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08 June 2024, Volume 28 Issue 16 Previous Issue   

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Bone metabolism in patients with osteonecrosis of the femoral head based on etiology and Association Research Circulation Osseous staging Chen Ligang, He Xiaoming, Tan Yu, Xiao Yuzhi, Ma Chuntao, Guo Liang 2024, 28 (16):  2461-2466.  doi: 10.12307/2024.282 Abstract ( 277 )   PDF (927KB) ( 62 )   Save BACKGROUND: Currently, there is a lack of large sample studies to analyze the bone metabolism level of patients with femoral head necrosis of different etiologies and stages, which is not conducive to the development of better necrosis-promoting repair strategies. OBJECTIVE: To study the bone metabolism of patients with osteonecrosis of the femoral head with different etiologies and Association Research Circulation Osseous (ARCO) stages.  METHODS: A retrospective study was performed on 401 patients diagnosed with osteonecrosis of the femoral head as the trial group, and 81 healthy subjects as the control group. The trial group could be divided into three groups according to different etiologies: steroid-induced osteonecrosis of the femoral head, alcoholic osteonecrosis of the femoral head and traumatic osteonecrosis of the femoral head, and were divided into stages II /III /IV according to different ARCO stages. Seven bone metabolism-related indicators of all subjects were collected, including bone metabolism-regulating hormone 25-hydroxyvitamin D and bone conversion markers:  N-terminal propeptide of type I procollagen, degradation product of type I collagen, n-terminal middle molecular fragment of osteocalcin, general biochemical markers of bone metabolism: serum calcium, serum phosphorus, serum alkaline phosphatase. The bone metabolism levels of each group were compared and the independent factors associated with osteonecrosis of the femoral head were determined by binary Logistic regression analysis.   RESULTS AND CONCLUSION: Compared with the control group, levels of degradation product of type I collagen, N-terminal propeptide of type I procollagen, n-terminal middle molecular fragment of osteocalcin, serum phosphorus and alkaline phosphatase in the trial group were significantly increased (all P < 0.05). Based on the presence or absence of the disease, according to binary Logistic regression analysis, degradation product of type I collagen, N-terminal propeptide of type I procollagen, and n-terminal middle molecular fragment of osteocalcin were independent factors associated with osteonecrosis of the femoral head. The levels of degradation product of type I collagen and N-terminal propeptide of type I procollagen in three groups of patients with different etiologies were higher than normal reference values. The bone metabolism-regulating hormone 25-hydroxyvitamin D and serum calcium in the alcoholic osteonecrosis of the femoral head group were higher than those in the other two groups (P < 0.05). The level of bone metabolism-regulating hormone 25-hydroxyvitamin D in steroid-induced and traumatic osteonecrosis of the femoral head groups was lower than the normal value. There were no significant differences in seven bone metabolism-related indicators in patients with ARCO stages II, III and IV osteonecrosis of the femoral head (all P > 0.05), but degradation product of type I collagen and N-terminal propeptide of type I procollagen in these three groups were higher than normal reference values. Bone metabolism-regulating hormone 25-hydroxyvitamin D in patients with ARCO stage II and ARCO stage IV was lower than the normal reference value. It is concluded that the bone metabolism level of osteonecrosis of the femoral head patients was abnormal. The degradation product of type I collagen and N-terminal propeptide of type I procollagen of osteonecrosis of the femoral head patients with different etiologies and ARCO stages were all higher than the normal reference value, and they were in a state of high bone turnover. Degradation product of type I collagen, N-terminal propeptide of type I procollagen and n-terminal middle molecular fragment of osteocalcin may be risk factors for the pathogenesis of osteonecrosis of the femoral head. Figures and Tables | References | Related Articles | Metrics

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Core stability training reduces risk of anterior cruciate ligament injury in landing movements Xue Boshi, Lin Changrui, Zheng Liangliang, Yang Chen, Zhou Zhipeng 2024, 28 (16):  2467-2472.  doi: 10.12307/2024.280 Abstract ( 277 )   PDF (1200KB) ( 89 )   Save BACKGROUND: Studies have shown that poor dynamic postural control may lead to abnormal movement patterns during exercise, which may increase the risk of lower limb joint and anterior cruciate ligament injury. The stability of the body core is the basis of good dynamic postural control. OBJECTIVE: To investigate the effects of core stability training on dynamic postural control and risk of injury in landing movements, and to compare the differences in training effects between genders.  METHODS: Thirty-five college students (male=19, female=16) were recruited for 6 weeks of core stability training. The results of the Y balance test, trunk extensor endurance test, trunk flexor endurance test, lateral bridge endurance test, and landing error scoring system were analyzed before and after training.  RESULTS AND CONCLUSION: The 6-week core stability training could improve trunk extensor endurance (P < 0.001), flexor endurance (P < 0.001), and lateral abdominal muscle endurance (P < 0.001). Core stability training could improve forward distance (P=0.026), backward inward distance (P < 0.001), backward outward distance (P=0.005) and comprehensive score (P < 0.001) of Y balance test for male and female college students. Landing error scoring system scores of both male and female college students significantly decreased after 6 weeks of core stability training (P < 0.001) while increasing knee (P < 0.001) and hip flexion angles (P < 0.001), decreasing knee valgus angle (P < 0.001) at the moment of touchdown, and could increase the maximum knee flexion angle (P < 0.001) and decrease the maximum knee valgus angle (P < 0.001). It is concluded that core stability training improves dynamic postural control and improves landing movement patterns, suggesting that it may help reduce the risk of anterior cruciate ligament injury. There are no sex differences in core stability training in terms of increased trunk flexor endurance, lateral bridge muscle group endurance, improved dynamic postural control, and reduced risk of anterior cruciate ligament injury. Figures and Tables | References | Related Articles | Metrics

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Clock genes regulate the browning of white fat in obese rats undergoing hypoxia exercise Shi Dongzi, Zhang Hua, Meng Chang, Li Xinrui, Dong Panpan, Tian Xuewen, Wang Qinglu 2024, 28 (16):  2473-2480.  doi: 10.12307/2024.234 Abstract ( 204 )   PDF (7418KB) ( 42 )   Save BACKGROUND: Hypoxic exercise can promote the degradation of body fat, and changes in the external environment can affect the circadian rhythm of animals, but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE: To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS: Forty obese rats were randomly selected and divided into four groups (n=10 per group): normoxic sedentary group, hypoxic sedentary group, normoxic exercise group, and hypoxic exercise group for 4 weeks of intervention. The rats in the sedentary groups were not intervened, while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6% for the whole day. In the exercise groups, adaptive training was performed in the 1st week, and the speed and length of training remained unchanged for the last 3 weeks. The body mass, body length and perirenal fat mass of obese rats were measured. Serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit. Liver fat content was observed by oil red O staining. Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups. RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue. The mRNA expressions of PGC-1α, Beclin 1, KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION: Hypoxic exercise intervention significantly decreased body mass, body fat percentage, Lee’s index, serum triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol levels (P < 0.01), and significantly increased high-density lipoprotein cholesterol level (P < 0.01). Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group, hypoxic sedentary group, and normoxic exercise group. RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp, Nr1d1, Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α) and downregulated the expression of Arntl(Bmal1), accompanied by the enhanced expression of genes related to substance metabolism. qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1 (P < 0.01). Therefore, these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise. Figures and Tables | References | Related Articles | Metrics

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Screening and analysis of differentially expressed genes for calcium homeostasis in ameloblasts with high fluoride intervention Huang Ting, Liu Xia, Wang Zhu, Chen Ting, Chen Bin, Bai Guohui, Wu Jiayuan, Tian Yuan 2024, 28 (16):  2481-2487.  doi: 10.12307/2024.309 Abstract ( 228 )   PDF (2669KB) ( 18 )   Save BACKGROUND: Fluorosis is a disorder of enamel development caused by long-term intake of large amounts of fluoride during enamel development. OBJECTIVE: To further explore the molecular mechanism of dental fluorosis formation by screening the differentially expressed genes associated with calcium homeostasis in ameloblasts by transcriptome sequencing technology. METHODS: LS8 cells were treated with 0, 0.4, 0.8, 1.6, 3.2 and 6.4 mmol/L sodium fluoride (NaF) for 24, 48 and 72 hours to observe the effects of different concentrations of NaF on the morphology, cell activity and intracellular Ca2+ concentration of LS8 cells. The differentially expressed genes were screened by transcriptome sequencing and validated. RESULTS AND CONCLUSION: After 24 hours of treatment, the cells treated with 0, 0.4, and 0.8 mmol/L NaF were in good growth condition, with increased cell number and clear cell outline. When the NaF concentration was ≥ 1.6 mmol/L, the cells were gradually shrunken and became smaller and the number of cells decreased with the increase of NaF concentration. After 48 and 72 hours of treatment, the number of cells increased in the 0, 0.4 mmol/L NaF groups, while gradually decreased in the 0.8, 1.6, 3.2 mmol/L NaF groups, with rounded and smaller cell morphology. The cells in the 6.4 mmol/L NaF group were shrunken, rounded and suspended in the medium, with almost no adherent cells. When treated with the same concentration of NaF, LS8 cells were in optimal growth after 24 hours of treatment. Results from cell counting kit-8 assay showed that when treated with the same concentration of NaF, the cell activity decreased with the increase of treatment time; when the treatment time was the same, the cell activity decreased with the increase of NaF concentration. After 24 hours of treatment, the intracellular Ca2+ concentration increased with the increase of NaF concentration. Transcriptome sequencing analysis identified genes involved in the regulation of cellular calcium homeostasis: Hsp90b1, Canx, Calr, and Hspa5 that were significantly upregulated (P < 0.05) and Cacna1a that was significantly downregulated (P < 0.05). To conclude, the inhibitory effect of NaF on LS8 cell proliferation may be related to the abnormal increase in intracellular Ca2+ concentration, and the mechanism may be caused by the upregulation of the expression of protein processing and synthesis pathways Hsp90b1, Canx, Calr, and Hspa5 and the downregulation of the expression of calcium signaling pathway Cacna1a. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which moxibustion pretreatment attenuates oxidative stress injury in a rat model of cerebral ischemia-reperfusion Jiang Jie, Liu Juan, Yu Yanyan, Yang Yue, Wang Qianhui 2024, 28 (16):  2488-2493.  doi: 10.12307/2024.308 Abstract ( 238 )   PDF (1110KB) ( 25 )   Save BACKGROUND: Pretreatment with moxibustion is a preventive treatment in traditional Chinese medicine. Pretreatment with moxibustion at the onset of prodromal symptoms can significantly reduce the symptoms and delay the onset of many diseases, but the exact mechanism remains to be studied. OBJECTIVE: To investigate the mechanism of SIRT1/FoxO3 pathway in moxibustion pretreatment to ameliorate oxidative stress injury in cerebral ischemia-reperfusion model rats.  METHODS: Forty-eight Sprague-Dawley rats were randomly divided into sham-operated group, model group, moxibustion pretreatment group, and moxibustion pretreatment+EX527 (SIRT1 inhibitor) group, with 12 rats in each group. The moxibustion pretreatment group was given moxibustion with seed-sized moxa cone at Baihui, Dazhui, and Zusanli before modeling, three moxa-cones per acupoint, once a day for 7 days. In the model group, moxibustion pretreatment group and moxibustion pretreatment+EX527 group, the rat model of middle cerebral artery occlusion was made by suturing of the middle cerebral artery 30 minutes after the last moxibustion. After 2 hours of cerebral ischemia, the middle artery suture was removed and the rats were reperfused for 12 hours. In the sham-operated group, only the common carotid artery, internal carotid artery, and external carotid artery were dissected without suturing the middle cerebral artery. In the moxibustion pretreatment+EX527 group, EX527 (15 mg/kg) was given intraperitoneally 30 minutes before each moxibustion. After 12 hours of reperfusion, the rats were scored for neurological deficits, and the cerebral infarct volume was calculated by 2,3,5-triphenyltetrazolium chloride staining method. The levels of oxidative stress factors in the infarcted tissues were detected by the kit method, and western-blot method was used to detect the expression levels of SIRT1, FoxO3, p-FoxO3 and brain-derived neurotrophic factor in the ischemic area of the cerebral cortex.  RESULTS AND CONCLUSION: After 12 hours of reperfusion, the neurobehavioral score in the model group was significantly higher than that in the sham-operated group (P < 0.01), while the score in the moxibustion pretreatment group was significantly lower than that in the model group (P < 0.01) and moxibustion pretreatment+EX527 group (P < 0.05). There were no obvious infarct foci in the brain tissue of the sham-operated rats, but obvious ischemic foci were observed in the right side of the brain tissue of the rats in the model group (P < 0.01). The right infarct volume in the moxibustion pretreatment group was significantly reduced compared with the model group (P < 0.01), while the right infarct volume in the moxibustion pretreatment+EX527 group was significantly enlarged compared with the moxibustion pretreatment group. After 12 hours of reperfusion, the level of malondialdehyde was significantly elevated (P < 0.01) and the expression of superoxide dismutase was significantly decreased (P < 0.01) in the model group compared with the sham-operated group. The levels of malondialdehyde was significantly decreased (P < 0.01, P < 0.05) and the expression of superoxide dismutase was significantly increased (P < 0.01, P < 0.05) in the moxibustion pretreatment group compared with the model group and the moxibustion pretreatment+EX527 group. Western blot results showed that the expression levels of SIRT1, FoxO3, p-FoxO3, and brain-derived neurotrophic factor proteins were significantly higher in the model group compared with the sham-operated group (P < 0.01); compared with the model group, the expression levels of SIRT1, FoxO3, and brain-derived neurotrophic factor were significantly higher in the moxibustion pretreatment group (P < 0.01), and p-FoxO3 expression was significantly lower (P < 0.01); compared with the moxibustion pretreatment+EX527 group, the expression levels of SIRT1, FoxO3, and brain-derived neurotrophic factor were elevated in the moxibustion pretreatment group (P < 0.05), and no statistically significant difference was found in the p-FoxO3 expression (P > 0.05). To conclude, moxibustion pretreatment can significantly improve neurological function in rats after cerebral ischemia-reperfusion, and the mechanism may be related to the activation of SIRT1/FoxO3 pathway to reduce oxidative stress injury in the rat model of cerebral ischemia-reperfusion. Figures and Tables | References | Related Articles | Metrics

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Grape seed extract inhibits apoptosis of rat growth plate chondrocytes and promotes tibial bone growth Zhang Shasha, Wang Na, Li Yongjun 2024, 28 (16):  2494-2499.  doi: 10.12307/2024.324 Abstract ( 246 )   PDF (1533KB) ( 58 )   Save BACKGROUND: Grape seed extract can inhibit chondrocyte apoptosis and aging, and improve osteoarthritis. However, the effects of grape seed extract on the apoptosis of chondrocytes in the growth plate and tibial growth are still unclear. OBJECTIVE: To investigate the effect of grape seed extract on interleukin-1β-induced apoptosis in rat growth plate cells and on tibial bone growth.  METHODS: (1) Cell experiment: Growth plate chondrocytes from Sprague-Dawley rats were isolated, cultured, and identified. The cells were then randomly divided into control group, model group, grape seed extract group, miR-138-5p NC group and miR-138-5p inhibitor group. In the model group, 20 ng/mL interleukin-1β was used to induce apoptosis in rat growth plate chondrocytes. In the grape seed extract group, 20 ng/mL interleukin 1β was added along with 10 μmol/L grape seed extract solution for 48 hours. Cells in the miR-138-5p NC and inhibitor groups were transfected with 5 nmol/L miR-138-5p NC and  5 nmol/L miR-138-5p inhibitor for 12 hours, respectively, followed by addition of 20 ng/mL interleukin-1β. qRT-PCR was used to detect miR-138-5p and caspase-3 expression. Luciferase reporter assay was used to analyze the relationship between miR-138-5p and caspase-3 targeting. Cell counting kit-8 was used to detect cell proliferation activity. Flow cytometry was used to detect cell apoptosis. Caspase-3 and Bcl-2 protein expressions were detected by western blot. (2) Animal experiment: The animals were divided into normal control group, grape seed extract group and miR-138-5p inhibitor group. The effects of grape seed extract on epiphyseal closure and tibial growth of the tibial plateau in rats were observed.  RESULTS AND CONCLUSION: miR-138-5p had a targeting relationship with caspase-3. Compared with the control group, cell proliferation was significantly reduced, apoptosis was significantly increased (P < 0.01), miR-138-5p, Bcl-2 expression was reduced (P < 0.01), and caspase-3 expression was increased (P < 0.01) in the model group. Compared with the mod group, the grape seed extract group showed a significant increase in cell proliferation, a significant decrease in apoptosis (P < 0.01), an increase in miR-138-5p and Bcl-2 expression (P < 0.01) and a decrease in caspase-3 expression (P < 0.01). Compared with the grape seed extract group, the miR-138-5p inhibitor group showed a significant decrease in cell proliferation, a significant increase in apoptosis (P < 0.01), a decrease in miR-138-5p and Bcl-2 expression (P < 0.05 or P < 0.01), and an increase in caspase-3 expression (P < 0.05). Intragastric administration of grape seed extract could delay epiphyseal closure of the tibial plateau and promote tibial bone growth in rats, whereas miR-138-5p inhibitor intervention inhibited the effect of grape seed extract on tibial bone growth in rats. To conclude, grape seed extract can inhibit apoptosis of rat growth plate chondrocytes through regulating the miR-138-5p/caspase-3 pathway, improve epiphyseal closure of rat tibial plateau and promote tibial bone growth. Figures and Tables | References | Related Articles | Metrics

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Bone morphogenetic protein/Smad signaling pathway involved in chondrodysplasia in the ankle of a rat congenital clubfoot model Chang Yu, Li Hui, Zhang Tianshui, Wang Chunyu, Yu Li, Wu Zimei, Li Wen, Wang Zhengdong 2024, 28 (16):  2500-2504.  doi: 10.12307/2024.328 Abstract ( 199 )   PDF (1108KB) ( 22 )   Save BACKGROUND: Congenital clubfoot mainly manifests as abnormal bone itself and abnormal cartilage development. The bone morphogenetic protein (BMP)/drosophila mothers against decapentaplegic protein (Smad) signaling pathway can direct the development of bone and cartilage during embryonic period, but its role in the field of clubfoot etiology has not been confirmed in animal experiments. OBJECTIVE: To explore the mechanism by which the BMP/Smad signaling pathway is involved in the regulation of foot and ankle chondroplasia in a rat congenital clubfoot model.  METHODS: Sprague-Dawley rats at 10 days of gestation with the same growth condition were randomly divided into experimental and control groups. The experimental group was intragastrically given 135 mg/kg retinoic acid to make the clubfoot model, while the control group was given the same amount of vegetable oil. The fetal rats were taken out after 21 days of gestation by cesarean section. In the experimental group, the 27 of 41 fetal rats had clubfoot, with a deformity rate of 65.9%; in the control group, no clubfoot was observed in all the 36 fetuses. The ankles tissues of the rats were collected for hematoxylin-eosin staining. Western blot assay, RT-qPCR and immunohistochemistry were performed to detect the expression levels of Smad5 and P-Smad5, the core proteins of the BMP/Smad signaling pathway, as well as SP7 and Sox9, the downstream proteins of the BMP/Smad signaling pathway. RESULTS AND CONCLUSION: Compared with the control group, hematoxylin-eosin staining showed that the cartilage matrix in the foot and ankle tissues increased and the gap between the bones increased in the experimental group. Immunohistochemical findings showed that the expression levels of Smad5 and SP7 decreased in the experimental group, while the mRNA expression of Sox9 increased. RT-qPCR results showed that the mRNA expression of Smad5 and SP7 decreased, while the mRNA expression of Sox9 increased in the foot and ankle tissues of rats in the experimental group. Western blot results showed that P-Smad5/Smad5 expression and SP7 expression were decreased and Sox9 expression was increased in the ankle of rats in the experimental group. To conclude, the occurrence of cartilage abnormalities in the foot and ankle of the rat model of congenital clubfoot is associated with impaired transmission of the BMP/Smad signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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Protective mechanism of alendronate granule in a rat osteoporosis model based on TMT proteomic analysis Huang Huimin, Xie Bingying, Huang Jingwen, Huang Xiaobin, Xie Lihua, Li Shengqiang, Ge Jirong 2024, 28 (16):  2505-2511.  doi: 10.12307/2024.355 Abstract ( 246 )   PDF (1412KB) ( 77 )   Save BACKGROUND: The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth.  OBJECTIVE: To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins.  METHODS: Female Sprague-Dawley rats were randomly divided into three groups (n=12 per group): model group, alendronate group and sham-operated group. Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups. At 4 weeks after modeling, rats in the alendronate group were gavaged with alendronate; the other two groups were given the equal volume of normal saline. After 12 weeks of continuous gavage, the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION: There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group. Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions, such as binding and catalytic activity, and in biological processes, such as cellular process and metabolic process. Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A. Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group, Hspa1l, Enpp3, Unc45a, Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism. Overall, these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A. Figures and Tables | References | Related Articles | Metrics

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Mechanism of NONHSAT248596.1 endogenous competition with miR-146a-5p regulating osteoarthritis cartilage degeneration Yang Guang, Li Yanlin, Wang Guoliang, Ning Ziwen, Yang Tengyun, He Renjie, Xiong Bohan, Yang Bing, Li Li 2024, 28 (16):  2512-2518.  doi: 10.12307/2024.283 Abstract ( 215 )   PDF (2011KB) ( 26 )   Save BACKGROUND: Currently, there have been studies on the regulatory mechanism of lncRNA\miRNA\mRNA co-expression network on the occurrence and development of osteoarthritis. Our research group has screened qualified NONHSAT248596.1 and miR-146a-5p through the database in the previous stage, but the corresponding in vivo experiments to verify the above regulatory mechanisms are still lacking.  OBJECTIVE: To explore the role of NONHSAT248596.1 in regulating competitive endogenous RNA of miR-146a-5p in cartilage degeneration mediated by stromal cell derived factor type 1/chemokine receptor 4 axis in vivo. METHODS: The models of osteoarthritis were established in 36 New Zealand rabbits by injecting stromal cell derived factor 1 solution into the knee joint of the right hind limb. According to the random number table method, they were divided into four groups. lncRNA group, miRNA group, ceRNA group and control group were injected with lentivirus vector overexpressing NONHSAT248596.1, lentivirus vector overexpressing miR-146a-5p, lentivirus vector overexpressing miR-146a-5p+NONHSAT248596.1 and empty lentivirus vector into the molded knee joint, respectively. At 4, 8 and 12 weeks of modeling, cartilage tissues and subchondral bone tissues of the knee joint were taken for relevant detection. RESULTS AND CONCLUSION: Hematoxylin-eosin staining and safranin fast green staining showed different degrees of degeneration in the four groups. At 4 weeks, the cartilage tissue of the lncRNA group showed swelling of chondrocytes, loss of cell polarity, destruction of extracellular matrix, surface erosion, fracture formation and partial or full layer loss of cartilage tissue. The degree of cartilage injury was gradually aggravated with time. The progression of articular cartilage inflammation in the miRNA group was the slowest among the four groups. qRT-PCR showed that at the same time point, mRNA expression levels of NONHSAT248596.1, chemokine receptor 4, matrix metalloproteinase 3, matrix metalloproteinase 9 and matrix metalloproteinase 13 in cartilage tissue of the lncRNA group were higher than those of the other three groups (P < 0.05). The mRNA expression levels of miR-146a-5p, aggrecan and type II collagen were lower than those of the other three groups (P < 0.05). The mRNA expression levels of NONHSAT248596.1, chemokine receptor 4, matrix metalloproteinase 3, matrix metalloproteinase 9 and matrix metalloproteinase 13 in the miRNA group were lower than those in the ceRNA group and control group at 8 and 12 weeks after the model construction (P < 0.05). The mRNA expressions of miR-146a-5p, aggrecan and type II collagen were higher than those of the ceRNA group and control group (P < 0.05). Western blot assay showed that at the same time point, the expression levels of aggrecan and type II collagen in cartilage tissue of the lncRNA group were always lower than those of the other three groups (P < 0.05). The expression levels of aggrecan and type II collagen in cartilage tissue of the miRNA group at 8 and 12 weeks after modeling were higher than those of the ceRNA group and control group (P < 0.05). The results showed that miR-146a-5p, as the target of NONHSAT248596.1, could be inhibited by the effect of its ceRNA. After acting on miR-146a-5p, NONHSAT248596.1 regulates the stromal cell derived factor type 1/chemokine receptor 4 axis to affect the expression of matrix metalloprotein, type II collagen, and aggrecan in osteoarthritis chondrocytes, resulting in the degradation of extracellular matrix and the loss of proteoglycan. Figures and Tables | References | Related Articles | Metrics

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Effects of transcranial magneto-acoustical stimulation on beta oscillations in neural circuits of healthy and Parkinson’s disease rats Zhang Shuai, You Shengnan, Du Wenjing, Wang Lei, Xu Guizhi 2024, 28 (16):  2519-2526.  doi: 10.12307/2024.302 Abstract ( 262 )   PDF (1513KB) ( 123 )   Save BACKGROUND: Transcranial magneto-acoustical electrical stimulation (TMAES) is a non-invasive, high-precision neurofocused stimulation method based on magneto-acoustic coupling electrical effect, which can regulate the rhythmic oscillation of nerve activity, thereby affecting the brain’s movement, cognition and other functions. OBJECTIVE: To explore the effect of TMAES on beta oscillations in the neural circuits of healthy rats and Parkinson’s rats. METHODS: (1) Animal experiments: Twenty-four Wistar rats were randomly divided into four groups (n=6 per group). The rats in the normal control group received no intervention, while those in the normal stimulation group received TMAES (the average spatial peak pulse intensity: 13.33 W/cm2, fundamental frequency: 0.4 MHz, the number of fundamental wave cycles: 1000, and pulse frequency: 200 Hz). The model control group and model stimulation group were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. After successful modeling, the rats in the model control group received sham TMAES stimulation in the prefrontal cortex, and those in the model stimulation group received TMAES in the prefrontal cortex, and the duration of stimulation was 2.0 minutes per day. After an interval of 8-10 minutes, the local field potential signals of rats were collected during the execution of T-maze test and the correct rate of behavior was recorded at the same time to compare and analyze the time-frequency distribution of local field potential signals and behavioral differences among the groups. The stimulation experiment and T-maze test were stopped when the correct rate of rats was higher than 80% for 3 consecutive days. (2) Modeling and simulation experiments: The cortical-basal ganglion circuit model under TMAES was established, and the ultrasonic emission period (5, 10, 20 ms), ultrasonic emission duty cycle (30%, 50%, 90%) and induced current density (20, 50, 100 μA/cm2) were changed respectively to compare the power spectral density values of beta oscillations in healthy rats and Parkinson’s rats under different stimulation parameters. RESULTS AND CONCLUSION: (1) Animal experiments: The spatial learning ability of the rats in the normal control group was stronger than that of the model control group (P < 0.001), the spatial learning ability of the rats in the normal stimulation group was stronger than that of the normal control group (P < 0.05), and the spatial learning ability of the rats in the model stimulation group was stronger than that of the model control group (P < 0.01). The distribution of beta oscillation energy in the normal control group was more concentrated, and the beta oscillation signal energy was reduced in the normal stimulation group compared with the normal control group. The beta oscillation energy was widely distributed and the energy value was significantly higher in the model control group and the model stimulation group than the normal control and normal stimulation groups. Moreover, the beta oscillation signal energy in the model stimulation group was significantly lower than that in the model control group. (2) Modeling and simulation experiments: the peak power spectral density of the beta band of healthy rats without stimulation (30 dB) was significantly lower than that of Parkinson’s rats (55 dB). The power spectral density value generally decreased after stimulation. The peak power spectral density in the beta band was positively correlated with the ultrasonic emission period and negatively correlated with the induced current density. In addition, the peak power spectral density value was the lowest when the duty cycle of ultrasonic emission was 50%. These findings indicate that TMAES suppresses beta oscillations in healthy and Parkinson's disease rats, thereby improving motor function and decision-making cognitive function in rats. Figures and Tables | References | Related Articles | Metrics

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Effects of Lipopharyngeal Qibi Formula on swallowing function and apoptosis in central cortical swallowing neurons in rats after stroke Li Yanjie, Li Sijin, Hua Xiaoqiong, Qin Hewei, Jin Xiaoqin, Zhang Zhixin 2024, 28 (16):  2527-2533.  doi: 10.12307/2024.305 Abstract ( 213 )   PDF (1455KB) ( 20 )   Save BACKGROUND: The treatment of post-stroke dysphagia with Lipopharyngeal Qibi Formula has achieved good efficacy, and 5-hydroxytryptamine in peripheral serum and neurotransmitters in the nucleus tractus solitarius are closely related to swallowing. Therefore, this study was conducted to explore the modulatory effects of peripheral serum and nucleus tractus solitarius neurotransmitters in swallowing by using modern medical experimental methods such as molecular biology, thereby developing new ideas for the exploration of their mechanisms.  OBJECTIVE: To verify the therapeutic effect of Lipopharyngeal Qibi Formula on post-stroke dysphagia and to investigate its mechanism of action.   METHODS: Thirty-eight Sprague-Dawley rats were randomly divided into model group (n=14), treatment group (n=14) and sham-operated group (n=10). Animals in the model and treatment groups were modeled by reperfusion after 90 minutes of transient cerebral ischemia by wire bolus method. At 6 hours after modeling, neurological function was scored, and rats with a score of 2 were selected for subsequent experiments. The treatment group was given compound Lipopharyngeal Qibi Formula by gavage starting from the 2nd day after modeling and the remaining two groups were given normal saline by gavage. Changes in body mass, 24-hour food and water intake were recorded on days 2, 7, 14 and 30. The swallowing initiation response time and the number of swallows were detected using a biosignal collector and a tonic transducer on days 14 and 30. After the swallowing test, the ischemic area of the brain in each group was measured by TTC staining. The expression of 5-hydroxytryptamine in the nucleus tractus solitarius of the medulla oblongata was measured by immunohistochemistry. The mRNA and protein expression levels of BCL-2 and BAX in the insula, premotor cortex, cingulate cortex and thalamus of rats in each group were measured by RT-PCR and Western blot, respectively. RESULTS AND CONCLUSION: Compared with the sham-operated group, the body mass, 24-hour food intake and water intake were reduced, the swallow initiation response time was prolonged, and the number of swallows was reduced in the treatment and model groups at day 14 of gavage (P < 0.05). Compared with the model group, the body mass, 24-hour food intake and water intake of rats were increased in the treatment group at day 30 of gavage (P < 0.05), but were still lower than those in the sham-operated group. Compared with the model group, the swallow initiation reaction time was shortened and the number of swallows increased in the treatment group, but the number of swallows was still significantly lower than that in the sham-operated group (P < 0.05). Cerebral ischemia area was reduced in the treatment group compared with the model group, and the number of 5-hydroxytryptamine-positive cells in the nucleus tractus solitarius of the medulla oblongata was increased in the treatment group compared with the model group, but it was still significantly lower than that in the sham-operated group (P < 0.05). Compared with the model group, the expression of BCL-2 mRNA and protein in the insula, cingulate cortex and thalamus of rats in the treatment group were significantly increased, the expression of BAX mRNA and protein were significantly decreased, and the BCL-2/BAX ratio was significantly increased (P < 0.05). To conclude, the Chinese herbal compound Lipopharyngeal Qibi Formula could improve the number of swallows and swallowing initiation response time, as well as 24-hour food intake, body mass and other swallowing-related indexes in rats with post-stroke dysphagia. The mechanism of action may be achieved by improving the area of cerebral ischemia, inhibiting the apoptosis of neuronal cells in the insula, cingulate cortex and thalamus of rats, thus improving the regulation of the higher centers on the medulla oblongata swallowing center, and regulating the level of 5-hydroxytryptamine in the nucleus tractus solitarius. Figures and Tables | References | Related Articles | Metrics

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Aerobic exercise modulates mitochondrial quality control system to reverse cardiac pathological remodeling in aging rats Tang Liang, Wang Hexia, Wang Qingbo, Pi Yihua, Zhang Yan 2024, 28 (16):  2534-2541.  doi: 10.12307/2024.225 Abstract ( 233 )   PDF (1722KB) ( 88 )   Save BACKGROUND: Aging is associated with increased susceptibility to cardiovascular disease, and mitochondrial dysfunction plays a key role in the pathogenesis of cardiovascular disease. Regular physical activity is beneficial to cardiovascular health and can prevent and treat chronic heart disease. However, the specific mechanism of mitochondria in the protective effect of exercise on the aging heart has not yet been clarified.  OBJECTIVE: To explore the effect of aerobic exercise on cardiac pathological remodeling in aging rats and to investigate the possible mechanism of mitochondrial quality control system.  METHODS: Sixty Wistar rats were randomly divided into young sedentary group (6 months old), old sedentary group (20 months old) and old exercise group (20 months old) with 20 rats in each group. Rats in the young sedentary and old sedentary groups were fed in cages for 12 weeks, while those in the old exercise group underwent moderate-intensity aerobic treadmill exercise (60% of the maximal running speed, slope 0°, 60 minute per day, 5 days per week) for 12 weeks. After the experiment, the heart was extracted for relevant indicator tests.  RESULTS AND CONCLUSION: Cardiac morphology and myocardial histopathology: compared with the young sedentary group, the rats in the old sedentary group presented with concentric cardiac hypertrophy, myocardial fibrosis, myocardial cell apoptosis and loss, and cardiac diastolic dysfunction (P < 0.05); compared with the old sedentary group, animals in the old exercise group showed reduced myocardial fibrosis and apoptosis rates, increased cell numbers, improved cardiac function (P < 0.05), and a transition in cardiac phenotype from pathological to physiological hypertrophy. Mitochondrial function: compared with the young sedentary group, the generation rate of mitochondrial hydrogen peroxide increased (P < 0.05), respiration rate and respiratory control ratio of state 3 and state 4 decreased (P < 0.05), activities of respiratory chain complexes I, II and IV decreased (P < 0.05), mitochondrial calcium retention capacity decreased (P < 0.05), and mitochondrial permeability transition pore opening increased (P < 0.05) in the old sedentary group. Compared with the old sedentary group, all of the above indicators were significantly improved in the old exercise group (P < 0.05). Mitochondrial quality control: compared with the young sedentary group, mitochondrial biogenesis decreased (P < 0.05), mitophagy activity increased (P < 0.05), mitochondrial fusion reduced (P < 0.05), and fission raised (P < 0.05) in the old sedentary group; compared with the old sedentary group, mitochondrial biogenesis and mitophagy activity increased (P < 0.05), mitochondrial fusion raised (P < 0.05) and fission decreased (P < 0.05) in the old exercise group. To conclude, regular aerobic exercises exert cardioprotective effects in aging rats by regulating the mitochondrial quality control system, thus reversing pathological cardiac remodeling and improving cardiac function. Figures and Tables | References | Related Articles | Metrics

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Effects of recombinant human collagen supplementation on extracellular matrix remodeling in mouse skeletal muscle after eccentric exercise Zhao Shasha, He Qing, Li Jia, Wu Ying 2024, 28 (16):  2542-2549.  doi: 10.12307/2024.304 Abstract ( 238 )   PDF (1983KB) ( 44 )   Save BACKGROUND: Collagen is the most abundant extracellular matrix component, which is closely related to the structure and function of the extracellular matrix of skeletal muscle, but the effect and mechanism of recombinant human collagen (rhC) produced by bioengineering technology on the extracellular matrix of skeletal muscle are unclear. OBJECTIVE: To investigate the effect of rhC supplementation on the remodeling of skeletal muscle extracellular matrix after eccentric exercise, thereby revealing the possible mechanism by which rhC improves the injury of skeletal muscle extracellular matrix and promote the recovery after exercise. METHODS: A total of 104 healthy male C57 mice aged 8 weeks old were randomly divided into control group (normal saline), low-dose rhC group (0.2 g/kg), medium-dose rhC group (1.0 g/kg), and high-dose rhC group (2.0 g/kg). Two mice in each group were selected after continuous 7 days of intragastric intervention, and organs were dissected for hematoxylin-eosin staining to determine inflammatory infiltrates. On the 8th day, the remaining mice were subjected to eccentric exercise. The structural changes of the skeletal muscle extracellular matrix were observed under scanning electron microscopy immediately (0), 24, 48, and 96 hours  after eccentric exercise. Meanwhile, grip strength, creatine kinase activity, and protein levels of matrix metalloproteinases 2, 9, 14 and tissue inhibitor of metalloproteinase-2 in skeletal muscle were detected by western blot assay. RESULTS AND CONCLUSION: Hematoxylin-eosin staining results indicated that short-term rhC supplementation showed no significant effects on the morphology of the heart, liver, spleen and kidney. After one-time eccentric exercise, the recovery rate of grip strength in the medium- and high-dose rhC groups was significantly increased (P < 0.01). The trend of creatine kinase changes was consistent in all groups and there was no significant difference between groups. The recovery process of the extracellular matrix in the low-dose rhC group was faster than that in the control group, and the muscle tract membrane in the medium- and high-dose rhC groups was more complete. The protein level of matrix metalloproteinase 9 in the high-dose rhC group was significantly decreased (P < 0.05). The protein levels of matrix metalloproteinase 14 in the medium- and high-dose rhC groups were significantly decreased (P < 0.05). The protein levels of matrix metalloproteinase 2 in the medium- and high-dose rhC groups were significantly decreased (P < 0.05). Tissue inhibitor of metalloproteinase-2 protein levels in the medium- and high-dose rhC groups were significantly increased (P < 0.05). The ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase-2 in each rhC group was significantly decreased (P < 0.05). To conclude, pre-supplementation of 1.0 and 2.0 g/kg rhC for 7 days can inhibit extracellular matrix degradation in skeletal muscle after exercise by modulating matrix metalloproteinases and matrix metalloproteinase inhibitors, thereby promoting recovery of skeletal muscle strength in mice. Figures and Tables | References | Related Articles | Metrics

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Establishment and analysis of osteoarthritis diagnosis model based on artificial neural networks Fan Yidong, Qin Gang, Su Guowei, Xiao Shifu, Liu Junliang, Li Weicai, Wu Guangtao 2024, 28 (16):  2550-2554.  doi: 10.12307/2024.294 Abstract ( 243 )   PDF (1724KB) ( 60 )   Save BACKGROUND: Rapid developments in the field of bioinformatics have provided new methods for the diagnosis of osteoarthritis. Artificial neural networks have powerful data computing and classification capabilities, which have shown better performance in disease diagnosis. OBJECTIVE: To establish a new diagnostic predictive model of osteoarthritis based on artificial neural network and to verify the diagnostic value of the model in osteoarthritis with an external dataset.  METHODS: The eligible osteoarthritis-related data sets were downloaded through GEO database search and divided into Train group and Test group. The gene expression matrix of the Train group was analyzed to screen the differentially expressed genes. GO and KEGG enrichment analyses were performed on the differentially expressed genes. Through Lasso regression model, support vector machine model and random forest tree model, the key genes of osteoarthritis were further identified from the differentially expressed genes. The R software “Neuralnet” package was then used to construct the osteoarthritis diagnosis model based on artificial neural network, and the model performance was evaluated by the five-fold cross-validation. Two independent data sets in the Test group were used to verify their diagnostic results.  RESULTS AND CONCLUSION: A total of 90 differentially expressed genes related to osteoarthritis were obtained by differential analysis, of which 33 were down-regulated and 57 were up-regulated. GO enrichment analysis showed that the differentially expressed genes were mainly involved in the following biological processes, including leukocyte-mediated immunity, leukocyte migration in bone marrow and chemokine production. KEGG enrichment analysis showed that these genes were mainly enriched in rheumatoid arthritis, interleukin-17 signaling pathway and osteoclast differentiation pathway. Five key genes for the diagnosis of osteoarthritis, HMGB2, GADD45A, SLC19A2, TPPP3 and FOLR2, were identified by three machine learning methods. The artificial neural network model of five key genes in the Train group showed that the accuracy was 96.36% and the area under the curve was 0.997. The five-fold cross validation of the neural network model showed that the average area under the curve was greater than 0.9 and the model was of robustness. Two independent data sets in the Test group showed its area under the curve was 0.814 and 0.788 respectively. Therefore, the establishment of an artificial neural network model for the diagnosis of osteoarthritis has a certain diagnostic value.  Figures and Tables | References | Related Articles | Metrics

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Regularity and mechanism of traditional Chinese medicine compound prescriptions in the treatment of primary osteoporosis Zhang Jingtao, Hu Minhua, Liu Shitao, Li Shuyuan, Jiang Zexin, Zeng Wenxing, Ma Luyao, Zhou Qishi 2024, 28 (16):  2555-2560.  doi: 10.12307/2024.326 Abstract ( 233 )   PDF (1897KB) ( 71 )   Save BACKGROUND: Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis, and the curative effect is definite, but the medication rule and mechanism are not clear. OBJECTIVE: Using the methodology of data mining and network pharmacology, to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis.  METHODS: The relevant documents included in CNKI, WanFang, VIP and PubMed were used as data sources, and the relevant data were statistically counted and extracted by Microsoft EXCEL2019, IBMSPSS25.0 and other software. The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis, and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results. The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking.  RESULTS AND CONCLUSION: Finally, 151 articles were included and 207 prescriptions were selected, involving 285 flavors of Chinese herbs. (1) Ten groups of important drug combinations were obtained through the above two analyses, among which the core drug combination with the highest confidence and improvement was “Drynaria-Eucommia-Angelica.” The key components of the combination in the treatment of primary osteoporosis were quercetin, kaempferol, naringenin and so on. The core targets were SRC proto-oncogene, phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene. The main pathways were cancer signaling pathway, JAK-STAT signaling pathway, VEGF signaling pathway, and NF-κB signaling pathway. (2) The key active components were docked with the core targets, and the two showed a good combination. To conclude, Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets, which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis. Figures and Tables | References | Related Articles | Metrics

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CeRNA interaction network and immune manifestation of ferroptosis-related signature genes in rheumatoid arthritis Xia Tian, Li Binglin, Xiao Fayuan, Zheng Enze, Chen Yueping 2024, 28 (16):  2561-2567.  doi: 10.12307/2024.321 Abstract ( 266 )   PDF (3357KB) ( 25 )   Save BACKGROUND: Ferroptosis-related genes have been found to play an important role in the pathogenesis of rheumatoid arthritis. However, there is currently a lack of immune expression of ferroptosis-related signature genes in rheumatoid arthritis and the construction of competing endogenous RNA (CeRNA) interaction networks. Machine learning, as a powerful signature gene selection algorithm based on bioinformatics, can more accurately identify ferroptosis-related signature genes that dominate the pathogenesis of rheumatoid arthritis. OBJECTIVE: To screen ferroptosis-related signature genes in rheumatoid arthritis using bioinformatics and machine learning methods, and to analyze the correlation between ferroptosis-related signature genes and immune infiltration and the construction of CeRNA network of ferroptosis-related signature genes. METHODS: Rheumatoid arthritis-related microarrays were obtained from the GEO database, and ferroptosis-related genes and their differential gene expression were extracted using R language. The differentially expressed genes were screened using machine learning methods. The LASSO regression and SVM-RFE methods were used for signature gene screening, and the genes filtered by both were re-intersected to finally obtain the signature genes in rheumatoid arthritis. Receiver operating characteristic curves were used to assess the accuracy of the screened signature genes for disease diagnosis. Immune infiltration of rheumatoid arthritis and normal synovial tissues was analyzed using the CIBERSORT algorithm, and the correlation between the signature genes and immune cells was analyzed. Finally, the CeRNA network of ferroptosis-related signature genes for rheumatoid arthritis was constructed and the disease signature genes were validated.  RESULTS AND CONCLUSION: A total of 150 ferroptosis-related genes in rheumatoid arthritis were obtained, including 55 up-regulated genes and 95 down-regulated genes. GO and KEGG enrichment analyses identified 18 GO significantly correlated entries and 30 KEGG entries respectively, mainly involving metal ion homeostasis, ferric ion homeostasis and oxidative stress response. Machine learning analysis finally identified disease signature genes GABARAPL1 and SAT1. GSEA analysis found that adipocytokine signaling pathway, drug metabolism cytochrome P450, fatty acid metabolism, PPAR signaling pathway, tyrosine metabolism were mainly concentrated when GABARAPL1 was highly expressed, and chemokine signaling pathway, intestinal immune network on IGA production were mainly concentrated when SAT1 was highly expressed. Immune infiltration analysis found that nine immune cells were significantly different in rheumatoid arthritis and normal synovial tissues, in which plasma cells, T-cell CD8, and T-cell follicular helper were highly expressed and the rest were lowly expressed in the disease group. Single gene and immune cell correlation analysis found that GABARAPL1 was positively correlated with dendritic resting cells, activated NK cells, and macrophage M1, with the most significant correlation with dendritic resting cells, while SAT1 was positively correlated with T cell CD4 and γδ T cells and negatively correlated with NK resting cells. GSVA analysis found that SAT1 was upregulated in ascorbic acid and aldehyde metabolism, while downregulated in B-cell receptor signaling pathway, Toll-like receptor signaling pathway, T-cell receptor signaling pathway, and natural killer cell-mediated cytotoxicity. GABARAPL1 showed a down-regulation trend in PPAR signaling pathway, metabolism of nicotinate and nicotinamide, tryptophan metabolism, fatty acid metabolism, and steroid biosynthesis. Sixty long non-code RNAs may play a key role in the development of rheumatoid arthritis. To conclude, the occurrence of rheumatoid arthritis is significantly correlated with the abnormal expression of rheumatoid arthritis-induced ferroptosis-related signature genes, and the signature genes induce disease development via relevant signaling pathways. By analyzing rheumatoid arthritis-related long non-code RNAs-mediated ceRNA networks, potential therapeutic targets and signaling pathways can be identified to further elucidate its pathogenesis and provide a reference basis for subsequent experimental studies. Figures and Tables | References | Related Articles | Metrics

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Prediction and validation of potential targets for the glucagon-like peptide-1 receptor agonist in the treatment of Alzheimer’s disease Han Weina, Xu Xiaoqing, Shi Jinning, Li Xinru, Cai Hongyan 2024, 28 (16):  2568-2573.  doi: 10.12307/2024.306 Abstract ( 241 )   PDF (2691KB) ( 85 )   Save BACKGROUND: In the process of exploring the mechanism of Alzheimer’s disease, the important role of bioinformatics for common target screening has been revealed, enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE: To predict the targets of liraglutide, a glucagon-like peptide-1 receptor agonist, in the treatment of Alzheimer’s disease by bioinformatics and molecular biology. METHODS: DisGeNET database and SEA database were used to obtain the common genes of Alzheimer’s disease and liraglutide. GO/KEGG enrichment analysis of common targets was conducted using DAVID online database. Protein-protein interaction networks were constructed using STRING database. The optimal dosage of liraglutide was determined using cell counting kit-8 assay. Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques. The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments, and the cells were randomly divided into three groups: HT22 group, HT22+Aβ group, and HT22+Aβ+Lir group. No special treatment was done in the HT22 group, while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group. In additional to modeling, liraglutide was added to the HT22+Aβ+Lir group for 12 hours.  RESULTS AND CONCLUSION: A total of 3 333 genes associated with Alzheimer’s disease were screened from DisGeNET database. Then 147 potential targets of liraglutide were obtained from SEA database. Finally, 64 common targets of Alzheimer’s disease and Liraglutide were determined using R packets. GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes: neuroactive ligand-receptor interaction, renin-angiotensin system, bladder cancer, endopeptidase activity, peptide receptor activity, G protein-coupled peptide receptor activity, and transport vesicles. The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction, and the top three genes, matrix metalloproteinases 2, 9 and interleukin 1β, were obtained. The activity of cultured cells was detected by the cell counting kit-8 kit. Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42. In the western blot and immunofluorescence assays, the expression of matrix metalloproteinases 2, 9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group (P < 0.05) but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group (P < 0.05). To conclude, the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer’s disease. Figures and Tables | References | Related Articles | Metrics

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The role and mechanism of estrogen receptor in the treatment of postmenopausal osteoporosis by Gushukang Chai Shuang, Ma Jiangtao, Yang Yanbing, Su Xiaochuan, Xie Yan, Teng Junyan, Qin Na 2024, 28 (16):  2574-2578.  doi: 10.12307/2024.298 Abstract ( 223 )   PDF (2460KB) ( 77 )   Save BACKGROUND: The specific mechanism of Gushukang, as a Chinese traditional patent medicine for the treatment of postmenopausal osteoporosis of kidney deficiency and blood stasis, needs further studies.  OBJECTIVE: To investigate the effect of Gushukang on serum sex hormones, bone microstructure and estrogen receptor in postmenopausal osteoporosis.  METHODS: Firstly, network pharmacological analysis was performed. The active ingredients and action targets of Gushukang and the targets of postmenopausal osteoporosis were obtained respectively. Cytoscape was used to construct the active ingredient - target network. STRING database and Cytoscape were used for protein-protein interaction analysis and screening of core targets. DAVID database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of intersection targets. Then the ovariectomized Sprague-Dawley rats were used in the animal experiment. Gushukang was administered by gavage for 3 months. The serum estrogen level was detected by ELISA, the bone microstructure was detected by microCT, and the protein expression of estrogen receptor α and estrogen receptor β in bone tiusse was detected by western blot.  RESULTS AND CONCLUSION: The network pharmacological research results identified 132 active ingredients and 150 targets of Gushukang and 1155 targets of postmenopausal osteoporosis. After intersections with 1155 postmenopausal osteoporosis targets, 87 targets of active ingredients of Gushukang against postmenopausal osteoporosis were obtained. By constructing the active ingredient - target network, it was found that the active ingredients at the core were quercetin, kaempferol, luteolin, naringin and isorhamnetin, and the targets at the core were NCOA2, ESR2, AR, F2, ESR1 and PTGS1. The final targets obtained after the protein-protein interaction analysis and screening included MAPK8, ESR1, JUN, R3C1, RELA and FOS, of which ESR1 was the common core target obtained from the two analyses. KEGG enrichment analysis showed estrogen, tumor necrosis factor, apoptosis and other signaling pathways. Therefore, animal experiments focused on the effect of Gushukang on different subtypes of estrogen receptors in the estrogen signaling pathway. The results showed that in the Gushukang group, bone microstructure was significantly improved, serum estrogen level had no significant change, but the protein expression of estrogen receptor α and β in bone tissue was significantly increased. All the findings indicate that the mechanism of Gushukang in the treatment of postmenopausal osteoporosis may be related to its hormone-like effect and the enhancement of estrogen receptor expression.  Figures and Tables | References | Related Articles | Metrics

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Finite element analysis of the effect of bone on occlusal adjustment of right upper first molar implants Chen Jiawen, Luo Siyang, Liu Yin, Chen Guangneng, Zuo Yuwen, He Xianyu, Ma Minxian 2024, 28 (16):  2579-2586.  doi: 10.12307/2024.299 Abstract ( 281 )   PDF (3258KB) ( 55 )   Save BACKGROUND: Bone tissue remodeling is closely related to stress loading. Currently, there are few studies or guidelines on the relationship between bone and occlusal adjustment of implant prostheses and there is also a lack of scientific evidence. OBJECTIVE: To investigate the effects of different implant occlusal gaps on stress distribution, stress peak and displacement at the implant-bone interface under I-IV bone conditions by a finite element method. METHODS: After scanning the equal-scale tooth model with an optical scanner, equal-scale models of the upper right first molar Straumann 4.8×8 mm BL RC implant and its related components was constructed using Solidworks 2022. Then, using Mimics, Geomagic, and Solidworks software, the maxillary and mandibular bone models of class I-IV bones were established based on the bone classification proposed by ZARB and LEKHOLM in the literature, and the NORTON and TRISI bone density classification method. The models were assembled with the occlusal gaps of 0, 20, 40, 60, 80, and 100 μm for the restorations, and an additional set of homogeneous models without density ratio settings was constructed for comparison. After the above models were imported into Hypermesh for meshing, the material assignment, boundary constraints and parameter setting were performed for the finite element analysis. Finally, 250 N was used as the loading force to simulate the maxillary and mandibular stress conditions. Stress distribution, peak stress and displacement of the implant-bone interface in each group of models were analyzed and compared. RESULTS AND CONCLUSION: Under the same loading conditions, the stresses in the implant restorations were evenly distributed with the occlusal contact points. When the occlusal gap reached 80 and 100 μm, stress interruptions occurred in the implant crowns under class I bone and class II, III and IV bones, respectively. The displacement of the implant-bone interface was mainly concentrated in the cortical bone region around the implant and transmitted down the long axis of the implant to the cancellous bone region at the bottom. With the changes of class I-IV jaw bones, the displacement and Von Mises stress in the cortical bone region increased in all groups, and were greater than those in the cancellous bone region. The Von Mises stress in the cancellous bone region was similar to that in the cortical bone region except that it showed a downward trend from class II bone. However, when the occlusal gap increased, the stress and displacement peak values in the cortical bone and the cancellous bone showed a decreasing trend. The stress of the implant-bone interface was between 20 MPa and 60 MPa when the occlusal gap was 0-40 μm for class II-IV bones and 60 μm for class IV bone, and the stress of the other groups was less than     20 MPa. The Von Mises stress was mainly concentrated in the neck of the implant, and the peak value of von Mises stress in class II-IV bones with the occlusal gap of 20 μm was higher than that (144.10 MPa) in class I bone with the occlusal gap of 0 μm. In the homogeneous model with different elastic moduli, the distribution of stress and displacement was more uniform than that in the heterogeneous model and the occlusal space should increase with the decrease of jaw bone density in clinical practice. To conclude, from the perspective of biomechanics, the alveolar bone should be taken into account in the occlusal adjustment of implant denture. An occlusal gap of 20-40 μm between a single dental implant and a natural tooth in the opposite jaw is a relatively suitable solution for occlusal adjustment under different bone conditions. However, due to the particularity of finite element analysis method, it needs to be further studied in combination with clinical practice.  Figures and Tables | References | Related Articles | Metrics

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Action mechanism of resveratrol intervention on ventricular remodeling in exercise-induced fatigue rats Zhang Libing, Xu Shang, Jin Qiguan, Hu Yulong 2024, 28 (16):  2587-2592.  doi: 10.12307/2024.284 Abstract ( 219 )   PDF (966KB) ( 83 )   Save BACKGROUND: Studies have shown that resveratrol can relieve exercise-induced fatigue and protect the heart, but its action mechanism needs further study.  OBJECTIVE: To explore the protective effect and regulatory mechanism of resveratrol on ventricular remodeling in exercise-induced fatigue rats.  METHODS: Totally 48 male Sprague-Dawley rats were randomly divided into four groups, with 12 rats in each group. Rats in the blank control group were fed conventionally. After one week of adaptive training, rats in the exercise-related fatigue group and exercise-related fatigue with resveratrol supplement group were trained by 6-week weight-bearing swimming (5% body mass lead block fixed in the tail, 70%-80% maximal oxygen uptake intensity), 6 days a week, 60 minutes a day. Rats in the resveratrol supplement group and exercise-related fatigue with resveratrol supplement group were given resveratrol (50 mg/kg per day) by gavage one hour after exercise intervention. Blank control group and exercise-related fatigue group were given the same volume of 2% dimethyl sulfoxide, 6 days a week, once a day for 6 weeks. The body mass and heart mass of the rats were measured 24 hours after the last intervention. Plasma creatine kinase isoenzyme, cardiac troponin 1, pyruvate dehydrogenase and uncoupling protein 1 levels in myocardial tissue were determined by ELISA. The mRNA expression levels of ventricular remodeling-related factor Foxp1, transforming growth factor β1 and endothelin 1 were detected by RT-PCR. RESULTS AND CONCLUSION: Compared with the blank control group, the body mass of rats decreased and the heart mass increased in the exercise-related fatigue group (P < 0.05). Compared with the exercise-related fatigue group, the body mass and heart mass of the rats reduced in the exercise-related fatigue with resveratrol supplement group (P < 0.05). Compared with the blank control group, the levels of creatine kinase isoenzyme, cardiac troponin 1 and uncoupling protein 1 increased (P < 0.01), and the level of pyruvate dehydrogenase decreased (P < 0.01) in the exercise-related fatigue group. Compared with the exercise-related fatigue group, the levels of creatine kinase isoenzyme, myocardial troponin 1 and uncoupling protein 1 decreased (P < 0.05), and the level of pyruvate dehydrogenase increased (P < 0.05) in the exercise-related fatigue with resveratrol supplement group. Compared with the blank control group, the expression of the Foxp1 gene decreased (P < 0.01), and the expression of transforming growth factor β1 and endothelin 1 gene increased (P < 0.01) in the myocardium of the exercise-related fatigue group. Compared with the exercise-related fatigue group, the expression of the Foxp1 gene in the myocardium of the exercise-related fatigue with resveratrol supplement group increased (P < 0.01), while the expression of the transforming growth factor β1 and endothelin 1 gene decreased (P < 0.05). It is suggested that exercise-induced fatigue can promote myocardial adaptability and cause compensatory hypertrophy. Resveratrol can improve myocardial injury and energy metabolism and delay ventricular energy remodeling in rats. This effect may be related to the regulation of Foxp1/transforming growth factor β1/endothelin 1 signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of miR-141-3p on dorsal root ganglion inflammation and lower limb pain in rats with lumbar disc herniation Xu Gang, Zhang Changchun, Zhu Kun, Ye Yuchen, Zhou Pinghui 2024, 28 (16):  2593-2598.  doi: 10.12307/2024.277 Abstract ( 390 )   PDF (940KB) ( 45 )   Save BACKGROUND: Studies have shown that insulin-like growth factor 1/platelet-derived growth factor has an inhibitory effect on fibroblast apoptosis. miR-141-3p in bone marrow stromal cells increases with age and has a relationship with the activation of inflammatory signaling pathways, suggesting that it may be a therapeutic target for lumbar disc herniation. OBJECTIVE: To explore the effects of miR-141-3p on dorsal root ganglion inflammation and lower limb pain in rats with lumbar disc herniation by regulating insulin-like growth factor 1/platelet-derived growth factor.  METHODS: Fifty male Sprague-Dawley rats, SPF level, were randomly divided into normal group, model group, miR-NC group, miR-141-3p inhibitor group and miR-141-3p mimics group, with 10 rats in each group. Except for the normal group, animal models of lumbar disc herniation were established in rats by autologous nucleus pulposus transplantation. After successful modeling, rats in the miR-NC, miR-141-3p inhibitor and miR-141-3p mimics groups were injected intrathecally with 10 μL of 20 μmol/L miR-NC, miR-141-3p inhibitor, miR-141-3p mimics, once a day for 28 days, respectively, while those in the normal and model groups were injected with the same volume of saline at the same location at the same time. Paw withdrawal thermal latency threshold was used to evaluate lower limb pain in rats. The mRNA expression of miR-141-3p in dorsal root ganglion tissue was detected by real-time fluorescence quantitative PCR, the levels of inflammatory factors in dorsal root ganglion tissue were detected by ELISA, and the expression of insulin-like growth factor 1/platelet-derived growth factor in dorsal root ganglion tissue was detected by western blot. The correlation between miR-141-3p and insulin-like growth factor 1/platelet-derived growth factor was analyzed. RESULTS AND CONCLUSION: There were no significant differences in all indexes between the miR-NC group and the model group. Paw withdrawal thermal latency threshold was significantly lower in the model group than in the normal group (P < 0.05), significantly lower in the miR-141-3p inhibitor group than the miR-NC group (P < 0.05), and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The mRNA expression of miR-141-3p in dorsal root ganglion tissue was significantly lower in the model group than in the normal group (P < 0.05), significantly lower in the miR-141-3p inhibitor group than in the miR-NC group (P < 0.05), and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The levels of tumor necrosis factor α, interleukin 1β, and interleukin 1 in dorsal root ganglion tissue were significantly higher in the model group than in the normal group (P < 0.05), significantly higher in the miR-141-3p inhibitor group than in the miR-NC group (P < 0.05), and significantly lower in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The protein expressions of insulin-like growth factor 1 and platelet-derived growth factor in dorsal root ganglion tissue were significantly lower in the model group than in the normal group (P < 0.05), significantly lower in the miR-141-3p inhibitor group than in the miR-NC group (P < 0.05), and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The expressions of insulin-like growth factor 1 and platelet-derived growth factor showed a positive correlation with miR-141-3p (r=0.904, P < 0.001; r=0.879, P < 0.001). To conclude, miR-141-3p can significantly improve lower limb pain and inhibit inflammation in dorsal root ganglia in rats with lumbar disc herniation, and its mechanism may be related to the promotion of insulin-like growth factor 1/platelet-derived growth factor expression. Figures and Tables | References | Related Articles | Metrics

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Effect of Gubitongxiao granules in a mouse model of steroid-induced necrosis of the femoral head Fang Xiang, Zhou Zhengxin, Zhu Lei, Rui Ren, Xu Maoyu, Zhu Caiyu 2024, 28 (16):  2599-2604.  doi: 10.12307/2024.285 Abstract ( 101 )   PDF (1310KB) ( 81 )   Save BACKGROUND:  Glucocorticoids can inhibit the expression of hub genes in the parathyroid hormone type I receptor (PTH1R)/protein kinase A (PKA) signaling axis and interfere with the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells, leading to the disruption of blood supply in bone and bone tissue structures. Previous studies of the research team showed that Gubitongxiao granules can induce blood vessel formation and inhibit osteoblast apoptosis, which has a certain effect on the prevention and treatment of steroid-induced femoral head necrosis. OBJECTIVE: To observe the therapeutic effect of Gubitongxiao granules in a mouse model of steroid-induced femoral head necrosis, and to explore its mechanism from the PTH1R/PKA signaling axis.  METHODS: An animal model of steroid-induced necrosis of the femoral head was established by intraperitoneal injection of lipopolysaccharide and gluteal muscle injection of prednisolone acetate. After identification by nuclear magnetic resonance method, 60 mice that were successfully modeled were divided into model group, Gubitongxiao granule group and Tongluo Shenggu capsule group, with 20 mice in each group. Another 12 normal mice were used as control group. The corresponding groups were intragastrically given the corresponding drugs for 12 weeks, and then the samples were taken under anesthesia. Histomorphology of femoral head samples was observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was used to detect the serum levels of bone alkaline phosphatase, type I amino-terminal extension peptide, parathyroid hormone, osteocalcin and alkaline phosphatase. Western blot and RT-qPCR were used to detect PTH1R, PKA, myocyte enhancer factor 2, sclerostin and guanylate-binding protein activity-stimulating peptide at protein and gene expression levels, respectively.  RESULTS AND CONCLUSION: Gubitongxiao granules may reduce the serum PTH level in mice, inhibit the activation of the PTH1R/PKA signal axis, further up-regulate the protein expressions of sclerostin and myocyte enhancer factor 2, and increase the levels of bone alkaline phosphatase, type I amino-terminal extension peptide, osteocalcin and alkaline phosphatase in mice, thus improving femoral head necrosis, which is comparable to the intervention effect of Tongluo Shenggu capsules. It is speculated that Gubitongxiao granules may prevent and treating hormonal femoral head necrosis by regulating the PTH1R/PKA signaling axis. Figures and Tables | References | Related Articles | Metrics

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Low-frequency pulsed magnetic field induces classical transient receptor potential channels 1 to relieve lower limb muscle weakness in patients recovering from COVID-19 Li Zhongshan, Bao Yijun, Liu Jie, Kong Weiqian, Li Wei, Chen Lin, Bai Shi, Yang Tieli, Wang Chunlu 2024, 28 (16):  2605-2612.  doi: 10.12307/2024.281 Abstract ( 159 )   PDF (1331KB) ( 57 )   Save BACKGROUND: Muscle weakness is a common symptom after coronavirus disease 2019 (COVID-19) infection and affects the ability to perform daily activities in humans during recovery. Low-frequency pulsed magnetic field stimulation at a strength of 1.5 mT and a frequency of 3 300 Hz can enhance the maximal voluntary contraction and strength endurance of human skeletal muscle by inducing and activating classical transient receptor potential channel 1 (TRPC1), which produces a series of pathological support effects on muscle tissue. It has not been studied whether this means will improve muscle weakness in patients recovering from COVID-19. OBJECTIVE: To select the low-frequency pulsed magnetic field for magnetic stimulation of lower limb muscle groups in patients with COVID-19, in order to observe the effect of this stimulation on the improvement of muscle weakness of lower limb muscle groups in patients with COVID-19 during the recovery period. METHODS: Fourteen patients infected with COVID-19 (Omicron strain) positive for Innovita COVID-19 Ab Test (Colloidal Gold) and accompanied by muscle weakness were recruited and randomly divided into two groups: a test group receiving magnetic field stimulation and a control group receiving sham treatment, respectively. The total duration of the trial was 3 weeks. The test group was given low-frequency pulsed magnetic stimulation of the lower limbs every 48 hours and the control group was given the same intervention procedure as the test group but with sham stimulation. Patients in both groups were not informed whether the magnetic stimulation apparatus was running or not. Nine sessions were performed in both groups and the changes in the maximum voluntary contraction, explosive leg force and strength endurance of the local muscle groups of the lower limbs were subsequently observed in both groups. RESULTS AND CONCLUSION: Among the eight local muscle groups collected, seven local muscle groups in the test group showed an increase in the maximum voluntary contraction value after 3 weeks of low-frequency pulsed magnetic field stimulation. In the control group, there were only three muscle groups with improvement in the maximum voluntary contraction. The rate of improvement in the anterior and posterior muscle groups of the left leg in the test group was significantly higher than that in the control group. The longitudinal jump height and peak angular velocity of the knee joint in both groups were improved compared with the pre-test measurement, and the elevation rate of jumping height in the test group was higher than that in the control group. Under the fatigue condition, the decline rates of peak angular velocity of the knee joint and jumping height in the test group decreased significantly, while those in the control group did not change significantly. The above data confirmed that the low-frequency pulsed magnetic field stimulation with the intensity of 1.5 mT and frequency of 3 300 Hz could improve the muscle strength of more local muscle groups in the lower limbs of patients with COVID-19 during the recovery period compared with the human self-healing process, and the whole-body coordination ability and functional status based on explosive leg force of the legs could be significantly improved. Therefore, low-frequency pulsed magnetic field stimulation can be used as an effective, non-exercise rehabilitation tool to improve muscle weakness in the lower limbs of patients with COVID-19. Figures and Tables | References | Related Articles | Metrics

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Ferroptosis in bone diseases: therapeutic targets of osteoporosis Xie Heng, Gu Ye, Gu Yingchu, Wu Zerui, Fang Tao, Wang Qiufei, Peng Yuqin, Geng Dechun, Xu Yaozeng 2024, 28 (16):  2613-2618.  doi: 10.12307/2024.286 Abstract ( 316 )   PDF (1183KB) ( 34 )   Save BACKGROUND:  With the aging of the global population, the incidence rate of osteoporosis is also increasing. It is very important to further understand its pathogenesis and propose new therapeutic targets. Recent studies have shown that ferroptosis is closely related to the pathogenesis of some bone diseases, such as inflammatory arthritis, osteoporosis and osteoarthritis. OBJECTIVE: To summarize the previous studies on the mechanism of ferroptosis in osteoporosis, so as to provide new therapeutic ideas and potential therapeutic targets for osteoporosis. METHODS: The first author used the computer to search the documents published from 2000 to 2022 in CNKI, WanFang, VIP, PubMed and Web of Science with the key words of “ferroptosis, osteoporosis, osteoblasts, osteoclasts, iron chelators, reactive oxygen species, nuclear factor erythroid 2-related factor 2, heme oxygenase-1, glutathione peroxidase 4, review” in Chinese and English. A total of 70 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION: Ferroptosis is significantly different from necrosis, apoptosis and autophagy. In terms of cell morphology and function, it does not have the morphological characteristics of typical necrosis, nor does it have the characteristics of traditional apoptosis, such as cell contraction, chromatin condensation, the formation of apoptotic bodies and the disintegration of cytoskeleton. Contrary to autophagy, ferroptosis does not form a classical closed bilayer membrane structure (autophagic vacuole). Morphologically, ferroptosis is mainly manifested by obvious contraction of mitochondria, increased membrane density, and reduction or disappearance of mitochondrial cristae, which are different from other cell death modes. Iron overload can destroy bone homeostasis by significantly inhibiting osteogenic differentiation and stimulating osteoclast formation, leading to osteoporosis. Iron overload interferes with the differentiation of stem cells to osteoblasts, leading to a weakened osteoblast function and further imbalance of bone metabolism in the body, which eventually leads to osteoporosis. Stimulated by iron overload, osteoclast bone resorption is enhanced and bone loss exceeds new bone formation. Iron chelators have been proved to have osteoprotective effects by inhibiting osteoclast activity and stimulating osteogenic differentiation of osteoblasts. Its potential mechanism is related to inhibiting osteoclast differentiation and promoting osteoblast differentiation. Antioxidants can prevent reactive oxygen species production and inhibit bone absorption, thus improving bone metabolism and effectively preventing osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Transforming growth factor beta/Smad signaling pathway and targeted therapy of keloid scars Yao Siqi, Li Wenzheng, Wang Hong 2024, 28 (16):  2619-2624.  doi: 10.12307/2024.337 Abstract ( 290 )   PDF (1008KB) ( 112 )   Save BACKGROUND: There are many studies focusing on keloid scars, but the pathogenesis is not fully understood. In recent years, there have been some new research advances in the pathogenesis of keloids, including transforming growth factor-β (TGF-β)/Smad signaling pathway, ischemic hypoxia, hypoxia-inducible factor 1 (HIF-1), and mitogen-activated protein kinase (MAPK) pathway. The TGF-β/Smad pathway is now more clearly studied, and activation of the TGF-β/Smad pathway promotes the development of keloid scars. OBJECTIVE: To review the TGF-β/Smad signaling pathway and evaluate the main therapeutic strategies targeting this pathway, with the aim of contributing to the development of more effective clinical treatments. METHODS: PubMed and Web of Science, CNKI and WanFang databases were searched by computer for relevant literature published from January 2017 to April 2023 with the search terms of “keloid, fibroblasts, TGF-β/Smad, extracellular matrix, collagen, treatment measures” in English and Chinese. Seventy-two articles were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: The mechanism of TGF-β/Smad signaling pathway in the occurrence and development of keloids is summarized: TGF-β1 and TGF-β2 are overexpressed in keloids, while TGF-β3 shows antifibrotic effects. Smad2/3 and Smad1/5/8 are combined with Smad4 to form a complex that enters the nucleus and plays a fibrotic role, while Smad6/7 can inhibit keloid hyperplasia. The TGF-β/Smad signaling pathway is currently the most clearly studied pathway in keloids, and there are many pathways targeted to inhibit the activation of this pathway, which can inhibit the occurrence and development of keloids to a greater extent. Currently, there is no single clinical gold standard treatment for keloids, and inhibition of the TGF-β/Smad pathway alone cannot completely inhibit the development of keloids. A comprehensive consideration of the association between all systemic systems and keloids is needed. Although many promising targets have been identified in the fibrosis cascade, more research is needed to translate this into targeted therapies in the clinic. Figures and Tables | References | Related Articles | Metrics