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    18 January 2025, Volume 29 Issue 2 Previous Issue    Next Issue
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    Effect and mechanism of different training modes on skeletal muscle remodeling in rats with heart failure induced by myocardial infarction
    Fu Changxi , He Ruibo , Ma Gang , Zhu Zheng , Ma Wenchao
    2025, 29 (2):  221-230.  doi: 10.12307/2025.211
    Abstract ( 312 )   PDF (1836KB) ( 204 )   Save
    BACKGROUND: Acute myocardial infarction can cause cardiac remodeling and heart failure, as well as skeletal myopathy, affecting patients' quality of life. Exercise therapy is an important rehabilitation method for patients with heart failure; however, the optimal exercise prescription has not been clarified.
    OBJECTIVE: To compare the effects of different exercise modes (aerobic exercise, resistance exercise) on skeletal muscle remodeling in rats with acute myocardial infarction induced heart failure and to explore the possible mechanism, so as to provide a basis for optimizing the exercise rehabilitation program.
    METHODS: Forty-eight Sprague-Dawley rats were randomly divided into sham operation group, myocardial infarction group, aerobic exercise group and resistance exercise group. Coronary artery ligation was used to create model of heart failure. After 3 months, animals in the aerobic exercise group and resistance exercise group underwent 12 weeks of corresponding exercise mode interventions, while those in the sham operation group and myocardial infarction group were kept quietly in mouse cages. After the experiment, maximal running speed and maximal weight-bearing load were measured by graded treadmill exercise test and ladder-climbing test respectively, and heart structure and function were evaluated by echocardiography. The heart was isolated, and hematoxylin-eosin staining and Sirius red staining were performed to detect cardiac remodeling. For the gstrocnemius muscle, ATPase staining was performed to observe changes in muscle fiber type and cell cross-sectional area, dihydroethidium method was used to evaluate reactive oxygen species levels, enzyme-linked immunosorbent method was used to determine malondialdehyde content and antioxidant enzyme activity, western blot was used to determine the expression of ubiquitin-proteasome system proteins, and the number of activated satellite cells (Pax7+/MyoD+) were detected by double immunofluorescence staining.
    RESULTS AND CONCLUSION: (1) Exercise performance: Compared with the sham operation group, maximal running speed and maximal weight-bearing load in the myocardial infarction group decreased (P < 0.05); compared with the myocardial infarction group, the maximal running speed of the aerobic exercise group and the maximal weight-bearing load of the resistance exercise group increased (P < 0.05). (2) Cardiac remodeling: Compared with the sham operation group, infarction area, myocardial cell cross-sectional area, and collagen content in the myocardial infarction group increased (P < 0.05), while left ventricular ejection fraction and shortening fraction decreased (P < 0.05); compared with the myocardial infarction group, there was no statistical difference in the above parameters in both aerobic exercise resistance exercise groups (P > 0.05). (3) Skeletal muscle remodeling: Compared with the sham operation group, gastrocnemius muscle mass, gastrocnemius muscle mass index, cell cross-sectional area, superoxide dismutase activity, glutathione peroxidase activity, and the number of activated satellite cells decreased in myocardial infarction group (P < 0.05), while reactive oxygen species content, malondialdehyde content, and the protein expression of ubiquitin, MuRF1 and MAFbx increased (P < 0.05); compared with the myocardial infarction group, gastrocnemius muscle mass index, superoxide dismutase activity, the number of activated satellite cells increased in both aerobic exercise and resistance exercise groups (P < 0.05), while reactive oxygen species content and the protein expression of ubiquitin, MuRF1, and MAFbx decreased (P < 0.05); compared with the aerobic exercise group, gastrocnemius muscle mass, gastrocnemius muscle mass index, cell cross-sectional area, reactive oxygen species content, malondialdehyde content, the number of activated satellite cells increased in resistance exercise group (P < 0.05), while superoxide dismutase activity, glutathione peroxidase activity down-regulated (P < 0.05). To conclude, aerobic exercise and resistance exercise can both improve exercise performance of rats with heart failure, and the mechanism is related to reducing oxidative stress, inhibiting ubiquitin-proteasome system activity and activating satellite cells to improve skeletal muscle remodeling. Aerobic exercise has a better effect on improving skeletal muscle oxidative stress, while resistance exercise has a more significant effect on promoting skeletal muscle regeneration.
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    Salidroside promotes osteogenic differentiation of MC3T3-E1 cells: an in vitro experiment
    Liu Zhaohui, Han Xiaoqian, Duan Xin, Guo Pengda, Zhang Yuntao
    2025, 29 (2):  231-237.  doi: 10.12307/2025.207
    Abstract ( 304 )   PDF (1865KB) ( 82 )   Save
    BACKGROUND: Bone defects can directly affect the success rate and long-term stability of dental implants. Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts, but less is reported on its pathways related to osteogenic differentiation.
    OBJECTIVE: To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments.
    METHODS: Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside (0.5, 1, 5, 10, and 50 μmol/L) in promoting the proliferation and differentiation of MC3T3-E1 cells. There were four groups in the experiment: control group, salidroside group, salidroside+ LY294002 group, and LY294002 group, which were cultured with osteogenic induction solution, osteogenic induction solution containing 10 μmol/L salidroside, osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002, and osteogenic induction solution containing 10 μmol/L LY294002, respectively. The effects of salidroside and LY294002, an inhibitor of the PI3K/Akt signaling pathway, on the expressions of genes and proteins related to osteogenesis were observed.
    RESULTS AND CONCLUSION: Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L. Compared with the control group, salidroside could promote mineralization, promote cell adhesion, reduce cell death, increase mRNA expression of Runx-2, osteocalcin and osteopontin (P < 0.01), and increase protein expression of Runx-2 and p-Akt (P < 0.01). However, the addition of LY294002 reversed the above results. These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins, which may be related to the activation of PI3K/Akt signaling pathway.
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    Effects of the prolyl hydroxylase 2 inhibitor cpd17 on mouse osteogenic precursor cells
    Du Zhongqiu, Qi Xiaoyang, Yang Ping, Yu Jianglin, Chen Yixin, Zhang Linjian, Qiu Xusheng
    2025, 29 (2):  238-244.  doi: 10.12307/2025.290
    Abstract ( 205 )   PDF (2124KB) ( 163 )   Save
    BACKGROUND: Prolyl hydroxylase domain 2 (PHD2) inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats. cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University. It is effective in the treatment of renal anemia with few side effects, but its effect on bone formation and bone resorption is still unclear. 
    OBJECTIVE: To investigate the effects of cpd17 on mouse osteogenic precursor cells.
    METHODS: Osteogenic precursor cells were treated with cpd17. Alkaline phosphatase activity and extracellular matrix mineralization were measured, and the expression levels of osteogenesis- and osteoclastogenesis-related markers, as well as PHD2 and hypoxia-inducible factor 1α, were detected. After inhibition of the hypoxia-inducible factor 1α pathway using LW6 (a hypoxia-inducible factor 1α pathway inhibitor), alkaline phosphatase activity and extracellular matrix mineralization were detected again, as well as the expression levels of osteogenesis- and osteoclastogenesis-related markers, PHD2 and hypoxia-inducible factor 1α. 
    RESULTS AND CONCLUSION: cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization, up-regulated the expression of osteogenesis-related markers, down-regulated the expression of osteoclastogenesis-related markers, up-regulated the expression of hypoxia-inducible factor 1α, down-regulate the expression of PHD2. However, cpd17’s effects were significantly attenuated by LW6. To conclude, the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.  
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    Carnosic acid inhibits osteoclast differentiation by inhibiting mitochondrial activity
    Li Haishan, Wu Yuheng, Liang Zixuan, Zhang Shiyin, Zhang Zhen, Mai Bin, Deng Wei, Li Yongxian, Tang Yongchao, , Zhang Shuncong, , Yuan Kai,
    2025, 29 (2):  245-253.  doi: 10.12307/2025.205
    Abstract ( 218 )   PDF (2118KB) ( 89 )   Save
    BACKGROUND: Carnosic acid, a bioactive compound found in rosemary, has been shown to reduce inflammation and reactive oxygen species (ROS). However, its mechanism of action in osteoclast differentiation remains unclear.
    OBJECTIVE: To investigate the effects of carnosic acid on osteoclast activation, ROS production, and mitochondrial function.
    METHODS: Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro. Different concentrations of carnosic acid (0, 10, 15, 20, 25 and 30 μmol/L) were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration. Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days. The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining, F-actin staining, H2DCFDA probe and mitochondrial ROS, and Mito-Tracker fluorescence detection. Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway.
    RESULTS AND CONCLUSION: Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton, with the highest inhibitory effect observed in the high concentration group 
    (30 μmol/L). Carnosic acid exhibited the most significant inhibitory effect during the early stages (days 1-3) of osteoclast differentiation compared to other intervention periods. Fluorescence imaging using the H2DCFDA probe, mitochondrial ROS, and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential, thereby influencing mitochondrial function. The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1, CTSK, MMP9, and C-fos proteins associated with osteoclast differentiation, and downregulate the expression of NFATc1, Atp6vod2, ACP5, CTSK, and C-fos genes related to osteoclast differentiation. Furthermore, carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation. Overall, carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.
    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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    Expression of IP3R2 and RYR2 mediated Ca2+ signals in a mouse model of delayed encephalopathy after acute carbon monoxide poisoning 
    Zhao Jili, Meng Tianyu, Yue Yarong, Zhang Xin, Du Wenqian, Zhang Xinyu, Xue Hui, Xiang Wenping
    2025, 29 (2):  254-261.  doi: 10.12307/2025.246
    Abstract ( 184 )   PDF (1480KB) ( 97 )   Save
    BACKGROUND: Ca2+ expression in astrocytes has been found to be closely related to cognitive function, and the Ca2+ signaling pathway regulated by inositol 1,4,5-trisphosphate receptors (IP3R2) and ryanodine receptor (RYR) 2 receptors has become a hot spot in the study of cognitive disorder-related diseases.
    OBJECTIVE: To investigate the expression of Ca2+ signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning, and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning.
    METHODS: C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group. An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group, and the same amount of air was inhaled in the control group. Behavioral and neuronal changes, astrocyte specific marker glial fibrillary acidic protein, IP3R2, RYR2 receptor and Ca2+ concentration in astrocytes of the two groups were detected using Morris water maze, hematoxylin-eosin staining, western blot, immunofluorescence double labeling and Ca2+ fluorescence probe at 21 days after modeling.
    RESULTS AND CONCLUSION: In the Morris water maze, the escape latency of the experimental group was significantly longer than that of the control group (P < 0.05). Hematoxylin-eosin staining results showed that in the experimental group, the number of hippocampal pyramidal cells decreased, the cell structure was disordered, and the nucleus was broken and dissolved. Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus, and the expressions of IP3R2, RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group (P < 0.05). Western blot analysis showed that the expressions of IP3R2, RYR2, and glial fibrillary acidic protein in the hippocampus of the experimental group were increased (P < 0.05). Ca2+ concentration in hippocampal astrocytes increased significantly in the experimental group (P < 0.05). To conclude, astrocytes may affect Ca2+ signals by mediating IP3R2 and RYR2 receptors, then impair the cognitive function of mice with carbon monoxide poisoning, and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.
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    Effects and mechanisms of swimming for inhibiting traumatic joint contracture in a rat model 
    Shui Xiaoping, Li Chunying, Zhang xin, Li Bin, Feng Chao, Zhou Hongyu, Chen Ke, Liao Yingying
    2025, 29 (2):  262-268.  doi: 10.12307/2025.241
    Abstract ( 293 )   PDF (2454KB) ( 61 )   Save
    BACKGROUND: Early exercise treatment is the main prevention way for traumatic joint contracture and is also a research focus. Swimming may be a potential intervention for joint contracture due to the special physical properties of water.  
    OBJECTIVE: To explore the effects of swimming on the development of joint contracture in a rat model and study its mechanisms. 
    METHODS: Twenty-four Sprague-Dawley rats were randomly divided into a blank control group (n=8) and a joint contracture group (n=16). After the surgical operation of knee joint contracture rat models, the joint contracture group was randomly subdivided into a surgical control group (n=8) and a swimming treatment group (n=8). Swimming started in the swimming treatment group in the second week after surgery and lasted for a total of 5 weeks. At the 6th week after surgery, the body mass, knee joint range of motion, and quadriceps diameter were tested, and the diameter/body mass index was calculated. Hematoxylin-eosin staining was performed to detect the pathological changes in the knee joint capsule and quadriceps muscle, and Masson staining was used to observe fibrotic changes in the knee joint capsule. Furthermore, the protein expression of transforming growth factor β1 and type I collagen in the knee joint capsule was quantified by immunohistochemical assay and western blot was performed to detect the protein expression of MuRF1 in the quadriceps femoris.
    RESULTS AND CONCLUSION: Compared with the blank control group, the knee range of motion decreased in the surgical control and swimming treatment groups (P < 0.01), and knee extension deficit and arthrogenic extension deficit were significantly increased (P < 0.01), the diameter of the quadriceps muscle was decreased (P < 0.01), the joint capsule showed significant fibrosis, the quadriceps muscle was atrophied, and the diameter/body mass index was decreased (P < 0.01). Compared with the surgical control group, the swimming treatment group showed a significant increase in knee joint range of motion and quadriceps diameter (P < 0.01), and significant improvement in joint capsule fibrosis and quadriceps atrophy. Compared with the blank control group, collagen fiber content and expression of transforming growth factor β1 and type I collagen were increased in the joint capsule of rats in both the surgical control group and the swimming treatment group (P < 0.01). Compared with the surgical control group, collagen fiber content and expression of transforming growth factor β1 and type I collagen protein in the joint capsule were decreased in the swimming treatment group. Compared with the blank control group, the expression of MuRF1 protein in the quadriceps muscle of rats in the surgical control group and the swimming treatment group was increased (P < 0.05). Compared with the surgical control group, the expression of MuRF1 protein in the quadriceps muscle of rats in the swimming treatment group was decreased 
    (P < 0.05). To conclude, early swimming intervention reduces transforming growth factor β1 and type I collagen expression in the joint capsule of traumatic joint contracture rats, decreases MuRF1 expression in the quadriceps muscle, and increases joint range of motion and quadriceps diameter, thereby inhibiting the development of joint contracture.
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    Effects of different exercise interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats 
    Hu Shujuan, Cheng Ping, Zhang Xiao, Ding Yiting, Liu Xuan, Pu Rui, Wang Xianwang
    2025, 29 (2):  269-278.  doi: 10.12307/2025.274
    Abstract ( 207 )   PDF (1807KB) ( 341 )   Save
    BACKGROUND: Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis. However, the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed.
    OBJECTIVE: To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats.
    METHODS: Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group (n=12) and modeling group (n=20) after 1 week of adaptive feeding. Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin. After successful modeling, the rats were randomly divided into diabetic control group (n=6), moderate-intensity exercise group (n=6) and high-intensity intermittent exercise group (n=6). The latter two groups were subjected to treadmill training at corresponding intensities, once a day, 50 minutes each, and 5 days per week. Exercise intervention in each group was carried out for 6 weeks. After the intervention, ELISA was used to detect blood glucose and blood lipids of rats. The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining. The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR. The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence.
    RESULTS AND CONCLUSION: Compared with the normal control group, fasting blood glucose, triglyceride, low-density lipoprotein cholesterol, insulin resistance index in the diabetic control group were significantly increased (P < 0.01), insulin activity was decreased (P < 0.05), and the mRNA and protein levels of carboxylesterase 1, never in mitosis gene A related kinase 7 (NEK7) and interleukin 18 in skeletal muscle tissue were upregulated (P < 0.05). Compared with the diabetic control group, fasting blood glucose, triglyceride, low-density lipoprotein cholesterol, and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated (P < 0.05), and insulin activity was increased (P < 0.05). Moreover, compared with the diabetic control group, the mRNA level of NEK7 and the protein levels of carboxylesterase 1, NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group (P < 0.05), while the mRNA levels of carboxylesterase 1, NEK7, NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group (P < 0.05). Hematoxylin-eosin staining showed that compared with the diabetic control group, the cavities of myofibers in the moderate-intensity exercise group became smaller, the number of internal cavities was reduced, and the cellular structure tended to be more intact; the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged, with irregular tissue shape and increased cavities in myofibers. To conclude, both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose, lipid, insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats. Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle, while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle. In addition, the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.
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    Gushukang interferes with osteoclasts: activation of nuclear factor erythroid 2-related factor 2 regulates the c-Fos/NFATc1 pathway in the treatment of osteoporosis
    Hou Chengzhi, Han Jiatong, Wei Guangcheng, Zhuo Zechuan, Li Qiuyue, Zhao Yong, Yu Zhangjingze
    2025, 29 (2):  279-285.  doi: 10.12307/2025.275
    Abstract ( 269 )   PDF (1282KB) ( 137 )   Save
    BACKGROUND: It has been shown that Gushukang affects bone metabolism by regulating nucleotide and amino acid metabolism and immune mechanisms. Current research on the mechanism of Gushukang in the treatment of osteoporosis primarily focuses on osteoblast regulation and requires further improvement from the perspective of osteoclasts.
    OBJECTIVE: To investigate the mechanism by which Gushukang interferes with osteoclasts in the treatment of osteoporosis using RAW264.7 cells as the research model. 
    METHODS: Twenty-four 8-week-old female Sprague-Dawley rats were randomly divided into four groups (n=6 per group): the three experimental groups were given 1, 2 and 4 g/kg osteoporosis solution by gavage (2 times per day), and the control group was given an equal amount of distilled water by gavage (2 times per day). After 7 days of intragastric administration, aortic blood samples were extracted to collect serum samples using centrifugation, and serum samples from the same groups were combined to obtain the low-, medium-, and high-concentration Gushukang-containing and normal sera for the subsequent experiments. (1) RAW264.7 cells were cultured in six groups: normal serum was added to the control group; low, medium, and high concentration groups were added with low, medium, and high concentrations of Gushukang-containing serum, respectively; ML385, a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor was given in the Nrf2 inhibitor group; and t-BHQ, a Nrf2 activator, was added in the Nrf2 activator group. Cell viability was detected using the cell counting kit-8 assay. (2) The 3rd generation RAW 264.7 cells were cultured and divided into five groups: the blank control group was added with normal serum, the osteoclast group was added with receptor activator of nuclear factor κB ligand (RANKL), and the low-, medium-, and high-concentration groups were added with low-, medium-, and high-concentration Gushukang-containing serum based on the addition of RANKL. Tartrate-resistant acid phosphate staining was performed after 5 days of culture. (3) RAW264.7 cells were cultured and divided into five groups: blank control group was cultured with normal serum, osteoclast group cultured with normal serum and RANKL, high concentration+osteoclast group cultured with RANKL+high concentration Gushukang-containing serum, osteoclast+Nrf2 agonist group cultured with RANKL+t-BHQ, and high concentration+osteoclast+Nrf2 inhibitor group cultured with RANKL+high concentration Gushukang-containing serum+ML385. Western blot assay and determination of reactive oxygen content were performed after 5 days of culture.
    RESULTS AND CONCLUSION: The cell counting kit-8 results indicated that Gushukang-containing serum, NRF2 inhibitor or agonist had no significant effect on RAW264.7 cell viability. Tartrate-resistant acid phosphate staining results demonstrated that Gushukang-containing serum exhibited a concentration-dependent inhibitory effect on osteoclast differentiation. Western blot analysis and determination of reactive oxygen species revealed that compared with the blank control group, Nrf2 protein expression was decreased in the osteoclast group (P < 0.05), while c-Fos and NFATc1 protein expression and reactive oxygen species content were elevated (P < 0.05); compared with the osteoclast group, Nrf2 protein expression was elevated and reactive oxygen species content was decreased in the high-concentration+osteoclast group, osteoclast+Nrf2 agonist group, and high-concentration+osteoclast+Nrf2 inhibitor group (P < 0.05), while c-Fos and NFATc1 protein expression was decreased in the high concentration+osteoclast group and osteoclast+Nrf2 agonist group (P < 0.05); compared with the high concentration+osteoclast group, Nrf2 protein expression was decreased (P < 0.05) and reactive oxygen species content was elevated (P < 0.05) in the high concentration+osteoclast+Nrf2 inhibitor group. To conclude, Gushukang reduces reactive oxygen species production by activating Nrf2, thereby inhibiting downstream of the c-Fos/NFATc1 pathway and suppressing osteoclast differentiation.
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    Changes in glucose metabolism and intestinal flora in patients with type 2 diabetes mellitus after high-intensity intermittent exercise 
    Yu Hanglin, Tian Haodong, Wen Shiyuan, Huang Li, Liu Haowei, Li Hansen, Wang Peisong, Peng Li
    2025, 29 (2):  286-293.  doi: 10.12307/2025.240
    Abstract ( 240 )   PDF (1619KB) ( 195 )   Save
    BACKGROUND: Exercise has a regulatory effect on intestinal flora and glucose metabolism, but the effects of high-intensity intermittent exercise on intestinal flora and glucose metabolism in patients with type 2 diabetes mellitus are unclear. 
    OBJECTIVE: To investigate the effects of high-intensity intermittent exercise on glucose metabolism and intestinal flora in patients with type 2 diabetes mellitus. 
    METHODS: Eleven patients with type 2 diabetes mellitus were recruited, among which, two were lost to the follow-up and nine were finally enrolled. High-intensity intermittent exercise intervention was conducted 3 times per week for 6 continuous weeks. Fasting blood and fecal samples were collected before and after the intervention. Glucose metabolism indexes were detected in the blood samples, and intestinal flora was detected in the fecal samples. Changes in glucose metabolism indexes and intestinal flora indexes of the patients with type 2 diabetes mellitus before and after the intervention were compared. 
    RESULTS AND CONCLUSION: After 6 weeks of high-intensity intermittent exercise intervention, fasting blood glucose and glycosylated serum protein levels in patients were significantly reduced (P < 0.05), and fasting insulin, although not significantly changed, was decreased compared with before intervention.  Alpha diversity analysis showed that the diversity (Shannon index), richness (Chao index) and coverage (Coverage index) did not change significantly. Venn diagrams showed that the relative abundance of Bacteroidetes, Actinobacteria, Proteobacteria, and Fusobacteria in the intestinal flora of the patients increased, and the relative abundance of Firmicutes decreased, and a significant decrease was seen in Ruminococcus_torques and Ruminococcus_gnavus in the Firmicutes, which were both positively correlated with the abnormalities of the glycemic metabolism-related indicators, as well as with other disease development. All these findings indicate that high-intensity intermittent exercise intervention has an improvement effect on the glycemic metabolism-related indexes of patients with type 2 diabetes mellitus, and the abundance of beneficial flora in the intestinal tract increases, and the abundance of harmful flora decreased, enhancing the stability of the intestinal flora in patients.
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    Weighted gene co-expression network analysis and machine learning identification of key genes in rheumatoid arthritis synovium
    Wu Yingkai, Shi Gaolong, Xie Zonggang
    2025, 29 (2):  294-301.  doi: 10.12307/2025.244
    Abstract ( 228 )   PDF (2702KB) ( 233 )   Save
    BACKGROUND: Rheumatoid arthritis is a condition that affects the entire immune system in the body and is known for causing inflammatory hyperplasia in the joints and destruction of articular cartilage. The pathogenesis of rheumatoid arthritis is still unclear; therefore, there is an urgent need to discover new highly sensitive and specific diagnostic biomarkers.
    OBJECTIVE: To identify and screen key genes in the synovium of rheumatoid arthritis patients using bioinformatics techniques and machine learning algorithms and to construct and validate a rheumatoid arthritis prediction model.
    METHODS: Three datasets containing synovial tissue samples from rheumatoid arthritis patients (GSE77298, GSE55235, GSE55457) were downloaded from the Gene Expression Omnibus (GEO) database. GSE77298 and GSE55235 were used as the training set, while GSE55457 served as the test set, with a total of 66 samples, including 39 samples from rheumatoid arthritis patients and 27 normal synovial samples. Differentially expressed genes in the training set were selected using R language, and then the weighted gene co-expression network analysis was used to modularize the genes in the training set. The most relevant module was selected, and feature genes within this module were identified. Differentially expressed genes and the feature genes from the module were intersected for the subsequent machine learning analysis. Three machine learning methods, namely the least absolute shrinkage and selection operator algorithm, support vector machine with recursive feature elimination, and random forest algorithm, were employed to further analyze the intersected genes and identify the hub genes. The hub genes obtained from these three machine learning algorithms were intersected again to obtain the key genes in the synovium of rheumatoid arthritis. A predictive rheumatoid arthritis model was constructed using these key genes as variables, and the risk of developing rheumatoid arthritis in patients was inferred based on the model. The receiver operating characteristic curve was used to determine the diagnostic value of the rheumatoid arthritis prediction model and its key genes.
    RESULTS AND CONCLUSION: Through the differential analysis, a total of 730 differentially expressed genes were identified in the training set, and 185 feature genes were identified in the weighted gene co-expression network analysis feature modules. There were 159 intersected genes obtained. There were 4 hub genes identified by the least absolute shrinkage and selection operator algorithm, 11 hub genes by the support vector machine with recursive feature elimination algorithm, and 5 hub genes by the random forest algorithm. After intersection, 2 key genes (TNS3 and SDC1) were obtained. Based on the two key genes, a nomogram model was constructed in the training and test sets, with good fit between the calibration prediction curve and the standard curve, and good clinical efficacy in predicting the onset of rheumatoid arthritis. These findings indicate that TNS3 and SDC1, obtained based on bioinformatics and machine learning algorithms, may become key targets for the diagnosis and treatment of rheumatoid arthritis.
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    Analysis of oxidative stress-related genes and immune infiltration in osteoarthritis
    Wu Ao, Yu Peng, Teng Jiawen, Kong Peng, Bian Sishan
    2025, 29 (2):  302-311.  doi: 10.12307/2025.245
    Abstract ( 302 )   PDF (9648KB) ( 42 )   Save
    BACKGROUND: At present, the pathogenesis of osteoarthritis is still unclear, and there is a lack of effective means to control the disease. Research on osteoarthritis is mostly concentrated in the field of immunity, and there are few studies in the field of oxidative stress. 
    OBJECTIVE: To explore the roles of oxidative stress and immune infiltration in osteoarthritis and to predict related miRNAs and therapeutic agents. 
    METHODS: The GSE55235 dataset (10 samples of osteoarthritis and 10 healthy control samples) and the GSE55457 dataset (10 samples of osteoarthritis and 10 healthy control samples) were obtained from the GEO database for merging to obtain their differentially expressed genes that were combined with oxidative stress genes to get the differentially expressed genes of oxidative stress. The differentially expressed genes of oxidative stress were analyzed for KEGG and GO enrichment, and the osteoarthritis pathways and biological processes were evaluated using GSEA enrichment analysis. The protein-protein interaction network was constructed using the STRING online website and Cytoscape software, and the Degree algorithm was run to get the key genes. The GSE1919 dataset was obtained from the GEO database as a validation dataset, and the key genes were analyzed by variance analysis and receiver operating characteristic curve analysis to get the core genes. In addition, immune infiltration was evaluated by CIBERSORT and the correlation between core genes and immune cells was explored. miRNA prediction of core genes was performed using TargetScan and target drugs were predicted using the DSigDB database. 
    RESULTS AND CONCLUSION: Sixty-five differentially expressed genes and five core genes (IL1B, CXCL8, MYC, NFKBIA, JUN) associated with oxidative stress were identified. Enrichment analysis showed that differentially expressed genes associated with oxidative stress were concentrated in the pathways of oxidative stress, interleukin-17, osteoclast differentiation, fluid shear stress and atherosclerosis. The area under the receiver operating characteristic curve for the five core genes exceeded 0.85, indicating their excellent specificity and sensitivity in diagnosing bone and joint conditions, as well as their close association with immune cells. The predicted miRNA was has-miR-3937, and the therapeutic small-molecule drugs were metformin, ionomycin and celecoxib. To conclude, oxidative stress and immune infiltration exist in osteoarthritis, and immune infiltration is involved in activating oxidative stress. The core genes and predicted miRNAs can be used as novel markers for the diagnosis of osteoarthritis, and small molecule drugs are predicted to treat osteoarthritis.
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    Mechanism by which KRT18 interacts with mRNA and long non-coding RNA to regulate intervertebral disc nucleus pulposus cell injury
    Liu Zhongyuan, Li Yang, Zhang Zhiwen
    2025, 29 (2):  312-321.  doi: 10.12307/2025.239
    Abstract ( 247 )   PDF (3200KB) ( 231 )   Save
    BACKGROUND: Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration, and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease, but its specific role in the nucleus pulposus cells has not yet been fully determined.
    OBJECTIVE: To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism.
    METHODS: Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration. iRIP-seq, functional enrichment analysis, and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18. Subsequently, KRT18 was knocked down in nucleus pulposus cells based on the analysis results, and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR, respectively.
    RESULTS AND CONCLUSION: Through iRIP-seq analysis, we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences, indicating that KRT18 may be involved in regulating RNA transcription, translation, stability or play a role in cell signaling pathways. It can stably bind to mature mRNA, among which highly expressed genes include CRLF1, IGFBP4, etc. At the same time, the peak genes of long non-coding RNA binding with it include SNHG25, SNHG12, NEAT1, USP32, EIF4A2 and CDH4. Most of these genes are involved in various biological processes such as apoptosis and inflammation, and can mediate related pathways of extracellular matrix metabolism. KRT18 can regulate their stability, transport, translation, splicing and other functions, thus affecting gene expression and cell function. We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells, and found that the level of extracellular matrix metabolism was inhibited and unbalanced, resulting in intervertebral disc degeneration in vitro. This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time, and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration, laying a foundation for future research on the key functions of KRT18.
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    Causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration
    Huang Renjun, Yang Jingyan, Ma She, Wang Chaoyi, Zhao Yuyang, Yu Dong
    2025, 29 (2):  322-330.  doi: 10.12307/2025.206
    Abstract ( 228 )   PDF (3834KB) ( 188 )   Save
    BACKGROUND: Observational studies have shown that intervertebral disc degeneration affects sedentary and physical activity levels; however, the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration is unclear.
    OBJECTIVE: To explore the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration using the Mendelian randomization method.
    METHODS: Five features associated with behavioral correlations in the Oswestry disability index score, including time spent watching TV, time spent on the computer, and light/moderate/vigorous physical activity, were selected from large-scale population-based genome-wide association studies, and instrumental variables were extracted for each of these behaviorally related features. Mendelian randomization analyses were performed in conjunction with the extraction of intervertebral disc degeneration as an outcome from the Finn Gen latest version 9 database. The results were analyzed using the inverse variance weighted, MR-Egger regression, simple mode, weighted mode, weighted median estimator, and regression model odds ratios (OR) and 95% confidence interval (CI) to assess the causal relationship between sedentary and physical activity levels in the Oswestry disability index scoring and intervertebral disc degeneration. Cochran’s Q was used to test for heterogeneity, MR-Egger intercept to test for multiplicity, and leave-one-out to test the sensitivity of single nucleotide polymorphisms to the causal relationship between exposure factors and disc degeneration.
    RESULTS AND CONCLUSION: The results of the Mendelian randomization analysis using inverse variance weighted method showed a positive causal association between time spent watching TV/on the computer and the risk of intervertebral disc degeneration (OR=1.775, 95% CI: 1.418-2.221, P < 0.001)/(OR=1.384, 95% CI: 1.041-1.839, P < 0.001), an inverse causal association between light physical activity and the risk of intervertebral disc degeneration (OR=1.000, 95% CI: 0.999-1.000, P=0.020). MR-Egger intercept analysis indicated there was potential horizontal polytropy between light physical activity and intervertebral disc degeneration (P=0.005), while there was no horizontal pleiotropy between time spent watching TV, time spent on the computer and intervertebral disc degeneration (P=0.521, P=0.851). Cochran’s Q analysis showed that heterogeneity was observed between time spent watching TV, time spent on the computer and intervertebral disc degeneration (P=3.33×10-11, P=0.001), and no significant heterogeneity was observed between light physical activity and intervertebral disc degeneration (P=0.186). Overall, there is a bidirectional causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration, i.e., not only does intervertebral disc degeneration affect sedentary and physical activity levels in the Oswestry disability index score, but sedentary and physical activity levels in the Oswestry disability index score also affect intervertebral disc degeneration. These findings add to the genetic evidence for a positive effect of light physical activity on intervertebral disc degeneration, indicate that moderate/vigorous physical activity shows no significant causal relationship with intervertebral disc degeneration, and expand the evidence base for sedentary behaviors such as prolonged time spent watching TV/on the computer as a risk factor for intervertebral disc degeneration.
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    Effect of ultrasound-guided needle-knife release of the ligamentum flavum on the expression of integrin alpha5 and beta1 in degenerative rabbit lumbar intervertebral discs
    Chen Can, Zhao Yu, Hu Binhan, Du Mengfan, Liu Junning, Niu Susheng, Zhang Yan
    2025, 29 (2):  331-338.  doi: 10.12307/2025.204
    Abstract ( 179 )   PDF (2104KB) ( 253 )   Save
    BACKGROUND: Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration, and ultrasound guidance can increase the precision of needle-knife release; however, the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified.
    OBJECTIVE: To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. 
    METHODS: Twenty-four New Zealand rabbits were randomized into control (n=6) and model (n=18) groups. A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine. After successful modeling, the model rabbits were subdivided into a control group, a model group, an ultrasonic needle-knife group, and a sham needle-knife group according to a random number table method, with six animals in each group. The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1, once every week, for a total of four times. The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group, but the ligamentum flavum was not released. At 30 days after the intervention, MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment. Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment. Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment. RT-PCR and western blot were used to detect the expression of integrin α5 and β1, p38, and nuclear factor κB in the L7/S1 segment.
    RESULTS AND CONCLUSION: MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color, and the gray value of the nucleus pulposus was significantly lower than that of the control group (P < 0.01). The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group, and the gray value of the nucleus pulposus was higher than that of the model group (P < 0.01). Results from hematoxylin-eosin staining showed that in the model group, the shape of the nucleus pulposus was irregular, the number of nucleus pulposus cells was reduced, the extracellular matrix was compressed, the fibrous ring was ruptured, the structure and boundary of the end plate were unclear, and the chondrocytes were arranged disorderly. Compared with the model group, the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus, an improvement in the rupture of the fibrous ring, and more regular arrangement of cartilage endplate cells. Results from immunohistochemical staining showed an increase in positive expression of type I collagen (P < 0.01) and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group (P < 0.01). RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5, integrin β1, p38, and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group (P < 0.01); the mRNA and protein expression of integrin α5, integrin β1, p38, and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group (P < 0.01). To conclude, ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits, which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.
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    Pinoresinol diglucoside activates the Wnt/beta-catenin signaling pathway to protect osteoblasts 
    Yu Peng, Meng Dongfang, Li Huiying, Liu Hongfei, He Zike
    2025, 29 (2):  339-346.  doi: 10.12307/2025.237
    Abstract ( 254 )   PDF (1477KB) ( 116 )   Save
    BACKGROUND: Pinoresinol diglucoside promotes bone formation and bone matrix synthesis and accelerates bone tissue repair. However, the mechanism of action and effects of this compound in osteoblasts need to be further explored.
    OBJECTIVE: To investigate the effect and mechanism of action of pinoresinol diglucoside on dexamethasone-treated osteoblasts based on the Wnt/β-catenin signaling pathway.
    METHODS: Different concentrations of dexamethasone groups and pinoresinol diglucoside groups were set to treat osteoblasts for 24 hours, and the optimal intervention concentrations were screened. Osteoblasts were treated with dexamethasone, pinoresinol diglucoside and inhibitor XAV-939. Then, control group, dexamethasone group, XVA-939 group, pinoresinol diglucoside group, pinoresinol diglucoside+XVA-939 group were set up. Cell counting kit-8 assay was used to detect cell activity. Alkaline phosphatase activity and caspase3/7 enzyme activity in cells were detected. Annexin V/PI staining and EdU assay were used to detect cell apoptosis and proliferation. Real-time qPCR and western blot were used to detect the mRNA and protein expression levels of Wnt3a, β-catenin, c-myc, osteocalcin, and type I collagen, respectively.
    RESULTS AND CONCLUSION: After dexamethasone and pinoresinol diglucoside intervened in osteoblasts for 24 hours, 10 μmol/L dexamethasone was found to be the optimal intervention concentration for cell inhibition, and cell proliferation was most pronounced at a concentration of pinoresinol diglucoside of 100 μmol/L. Compared with the dexamethasone group, alkaline phosphatase activity was significantly enhanced (P < 0.05) and caspase3/7 enzyme activity was significantly reduced (P < 0.05) in the pinoresinol diglucoside group. Annexin V/PI staining and cell proliferation assay by EdU method showed that pinoresinol diglucoside inhibited apoptosis and promoted proliferation of osteoblasts after dexamethasone intervention. The mRNA and protein expression levels of Wnt3a, β-catenin, c-myc, osteocalcin, and type I collagen were significantly higher in the pinoresinol diglucoside group and pinoresinol diglucoside+XVA-939 group compared with the dexamethasone and XVA-939 groups (P < 0.05). To conclude, pinoresinol diglucoside can inhibit osteoblast apoptosis after dexamethasone intervention, protect osteoblast activity and promote osteoblast proliferation by activating the Wnt/β-catenin signaling pathway, which may play a role in delaying steroid-induced osteonecrosis of the femoral head .

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    Effects of long non-coding RNA nuclear enriched abundant transcript 1 on the proliferation, apoptosis and migration of keloid fibroblasts 
    Zhang Yanfeng, Zhang Huimin, He Xiang, Zheng Yuping
    2025, 29 (2):  347-354.  doi: 10.12307/2025.210
    Abstract ( 209 )   PDF (1669KB) ( 63 )   Save
    ACKGROUND: It has been elucidated that downregulation of nuclear enriched abundant transcript 1 (NEAT1) inhibits the progression of keloid fibroblasts, but the exact mechanism is not fully understood.
    OBJECTIVE: To investigate the influences of long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) on the proliferation, apoptosis and migration of keloid fibroblasts by regulating the miR-136-5p/ubiquitin-specific protease 4 (USP4) axis. 
    METHODS: Keloid fibroblasts were divided into five groups: si-NC group, control check group, si-NEAT1 group, si-NEAT1+miR-136-5p inhibitor group, and         si-NEAT1+inhibitor-NC group. qRT-PCR was performed to measure the expressions of NEAT1 and miR-136-5p; cell counting kit-8 assay and EDU staining were performed to measure cell proliferation; flow cytometry was performed to measure apoptosis; scratch-healing experiment was performed to measure cell migration; western blot assay was performed to measure the protein expressions of USP4, p27, Bax, matrix metalloproteinase-9, α-smooth muscle actin, and type I collagen α1 chain; dual-luciferase assay was performed to examine the relationship of NEAT1 with miR-136-5p as well as the relationship of miR-136-5p with USP4. 
    RESULTS AND CONCLUSION: Compared with the si-NC group, the NEAT1 expression, absorbance value at 450 nm, percentage of EDU positive cells, scratch-healing rate, the protein expressions of USP4, matrix metalloproteinase-9, α-smooth muscle actin, and type I collagen α1 chain decreased in the si-NEAT1 group (P < 0.05), while the expression of miR-136-5p, apoptosis rate, and the protein expressions of p27 and Bax increased (P < 0.05). miR-136-5p inhibitor reversed the effect of silencing NEAT1 on the biological behavior of keloid fibroblasts. There was a targeted regulatory relationship between NEAT1 and miR-136-5p as well as between miR-136-5p and USP4. To conclude, silencing NEAT1 may inhibit the proliferation and migration of keloid fibroblasts and induce apoptosis by regulating the miR-136-5p/USP4 axis.

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    Effect and mechanism of BYL-719 on Mycobacterium tuberculosis-induced differentiation of abnormal osteoclasts 
    Zhang Jun, Guo Jian, Jia Qiyu, Tang Lili, Wang Xi, Abudusalamu · Alimujiang, Wu Tong, Maihemuti · Yakufu, Ma Chuang
    2025, 29 (2):  355-360.  doi: 10.12307/2024.833
    Abstract ( 246 )   PDF (2526KB) ( 113 )   Save
    BACKGROUND: The phosphatidylinositol 3-kinase/protein kinase (PI3K/AKT) signaling pathway plays a pivotal role in regulating osteoclast activation, which is essential for maintaining bone homeostasis. Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection. However, the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear.
    OBJECTIVE: To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis.
    METHODS: RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine, and Ag85B was used for cellular immunofluorescence staining. The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719. There were four groups in the experiment: blank control group, BYL-719 group, BCG group, and BCG+BYL-719 group. Under the induction of receptor activator of nuclear factor kappa-B ligand, the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining. RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins, and further investigate the mechanism of action.
    RESULTS AND CONCLUSION: Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis. Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells. Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection. RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes (including c-Fos, NFATc1, matrix metalloproteinase 9, and CtsK) induced by Mycobacterium tuberculosis infection (P < 0.05). Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65. To conclude, BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65. Therefore, the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis, and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis. BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

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    Compound 3k for osteoarthritis: mechanism of modulating oxidative stress pathway to improve chondrocyte glycolysis 
    Guo Surong, Cao Shisheng, Mu Xingtong, Yang Qing, Zhang Juan
    2025, 29 (2):  363-370.  doi: 10.12307/2025.201
    Abstract ( 319 )   PDF (2075KB) ( 260 )   Save
    BACKGROUND: Osteoarthritis is now considered a metabolic disease. Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis. Compound 3k, as a novel small molecule inhibitor of glycolysis, has anti-inflammatory and anti-tumor effects. Therefore, it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis.
    OBJECTIVE: To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha (HIF-1α)/reactive oxygen species (ROS) pathway.
    METHODS: ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours. The cytotoxicity of Compound 3k at different concentrations (0.25, 0.5, 1, 2.5, 5, 10, 15 μmol/L) was detected by cell counting kit-8 assay, and the appropriate concentrations were selected for the subsequent experiments. The chondrocytes were randomly divided into control, model and treatment groups. The model group was induced with 10 ng/mL interleukin 1β, and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β. The proliferation of the cells in each group was detected by the cell counting kit-8 assay; the inflammatory level of the cells in each group was detected by the ELISA kit; the ROS, extracellular lactate and glucose contents were detected using the kit; qRT-PCR and western blot were used to detect the levels of related inflammatory factors, interleukin-6 and tumor necrosis factor-α, glycolysis-related genes glucose transporter protein-1, glyceraldehyde 3-phosphate dehydrogenase, monocarboxylate transporter protein-1 and HIF-1α.
    RESULTS AND CONCLUSION: Compared with the control group, the model group showed a decrease in cell proliferative activity, active glycolysis level, manifested by an increase in extracellular lactate content (P < 0.001) and a decrease in glucose content (P < 0.001), interleukin-6 (P < 0.000 1) and tumor necrosis factor-α (P < 0.001). The expression levels of glycolysis-related genes glucose transporter protein-1 (P < 0.001), glyceraldehyde 3-phosphate dehydrogenase (P < 0.001), monocarboxylic acid transporter protein-1 (P < 0.001) and HIF-1α (P < 0.001) in the model group were all up-regulated, accompanied by oxidative stress and overproduction of ROS. Compared with the model group, Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis (P < 0.001), while suppressing the expression of genes related to inflammation (P < 0.001) and glycolysis in osteoarthritic chondrocytes, inhibiting oxidative stress, downregulating the expression level of HIF-1α (P < 0.000 1) and decreasing the content of ROS. To conclude, Compound 3k inhibits interleukin-1β induced chondrocyte inflammation, and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

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    Jiawei Chunze Decoction treats urinary retention after spinal cord injury in rats based on the regulation of endoplasmic reticulum stress apoptosis
    Zhu Bochao, Li Yanjie, Qin Hewei, Zhao Nannan, Liu Haoyuan, Xu Zhenhua, Wang Yupu
    2025, 29 (2):  371-378.  doi: 10.12307/2025.232
    Abstract ( 191 )   PDF (1441KB) ( 240 )   Save
    BACKGROUND: Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury. Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway is closely related to the degree of bladder dysfunction.
    OBJECTIVE: To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. 
    METHODS: Sixty female Sprague-Dawley rats were randomly divided into sham operation group, model group, Jiawei Chunze Decoction low-dose group, Jiawei Chunze Decoction high-dose group and agonist group. In the sham operation group, the spinal cord was exposed but not transected. In the other groups, the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury. At 24 hours after modeling, the sham operation group and model group were intragastrically given equal volume of normal saline, Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg, respectively, via intragastric administration for 4 weeks, and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg. After 4 weeks of treatment, the maximum bladder capacity, leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics. The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test. The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining. The concentrations of GRP78, CHOP and Caspase-12 in serum were detected by ELISA, and the mRNA and protein expressions of PI3K, Akt, GRP78, CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot, respectively. 
    RESULTS AND CONCLUSION: Compared with the sham operation group, the maximum bladder volume, bladder compliance and minimum systolic tension of rats in the model group were increased (P < 0.05), and the leakage point pressure and bladder contraction frequency were decreased (P < 0.05); serum GRP78, CHOP, and Caspase-12 levels were also increased (P < 0.05). The arrangement of bladder epithelial cells in the model group was disordered, and there was monocyte infiltration between cells, tissue edema, and detrusor tract atrophy. The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group, while those of GRP78, CHOP and Caspase-12 were increased (P < 0.05). Compared with the model group, the maximum bladder volume, bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose, high-dose and agonist groups after 4 weeks of intervention (P < 0.05), while the leakage point pressure and bladder contraction frequency were increased (P < 0.05); serum GRP78, CHOP, Caspase-12 levels were decreased (P < 0.05). The bladder epithelial cells in the three intervention groups were distributed evenly, arranged neatly, with less inflammatory cell infiltration and fuller detrusor muscle bundle. Compared with the model group, the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups , while those of GRP78, CHOP and Caspase-12 were decreased (P < 0.05). The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group. To conclude, Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury, and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway, and then alleviating apoptosis.

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    Advantages of modified ligation method for spinal cord injury modeling 
    Li Daohui, Xu Xiaoshuang, Li Zhengtao, Tian Xinpeng, Bi Hangchuan, Liu Yuan, Dai Yongwen, Chen Lingqiang
    2025, 29 (2):  379-384.  doi: 10.12307/2025.271
    Abstract ( 227 )   PDF (1976KB) ( 118 )   Save
    BACKGROUND: Currently, different methods of model establishment have been derived from different injury modes of spinal cord injury. Traditional physical injury modeling methods have their own advantages and disadvantages, and there is a lack of more effective and stable animal models of spinal cord injury.
    OBJECTIVE: To establish a reproducible, controllable, trauma-free, low-mortality, more stable, widely applicable, and short-term postoperative care rat model of spinal cord injury.
    METHODS: Forty Sprague-Dawley rats with similar body mass and ages were randomly divided into a control group and an improved group, with 20 rats in each group. Animal models of spinal cord injury in the control group were constructed using a clip model method, while the improved group used a modified ligation method based on the compression method to make the spinal cord injury models using suture ligation based on fenestration. Postoperative comparisons were made between the two groups, assessing urination behavior, hematuria, pyuria (infection rate), mortality, scoliosis rate and Basso-Beattie-Bresnahan locomotor rating scale scores at 1, 3, 5, and 7 days after modeling.
    RESULTS AND CONCLUSION: Compared with the conventional modeling method, the modified ligation method based on the compression method resulted in faster recovery of urination behavior, lower hematuria rate, lower infection rate, lower mortality rate, lower scoliosis rate, and more concentrated and stable Basso-Beattie-Bresnahan scores (all below 2 points within 1 week). This proves that the modified ligation method based on compression is more suitable for the establishment of spinal cord injury models in rats.
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    Effect of deep muscle stimulation combined with electromyographic biofeedback on the spasms of the triceps surae and gait changes after stroke 
    Zhang Qiming, Liao Di, Zhong Zhiliang, Lin Lihua, Zheng Xiang, Li Qiong, Shan Sharui
    2025, 29 (2):  385-392.  doi: 10.12307/2025.202
    Abstract ( 267 )   PDF (1229KB) ( 327 )   Save
    BACKGROUND: Deep muscle stimulation has the effects of releasing muscle adhesion, relieving muscle spasm, improving and restoring muscle compliance and elasticity. Electromyographic biofeedback therapy can promote nerve recovery and improve lower limb motor function and gait. 
    OBJECTIVE: To observe the effect of the effect of deep muscle stimulation combined with electromyographic biofeedback therapy on the spasm of the triceps surae and gait changes after stroke by using a digital muscle detector and three-dimensional gait analysis system.
    METHODS: A total of 72 patients who met the inclusion criteria were selected from the Rehabilitation Department of the First Affiliated Hospital of Guangdong Pharmaceutical University from October 2020 to October 2023. And they were enrolled and randomly divided into two groups (n=36 per group): a control group and a combined group. The control group received routine rehabilitation therapies, electromyographic biofeedback and pseudo deep muscle stimulation, while the combined group received true deep muscle stimulation treatment on the basis of the control group, five times per week, for 4 consecutive weeks. The oscillation frequency and dynamic stiffness of the affected gastrocnemius muscle, active range of motion of the ankle dorsiflexion muscle, electromyographic signal of the tibialis anterior muscle, Fugl-Meyer assessment of the lower limbs, and three-dimensional gait analysis parameters were statistically analyzed before and after treatment in two groups.  
    RESULTS AND CONCLUSION: After treatment, oscillation frequency and dynamic stiffness values of the inner and outer sides of the affected gastrocnemius muscle in both groups of patients were significantly reduced compared with before treatment (P < 0.05), and the combined group showed a more significant decrease compared with the control group (P < 0.05). The active range of motion of the ankle dorsiflexion muscle, electromyographic signal of the tibialis anterior muscle, and Fugl-Meyer scores after treatment were significantly increased or improved compared with before treatment (P < 0.05), while the combined group showed a more significant increase or improvement compared with the control group (P < 0.05). In terms of gait parameters, the walking speed, frequency, and stride in both groups of patients were significantly increased compared with before treatment (P < 0.05), while the combined group showed a more significant increase compared with the control group (P < 0.05). The percentage time of support phase on the healthy side was shortened compared with before treatment (P < 0.05), while the combined group showed a more significant decrease compared with the control group (P < 0.05). In addition, there was no significant difference between the two groups except for the percentage of healthy side support (P > 0.05). To conclude, the combination of deep muscle stimulation and electromyographic biofeedback can effectively alleviate triceps spasm in the short term after stroke, improve ankle dorsiflexion function, enhance lower limb motor function, and improve gait. The treatment effect is significant and worthy of clinical promotion and application.

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    Effects of low-load blood flow restriction exercise and high-intensity resistance exercise on the thigh microcirculation function of athletic young men
    Peng Yong, Hu Jiangping, Zhu Huan
    2025, 29 (2):  393-401.  doi: 10.12307/2025.233
    Abstract ( 315 )   PDF (1017KB) ( 257 )   Save
    BACKGROUND: Microcirculation, as the only place for the energy metabolism of body substances, is closely related to the human movement ability. Resistance exercise is an effective way to improve the function of microcirculation, but some studies have also pointed out that blood flow restriction exercise can also improve the function of microcirculation and has the advantages of small load and high safety.
    OBJECTIVE: To compare the effects of 6-week low-load blood flow restriction exercise and high-intensity resistance exercise on the thigh microcirculation function of athletic young men, and to explore the possible mechanism by which exercises improve microcirculation function from the perspective of vascular endothelial function.
    METHODS: Sixty sports students from Hubei Minzu University were divided into control group, high-intensity resistance exercise group and low-load blood flow restriction exercise group according to the random number table method, with 20 students in each group. The low-load blood flow restriction exercise group performed a low-load blood flow restriction exercise for 6 weeks (three times a week, 90 minutes each, at an exercise intensity of 30% 1RM). The high-intensity resistance exercise group received a high-intensity resistance exercise for 6 weeks (three times a week, 90 minutes each, at an exercise intensity of 70% 1RM). The control group did not perform any form of exercise training during this period. Microcirculatory blood perfusion, transcutaneous partial pressure, muscle oxygen saturation, nitric oxide, endothelial nitric oxide synthase, endothelin 1, vascular endothelial cell growth factor, thigh circumference, and muscle strength were tested in each group on the day before the intervention and the morning after the end of the 6-week intervention.
    RESULTS AND CONCLUSION: After the exercise intervention, heating values of microcirculatory blood flow perfusion and blood cell movement speed in the low-load blood flow restriction exercise group and the high-intensity resistance exercise group were significantly different from those in the control group and before the exercise intervention (P < 0.05). The heating values of microcirculatory blood flow perfusion and blood cell movement speed showed significant differences between the low-load blood flow restriction exercise group and the high-intensity resistance exercise group (P < 0.05). After the exercise intervention, the levels of nitric oxide, endothelial nitric oxide synthase, endothelin 1, and vascular endothelial cell growth factor were significantly different in the low-load blood flow-limiting exercise group and the high-intensity resistance exercise group compared with the control group and the pre-exercise intervention (P < 0.05). After the exercise intervention, thigh circumference and thigh muscle strength were significantly different in low-load blood flow restriction group and high-intensity resistance exercise groups compared with the pre-exercise intervention (P < 0.05). All these findings indicate that 6-week low-load blood flow restriction exercise and high intensity resistance exercise may regulate the secretion of vascular factors such as endogenous nitric oxide synthase, endothelin-1 and vascular endothelial growth factor to improve the function of thigh microcirculation and increase the contractile strength of the thigh muscle. In addition, And low-load blood flow restriction exercise has better intervention effects on microcirculatory blood perfusion volume and blood cell movement speed, so low-load blood flow restriction exercise is more advantageous than high-intensity resistance exercise in improving microcirculation function.
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    Effect of electroacupuncture combined with low-frequency transcranial ultrasound stimulation on the electroencephalographic signals of rats with traumatic brain injury 
    Gao Simiao, Han Xue, Wu Xiaoguang, Zheng Jinyu, Gao Fangwen, Li Kuihua, Peng Yong, Liu Lanxiang
    2025, 29 (2):  402-408.  doi: 10.12307/2025.231
    Abstract ( 206 )   PDF (917KB) ( 251 )   Save
    BACKGROUND: Traumatic brain injury is a condition in which the normal function of the brain is disrupted by a bump or impact to the head. It is necessary to find effective treatments and objective targets that can help doctors diagnose the injury status and restore the brain function of patients.
    OBJECTIVE: To explore the effect of electroacupuncture combined with low-frequency transcranial ultrasound stimulation on the electroencephalographic signals of rats with traumatic brain injury.
    METHODS: Forty 6-week-old SPF male Sprague-Dawley rats were randomly divided into five groups: sham group, model group, electroacupuncture group, low-frequency transcranial ultrasound stimulation group and combined group (electroacupuncture+low-frequency transcranial ultrasound stimulation), with eight rats in each group. Feeney weight-drop method was used to establish the animal model of traumatic brain injury. In the sham group, the bone window was only opened without impact. Interventions were started at 1 day after modeling. Electroacupuncture in the electroacupuncture group, low-frequency transcranial ultrasound stimulation in the low-frequency transcranial ultrasound stimulation group, and electroacupuncture+low-frequency transcranial ultrasound stimulation in the combined group were performed for days in total. The modified neurological severity scale score for assessing rats’ neurological deficits was performed at 8 hours after modeling. The percentage of spontaneous alternation behavior in the Y-maze was measured at 7 days after modeling. Then, the electroencephalographic signals were collected and electroencephalographic data of α, β, θ, and δ waves were extracted by fast Fourier transform, and the value of oscillation amplitude and energy ratio were calculated in α, β, θ, and δ waves, as well as the Lempel-Ziv complexity and sample entropy.
    RESULTS AND CONCLUSION: Compared with the sham group, the modified neurological severity scale scores in the model group, electroacupuncture group, low-frequency transcranial ultrasound stimulation group and combined group were significantly increased at 8 hours after modeling (P < 0.05). Compared with the sham group, the value of oscillation amplitude in δ wave and the value of δ energy ratio were significantly increased in the model group at 7 days after modeling, meanwhile the percentage of spontaneous alternation behavior in Y-maze, and the value of α/β energy ratio, Lempel-Ziv complexity, and sample entropy were significantly decreased (P < 0.05). Compared with the model group, the value of oscillation amplitude in α and δ waves was significantly decreased in the combined group (P < 0.05), while the value of α/β energy ratio was significantly increased (P < 0.05) and the value of δ energy ratio was significantly decreased (P < 0.05) in the electroacupuncture group, low-frequency transcranial ultrasound stimulation group and combined group. Compared with the electroacupuncture group and low-frequency transcranial ultrasound stimulation group, the value of δ energy ratio was significantly decreased in the combined group (P < 0.05), while the percentage of spontaneous alternation behavior, the value of α/β energy ratio, the Lempel-Ziv complexity, and the sample entropy were significantly increased (P < 0.05). To conclude, abnormal electroencephalographic signals can appear in rats with traumatic brain injury, while the electroacupuncture combined with low-frequency transcranial ultrasound stimulation can alleviate the abnormal electroencephalographic signals in rats, which suggests the electroencephalographic frequency domain value and nonlinear features can be used to assess the severity of traumatic brain injury.

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    Sports injury prediction model based on machine learning
    Wei Mengli, Zhong Yaping, Gui Huixian, Zhou Yiwen, Guan Yeming, Yu Shaohua
    2025, 29 (2):  409-418.  doi: 10.12307/2025.234
    Abstract ( 654 )   PDF (917KB) ( 289 )   Save
    BACKGROUND: The sports medicine community has widely called for the use of machine learning technology to efficiently process the huge and complicated sports data resources, and construct intelligent sports injury prediction models, enabling accurate early warning of sports injuries. It is of great significance to comprehensively summarize and review such research results so as to grasp the direction of early warning model improvement and to guide the construction of sports injury prediction models in China.
    OBJECTIVE: To systematically review and analyze relevant research on sports injury prediction models based on machine learning technology, thereby providing references for the development of sports injury prediction models in China.
    METHODS: Literature search was conducted on CNKI, Web of Science and EBSCO databases, which mainly searched for literature related to machine learning techniques and sports injuries. Finally, 61 articles related to sports injury prediction models were included for analysis.
    RESULTS AND CONCLUSION: (1) In terms of external risk feature indicators, there is a lack of competition scenario indicators, and the inclusion of related feature indicators needs to be further improved to further enrich the dimensions of the dataset for model training. In addition, the inclusion feature weighting methods of the sports injury prediction model are mainly based on filtering methods and the use of embedding and wrapping weighting methods needs to be strengthened in order to enhance the analysis of the interaction effects of multiple risk factors. (2) In terms of model body training, supervised learning algorithms become the mainstream choice. Such algorithms have higher requirements for the completeness of sample labeling information, and the application scenarios are easily limited. Therefore, the application of unsupervised and semi-supervised algorithms can be increased in the later stage. (3) In terms of model performance evaluation and optimization, the current studies mainly adopt two verification methods: HoldOut crossover and k-crossover. The range of AUC values is (0.76±0.12), the range of sensitivity is (75.92±11.03)%, the range of specificity is (0.03±4.54)%, the range of F1 score is (80.60±10.63)%, the range of accuracy is (69.96±13.10)%, and the range of precision is (70±14.71)%. Data augmentation and feature optimization are the most common model optimization operations. The accuracy and precision of the current sports injury prediction model are about 70%, and the early warning effect is good. However, the model optimization operation is relatively single, and data augmentation methods are often used to improve model performance. Further adjustments to the model algorithm and hyperparameters are needed to further improve model performance. (4) In terms of model feature extraction, most of the internal risk profile indicators included are mainly based on anthropometrics, training load, years of training, and injury history, but there is a lack of sports recovery and physical function indicators. 

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    Epigenetic changes and exercise regulation: mechanisms underlying skeletal muscle aging and improvement 
    Fan Rao, Kong Jianda, Li lin, Zhai teng, Yang zirou, Zhu Lei
    2025, 29 (2):  419-429.  doi: 10.12307/2025.235
    Abstract ( 473 )   PDF (2511KB) ( 425 )   Save
    BACKGROUND: Muscle aging is closely related to various epigenetic changes, and exercise has a certain regulatory effect on these epigenetic changes. However, the specific mechanism is not fully understood. 
    OBJECTIVE: To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms, aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. 
    METHODS: During the period from June 1st to August 1st, 2023, literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science, PubMed, CNKI, WanFang, and VIP. The search terms used included “skeletal muscle,” “muscle,” “aging,” “older adult,” “aging,” “exercise,” “physical exercise,” “epigenetic,” and “epigenetics” in Chinese as well as “skeletal muscle, muscle, aging, older adult, senescence, age, exercise, sports, physical activity, epigenetic, epigenetics” in English. Boolean logic operators were used to connect the search terms for retrieval, and corresponding strategies were developed. According to the predetermined inclusion and exclusion criteria, 70 eligible articles were selected. 
    RESULTS AND CONCLUSION: Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence, and epigenetic changes in skeletal muscle are an important field. The epigenetic mechanisms of skeletal muscle play an important role in muscle aging, mainly involving DNA methylation, histone modification, regulation of non-coding RNAs, chromatin remodeling, changes in mitochondrial function and expression changes of aging-related genes. Exercise significantly regulates the epigenetics of skeletal muscle, including promoting DNA methylation, muscle histone modification, regulating miRNA expression, and regulating lncRNA expression, regulating muscle factors (such as interleukin-6), regulating mitochondrial function (such as peroxisome proliferators-activated receptors γ co-activator 1α). Future studies are recommended for long-term, cross-diverse population-based exercise interventions; the application of multi-omics techniques such as proteomics and metabolomics; strengthening the understanding of epigenetic changes at the single-cell level; cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans; strategies for combining exercise and pharmacological interventions to assess their synergistic effects; and epigenetic studies of crosstalk interactions between skeletal muscle and different organs. 


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    Macrophage efferocytosis: a new target for the treatment of obesity-related metabolic diseases #br#
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    Yang Fengying, Zhao Yuqing, You Huijuan, Zhang Pengyi, Chen Yan, Wang Qinglu, Liu Yingying
    2025, 29 (2):  430-440.  doi: 10.12307/2025.273
    Abstract ( 706 )   PDF (1679KB) ( 484 )   Save
    BACKGROUND: Dysfunction of macrophage efferocytosis can induce local and systemic inflammatory damage and is associated with a variety of obesity-related metabolic diseases. Moreover, compounds targeting efferocytosis have shown good therapeutic effects.
    OBJECTIVE: By reviewing the effects of obesity on macrophage efferocytosis, to analyze the key mechanism by which obesity inhibits efferocytosis, to summarize the research progress in compounds targeting efferocytosis to treat obesity-related metabolic diseases, so as to provide new ideas for fully understanding efferocytosis and its relationship with metabolic diseases, aiming to provide new strategies for disease prevention and treatment.
    METHODS: The English search terms were “efferocytosis, metabolism, obesity, obese, atherosclerosis, non-alcoholic steatohepatitis, neurodegeneration, tumor, osteoarthritis, diabetes, compound, medicine, treatment,” which were used for literature retrieval in PubMed and Web of Science. The Chinese search term was “efferocytosis,” which was used for literature retrieval in CNKI, VIP and WanFang datebases. Ninety-nine papers were finally included in the review analysis after a rigorous screening process.
    RESULTS AND CONCLUSION: In the process of efferocytosis, the “Find me” and “Eat me” processes involving a large number of apoptotic cell derived factors are mainly regulated by apoptotic cells. The efferocytosis factor involved in cytoskeletal remodeling and digestion are mainly derived from macrophages, which are crucial for efferocytosis activity. These results suggest that the “Find me” and “Eat me” factors mainly reflect the condition of apoptosis, and it is more scientific to select the expression of factors involved in cytoskeletal remodeling and digestion when evaluating the efferocytosis activity of macrophages. Obesity inhibits efferocytosis, and shows an inhibitory effect on most digestive factors, but has a stress-induced activation effect on most “Find me,” “Eat me” and cytoskeletal recombination factors, which further indicates the decisive effect of digestive stage on efferocytosis and suggests that it is not reliable for some studies to evaluate the efferocytosis based on the increased expression of “Find me” and “Eat me” factors. Targeting cytokines in the digestive phase may be more effective when discussing future intervention strategies targeting macrophages efferocytosis. The efferocytosis activators of macrophages are effective in the treatment of various metabolic diseases, but the efferocytosis inhibitors in tumor tissue show good anticancer effects, suggesting that the role of efferocytosis should be rationally evaluated according to the characteristics of tissue inflammation. Efferocytosis is a relatively new concept proposed in 2003, with a short research history and complex efferocytosis factors. Current studies on obesity and efferocytosis only involve a tip of the iceberg and most of them are at a superficial level and a large number of scientific experiments are needed to further validate the mechanisms.
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