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    18 April 2025, Volume 29 Issue 11 Previous Issue    Next Issue
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    Regulatory mechanism of urolithin B in osteoclastic differentiation of bone marrow-derived macrophages
    Luo Xi, Chen Jianquan
    2025, 29 (11):  2201-2209.  doi: 10.12307/2025.368
    Abstract ( 441 )   PDF (2274KB) ( 131 )   Save
    BACKGROUND: Urolithin B plays an important role in regulating the body’s immune response and has antioxidant, anti-cancer and anti-inflammatory properties. Notably, urolithin B has been reported to have inhibitory effects on osteoclast differentiation of Raw 264.7 cells. However, a more comprehensive understanding of its specific mechanism of action in the context of osteoclast differentiation in bone is worth exploring. Systematic research on the regulatory mechanisms of osteoclast overactivation can help to explore new therapeutic targets, screen and develop safer and more effective therapeutic drugs, and provide new ideas to block the overactivation of osteoclasts.
    OBJECTIVE: By establishing an in vitro osteoclast differentiation model using bone marrow-derived macrophages, to investigate the effect of urolithin B on nuclear factor-κB receptor-activating factor ligand-mediated osteoclast differentiation and to systematically analyze its mechanism of action.
    METHODS: (1) The safe working concentration of urolithin B was screened by cell counting kit-8 method. (2) Different concentrations of urolithin B (0, 12.5, 25, and 50 μmol/L) were used to intervene with the osteoclast differentiation of bone marrow-derived macrophages, and the number of osteoclasts and the size of osteocytes were observed using tartrate-resistant acid phosphatase staining. (3) Different concentrations of urolithin B (0, 12.5, 25, and 50 μmol/L) were used to intervene with the osteoclast differentiation of bone marrow-derived macrophages, and the relative expression levels of osteoclast-specific genes were detected using real-time fluorescence quantitative PCR. (4) The effect of urolithin B on the P65 and ERK signaling pathways of bone marrow-derived macrophages was observed by western blot. (5) The effect of urolithin B on the key transcription factors nuclear factor of activated T cells 1 and c-Fos in the osteoclastic differentiation of bone marrow-derived macrophages was detected by western blot.
    RESULTS AND CONCLUSION: 50 μmol/L or lower concentration of urolithin B had no effect on the proliferation of bone marrow-derived macrophages but significantly inhibited osteoclastic differentiation of bone marrow-derived macrophages. Urolithin B mainly inhibited osteoclastic differentiation of bone marrow-derived macrophages in pre-medium term. Urolithin B down-regulated the relative expression levels of osteoclast specific genes in bone marrow-derived macrophages. 50 μmol/L urolithin B inhibited the phosphorylation levels of P65 and ERK in bone marrow-derived macrophages, which led to the inhibition of osteoclast formation. 50 μmol/L urolithin B inhibited the expression of key transcription factors nuclear factor of activated T cells 1 and c-Fos in bone marrow-derived macrophages into osteoclasts. To conclude, urolithin B inhibits bone marrow-derived macrophages from differentiating into osteoclasts by suppressing the expression of downstream osteoclastogenic-related signature genes and downregulating the expression of the important osteoclastogenic transcription factors, nuclear factor of activated T cells 1 and c-Fos, via the P65/ERK signaling axis.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Conditioned medium of osteoclasts promotes angiogenesis in endothelial cells after lactic acid intervention
    Huang Hongli, Nie Wen, Mai Yuying, Qin Yuan, Liao Hongbing
    2025, 29 (11):  2210-2217.  doi: 10.12307/2025.352
    Abstract ( 335 )   PDF (2657KB) ( 82 )   Save
    BACKGROUND: As a degradable scaffold material for bone tissue engineering, lactic acid is widely used in tissue regeneration and repair research, and plays an important role in promoting tissue healing, new bone formation and angiogenesis.
    OBJECTIVE: To observe the effect of lactic acid degradation products on osteoclasts and to investigate the effects of lactic-interfered osteoclast conditioned medium on the proliferation, migration and tube-forming capacity of human umbilical vein endothelial cells.
    METHODS: (1) The mouse monocyte macrophage cell line RAW264.7 at logarithmic growth period was selected, and adherent cells were cultured in the osteoclast induction medium (DMEM medium with nuclear factor-κB receptor-activating factor ligand and 10% fetal bovine serum) containing different concentrations of lactic acid (0, 5, 10, 20 mmol/L). After 5 days of culture, tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining were conducted. After 24 hours of culture, RT-PCR was used to detect the mRNA expression of tartrate-resistant acid phosphatase 5. (2) RAW264.7 cells at logarithmic growth period were selected and adherent cells were divided into two groups. Control group was cultured in the osteoclast induction medium, while experimental group was cultured in the osteoclast induction medium containing 10 mmol/L lactic acid. After 5 days of culture, the medium in each group was removed and the cells in the two groups were cultured in the serum-free DMEM medium for another 24 hours. Cell supernatant was then collected and used as the conditioned medium after mixed with an equal volume of DMEM medium containing 10% fetal bovine serum. Human umbilical vein endothelial cells at the logarithmic growth phase were taken and separately co-cultured with the conditioned medium of the control and experimental groups. The proliferation, migration and tube-forming ability of human umbilical vein endothelial cells were observed by cell counting kit-8 assay, migration assay, scratch assay and tube-forming assay. The mRNA and protein expression of angiogenesis-related genes and proteins were observed by RT-PCR and western blot.
    RESULTS AND CONCLUSION: Tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining showed that 5 and 10 mmol/L lactic acid promoted osteoclastic differentiation of RAW264.7 cells and the promoting effect of 10 mmol/L lactate was more significant. RT-PCR results showed that the expression of tartrate-resistant acid phosphatase-5 mRNA of osteoclast-related genes was the highest when the lactic acid concentration was 5, 10, and 20 mmol/L (P < 0.05), especially 10 mmol/L. Compared with the control group, the proliferation, migration and tube-forming abilities of human umbilical vein endothelial cells were significantly increased in the experimental group (P < 0.05). Compared with the control group, the expression levels of vascular endothelial growth factor and angiogenin 1 mRNA and protein were increased in the experimental group (P < 0.05). To conclude, lactate-induced osteoclast conditioned medium could promote the angiogenesis of endothelial cells, and the mechanism may be related to the promotion of the expression of vascular endothelial growth factor and angiogenin 1.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Pathological changes in the total knee joint during spontaneous knee osteoarthritis in guinea pigs at different months of age
    Hu Xiaoshen, Li Huijing, Lyu Junling, Xiao Xianjun, Li Juan, Li Xiang, Liu Ling, Jin Rongjiang
    2025, 29 (11):  2218-2224.  doi: 10.12307/2025.369
    Abstract ( 247 )   PDF (2925KB) ( 81 )   Save
    BACKGROUND: The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans.
    OBJECTIVE: To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. 
    METHODS: Eight healthy female Hartley guinea pigs in each age group of 1, 6, 10, 14, 16, and 18 months old were selected. The quadriceps femoris was taken for hematoxylin-eosin staining, and the total knee joint was stained with hematoxylin-eosin and toluidine blue. The histopathology of the cartilage, subchondral bone, synovium, meniscus, and muscles were observed under light microscope. Mankin’s score and synovitis score were compared, and the correlation analysis was conducted. 
    RESULTS AND CONCLUSION: As the guinea pig age increased, the Mankin’s score increased (P < 0.05), and the pathological score of synovitis also gradually increased (P < 0.05), and there was a significant positive correlation between the two (r=0.641, P < 0.001). The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%, and the incidence of meniscus injury was 37.5%. In addition, osteophyte and narrowing of the joint space were observed, and only a few guinea pigs had inflammation in the quadriceps femoris. To conclude, guinea pigs develop significant cartilage defects, synovial inflammation, subchondral bone lesions, meniscus injury, osteophyte formation, and joint space narrowing as they age, all of which are similar to the pathological processes of primary knee osteoarthritis in humans, making it an ideal model of spontaneous knee osteoarthritis.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Effect of vibration therapy combined with suspension training on movement and knee joint function after anterior cruciate ligament reconstruction
    Chen Wenhan, Men Jie, Yang Wei, Zhao Xiaoyu
    2025, 29 (11):  2225-2230.  doi: 10.12307/2025.384
    Abstract ( 281 )   PDF (1067KB) ( 105 )   Save
    BACKGROUND: Physiotherapy is very important for the recovery after anterior cruciate ligament reconstruction. In recent years, many doctors are optimizing the physical rehabilitation program after anterior cruciate ligament reconstruction. However, there is still a lack of efficient rehabilitation training after anterior cruciate ligament reconstruction.
    OBJECTIVE: To investigate the effect of vibration therapy combined with suspension training on movement and knee joint function after anterior cruciate ligament reconstruction.
    METHODS: A total of 80 patients undergoing first unilateral anterior cruciate ligament reconstruction at the Affiliated Sport Hospital, Shanghai University of Sport were randomly divided into vibration therapy group (n=40) and vibration therapy+suspension training group (n=40). In the vibration therapy group, vibration therapy (10 minutes each, once a day, 6 times per week) was performed at the 13th week after anterior cruciate ligament reconstruction. Patients in the vibration therapy+suspension training group were treated with vibration therapy (10 minutes each, once a day, 6 times per week) and suspension training (twice a week) at the 13th week after anterior cruciate ligament reconstruction. Training in each group was performed for 8 weeks. Knee joint function was evaluated by knee joint Lysholm score before and 8 weeks after training. The symmetry index was evaluated by the isokinetic muscle strength evaluation training system. The balance test system was used to evaluate the average trace error difference of the bilateral multi-axes.
    RESULTS AND CONCLUSION: Compared with those before training, the knee Lysholm score and the knee extension and flexion symmetry indexes increased 
    (P < 0.05), and the average trace error difference decreased after training (P < 0.05). Compared with the vibration therapy group, the knee Lysholm score in the vibration therapy+suspension training group increased (P < 0.05), the knee extension and knee flexion symmetry index increased (P < 0.05), and the average trace error difference decreased (P < 0.05). To conclude, compared with vibration therapy training alone, vibration therapy combined with suspension training can significantly improve knee joint function, increase muscle strength and symmetry, and improve balance stability in patients undergoing anterior cruciate ligament reconstruction.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Effects of erythropoietin on restorative dentin formation and expression of bone morphogenetic protein 2 after pulp injury
    Cheng Ruiqing, Sun Honglei, Geng Shuangshuang, Wang Chao, Li Junke, Chen Yanfang
    2025, 29 (11):  2231-2242.  doi: 10.12307/2025.356
    Abstract ( 202 )   PDF (4577KB) ( 280 )   Save
    BACKGROUND: Erythropoietin has anti-inflammatory, anti-apoptotic, and pro-bone defect repair effects. To date, fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury.
    OBJECTIVE: To explore the effect of erythropoietin on restorative dentin formation after pulp injury. 
    METHODS: (1) Animal experiment: Thirty-two rats were randomly divided into control group (n=16) and experimental group (n=16). In the experimental group, collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury, and in the control group, collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury. The cavity was then closed with glass ionomer adhesive. After 2 and 4 weeks of treatment, the maxillary bones of the two groups were collected, and the expression of nestin in dentin was detected by immunohistochemistry, and the reparative dentin production was observed by hematoxylin-eosin staining. The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth. (2) Cell experiment: Human dental pulp cells, human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue, periodontal ligament, and gingival tissue. Real-time reverse transcription PCR (RT-PCR) was used to detect the mRNA expression of erythropoietin. Erythropoietin, dentin sialophosphoprotein, dentin matrix protein 1, and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation. After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation, the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR, and the formation of mineralized nodules was detected by alizarin red S staining, and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot, respectively. 
    RESULTS AND CONCLUSION: (1) Animal experiment: Compared with the control group, the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment. The expression of erythropoietin was weakly positive in pulp, odontoblastic cell layer and periodontal membrane of the rat’s first maxillary molar, and strongly positive in odontoblasts. (2) Cell experiment: The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells. The mRNA expressions of dentin sialophosphorin, dentin matrix protein 1, nestin, erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions. The mRNA expression of dentin sialophosphoprotein, dentin matrix protein 1, nestin, bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation, and the protein expression of bone morphogenetic protein 2 was also decreased. After exogenous erythropoietin intervention, the expression of the above indexes in human dental pulp cells increased. To conclude, erythropoietin can promote the formation of dentin to some extent.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Mechanism by which exogenous basic fibroblast growth factor promotes wound healing in rats
    Li Zhenchao, Du Xiling, Han Zhixin, Niu Dawei, Fan Changwei
    2025, 29 (11):  2243-2251.  doi: 10.12307/2025.350
    Abstract ( 256 )   PDF (4801KB) ( 98 )   Save
    BACKGROUND: This study provided insight into the molecular mechanisms by which exogenous basic fibroblast growth factor (bFGF) promotes wound healing.
    OBJECTIVE: To investigate the effect of exogenous bFGF on macrophage phenotype transition and granulation regeneration during wound repair in rats. 
    METHODS: (1) In vitro experiment: Cells were divided into normal control group, low-dose bFGF group, high-dose bFGF group, and bFGF+valproic acid group. 100 and 200 μg/L bFGF was added into the cell culture medium of low-dose bFGF group and high-dose bFGF group, respectively, while 200 μg/L bFGF and 20 mmol/L valproic acid were added into the cell culture medium of valproic acid group. EdU test, scratch test and tubule formation test were used to detect the effects of bFGF on proliferation, migration and angiogenesis of human umbilical vein endothelial cells. (2) In vivo experiment: Sprague-Dawley rats were randomly divided into model group, low-dose bFGF group, high-dose bFGF group and bFGF+valproic acid group. The open wound model of full-thickness skin defect was established in low-dose bFGF group, high-dose bFGF group and bFGF+valproic acid group. Rats in the low- and high-dose bFGF groups were given 100 and 200 μg/L bFGF through subcutaneous injection, while those in the bFGF+valproic acid group received subcutaneous injection of 200 μg/L bFGF and intraperitoneal injection of 10 mg/kg valproic acid. The wound healing rate of rats was detected at 7 and 14 days of administration. TUNEL was used to detect the apoptosis of cells in wound tissue. Enzyme linked immunosorbent assay was used to detect the serum levels of malondialdehyde, superoxide dismutase, tumor necrosis factor-α and interleukin-10. Immunofluorescence detection was conducted to detect the phenotypic transformation of macrophages in wound tissue. Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen, platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor in wound tissue. Western blot was used to detect the expression of Notch1 and Jagged1 in wound tissue. 
    RESULTS AND CONCLUSION: (1) Compared with the normal control group, bFGF could significantly promote the proliferation, migration and angiogenesis of human umbilical vein endothelial cells in a dose-dependent manner. (2) Compared with the model group, bFGF could significantly promote wound healing, downregulate the rate of apoptosis in wound tissue, decrease the levels of malondialdehyde and tumor necrosis factor-α in serum, increase the levels of superoxide dismutase and interleukin-10, promote the conversion of macrophages to type M2 in wound tissue, upregulate the expression of proliferating cell nuclear antigen, CD31 and vascular endothelial growth factor in wound tissue, and inhibit the expression of Notch1 and Jagged1 in a dose-dependent manner. Valproic acid could partially reverse the promoting effect of bFGF on wound healing. To conclude, bFGF can significantly promote wound healing and granulation regeneration and induce the conversion of macrophages to M2, which may be related to the regulation of Notch1/Jagged1 signaling pathway.
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    Repetitive trans-spinal magnetic stimulation promotes motor function recovery in mice after spinal cord injury
    Song Haiwang, Jiang Guanhua, Mu Yingying, Fu Shanyu, Sun Baofei, Li Yumei, Yu Zijiang, Yang Dan
    2025, 29 (11):  2252-2260.  doi: 10.12307/2025.363
    Abstract ( 216 )   PDF (2046KB) ( 105 )   Save
    BACKGROUND: Repetitive trans-spinal magnetic stimulation (rTSMS) can inhibit inflammatory responses following spinal cord injury. rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission, thereby promoting plasticity and repair of the nervous system.
    OBJECTIVE: To observe the effects of rTSMS on the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery.
    METHODS: Male C57BL/6J mice, SPF grade, were randomly divided into sham surgery group, spinal cord injury group, and rTSMS group. The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord, and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model. Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury. The stimulation lasted 10 minutes per day, 5 days per week with an interval of 2 days. Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1, 3, 7, 14, and 21 days after spinal cord injury. Western blot was employed to detect the expression of AQP4, apoptotic factors Bax, Bcl-2, CL-Caspase-3, inflammatory factors tumor necrosis factor-α, interferon-γ, interleukin-6, interleukin-4, and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord. Oxidative stress assay kit was used to measure the activity of superoxide dismutase, glutathione peroxidase, and malondialdehyde content at the site of spinal cord injury. Immunofluorescence staining was performed to detect the expression of neuronal nuclei (NeuN).
    RESULTS AND CONCLUSION: The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group (P < 0.05). 
    Compared with the spinal cord injury group, the rTSMS group showed a reduction in spinal cord water content. The expression of AQP4 protein, malondialdehyde content, and expression of Bax, Bcl-2, CL-Caspase-3, tumor necrosis factor-α, interferon-γ, interleukin-6, and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group, while the activities of superoxide dismutase and glutathione peroxidase, as well as the expression of Bcl-2, interleukin-4, and NeuN, were all increased (P < 0.05). These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway, alleviating symptoms after spinal cord injury such as spinal cord edema, oxidative stress, apoptosis, and inflammation, exerting neuroprotective effects, and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Effects of silver needle comprehensive therapy on the ultrasonographic morphology of multifidus muscles in patients with lumbar disc herniation: an ultrasound morphologic assessment 
    Cao Zhengpei, Lu Shengsheng, Zhang Jiahuan, Wang Xiaoying
    2025, 29 (11):  2261-2267.  doi: 10.12307/2025.357
    Abstract ( 217 )   PDF (1362KB) ( 87 )   Save
    BACKGROUND: Many studies have focused on acupuncture, such as silver needles, for the treatment of lumbar disc herniation, but there are few studies based on the myofascial trigger point theory.
    OBJECTIVE: To observe the effects of silver needle comprehensive therapy on the ultrasound morphology and clinical efficacy of multifidus muscles in patients with lumbar disc herniation based on the theory of myofascial trigger points. 
    METHODS: A total of 159 patients with lumbar disc herniation who were seen from January 2022 to April 2023 were selected as the research subjects and randomly divided into three groups: conventional group (n=53), traditional acupuncture group (n=53), and silver needle group (n=53). The conventional group received routine western medicine treatment; the traditional acupuncture group used traditional acupuncture therapy based on meridian pathways and symptom localization; and the silver needle group used silver needle warm acupuncture at myofascial trigger points for intervention. All three groups received continuous treatment for 4 weeks. The number of myofascial trigger points, pain assessment, lumbar function evaluation, ultrasound morphology changes of multifidus muscles, clinical efficacy, and traditional Chinese medicine symptom score were recorded before and after treatment in the three groups.
    RESULTS AND CONCLUSION: (1) After treatment, the number of myofascial trigger points in the lumbar muscles decreased in all groups, and the silver needle group showed a significant reduction compared with the traditional acupuncture group and the conventional group (P < 0.05). (2) The pain rating index score, visual analogue scale score, present pain intensity score, Oswestry disability index score, and Roland-Morris disability questionnaire score in the silver needle group were lower than those in the traditional acupuncture group and the conventional group (P < 0.05). (3) The ultrasound morphology indexes of multifidus muscles in the silver needle group were superior to those in the traditional acupuncture group and the conventional western medicine group (P < 0.05). (4) Traditional Chinese medicine symptom scores in the silver needle group were lower than those in the traditional acupuncture group and the conventional western medicine group (P < 0.05). (5) There were significant differences in clinical efficacy among the three groups (P < 0.05). To conclude, applying silver needle comprehensive therapy based on the theory of myofascial trigger points can effectively reduce pain, improve clinical efficacy, and enhance lumbar spine dysfunction and multifidus muscle morphology in patients with lumbar disc herniation.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Neurotrophin-3 receptor switching promotes neural functional recovery in rats after spinal cord injury
    Cong Yan, Yu Jian, Sun Zhide, Kang Dawei
    2025, 29 (11):  2268-2276.  doi: 10.12307/2025.344
    Abstract ( 244 )   PDF (3092KB) ( 60 )   Save
    BACKGROUND: Neurotrophins represent a novel therapeutic approach for spinal cord injury, showing promising clinical applicability. Autophagy modulation is one of the mechanisms by which neurotrophins exert their effects, yet the specific signaling pathways involved remain unclear. 
    OBJECTIVE: To explore how neurotrophin-3 (NT-3) modulates autophagy in oligodendrocytes via switching between P75NTR and TrkC receptors and promotes neurological function recovery after spinal cord injury, aiming to further clarify the specific molecular mechanisms involved.
    METHODS: Twenty-four Sprague-Dawley rats were randomly divided into three groups: sham operation, spinal cord injury, and NT-3 groups. The therapeutic effect of NT-3 on spinal cord injury in rats was evaluated using the Basso, Beattie, and Bresnahan locomotor rating scale. The expression levels of NT-3, Olig1, myelin basic protein, and the autophagy marker LC3B in rat spinal cord tissue were detected by western blot. In a cellular experiment, oligodendrocytes were cultured in vitro and divided into six groups: oxygen-glucose deprivation (OGD), OGD+NT-3, OGD+NT-3+P75NTR plasmid, OGD+NT-3+TrkC plasmid, OGD+3-methyladenine (an autophagy inhibitor), and OGD+rapamycin (an autophagy activator). Oligodendrocyte morphology was observed under a light microscope, cell apoptosis was assessed by TUNEL staining, and the expression of TrkC receptor, P75NTR, LC3B, and the phosphorylation status of the PI3K/AKT/mTOR and AMPK/mTOR signaling pathways were evaluated by western blot.
    RESULTS AND CONCLUSION: Animal experiments demonstrated that compared with the sham operation group, NT-3 expression significantly increased after spinal cord injury (P < 0.05); exogenous NT-3 treatment accelerated neurological function recovery in rats post spinal cord injury (P < 0.05) and increased the expression of Olig1 and myelin basic proteins (P < 0.05). Cellular experiments revealed that 3 hours marked the early to middle/late phase transition. Compared with the OGD group, oligodendrocytes in the OGD+NT-3 group could maintain their morphology for a longer period of time, TrkC receptor expression was lower in the early phase and significantly upregulated in the middle/late phase (P < 0.05), whereas P75NTR protein expression was upregulated in the early phase and downregulated in the middle/late phase (P < 0.05), and autophagy levels showed an initial increase followed by a decrease (P < 0.05). By comparing the morphology and TUNEL staining results of cells in the OGD+NT-3, OGD+rapamycin, and OGD+3-methyladenine groups, we found that either promoting or inhibiting autophagy alone had adverse effects on oligodendrocyte survival, whereas modulating autophagy in a manner similar to NT-3 could maximally maintain cell survival. NT-3 could promote autophagy in the early phase via the P75NTR/AMPK/mTOR signaling pathway and inhibit autophagy in the later phase through the TrkC/PI3K/AKT/mTOR signaling pathway. Based on these findings, it is concluded that NT-3 can bidirectionally regulate autophagy in oligodendrocytes through the switching of P75NTR/TrkC receptors, thereby maintaining cell survival and facilitating the recovery of neurological functions in rats after spinal cord injury.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Metabolomics analysis of the lumbar spine after alendronate sodium intervention in ovariectomized rats with osteoporosis
    Chen Xinfei, Dai Yahui, Xie Bingying, Huang Xiaobin, Huang Huimin, Huang Jingwen, Li Shengqiang, Ge Jirong
    2025, 29 (11):  2277-2284.  doi: 10.12307/2025.375
    Abstract ( 210 )   PDF (3121KB) ( 95 )   Save
    BACKGROUND: Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis.
    OBJECTIVE: To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry, and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis.
    METHODS: A total of 36 female Sprague-Dawley rats were randomly divided into model group, alendronate sodium group and sham operation group. The osteoporosis model was established by ovariectomy in the first two groups. Four weeks after modeling, the rats in the alendronate group were intragastrically given alendronate sodium, while those in the sham operation group and model group were given equal volume of normal saline. After 12 weeks of continuous gavage, the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry, and the common differential metabolites were obtained, which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway.
    RESULTS AND CONCLUSION: Totally 17 different metabolites were obtained in the three groups. The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis, linoleic acid metabolism and other pathways to protect ovariectomized rats. These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism, so as to achieve the purpose of preventing osteoporosis.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Liuwei Dihuang Wan inhibits oxidative stress in premature ovarian failure mice by regulating intestinal microbiota #br#
    #br#
    Zhong Jiawen, Jiang Bo, Zhang Wenyan, Li Xiaorong, Qin Ling, Gao Ting
    2025, 29 (11):  2285-2293.  doi: 10.12307/2025.366
    Abstract ( 253 )   PDF (2483KB) ( 225 )   Save
    BACKGROUND: Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure.
    OBJECTIVE: To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. 
    METHODS: Forty-five female ICR mice were randomized into three groups: blank group (normal mice), model group (premature ovarian failure mice), and Liuwei Dihuang Wan group. A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide (120 mg/kg) 
    in the latter two groups. After successful modeling, the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days, and the other two groups were intragastrically administered with the same amount of normal saline for 28 days. Mouse body mass was recorded weekly and ovarian index was calculated. The development of mouse follicles was observed using hematoxylin-eosin staining. ELISA method was used to detect serum levels of anti-Mullerian hormone, estradiol, follicle stimulating hormone, superoxide dismutase, glutathione peroxidase, and malondialdehyde. Meanwhile, the gut microbiome of all mice was detected through 16S rDNA sequencing.
    RESULTS AND CONCLUSION: The mice in the model group had loose hair, decreased vigor and grip strength, almost no increase in body mass, and decreased ovarian index. Whereas, the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan (P < 0.05). The estrous cycle of mice in the model group was disorganized; Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure. The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased (P < 0.01), while the levels of estradiol, anti-Mullerian hormone, superoxide dismutase, and glutathione peroxidase significantly decreased (P < 0.01). Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde (P < 0.01), and increase the levels of estradiol, anti-Mullerian hormone, superoxide dismutase, and glutathione peroxidase. According to the 16S rDNA sequencing results, Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota, and increase the relative abundance of beneficial bacteria. KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in different environments, and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan. To conclude, the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure. Liuwei Dihuang Wan can regulate the structure of intestinal microbiome, increase the number of beneficial bacteria, reduce the number of harmful bacteria, and thus improve the balance of intestinal microbiota. This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.
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    Role of prohibitin 2 in mitophagy pathway against atherosclerosis in rats undergoing endurance training
    Song Mingxiao, Chen Junshunzi, Wang Ningwei, Cai Huan, Feng Hong
    2025, 29 (11):  2294-2300.  doi: 10.12307/2025.343
    Abstract ( 226 )   PDF (1743KB) ( 97 )   Save
    BACKGROUND: Exercises can reduce blood lipids and slow down the development of atherosclerosis. Atherosclerosis begins with mitochondrial dysfunction, and prohibitin 2 is involved in mitophagy by endurance training. 
    OBJECTIVE: To explore the role of endurance training in the intervention of prohibitin 2 protein in the mitophagy autophagy pathway in atherosclerosis. 
    METHODS: A total of 40 Wistar rats were randomly divided into control group, exercise group, atherosclerosis group and atherosclerosis combined with exercise group, with 10 rats in each group. A rat model of atherosclerosis was constructed by combining a high-fat diet (9 weeks) with vitamin D injections (weeks 1, 3, and 6) in the latter two groups, while the two exercise groups were subjected to progressing intensity endurance training for 9 weeks. After the intervention, lipid and pathological detections were conducted to observe the modeling and interventional effects. Mitochondrial membrane potential and mitophagy proteins were detected by microplate reader and western blot. Immunofluorescence staining was used to observe the co-localization of mitophagy proteins in aortic tissue. 
    RESULTS AND CONCLUSION: Lipid and pathological sections showed that compared with the atherosclerosis group, the serum low-density lipoprotein cholesterol and total cholesterol levels and aortic lipid deposition area were significantly reduced in the atherosclerosis combined with exercise group (P < 0.001). The results of mitochondrial membrane potential showed that the significant decrease in mitochondrial membrane potential of the aorta in the atherosclerosis combined with exercise group was reversed (P < 0.01). The results of western blot assay showed that compared with the control group, the mitochondrial protein expression of prohibitin 2, LC3II/I, PINK1 and Parkin was significantly increased (P < 0.05), and the protein expression of PARL and PGAM5 decreased (P < 0.05). Compared with the atherosclerosis group, the protein expression of PINK1 and Parkin in the mitchondria of rats in the atherosclerosis combined with exercise group was significantly decreased (P < 0.05), and the protein expressions of prohibitin 2, LC3II/I, PARL and PGAM5 were significantly increased (P < 0.05). Immunofluorescence results showed that compared with the control group, the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis group (P < 0.05), while compared with the atherosclerosis group, the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis combined with exercise group (P < 0.05). Co-localization of LC3 and PARL with prohibitin 2 was significantly increased in the atherosclerosis group compared with the control group (P < 0.01), co-localization of LC3 with prohibitin 2 was significantly increased in the atherosclerosis combined with exercise group compared with the atherosclerosis group (P < 0.01), and co-localization of PARL protein with prohibitin 2 was significantly decreased in the atherosclerosis combined with exercise group compared with the atherosclerosis group (P < 0.01). To conclude, endurance training can induce the expression of prohibitin 2 in the inner mitochondrial membrane and promote the binding of prohibitin 2 to the mitophagy junction protein to complete mitophagy, restore mitochondrial function, and slow down the occurrence of atherosclerosis.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Establishment and evaluation of a rat model of phlegm-heat and Fu-organ excess syndrome following ischemic stroke
    Ping Xingfeng, Lyu Junying, Li kai, Huang Zongxuan, Yin Jianxin
    2025, 29 (11):  2301-2309.  doi: 10.12307/2025.353
    Abstract ( 214 )   PDF (2279KB) ( 129 )   Save
    BACKGROUND: Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke. In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease, it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. 
    OBJECTIVE: To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. 
    METHODS: Sixty male Sprague-Dawley rats were randomly divided into four groups: blank control group (n=12), ischemic stroke group (n=18), disease+syndrome group (n=18), phlegm-heat and Fu-organ excess syndrome group (n=12), all of which were given high-fat diet for 25 days. On the 26th day, the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet, while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days. After gavage, ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group. The changes in diet, water intake, body mass, body temperature, fecal traits, nasal secretions, sputum in the throat, and tongue image were recorded. Neurological deficits, tongue image, blood lipid levels, morphological changes of brain tissue and carotid artery, and the serum levels of motilin and somatostatin were detected. 
    RESULTS AND CONCLUSION: Compared with the control group, the rats in the disease+syndrome group had shortness of breath, listlessness, irritability, bradykinesia, a large number of secretions around the nose, audible and heavy sputum in the throat, decreased diet and water intake, increased body mass, body temperature, and slingual vein score, decreased fecal pellet count, Bristol score and fecal moisture content, increased serum total cholesterol, triglyceride, low-density lipoprotein and somatostatin levels, decreased motilin level, increased neurological deficit score, significant pathological changes of the carotid artery, and significant morphological changes of the brain tissue. The ischemic stroke group only showed pathological changes of ischemic brain tissue, without the characteristics of phlegm-heat and Fu-organ excess syndrome. The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes, without the pathological changes of brain tissue with ischemic stroke. To conclude, the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Comparison of different intensity exercises to improve autophagy in diabetic rats by inhibiting renal phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway
    Zhou Hongyan, Zhang Yidan, Ji Wei, Liu Xia
    2025, 29 (11):  2310-2318.  doi: 10.12307/2025.364
    Abstract ( 264 )   PDF (1292KB) ( 115 )   Save
    BACKGROUND: Type 2 diabetes mellitus impairs renal function, and studies have shown that exercise interventions can protect the kidneys. Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.
    OBJECTIVE: To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway, as well as to analyze the differences in the effects of different modalities of exercise.
    METHODS: Six-week-old Sprague-Dawley rats were randomly divided into a blank control group (normal rats) and a diabetic group, and then the diabetic group was randomly divided into a diabetic model group, a moderate-intensity continuous exercise group, and a high-intensity intermittent exercise group after successful modeling using high-fat, high-sugar feeding plus intraperitoneal administration of low-dose 1% streptozotocin (30 mg/kg). The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities. The fasting blood glucose concentration was detected by glucose oxidase method, glycated hemoglobin levels was measured using a kit, serum insulin concentration was detected by Elisa method, and insulin resistance index was calculated. Gene expression of PI3K, AKT, mTOR, Beclin-1, podocin, and nephrin was detected by RT-PCR. Protein expression of mTOR and autophagy marker proteins LC3-1, LC3-2, and Beclin-1 was detected by western blot
    RESULTS AND CONCLUSION: Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased, insulin resistance levels were significantly increased, and insulin levels were significantly decreased in type 2 diabetic rats. Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels, significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats. Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group. The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression. There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group, but there was no significant difference. The mRNA and protein expression of PI3K, AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased, and the expression of autophagy marker proteins Beclin-1 and LC3-2 
    and LC3-2/LC3-1 were significantly decreased. Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K, AKT, and mTORC1, and significantly increased the autophagy marker proteins Beclin-1, LC3-2, and LC3-2/LC3-1 in renal tissues. Compared with the moderate-intensity continuous exercise group, there was a trend toward further decreases in mRNA expression of PI3K, AKT, and mTORC1 and protein expression of mTOR, and a trend toward further elevation of Beclin-1, LC3-2, and LC3-2/LC3-1 in the high-intensity intermittent exercise group, but only Beclin-1 showed a significant difference between groups. In summary, renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway. Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney, reduce podocyte damage, and restore renal podocyte autophagy, which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway. High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise, but with a slight decrease in podocyte protein expression.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Differences in dynamic stability across different height barriers between obese and average men
    Zhang Wenli, Zhao Ziqi, Liang Leichao, Tang Yunqi, Wang Yong
    2025, 29 (11):  2319-2326.  doi: 10.12307/2025.355
    Abstract ( 222 )   PDF (1586KB) ( 72 )   Save
    BACKGROUND: Obesity negatively affects dynamic balance during walking, and crossing barriers is a more routine functional activity that requires more stability in controlling body posture.
    OBJECTIVE: To investigate the differences in dynamic stability between obese and average males, and to assess the balance ability of obese males using a relatively more challenging obstacle crossing.
    METHODS: A total of 24 male youths (12 each in the obese and normal groups) were recruited to complete the tests of walking on level ground and crossing obstacles of different heights (4 cm, 11 cm, 15 cm) in random order. Kinematic and dynamic data were collected using the Qualisys motion capture system and Kistler force stage. Statistical analysis was performed using two-factor (2 groups * 4 movement types) repeated measures analysis of variance.
    RESULTS AND CONCLUSION: The obese group had a lower step speed than the normal group (P < 0.05), the proportion of the first single support period decreased and the proportion of the second double support period increased when crossing the 11 cm versus 15 cm hurdles (P < 0.05). When walking on level ground, the margin of stability in the internal and external directions in the normal group was greater than that of the obese group (P < 0.05). When crossing the 4 cm hurdles, the margin of stability in the obese group was less than that in the normal group (P < 0.05). When crossing the 11 cm hurdles, there was no significant difference between the two groups in the anterior-posterior direction (P > 0.05), while there was a significant difference in the internal-external direction (P < 0.05). When crossing the 15 cm hurdles, the margin of stability in the obese group was lower than that in the normal group (P < 0.05). Overall, obesity decreases the body’s ability to control the body, reduces dynamic stability during crossing the barrier, and increases the risk of falls compared with the general population. In addition, compared with level ground walking, the decrease in the dynamic stability when crossing barriers is more significant in the obese group than the general population.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Effect of wogonin on nerve injury in rats with diabetic cerebral infarction
    Wang Huanhuan, Liang Panpan, Yang Jinshui, Jia Shuxian, Zhao Jiajia, Chen Yuanyuan, Xue Qian, Song Aixia
    2025, 29 (11):  2327-2333.  doi: 10.12307/2025.349
    Abstract ( 228 )   PDF (1670KB) ( 50 )   Save
    BACKGROUND: Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis. Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury, and can also reduce blood sugar and complications in diabetic mice, but its role and mechanism in diabetic cerebral infarction remain unclear.
    OBJECTIVE: To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. 
    METHODS: Sprague-Dawley rats were randomly divided into six groups: control group, model group, low-dose wogonin group, medium-dose wogonin group, high-dose wogonin group, and high-dose wogonin+ Ras homolog gene family member A (RhoA) activator group. Except for the control group, the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion. Low, medium- and high-dose wogonin groups were intragastrically given 10, 20, 40 mg/kg wogonin, respectively; high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid; control group and model group were given the same amount of normal saline once a day for 7 consecutive days. Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose. TTC staining was applied to detect the volume of cerebral infarction. Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue. ELISA kit was applied to detect tumor necrosis factor-α, interleukin-6, malondialdehyde, and superoxide dismutase levels in brain tissue. Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase (ROCK) 2 in brain tissue. 
    RESULTS AND CONCLUSION: Compared with the control group, the neuronal structure of rats in the model group was severely damaged, with cell necrosis and degeneration, the neurological deficit score, blood glucose level, and infarct volume were significantly elevated (P < 0.05), the levels of tumor necrosis factor-α, interleukin-6, and malondialdehyde, and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased (P < 0.05), and the superoxide dismutase level was decreased (P < 0.05). Compared with the model group, the low-, medium-, and high-dose wogonin groups showed improved neuronal damage, reduced cell degeneration and necrosis, a significant reduction in neurological deficit score, blood glucose level, infarct volume, and the levels of tumor necrosis factor-α, interleukin-6, and malondialdehyde, and the protein expression of RhoA and ROCK2 in brain tissue, and an increase in the superoxide dismutase level (P < 0.05). Compared with the high-dose wogonin group, the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction (P < 0.05). To conclude, wogonin can improve the blood glucose level in rats with diabetic cerebral infarction, reduce cerebral infarction and nerve injury, and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Mechanism of Feibi prescription on mitochondrial apoptosis of alveolar epithelial cells in mice with pulmonary fibrosis
    Cheng Xue, Jing Huanxi, Zhang Yunke, Fang Hong
    2025, 29 (11):  2334-2339.  doi: 10.12307/2025.340
    Abstract ( 227 )   PDF (1651KB) ( 78 )   Save
    BACKGROUND: Studies have shown that mitochondrial apoptosis of alveolar epithelial cells plays an important role in the pathogenesis of pulmonary fibrosis, and Feibi prescription can attenuate pulmonary fibrosis and inhibit the transformation of extracellular mechanisms in mice with pulmonary fibrosis.  
    OBJECTIVE: To investigate the mechanism of Feibi prescription on mitochondrial apoptpsis of alveolar epithelial cells in bleomycin induced pulmonary fibrosis mice. 
    METHODS: Forty male C57BL/6 mice were randomly divided into blank control group, model group, pirfenidone group, and Feibi prescription group. There were 10 mice in each group. Except for the blank control group, the other three groups were intraperitoneally injected with bleomycin (7.5 mg/kg per day) for 10 continuous days to establish the model of pulmonary fibrosis. On day 1 after modeling, the mice in corresponding drug groups were intragastrically administered with pirfenidone (51.43 mg/kg per day) or Feibi prescription (12.86 mg/kg per day). Drug administration lasted for 28 days. Then, morphological changes of lung tissue in mice were observed by hematoxylin-eosin staining and Masson staining. The levels of interleukin-1, interleukin-6, interleukin-17, and interleukin-37 in the serum were detected by ELISA, and the expression of Bax, Bcl-2, Beclin-1, and Caspase3 in the lung tissue was detected by western blot assay. 
    RESULTS AND CONCLUSION: Morphological observation of lung tissue showed that in the model group, the alveolar septum and alveolar lumen were infiltrated with a large number of inflammatory cells, and there were large clusters of fibrous foci; in the pirfenidone group, alveolar septa were thickened, with a small infiltration of inflammatory cells and the appearance of pulmonary fibrous foci; in the Feibi prescription group, the alveolar structure was widened, with a small amount of inflammatory cell infiltration, and the alveolar structure was almost not obviously damaged, with a small number of lung fibrous foci. Compared with the blank control group, the mass concentrations of interleukin-1, interleukin-6, interleukin-17, and interleukin-37 were significantly higher in the model group (P < 0.01), while the levels were significantly lower in the two drug groups than the model group (P < 0.01). Moreover, the mass concentrations of interleukin-1, interleukin-6, interleukin-17, and interleukin-37 in the Feibi prescription group were lower than those in the pirfenidone group. Compared with the blank control group, the expression of Bax and Caspase3 proteins in the lung tissue of mice was significantly higher in the model group, while the expression of Bax and Caspase3 proteins was significantly lower in the two drug groups than the model group. Compared with the blank control group, the expression of Bcl-2 and Beclin-1 proteins in the lung tissue of mice was significantly lower in the model group, while the expression of Bcl-2 and Beclin-1 proteins was significantly higher in the two drug groups than the model group. To conclude, Feibi prescription can reduce pulmonary fibrosis and its mechanism may be related to the downregulation of interleukin-1, interleukin-6, interleukin-17, and interleukin-37 levels. This prescription can also reduce the apoptosis of alveolar epithelial cells by regulating mitochondrial apoptosis-related proteins, Bax, Bcl-2, Beclin-1 and Caspase3.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Effects of training modalities and training cycles on visceral and subcutaneous fat in recessively obese individuals
    Guo Xinfeng, Liang Zhidong, Chen Huiyu, Li Yang
    2025, 29 (11):  2340-2346.  doi: 10.12307/2025.331
    Abstract ( 258 )   PDF (1086KB) ( 102 )   Save
    BACKGROUND: Research suggests that exercise interventions may be more advantageous than pharmacologic treatments or dietary restriction alone for fat loss, but fewer studies have simultaneously examined the effects of training modalities and training cycles on visceral and subcutaneous fat in obese populations.
    OBJECTIVE: To investigate the impact of training modalities and training cycles on visceral and subcutaneous fat in recessive obesity female college students.
    METHODS: Sixty-three female college students with hidden obesity (body mass index < 24 kg/m2 and body fat content percentage ≥ 30%) were recruited from Zhengzhou College of Commerce and Industry, and were randomly divided into a high-intensity intermittent training group (n=32) and a moderate-intensity continuous training group (n=31) using the lottery method. Subjects in both groups performed exercise training of corresponding intensity on a running platform and ensured that the exercise volume of both groups was equal, 3 times per week, every 4 weeks as one training cycle for 16 weeks. Before training and at the end of each training cycle, subjects’ visceral fat, subcutaneous fat, and overall fat were measured using the corresponding test devices. 
    RESULTS AND CONCLUSION: The repeated measures F results indicated that the main effects of training cycles on visceral fat area, visceral fat index, abdominal subcutaneous fat thickness, percentage of body fat and body mass index were significant, while the main effects of training modalities were significant for subcutaneous fat thickness in the triceps brachii and scapula regions. All the interaction effects between training modalities and training cycles were significant 
    (P < 0.05). Results from the simple effect tests revealed that the significant simple effects of training modalities at the 4th and 12th weeks for visceral fat area and visceral fat index, at the 8th and 12th weeks for subcutaneous fat thickness in the triceps brachii, scapula region, and abdominal regions, and at the 8th week for the percentage of body fat and body mass index. Simple effects of training cycles were significant for all measures within each group. (3) The results of multiple comparison tests indicated that in the high-intensity intermittent training group, visceral fat area, visceral fat index, percentage of body fat, body mass index and abdominal subcutaneous fat thickness decreased sequentially at the 4th, 8th, 12th, and 16th weeks, and subcutaneous fat thickness of the triceps brachii and scapula decreased sequentially at the 8th, 12th, and 16th weeks (P < 0.05). In the moderate-intensity continuous training group, visceral fat area, visceral fat index, subcutaneous fat thickness of the triceps brachii and scapula, percentage of body fat and body mass index decreased successively at the 8th, 12th, and 16th weeks, while abdominal subcutaneous fat thickness decreased successively at the 4th, 8th, 12th, and 16th weeks (P < 0.05). To conclude, both training modalities and training cycles are factors influencing visceral and subcutaneous fat in recessive obesity female college students. Training modality primarily affects subcutaneous fat in the triceps brachii and scapular region, but the fat loss effects may converge over a longer training cycle; training cycle primarily affects visceral fat area, visceral fat index, abdominal subcutaneous fat, body fat content, and body mass index.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Mining and verification of inflammation-related genes in skeletal muscle of exhaustive exercise rats undergoing cannabidiol intervention
    Zhu Wenning, Sun Lili, Peng Lina, Si Juncheng, Zang Wanli, Yin Weidong, Li Mengqi
    2025, 29 (11):  2347-2356.  doi: 10.12307/2025.338
    Abstract ( 191 )   PDF (2708KB) ( 54 )   Save
    BACKGROUND: Cannabidiol is effective in ameliorating the body’s inflammatory response, but no clear mechanistic studies have been conducted to ameliorate skeletal muscle inflammation induced by exhaustive exercise.
    OBJECTIVE: To explore the mechanism by which cannabidiol improves skeletal muscle inflammation during exhaustive exercise by using transcriptome sequencing technology. 
    METHODS: Thirty-six Sprague-Dawley rats were randomly divided into six groups: blank control group, exercise coconut oil group, exercise control group, 50 mg/kg cannabidiol group, 60 mg/kg cannabidiol group, and 70 mg/kg cannabidiol group, with six rats in each group. Except for rats in the blank control group, rats in each group were subjected to swimming exercise for 9 days to produce the exhaustive exercise model. At the end of each swimming exercise, rats in the cannabidiol groups were given 2 mL of fat-soluble cannabidiol at different concentrations (50, 60, and 70 mg/kg) by gavage; rats in the exercise coconut oil group were given the same volume of coconut oil by gavage until the end of the exercise on the 9th day; and rats in the blank control group and the exercise control group were not given any special treatment. The levels of inflammatory factors and differentially expressed genes in the skeletal muscle of rats in each group were determined using ELISA and transcriptome sequencing techniques. Differentially expressed genes obtained were subjected to KEGG analysis, and the accuracy of the sequencing data was verified by fluorescence quantitative PCR. 
    RESULTS AND CONCLUSION: The results of ELISA showed that the contents of interleukin-6 (P < 0.05), tumor necrosis factor-α (P < 0.01), interleukin-10 and other inflammatory factors in the exercise group increased significantly compared with the blank control group and the coconut oil group. After cannabidiol intervention, the mass concentrations of interleukin-6 and tumor necrosis factor-α showed a sequential decrease with increasing cannabidiol concentration. By comparing GO and KEGG databases, the functional properties of differentially expressed genes were analyzed, and the results showed that the differentially expressed genes were mainly involved in the tumor necrosis factor signaling pathway and the Toll-like receptor signaling pathway. RT-qPCR results showed that the trends of five randomly selected differentially expressed genes were in agreement with the transcriptome sequencing results. To conclude, cannabidiol can improve skeletal muscle inflammation caused by exhaustive exercise.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Relationship between long non-coding RNA and osteoarthritis
    Zheng Shanbin, Xia Tianwei, Sun Jiahao, Chen Zhiyuan, Cao Xun, Zhang Chao, Shen Jirong
    2025, 29 (11):  2357-2367.  doi: 10.12307/2025.360
    Abstract ( 273 )   PDF (1509KB) ( 126 )   Save
    BACKGROUND: As a common disease in middle-aged and elderly, osteoarthritis is difficult to cure, and the pathogenesis is not clear. Long non-coding RNA participates in the pathogenesis of osteoarthritis through many ways, such as regulating translation, promoting or inhibiting mRNA, and adsorbing miRNAs.
    OBJECTIVE: To review the types of common long non-coding RNA in osteoarthritis, and the influence of multiple long non-coding RNAs on the pathological factors related to osteoarthritis, to analyze the future application of long non-coding RNAs in osteoarthritis.
    METHODS: Literature retrieval was conducted in CNKI, WanFang Data, VIP database, PubMed, Web of Science and Sciencedirect databases, using the search terms of “osteoarthritis, degenerative joint disease, degenerative arthritis, OA, LncRNA, long non-coding RNA, long noncoding RNA, long intergenic non-coding RNA” in Chinese and English. All relevant literature published from 1976 and May 2024 was retrieved. After literature screening, induction, analysis and summary, 93 articles were finally included for review.
    RESULTS AND CONCLUSION: This review collected 25 long non-coding RNAs that are well studied with osteoarthritis. Long non-coding RNAs, as a molecular sponge for miRNA, are competing endogenous RNAs to competitively adsorb miRNAs and then affect downstream targets. Long non-coding RNAs can regulate physiopathological processes such as chondrocyte apoptosis and proliferation, cartilage extracellular matrix degradation, and inflammatory responses. Long non-coding RNAs are expected to become a biomarker and potential therapeutic target for the clinical diagnosis and therapeutic prognosis of osteoarthritis, and it may become a new strategy for the clinical treatment of osteoarthritis in the future.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Role and mechanism of alkaloid components of traditional Chinese medicine against knee osteoarthritis
    Shen Xuyu, Luo Chengnuo, Zhang Xiaoyun, Jiang Zhouying, Chai Yuan
    2025, 29 (11):  2368-2376.  doi: 10.12307/2025.365
    Abstract ( 230 )   PDF (1865KB) ( 333 )   Save
    BACKGROUND: At present, modern medical treatment has certain limitations on the treatment of knee osteoarthritis. Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms.
    OBJECTIVE: To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis, providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis.
    METHODS: CNKI, WanFang, PubMed, Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024. The key words were “knee osteoarthritis”“osteoarthritis”“osteoclast”“chondrocyte”“alkaloids”in Chinese and English. Duplicates and obsolete non-referenced literature were excluded, and a total of 68 eligible papers were included for further review. 
    RESULTS AND CONCLUSION: Although traditional Chinese medicine has a long history of treating knee osteoarthritis, only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis. Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis, among which, sophocarpidine, oxymatrine, sinomenine, and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways. Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response, exerting antioxidant response, inhibiting chondrocyte apoptosis, promoting chondrocyte proliferation, and inhibiting osteoclast formation and differentiation.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Exercise therapy for the treatment of chronic nonspecific lower back pain through mechanical-chemical coupling
    Zhang Jiale, Wang Fusen, Qiu Zhenrui, Fan Xinming, Zou Jilong, Bi Zhenggang, Sun Jiabing
    2025, 29 (11):  2377-2384.  doi: 10.12307/2025.373
    Abstract ( 221 )   PDF (1126KB) ( 236 )   Save
    BACKGROUND: Currently, exercise therapy is an effective non-pharmacological treatment for low back pain, and exercise therapy can maintain lumbar spine stabilization through mechanical-chemical coupling between bones and muscles, but there is no clear description of the research progress and optimal treatment protocols for exercise therapy to relieve chronic non-specific lower back pain through mechanical-chemical coupling.
    OBJECTIVE: To review the research progress related to the influence of paravertebral muscles on lumbar spine stabilization during exercise therapy through mechanical-chemical coupling, which in turn relieves chronic non-specific lower back pain, as well as the current optimal treatment protocols of exercise therapy for chronic non-specific lower back pain.
    METHODS: Literature searches were performed in WanFang database, CNKI, VIP, Web of Science, and PubMed database, with search terms of “chronic non-specific low back pain, lumbar spine stabilization, paravertebral muscles, exercise therapy” in Chinese and English. Relevant literature published from database inception to January 2024 was searched and 93 articles were included for final summarization.
    RESULTS AND CONCLUSION: Exercise therapy can act on the paravertebral muscles and bones through appropriate mechanical stimulation and produce corresponding changes. Exercise therapy is an important intervention for chronic non-specific lower back pain as it improves the quality of the paravertebral muscles, primarily through mechanical-chemical coupling, and thus maintains lumbar spine stabilization for better relief of chronic non-specific lower back pain. However, there are no clear reports on the exact effective protocols for exercise therapy to treat chronic non-specific lower back pain through lumbar spine stabilization. The development of an individualized exercise program is particularly important for the treatment and prognosis of chronic non-specific low back pain. Muscle mass and bone mass of the same individual are closely related, and imaging assessment of paravertebral muscle mass and quantity is important for disease detection and intervention. 

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Application of deep learning in oral imaging analysis
    Yang Yuxuan, Tan Jingyi, Zhou Lili, Bian Zirui, Chen Yifan, Wu Yanmin
    2025, 29 (11):  2385-2393.  doi: 10.12307/2025.367
    Abstract ( 411 )   PDF (1421KB) ( 388 )   Save
    BACKGROUND: In recent years, deep learning technologies have been increasingly applied in the field of oral medicine, enhancing the efficiency and accuracy of oral imaging analysis and promoting the rapid development of intelligent oral medicine.
    OBJECTIVE: To elaborate the current research status, advantages, and limitations of deep learning based on oral imaging in the diagnosis and treatment decision-making of oral diseases, as well as future prospects, exploring new directions for the transformation of oral medicine under the backdrop of deep learning technology.
    METHODS: PubMed was searched for literature related to deep learning in oral medical imaging published from January 2017 to January 2024 with the search terms “deep learning, artificial intelligence, stomatology, oral medical imaging.” According to the inclusion criteria, 80 papers were finally included for review.
    RESULTS AND CONCLUSION: (1) Classic deep learning models include artificial neural networks, convolutional neural networks, recurrent neural networks, and generative adversarial networks. Scholars have used these models in competitive or cooperative forms to achieve more efficient interpretation of oral medical images. (2) In the field of oral medicine, the diagnosis of diseases and the formulation of treatment plans largely depend on the interpretation of medical imaging data. Deep learning technology, with its strong image processing capabilities, aids in the diagnosis of diseases such as dental caries, periapical periodontitis, vertical root fractures, periodontal disease, and jaw cysts, as well as preoperative assessments for procedures such as third molar extraction and cervical lymph node dissection, helping clinicians improve the accuracy and efficiency of decision-making. (3) Although deep learning is promising as an important auxiliary tool for the diagnosis and treatment of oral diseases, it still has certain limitations in model technology, safety ethics, and legal regulation. Future research should focus on demonstrating the scalability, robustness, and clinical practicality of deep learning, and finding the best way to integrate automated deep learning decision support systems into routine clinical workflows.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Effects of exercise intervention on intestinal flora in college students: a systematic review
    Liu Zhaozhi, Huang Li, Tian Haodong, Li Lan, Chen Xiao, Tao Yunfei, Peng Li
    2025, 29 (11):  2394-2401.  doi: 10.12307/2025.354
    Abstract ( 237 )   PDF (1459KB) ( 120 )   Save
    BACKGROUND: The regulation of intestinal flora by exercise is closely related to human health, but intestinal flora involves many factors. Existing studies have lacked consistent evidence on the effect of exercise on the intestinal flora of college students.
    OBJECTIVE: To explore the effects of exercise on intestinal flora diversity and species composition of college students. 
    METHODS: Through systematic search of PubMed, Web of Science, Embase, Medline, Cochrane Library, CNKI, WanFang Database and VIP database, eight empirical studies were selected and included, and semi-quantitative analysis was performed on them. 
    RESULTS AND CONCLUSION: In terms of the species diversity of the intestinal flora, both high-intensity interval training and Tai Chi exercise significantly enhance the species diversity of intestinal flora in college students, while aerobic exercise does not have a significant effect on the enhancement of intestinal flora diversity in college students. In terms of the species composition of the intestinal flora, all three exercise modalities significantly alter the compositional structure of the intestinal flora in college students, which can increase the abundance of beneficial bacteria such as Ruminalococcus, Faecalis prevotelli, Blautia, and decrease the abundance of harmful bacteria such as Escherichia spp. Compared with high-intensity interval training, aerobic and Tai Chi exercise causes more elevated abundance of beneficial bacteria. In addition to changes in intestinal flora characteristics, exercise improves body composition, cardiorespiratory function, and executive function in college students, and these health benefits are closely linked to exercise-induced changes in intestinal flora that can produce health benefits for the body through metabolic regulation, barrier function, and neuromodulation. Although studies have confirmed the association between exercise and intestinal flora, the mechanism by which exercise affects intestinal flora has not yet been clarified, and at the same time, localizing the flora related to the host health is the key to targeting intestinal flora as a therapeutic target in the future, all of which are worthy of further attention and investigation.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Machine learning identification of mitochondrial autophagy diagnostic biomarkers and immune infiltration analysis in steroid-induced osteonecrosis of the femoral head
    Huang Keqi, Chen Yueping, Chen Shangtong, Li Jiagen
    2025, 29 (11):  2402-2410.  doi: 10.12307/2025.332
    Abstract ( 223 )   PDF (4239KB) ( 144 )   Save
    BACKGROUND: Mitochondrial autophagy is closely related to the occurrence and development of steroid-induced osteonecrosis of the femoral head (SONFH), but specific biomarkers and regulatory mechanisms remain unclear.
    OBJECTIVE: To identify the key biomarkers of mitochondrial autophagy in steroid-induced osteonecrosis of the femoral head using machine learning algorithms and to conduct an immune infiltration analysis.
    METHODS: The SONFH datasets GSE123568 and GSE74089 were downloaded from the GEO database, serving as the training and validation sets, respectively. Differentially expressed genes between SONFH and control groups were selected, and weighted gene co-expression network analysis was performed. Mitochondrial autophagy-related genes were obtained from MitoCarta3.0 and intersected with differentially expressed genes and module genes. Two machine learning algorithms were utilized to identify key genes of SONFH mitochondrial autophagy, and validated using an external validation set. CIBERSORT and immune infiltration analysis were employed to assess the proportion of immune cells, and ssGSEA was used to analyze the correlation between mitochondrial autophagy genes and immune cells.
    RESULTS AND CONCLUSION: Differential analysis identified a total of 1 163 differentially expressed genes, including 663 upregulated genes and 500 downregulated genes. Weighted gene co-expression network analysis identified 4 key modules, comprising 1 412 module genes. Intersection with mitochondrial autophagy genes yielded 39 intersecting genes as disease-related mitochondrial autophagy genes. Gene ontology enrichment analysis showed that the biological processes were mainly related to heme metabolism, mitochondrial transport, nucleotide bisphosphate metabolism and thioester metabolism, and the cellular components were mainly related to mitochondrial matrix, mitochondrial outer membrane, organelle outer membrane and mitochondrial inner membrane, and the molecular functions were mainly related to fatty acid ligase activity, iron-sulfur cluster binding, and cofactor A ligase activity. Kyoto Encyclopedia of Genes and Genomes enrichment analysis mapped out a total of six pathways, which were mainly related to fatty acid degradation, mitochondrial autophagy, butyric acid metabolism, fatty acid biosynthesis and cofactor biosynthesis. Through LASSO regression and RFE-SVM algorithm analysis, four intersecting genes (ALDH5A1, FBXL4, MCL1, and STOM) were identified. The receiver operating characteristic curves of the four core genes and the diagnostic column chart validation set were all greater than 0.9. The occurrence and development of SONFH were related to immune cells such as dendritic cells, bone marrow-derived suppressor cells, regulatory T cells, and central memory CD8 T cells. To conclude, the four key mitochondrial autophagy genes ALDH5A1, FBXL4, MCL1, and STOM play a crucial role in the progression of SONFH through osteoclast differentiation and immune mechanisms. Additionally, all four genes have good disease prediction efficacy and can serve as biomarkers for the diagnosis and treatment of SONFH.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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    Machine learning identification of LRRC15 and MICB as immunodiagnostic markers for rheumatoid arthritis
    Tian Yanhu, Huang Xinan, Guo Tongtong, Rusitanmu·Ahetanmu, Luo Jiangmiao, Xiao Yao, Wang Chao, Wang Weishan
    2025, 29 (11):  2411-2420.  doi: 10.12307/2025.361
    Abstract ( 216 )   PDF (6899KB) ( 401 )   Save
    BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disease. Early diagnosis is crucial for preventing disease progression and for effective treatment. Therefore, it is of significance to investigate the diagnostic characteristics and immune cell infiltration of rheumatoid arthritis.
    OBJECTIVE: Based on the Gene Expression Omnibus (GEO) database, to screen potential diagnostic markers of rheumatoid arthritis using machine learning algorithms and to investigate the relationship between the diagnostic characteristics of rheumatoid arthritis and immune cell infiltration in this pathology.
    METHODS: The gene expression datasets of synovial tissues related to rheumatoid arthritis were obtained from the GEO database. The data sets were merged using a batch effect removal method. Differential expression analysis and functional correlation analysis of genes were performed using R software.  Bioinformatics analysis and three machine learning algorithms were used for the extraction of disease signature genes, and key genes related to rheumatoid arthritis were screened. Furthermore, we analyzed immune cell infiltration on all differentially expressed genes to examine the inflammatory state of rheumatoid arthritis and investigate the correlation between their diagnostic characteristics and infiltrating immune cells.
    RESULTS AND CONCLUSION: In both rheumatoid arthritis and normal synovial tissues, we identified 179 differentially expressed genes, with 124 genes up-regulated and 55 genes down-regulated. Enrichment analysis revealed a significant correlation between rheumatoid arthritis and immune response. Three machine learning algorithms identified LRRC15 and MICB as potential biomarkers of rheumatoid arthritis. LRRC15 (area under the curve=0.964, 95% confidence interval: 0.924-0.992) and MICB (area under the curve=0.961, 95% confidence interval: 0.923-0.990) demonstrated strong diagnostic performance on the validation dataset. The infiltration of 13 types of immune cells was altered, with macrophages being the most affected. In rheumatoid arthritis, the majority of proinflammatory pathways in immune cell function were activated. Immunocorrelation analysis revealed that LRRC15 and MICB had the strongest correlation with M1 macrophages. To conclude, this study identified LRRC15 and MICB as potential diagnostic markers for rheumatoid arthritis, with strong diagnostic performance and significant correlation with immune cell infiltration. Machine learning and bioinformatics analysis deepened the understanding of immune infiltration in rheumatoid arthritis and provided new ideas for the diagnosis and treatment of rheumatoid arthritis.

    中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程
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