intensity pulsed ultrasound” as English and Chinese search terms. A total of 58 articles were selected for review.   RESULTS AND CONCLUSION: (1) Physical interventions have been applied to regulate the proliferation and differentiation of bone marrow mesenchymal stem cells by altering specific microenvironments, but the parameters have not yet been unified. The future investigation should further optimize and explore the best parameters and conditions of action of the relevant physical factors on the role of bone marrow mesenchymal stem cell proliferation and differentiation. (2) It is difficult to carry out the application of certain special physical environmental conditions through low-cost conventional means, pending subsequent research and development to further reduce the difficulty of constructing special physical conditions. (3) The use of physical factors to rationally intervene in differentiation and proliferation of bone marrow mesenchymal stem cells has not yet been widely applied in the clinic, and further research is needed to promote clinical translation in the future. Figures and Tables | References | Related Articles | Metrics

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Research on hair follicle organoids: current status, challenges and prospects Wang Zhao, Gong Lin, Piao Yongjun 2025, 29 (31):  6733-6742.  doi: 10.12307/2025.536 Abstract ( 357 )   PDF (1749KB) ( 294 )   Save BACKGROUND: In vitro reconstruction of hair follicles depends on the self-assembly behavior of dermal papilla cells and keratinocytes during three dimensional co-culture, which is very similar to the development of hair follicle embryos. Therefore, hair follicle organoids can be used as a good model in vitro for basic research of hair follicle regeneration. Currently, wholly humanized follicle organoids cultured by biomimetic system have been successfully transplanted into animals. Research on hair follicle organoids makes it possible to regenerate hair follicles, but there is no uniform conclusion on the construction method, and there are still many challenges. OBJECTIVE: To review the current research progress of hair follicle organoids, summarize their culture methods and characterization, and expound their application prospects, so as to provide reliable basis for subsequent research, in order to promote its clinical transformation in tissue engineering and alopecia treatment. METHODS: CNKI and PubMed databases were searched by a computer, using “hair follicle regeneration, hair regeneration, organoid” as Chinese search terms and “hair growth, hair loss, hair regeneration, hair follicle, dermal papilla cell, organoid” as English search terms. The domestic and foreign literature on hair follicle organoids was reviewed and a total of 67 articles were included for follow-up analysis. RESULTS AND CONCLUSION: (1) Dermal papilla cells and keratinocytes from different sources can be used to construct hair follicle organoids in vitro to obtain mouse-derived, human-mouse chimeric and human-derived hair follicle organoids, which have been successfully used in rodent transplantation models. (2) A variety of programming methods, such as electrical stimulation, addition of recombinant protein, and dissociation of cell gene expression, can be used to promote hair follicle organoid such as hair follicle germ formation and hair shaft elongation. Simultaneously, the application of various 3D printing technologies has achieved controllable hair follicle organoid to the size of the quantity production, which greatly improves the production efficiency. (3) When melanocytes are added to the dissociated cell co-culture system, the problem of pigment deficiency in new hair follicles may be solved. When human umbilical vein endothelial cells are added, the new blood vessels in the cell aggregates can improve their nutrient supply and reduce necrosis in the central area. (4) As the technology of engineered hair follicle organoid gradually maturates, hair follicle organoids constructed from patient's autologous cells may be used for individualized treatment of severe alopecia. Figures and Tables | References | Related Articles | Metrics

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Effects and mechanisms of exosomal miRNA in treatment of multiple myeloma Zhao Yihan, Sun Xuhang, Zhao Lin, Jiang Shiqing 2025, 29 (31):  6743-6752.  doi: 10.12307/2025.539 Abstract ( 134 )   PDF (1906KB) ( 283 )   Save BACKGROUND: Multiple myeloma is one of the most common hematological malignancies, which is difficult to treat, prone to relapse, and resistant to drugs. The endogenous transport system of exosomes plays a communication role by affecting the exchange of functional components between cells. Among them, miRNA is more easily packaged in exosomes due to its small size, so it affects cell function in many ways and over a wide range. OBJECTIVE: To summarize the mechanism of exosomal miRNA in multiple myeloma and to propose potential targets.  METHODS: The terms “multiple myeloma, bone marrow mesenchyml stem cell, fibroblasts, peripheral blood, complication, progression, drug resistance, exosomal miRNA” were used as English search terms in the PubMed database. The time frame of the search was from the inception to June 2024. After reading the titles and abstracts, we excluded irrelevant or repetitive literature, and finally included 81 papers for review. RESULTS AND CONCLUSION: (1) Multiple myeloma cells participate in multiple myeloma bone lesions by regulating the balance of osteogenic and osteoclast functions through various miRNA mediated exosomes, regulating erythrocyte calcium ion efflux channels to participate in the occurrence of hypercalcemia, promoting renal epithelial mesenchymal transition leading to renal fibrosis and renal dysfunction, and upregulating bone marrow-derived mononuclear suppressor cells to promote suppression of the immune microenvironment. In addition, miRNAs in the exosomes of multiple myeloma cells are also involved in the occurrence and development of immunotherapy resistance, as well as pathological processes such as angiogenesis, cell proliferation, and cell aging. (2) Both bone marrow mesenchymal stem cells and tumor-associated fibroblasts can affect the proliferation, metastasis, and apoptosis of multiple myeloma cells through exosomal miRNA, interfere with angiogenesis, and regulate the resistance of chemotherapy drugs. (3) Peripheral blood circulating exosomal miRNAs, as cutting-edge noninvasive biomarkers, can play a key role in judging the stage and progression of multiple myeloma disease, predicting patient formation and prognosis, and evaluating drug sensitivity and drug resistance. (4) Multiple myeloma exosomes long non-coding RNA, circular RNA, miRNA, mRNA and target gene can form different combinations, and the flexible construction of new biological axes and biomolecular networks is in line with the development concept of holistic medicine. (5) Exosome miRNA has great development potential as a therapeutic target for predictive biomarkers and new drug research and development. How to maximize the use of exosome miRNA and how to accelerate the clinical transformation of related scientific research results deserve further investigation. Figures and Tables | References | Related Articles | Metrics

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Anti-tumor effects of engineered exosomes for targeted drug delivery Dai Yueyou, Guo Dandan, Wang Qianqian, Wang Baiyan, Feng Shuying 2025, 29 (31):  6753-6764.  doi: 10.12307/2025.671 Abstract ( 140 )   PDF (1590KB) ( 1348 )   Save BACKGROUND: At present, chemotherapeutic drugs are mainly used for the treatment of tumors, but there are problems such as drug resistance and adverse reactions. The exosome drug delivery system not only avoids the toxicity of synthetic nanoparticles, but also increases the bioavailability and biocompatibility of the drugs. It can be modified by biological, physical, and chemical methods to form a new type of nano-drug delivery platform. OBJECTIVE: To review the construction strategy of exosome drug delivery system, the application status of exosome drug delivery system in tumor diseases and the current challenges.  METHODS: PubMed and CNKI were searched with “exosomal, tumor, microvesicle, extracellular vesicles, engineered, therapeutics, characterization, isolation, drug delivery, targeting, modification strategies, physics, chemistry, biology” as English search terms and “exosomes, drug delivery, tumor” as Chinese search terms. A total of 132 articles were included for in-depth induction and discussion. RESULTS AND CONCLUSION: (1) The technical methods of exosome extraction, including ultracentrifugation, filtration, and kit extraction, can efficiently isolate exosomes, but the process is complicated and time-consuming, and large-scale extraction of exosomes cannot be achieved. (2) Engineered exosomes can be divided into four categories: gene editing engineering, which improves function through genetic modification; endogenous engineering, using inflammatory factors and other pretreatment to enhance drug delivery; exogenously engineered to encapsulate drugs directly in exosomes; hybrid engineering, combining exosomes with lipid nanoparticles to form new particles. Some have entered clinical trials for cancer treatment, but most are at an early stage. In contrast, genetically engineered exosomes are considered as an important direction for future drug delivery due to their high targeting and customization potential. (3) There are still many limitations to realize the clinical transformation of engineered exosomes. At the technical level, large-scale production, purification, and drug loading efficiency are urgent to be solved. In production, high cost and batch stability affect its popularity. In terms of safety, immunogenicity and potential toxicity need to be comprehensively evaluated. Furthermore, the imperfect regulatory policies and the complexity of the approval process also constitute obstacles to its clinical translation. (4) In the future, it is necessary to promote the clinical translation process through technical innovation, cost control, safety improvement, and policy improvement.  Figures and Tables | References | Related Articles | Metrics

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Plant-derived exosome-like nanovesicles stimulate osteoblasts, inhibit osteoclasts, and promote osteogenesis Yao Wenxin, Wang Yi, Cai Lin, Feng Xiaobo 2025, 29 (31):  6765-6771.  doi: 10.12307/2025.541 Abstract ( 357 )   PDF (1012KB) ( 693 )   Save BACKGROUND: Osteoporosis affects the quality of life of patients and is prone to pathological fractures, and plant-derived exosome-like nanovesicles play an important role in regulating bone balance in patients with osteoporosis. OBJECTIVE: To review the research status and prospect of different plant-derived exosome-like nanovesicles in the treatment of osteoporosis.  METHODS: Relevant literature in PubMed, Web of Science, and CNKI databases were searched by computer. Search time was from January 1995 to March 2024. The Chinese and English search terms were “osteoporosis, plant-derived exosome-like nanovesicles, exosomes, osteoblasts, osteoclasts.” Finally, 53 articles were included and analyzed.  RESULTS AND CONCLUSION: Plant-derived exosom-like nanovesicles have the advantages of low biocompatibility, low toxicity, and natural targeting. These properties not only ensure its stable presence and effective effect in the body, but also avoid unnecessary immune responses, laying the foundation for the design of long-term treatment strategies. Plant-derived exosome-like nanovesicles can be anti-osteoporosis by stimulating osteoblast proliferation, inhibiting osteoclast differentiation, and promoting osteo-inhibition osteoclasts. In addition, some plant-derived exosome-like nanovesicles may be widely used in the diagnosis and treatment of osteoporosis in the future as novel tracer targets and treatment options due to their bone-targeting. Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells and their derived extracellular vesicles target macrophages to intervene in autoimmune diseases Yao Lanxuan, Wang Xuefei, Liu Yang, Yang Yujia, Zhao Yi, Qi Fangfang, Li Yinghui 2025, 29 (31):  6772-6781.  doi: 10.12307/2025.712 Abstract ( 54 )   PDF (1660KB) ( 408 )   Save BACKGROUND: Macrophages are an important part of innate immunity. When the internal environment of the body changes, macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function. Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body, which have the functions of intercellular signaling and immune regulation. Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases. OBJECTIVE: To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages, as well as the related research progress of engineered extracellular vesicles in this field. METHODS: The first author searched the relevant literature published in PubMed, CNKI and other databases until June 2024. Chinese search terms were “mesenchymal stem cells, extracellular vesicles, exosomes, apoptotic bodies, apoptotic vesicles, macrophage polarization, M1 polarization, M2 polarization, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, inflammatory bowel disease, autoimmune dacryadenitis, engineered extracellular vesicles, engineering exosomes, drug delivery.” English search terms were “macrophage polarization, M1 macrophage, M2 macrophage, autoimmune disease, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, autoimmune dacryadenitis, inflammatory bowel disease, mesenchymal stem cells, extracellular vesicles, engineered extracellular vesicles, engineering exosomes, drug delivery.” The title and abstract of each paper were read and initially screened. Finally, 70 articles were selected for induction and analysis. RESULTS AND CONCLUSION: (1) Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins. (2) Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome. (3) Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy. (4) Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages. (5) Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN, NOTCH, nuclear factor κB, Toll-like receptors, PI3K/AKT and other pathways. (6) Engineered extracellular vesicles can achieve non-invasive targeted drug delivery, prolong the half-life of drugs, promote the oral administration of exosomes, reduce allograft reaction, improve the bioavailability of Chinese herbs and overcome the blood-brain barrier, opening up a new path for drug delivery. Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells and extracellular vesicles in repair of endometrial injury Xiong Zhenghua, Zhou Jianghong, Shen Yi, Han Xuesong 2025, 29 (31):  6782-6791.  doi: 10.12307/2025.660 Abstract ( 90 )   PDF (1636KB) ( 245 )   Save BACKGROUND: Endometrial injury is a common benign disease in women of reproductive age, which seriously affects their fertility and reproductive health. In recent years, mesenchymal stem cells and their secreted extracellular vesicles, as a new therapeutic strategy, have received much attention in the repair of endometrial injury. OBJECTIVE: To review the application of mesenchymal stem cells and their secreted extracellular vesicles in the treatment of endometrial injury, to comprehensively understand the therapeutic mechanism and efficacy of endometrial injury, and to discuss the potential and challenges of the application of mesenchymal stem cells and their secreted extracellular vesicles in the treatment of endometrial injury, in order to provide theoretical basis for further basic and clinical research.  METHODS: Literature searches were conducted in the China National Knowledge Infrastructure (CNKI), Chinese Medical Full-text Database, and PubMed electronic databases using search terms “mesenchymal stem cells, extracellular vesicles derived from mesenchymal stem cells, exosome, endometrial injury, intrauterine adhesion, Asherman’s syndrome” in Chinese and English. Articles were selected through manual screening to exclude duplicates and irrelevant studies, resulting in the inclusion of 87 articles.   RESULTS AND CONCLUSION: Mesenchymal stem cells and their secreted extracellular vesicles can participate in endometrial damage repair through a variety of molecular mechanisms, such as anti-fibrosis, promoting angiogenesis and cell proliferation, cell homing, immune regulation, and endometrial receptibility regulation. A large number of research results have been achieved in cell and animal experiments, and preliminary results of clinical studies have also achieved certain curative effects, including increased endometrial thickness, improved menstrual volume and fertility. However, difficulty and challenges persist in the application of mesenchymal stem cells and their secreted extracellular vesicles for endometrial injury treatment. During treatment, it is necessary to enhance the quality and stability of mesenchymal stem cells and their secreted extracellular vesicles, as well as clarifying their roles in processes such as cell proliferation, migration, and differentiation. Moreover, large-scale multicenter clinical trials are needed to validate the long-term safety and efficacy of mesenchymal stem cells and their secreted extracellular vesicles in endometrial repair, and to determine optimal dosages and administration routes. Continuous advancements in scientific technologies and the auxiliary application of bioengineering materials offer hope for developing more effective and safer therapeutic methods for endometrial injury treatment and the above problems will be solved in the future.   Figures and Tables | References | Related Articles | Metrics

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Effect and mechanism of perinatal mesenchymal stem cells and their combination with hydrogels in treatment of intrauterine adhesions Zhong Min, Wang Cheng, Fan Zhenhai, Li Linyan, Yu Limei 2025, 29 (31):  6792-6799.  doi: 10.12307/2025.552 Abstract ( 62 )   PDF (2091KB) ( 72 )   Save BACKGROUND: The therapeutic efficacy of moderate or severe intrauterine adhesions is poor. After synechotomy, the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age, which is an urgent problem to be solved in clinical practice. Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages, and they have received particular attention on the treatment of intrauterine adhesions.  OBJECTIVE: To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions. METHODS: Search terms were “mesenchymal stem cells, perinatal period, hydrogel, intrauterine adhesions, endometrial injury” in Chinese and English. Relative articles published from 2010 to 2024 were retrieved on PubMed, CNKI, and WanFang databases. As a result, 80 articles that met the inclusion criteria were reviewed and analyzed.  RESULTS AND CONCLUSION: (1) Similar to other sources of mesenchymal stem cells, perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions, and can meet the needs of autologous and allogeneic transplantation. (2) The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord, amniotic membrane, placenta, and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation, cellular immunity, paracrine, and promoting endometrial regeneration and angiogenesis, immune regulation, anti-endometrial cell apoptosis, inhibition of epithelial-mesenchymal transition, and anti-fibrosis. (3) Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions. On the basis of the effect of mesenchymal stem cells, the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells, promoting cell migration and adhesion, which is helpful to better promote endometrial regeneration and anti-fibrosis. It is beneficial to repair the damaged endometrial, improve endometrial receptivity and fertility, and reduce the recurrence rate. (4) A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions. Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels, and other effects and molecular mechanism of combined treatment of intrauterine adhesions.  Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells for treatment of aplastic anemia: inhibiting or activating relevant targets in its pathological evolution Zhang Pulian, Liu Baoru, Yang Min 2025, 29 (31):  6800-6810.  doi: 10.12307/2025.684 Abstract ( 95 )   PDF (1637KB) ( 140 )   Save BACKGROUND: Currently, the main treatment for aplastic anemia is hematopoietic stem cell transplantation and immunosuppressive therapy. However, treatment-induced complications and adverse effects seriously affect the prognosis and quality of life of patients with aplastic anemia. Mesenchymal stem cells have a unique low immunogenicity, which can inhibit the proliferation and activation of T-lymphocytes, B-lymphocytes, dendritic cells, and natural killer cells, and regulate the body’s immunity. Mesenchymal stem cells hold promise for cell therapy for aplastic anemia and graft-versus-host disease. OBJECTIVE: To review the progress of the application of mesenchymal stem cells in aplastic anemia in recent years, and the correlation between mesenchymal stem cells and the pathogenesis of aplastic anemia. This article hopes to provide patients with aplastic anemia with a new theoretical basis for treatment and more effective treatment options. METHODS: PubMed database and CNKI database were searched from January 2003 to February 2024. The search terms included “aplastic anemia, mesenchymal stem cells, hematopoietic stem cells, hematopoiesis, hematopoietic microenvironment, hematopoietic stem cell transplantation, biology, immunity, graft-versus-host disease” in Chinese and “aplastic anemia, mesenchymal stem cell, hematopoietic stem cell, hematopoiesis, hematopoietic microenvironment, hematopoietic stem cell transplantation, biology, immuno-modulatory, immune regulation, graft-versus-host disease, chronic graft-versus-host disease, acute graft-versus-host disease” in English. Low-quality, repetitive, and outdated articles were excluded, and 88 papers were finally included for review and analysis.  RESULTS AND CONCLUSION: (1) As a kind of pluripotent stem cells, mesenchymal stem cells can remodel hematopoietic function through direct cell-to-cell contact, secretion of various hematopoietic-related factors, and participation in hematopoietic-related pathways. (2) Compared with mesenchymal stem cells combined with immunosuppressant infusion and infusion of mesenchymal cells alone, mesenchymal stem cells combined with hematopoietic stem cell transplantation for the treatment of patients with aplastic anemia can better utilize the therapeutic efficacy of the two types of stem cells, significantly reduce the incidence of chronic and III-IV acute graft-versus-host disease, and improve the overall survival of patients. (3) Protocols that use mesenchymal stem cells of umbilical cord origin and <6 passages and that are infused prior to hematopoietic stem cell transplantation may be more effective therapeutic options. (4) There is a close link between mesenchymal stem cells and the pathogenesis of aplastic anemia, which may lead to new therapeutic options for aplastic anemia through the inhibition or activation of relevant targets in the pathological evolution of aplastic anemia. Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells from different sources in treatment of inflammatory bowel disease Yuan Xiao, Liang Songlin, Xie Yanan, Guan Dongmei, Fan Longyu, Yin Xiaoxuan 2025, 29 (31):  6811-6820.  doi: 10.12307/2025.548 Abstract ( 122 )   PDF (2109KB) ( 173 )   Save BACKGROUND: The incidence of inflammatory bowel disease has been steadily rising, accompanied by a lack of definitive therapeutic strategies. Recent research endeavors have illuminated the promising potential of mesenchymal stem cells in mitigating the symptoms of inflammatory bowel disease, offering a glimmer of hope for afflicted patients. OBJECTIVE: To review the mechanisms of action of mesenchymal stem cells derived from various sources in the management of inflammatory bowel disease, aiming to provide insights for future research endeavors. METHODS: Utilizing the keywords “mesenchymal stem cells, MSCs, exosomes, extracellular vesicles, EVs, inflammatory bowel disease, IBD, ulcerative colitis, UC, Crohn’s disease, CD” in English and their Chinese equivalents in CNKI and PubMed databases, a total of 89 eligible articles were selected for this review. RESULTS AND CONCLUSION: Currently, six types of mesenchymal stem cells are being explored for inflammatory bowel disease therapy: bone marrow-derived mesenchymal stem cells, adipose tissue-derived mesenchymal stem cells, perinatal tissue-derived mesenchymal stem cells, induced pluripotent stem cell-derived mesenchymal stem cells, embryonic stem cell-derived mesenchymal stem cells, and gingival mesenchymal stem cells. Five administration routes have been adopted, with intravenous and intraperitoneal injections being the most prevalent, followed by local, mesenteric, and intrarectal injections. Their therapeutic mechanisms encompass differentiation, regeneration, anti-inflammatory effects, immune modulation, neuroprotection, antioxidant stress response, homing, modulation of gut microbiota, autophagy, ferroptosis, and endoplasmic reticulum stress. While sharing functional similarities, mesenchymal stem cells from different sources exhibit unique characteristics that confer them with distinct advantages and therapeutic potentials. Nevertheless, research into the specific properties of these mesenchymal stem cells remains limited, necessitating deeper exploration of their nuanced differences to optimize their therapeutic efficacy in inflammatory bowel disease. Additionally, the clinical safety of mesenchymal stem cells-based therapies warrants further observation and evaluation.  Figures and Tables | References | Related Articles | Metrics