1.Regulation of osteogenic effects by bone morphogenetic protein/Wnt signaling pathway:revealing molecular mechanisms of bone formation and remodeling
Haowen LIU ; Weiping QIAO ; Zhicheng MENG ; Kaijie LI ; Xuan HAN ; Pengbo SHI
Chinese Journal of Tissue Engineering Research 2025;29(3):563-571
BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.
2.Establishment and validation of a Nomogram prediction model for risk factors of osteonecrosis of the femoral head in systemic lupus erythematosus
Wenbo XU ; Lihe WANG ; Songwei LI ; Pengbo SHI
Chinese Journal of Tissue Engineering Research 2025;29(15):3215-3226
BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P<0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P<0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95%CI=0.742-0.862)in the training set and 0.811(95%CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.
3.Triptolide ameliorates renal interstitial fibrosis in mice with unilateral ureteral obstruction by inhibiting NLRP3-mediated pyroptosis
Linting WEI ; Pengbo GE ; Yan LI ; Ke LI ; Yinhong WANG ; Weihao ZHAO ; Chenkai CUI ; Rongguo FU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):947-952
Objective To investigate the effect of triptolide(TPL)on renal interstitial fibrosis in mice with unilateral ureteral obstruction(UUO)and its mechanism.Methods Six male C57BL/6J mice were randomly selected as the sham group,and 12 mice with UUO modeling were randomly divided into the model group(UUO)and the triptolide group(TPL).Changes in serum creatinine(SCr),blood urea nitrogen(BUN),and body weight were compared among the groups.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.Immunohistochemistry staining was performed to observe the expression of α-smooth muscle actin(α-SMA)and fibronectin(Fn)in kidney tissues.Western blotting analysis was used to detect the protein expression levels of nucleotide combined with structure of oligomerization domain receptor protein 3(NLRP3),GSDMD,cGSDMD,IL-1β and IL-18.Results At week 1,the body weight of mice in the UUO and TPL groups significantly decreased compared with that in the sham group(P<0.05).Body weight reduced in the TPL group compared with that in the Sham group at week 2(P<0.01).There was no significant difference in body weight between the TPL and UUO groups.BUN levels did not differ significantly between the three groups.Compared with the sham group,the SCr level in the UUO group significantly increased[(15.680±1.508)μmol/L](P<0.01).A reduction in SCr level was observed following TPL administration[(12.550±3.004)μmol/L](P<0.05).HE staining showed that the renal tubules of mice in the UUO group were significantly dilated and atrophic,with interstitial edema and increased inflammatory cell infiltration,while the pathological damage of renal tissues was significantly alleviated after TPL treatment.Masson staining revealed that interstitial collagen deposition significantly increased in the UUO group(36.350±5.183)%(P<0.01)and reduced after TPL administration(20.820±3.290)%(P<0.01).Immunohistochemistry results demonstrated that the IOD levels of α-SMA(1.233±0.045)and Fn(1.337±0.045)were higher in UUO group mice than in the sham group,while the IOD levels of α-SMA(1.047±0.025)and Fn(1.113±0.021)were lower in the TPL group than in the UUO group(P<0.05).Western blotting analysis indicated that the expression levels of NLRP3,cGSDMD,IL-1β and IL-18 in the UUO group mice were higher than those in the sham group,while the protein expression levels of the above-mentioned indicators significantly decreased after TPL treatment(P<0.05).Conclusion TPL ameliorates renal interstitial fibrosis in mice with UUO by inhibiting NLRP3-mediated pyroptosis.
4.Epidemiological characteristics and trend prediction of hemorrhagic fever with renal syndrome in Weinan City, Shaanxi Province from 2010 to 2023
Dandan LI ; Wei LIU ; Ning MA ; Caimei JING ; Lin CHENG ; Gang LIU ; Zhen DANG ; Pengbo YU ; Lin DANG
Chinese Journal of Endemiology 2025;44(3):209-214
Objective:To investigate the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Weinan City, Shaanxi Province, and study the predictive effect of the seasonal autoregressive integrated moving average (SARIMA) model.Methods:Relevant information on HFRS cases reported by the China Disease Prevention and Control Information System from January 2010 to August 2024 in Weinan City, as well as the epidemiological investigation data on clinical diagnosis and confirmed HFRS cases in Weinan City were collected. Epidemiological characteristics of HFRS were analyzed by descriptive epidemiological methods. At the same time, a SARIMA model was constructed based on the monthly incidence of HFRS from 2010 to 2023, the incidence of HFRS from January to August 2024 was used to test the simulation prediction effect, and the optimal model was used to predict the incidence of HFRS from September to December 2024.Results:A total of 4 373 HFRS cases were reported in Weinan City from 2010 to 2023, with an average annual incidence of 6.39/100 000. The incidence rate showed a cyclical fluctuation trend, reaching two peaks in 2012 (10.25/100 000) and 2021 (12.26/100 000), respectively. The incidence of HFRS presented a seasonal bimodal distribution, with the peak predominantly in autumn and winter (from October to January of the following year), accounting for 67.83% (2 966/4 373), and the peak in spring and summer (form May to July) accounting for 17.27% (755/4 373). HFRS cases were reported in all counties (cities and districts) of Weinan City, and the top 3 annual incidence rates were Huazhou District (17.84/100 000), Linwei District (16.10/100 000) and Huayin City (9.15/100 000). The age of onset was mainly concentrated in the age group of 15 - 59 years old, accounting for 68.31% (2 987/4 373). The male to female ratio was 2.96∶1.00 (3 268∶1 105). The main occupation was farmers, accounting for 82.07% (3 589/4 373). SARIMA (1, 0, 1) (2, 1, 1) 12 model was the optimal model for short-term prediction of HFRS incidence rate in Weinan City, and the residual difference was listed as white noise ( Q = 7.45, P = 0.878), the model could be used for disease prediction. The model was used to predict the incidence of HFRS from September to December 2024, and the predicted values of each month were 0.17/100 000, 0.59/100 000, 1.85/100 000 and 1.61/100 000, respectively. Conclusions:The epidemic range of HFRS in Weinan City is wide, and the incidence has obvious seasonality. The population are mainly males, young and middle-aged adults and farmers. The SARIMA (1, 0, 1) (2, 1, 1) 12 model constructed can be used for predicting the short-term incidence trend of HFRS in Weinan City.
5.Establishment and validation of a Nomogram prediction model for risk factors of osteonecrosis of the femoral head in systemic lupus erythematosus
Wenbo XU ; Lihe WANG ; Songwei LI ; Pengbo SHI
Chinese Journal of Tissue Engineering Research 2025;29(15):3215-3226
BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P<0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P<0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95%CI=0.742-0.862)in the training set and 0.811(95%CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.
6.Triptolide ameliorates renal interstitial fibrosis in mice with unilateral ureteral obstruction by inhibiting NLRP3-mediated pyroptosis
Linting WEI ; Pengbo GE ; Yan LI ; Ke LI ; Yinhong WANG ; Weihao ZHAO ; Chenkai CUI ; Rongguo FU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):947-952
Objective To investigate the effect of triptolide(TPL)on renal interstitial fibrosis in mice with unilateral ureteral obstruction(UUO)and its mechanism.Methods Six male C57BL/6J mice were randomly selected as the sham group,and 12 mice with UUO modeling were randomly divided into the model group(UUO)and the triptolide group(TPL).Changes in serum creatinine(SCr),blood urea nitrogen(BUN),and body weight were compared among the groups.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.Immunohistochemistry staining was performed to observe the expression of α-smooth muscle actin(α-SMA)and fibronectin(Fn)in kidney tissues.Western blotting analysis was used to detect the protein expression levels of nucleotide combined with structure of oligomerization domain receptor protein 3(NLRP3),GSDMD,cGSDMD,IL-1β and IL-18.Results At week 1,the body weight of mice in the UUO and TPL groups significantly decreased compared with that in the sham group(P<0.05).Body weight reduced in the TPL group compared with that in the Sham group at week 2(P<0.01).There was no significant difference in body weight between the TPL and UUO groups.BUN levels did not differ significantly between the three groups.Compared with the sham group,the SCr level in the UUO group significantly increased[(15.680±1.508)μmol/L](P<0.01).A reduction in SCr level was observed following TPL administration[(12.550±3.004)μmol/L](P<0.05).HE staining showed that the renal tubules of mice in the UUO group were significantly dilated and atrophic,with interstitial edema and increased inflammatory cell infiltration,while the pathological damage of renal tissues was significantly alleviated after TPL treatment.Masson staining revealed that interstitial collagen deposition significantly increased in the UUO group(36.350±5.183)%(P<0.01)and reduced after TPL administration(20.820±3.290)%(P<0.01).Immunohistochemistry results demonstrated that the IOD levels of α-SMA(1.233±0.045)and Fn(1.337±0.045)were higher in UUO group mice than in the sham group,while the IOD levels of α-SMA(1.047±0.025)and Fn(1.113±0.021)were lower in the TPL group than in the UUO group(P<0.05).Western blotting analysis indicated that the expression levels of NLRP3,cGSDMD,IL-1β and IL-18 in the UUO group mice were higher than those in the sham group,while the protein expression levels of the above-mentioned indicators significantly decreased after TPL treatment(P<0.05).Conclusion TPL ameliorates renal interstitial fibrosis in mice with UUO by inhibiting NLRP3-mediated pyroptosis.
7.Fatigue gait recognition of athletes based on fish swarm algorithm
Jian ZHANG ; Feng CAI ; Tingwen LI ; Pengbo REN
Chinese Journal of Tissue Engineering Research 2025;29(30):6489-6498
BACKGROUND:Gait movements are one of the important characteristics exhibited by athletes during exercise,reflecting their physical condition and athletic ability.In a state of fatigue,athletes may exhibit abnormal gait movements,such as reduced stride and body shaking,which can cause harm to their bodies.OBJECTIVE:To promote technological progress in the field of sports science by applying advanced algorithms and data analysis techniques to the training practice of athletes,so as to further improve the recognition accuracy of gait movements under sports fatigue.METHODS:A gait recognition method for athletes in fatigue state was based on fish swarm algorithm.By utilizing the normalized autocorrelation function and the principle of motion energy distribution,a single cycle gait energy map of athletes was obtained.Singular value decomposition was used to transform the image to highlight visual differences,generating a gait energy map of athletes.A convolutional neural network was used to construct a gait action recognition model,and the parameters of the model were solved using the fish swarm algorithm to improve the accuracy and efficiency of fatigue gait action recognition.RESULTS AND CONCLUSION:(1)The fish swarm algorithm had a small loss value in gait action recognition,and could accurately and quickly identify the gait actions of athletes,and dynamically monitor their physical fatigue.(2)The research on fatigue gait recognition of athletes based on fish swarm algorithm could effectively identify the gait movements of athletes in fatigue state and achieve accurate capture of subtle gait changes.(3)The system stability of this method is good,which can reduce the volatility of experimental test results and improve recognition efficiency,can more effectively manage sports fatigue and prevent sports injuries.In addition,when the gait characteristics of normal people change significantly,the system can give an early warning,indicating that the individual may be in a state of fatigue and need to rest or adjust the intensity of activity.
8.Epidemiological characteristics and trend prediction of hemorrhagic fever with renal syndrome in Weinan City, Shaanxi Province from 2010 to 2023
Dandan LI ; Wei LIU ; Ning MA ; Caimei JING ; Lin CHENG ; Gang LIU ; Zhen DANG ; Pengbo YU ; Lin DANG
Chinese Journal of Endemiology 2025;44(3):209-214
Objective:To investigate the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Weinan City, Shaanxi Province, and study the predictive effect of the seasonal autoregressive integrated moving average (SARIMA) model.Methods:Relevant information on HFRS cases reported by the China Disease Prevention and Control Information System from January 2010 to August 2024 in Weinan City, as well as the epidemiological investigation data on clinical diagnosis and confirmed HFRS cases in Weinan City were collected. Epidemiological characteristics of HFRS were analyzed by descriptive epidemiological methods. At the same time, a SARIMA model was constructed based on the monthly incidence of HFRS from 2010 to 2023, the incidence of HFRS from January to August 2024 was used to test the simulation prediction effect, and the optimal model was used to predict the incidence of HFRS from September to December 2024.Results:A total of 4 373 HFRS cases were reported in Weinan City from 2010 to 2023, with an average annual incidence of 6.39/100 000. The incidence rate showed a cyclical fluctuation trend, reaching two peaks in 2012 (10.25/100 000) and 2021 (12.26/100 000), respectively. The incidence of HFRS presented a seasonal bimodal distribution, with the peak predominantly in autumn and winter (from October to January of the following year), accounting for 67.83% (2 966/4 373), and the peak in spring and summer (form May to July) accounting for 17.27% (755/4 373). HFRS cases were reported in all counties (cities and districts) of Weinan City, and the top 3 annual incidence rates were Huazhou District (17.84/100 000), Linwei District (16.10/100 000) and Huayin City (9.15/100 000). The age of onset was mainly concentrated in the age group of 15 - 59 years old, accounting for 68.31% (2 987/4 373). The male to female ratio was 2.96∶1.00 (3 268∶1 105). The main occupation was farmers, accounting for 82.07% (3 589/4 373). SARIMA (1, 0, 1) (2, 1, 1) 12 model was the optimal model for short-term prediction of HFRS incidence rate in Weinan City, and the residual difference was listed as white noise ( Q = 7.45, P = 0.878), the model could be used for disease prediction. The model was used to predict the incidence of HFRS from September to December 2024, and the predicted values of each month were 0.17/100 000, 0.59/100 000, 1.85/100 000 and 1.61/100 000, respectively. Conclusions:The epidemic range of HFRS in Weinan City is wide, and the incidence has obvious seasonality. The population are mainly males, young and middle-aged adults and farmers. The SARIMA (1, 0, 1) (2, 1, 1) 12 model constructed can be used for predicting the short-term incidence trend of HFRS in Weinan City.
9.Fatigue gait recognition of athletes based on fish swarm algorithm
Jian ZHANG ; Feng CAI ; Tingwen LI ; Pengbo REN
Chinese Journal of Tissue Engineering Research 2025;29(30):6489-6498
BACKGROUND:Gait movements are one of the important characteristics exhibited by athletes during exercise,reflecting their physical condition and athletic ability.In a state of fatigue,athletes may exhibit abnormal gait movements,such as reduced stride and body shaking,which can cause harm to their bodies.OBJECTIVE:To promote technological progress in the field of sports science by applying advanced algorithms and data analysis techniques to the training practice of athletes,so as to further improve the recognition accuracy of gait movements under sports fatigue.METHODS:A gait recognition method for athletes in fatigue state was based on fish swarm algorithm.By utilizing the normalized autocorrelation function and the principle of motion energy distribution,a single cycle gait energy map of athletes was obtained.Singular value decomposition was used to transform the image to highlight visual differences,generating a gait energy map of athletes.A convolutional neural network was used to construct a gait action recognition model,and the parameters of the model were solved using the fish swarm algorithm to improve the accuracy and efficiency of fatigue gait action recognition.RESULTS AND CONCLUSION:(1)The fish swarm algorithm had a small loss value in gait action recognition,and could accurately and quickly identify the gait actions of athletes,and dynamically monitor their physical fatigue.(2)The research on fatigue gait recognition of athletes based on fish swarm algorithm could effectively identify the gait movements of athletes in fatigue state and achieve accurate capture of subtle gait changes.(3)The system stability of this method is good,which can reduce the volatility of experimental test results and improve recognition efficiency,can more effectively manage sports fatigue and prevent sports injuries.In addition,when the gait characteristics of normal people change significantly,the system can give an early warning,indicating that the individual may be in a state of fatigue and need to rest or adjust the intensity of activity.
10.Study on the protective effect and mechanism of soybean isoflavones against threatened miscarriage model rats
Sanyang LI ; Pengbo JIN ; Qiuhong WANG ; Jingjing WANG ; Ting MIAO ; Dongfang CHEN ; Boyuan ZHENG
China Pharmacy 2024;35(12):1482-1488
OBJECTIVE To study the protective effect and possible mechanism of soybean isoflavones against threatened miscarriage rats. METHODS Female mice were selected to promote estrus and mate with male mice. After pregnancy, they were randomly divided into normal group (purified water, i.g., n=10), model group (purified water, i.g., n=9), positive control drug group (progesterone 4 mg/kg, i.m., n=9), low-, medium- and high-dose soybean isoflavone groups (25, 50 and 100 mg/kg, i.g., n=10). Except for the normal group, the rest were given mifepristone+misoprostol on the 8th day of pregnancy to establish threatened miscarriage model, and then given purified water or drugs, once a day, on days 1-7 and 9-12 of pregnancy, respectively. At 14 days of pregnancy, the rates of fetal protection were counted. Serum levels of β-human chorionic gonadotrophin (β-HCG) and progesterone (P) in rats were detected. Pathological and morphological changes in rat placenta and decidua tissues were observed, and the apoptosis indexes of cells were detected; mRNA and protein expressions of factor of apoptosis related (Fas), factor of apoptosis related ligand (FasL), proliferating cell nuclear antigen (PCNA) and heparin binding epidermal growth factor (HB-EGF) were determined in placenta tissues, and mRNA and protein expressions of Fas, PCNA and HB-EGF in decidua tissues were detected. RESULTS In the model group, the placental tissues of rats were hyperemia and dilatation, with fewer and irregular blood vessels; severe stromal edema,inflammatory cell infiltration and iron-choledrin depositionwere observed. Compared with model group, the fetal survival rates, serum levels of β-HCG and P, the expressions of PCNA and HB-EGF mRNA and proteins in the placenta and decidua tissue of soybean isoflavone groups increased significantly (P< 0.05), while pathological changes were improved significantly; cell apoptosis index in the placenta and decidua tissue, the expressions of Fas, FasL mRNA and proteins in the placenta and Fas mRNA and protein in the decidua tissue decreased significantly (P<0.05). The effect of soybean isoflavones was dose-dependent (P<0.05). CONCLUSIONS Soybean isoflavone has protective effect on threatened miscarriage, the mechanism of which is related to down-regulating the expressions of Fas and FasL mRNA and protein at the maternal-fetal interface, and up-regulating the expressions of mRNA and protein of PCNA and HB- EGF.

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