1.The splicing factor HNRNPH1 regulates Circ-MYOCD back-splicing to modulate the course of cardiac hypertrophy.
Rui CAI ; Zhuo HUANG ; Wenxia HE ; Tianhong AI ; Xiaowei SONG ; Shuting HU
Journal of Southern Medical University 2025;45(3):587-594
OBJECTIVES:
To explore the mechanism of Circ-MYOCD back-splicing and its regulatory role in myocardial hypertrophy.
METHODS:
Sanger sequencing and RNase R assays were performed to verify the circularity and stability of Circ-MYOCD, whose subcellular distribution was determined by nuclear-cytoplasmic fractionation. Bioinformatics analysis and mass spectrometry from pull-down assays were conducted to predict the RNA-binding proteins (RBPs) interacting with Circ-MYOCD. In rat cardiomyocytes H9C2 cells, the effects of HNRNPH1 and HNRNPL knockdown and overexpression on Circ-MYOCD back-splicing were evaluated. In a H9C2 cell model of angiotensin II (Ang II)-induced myocardial hypertrophy, the expression of HNRNPH1 was detected, the effects of HNRNPH1 knockdown and overexpression on progression of myocardial hypertrophy were assessed, and the regulatory effect of HNRNPH1 on Circ-MYOCD back-splicing was analyzed.
RESULTS:
Sanger sequencing confirmed that the junction primers could amplify the correct Circ-MYOCD sequence. RNase R and nuclear-cytoplasmic fractionation assays showed that Circ-MYOCD was stable and predominantly localized in the cytoplasm. Bioinformatics analysis and mass spectrometry from the Circ-MYOCD pull-down assay identified HNRNPH1 and HNRNPL as the RBPs interacting with Circ-MYOCD. In H9C2 cells, HNRNPH1 knockdown significantly enhanced while its overexpression inhibited Circ-MYOCD back-splicing; HNRNPH1 overexpression obviously increased the expressions of myocardial hypertrophy markers ANP and BNP, while its knockdown produced the opposite effect. In Ang II-induced H9C2 cells, which exhibited a significant increase of HNRNPH1 expression and increased expressions of ANP and BNP, HNRNPH1 knockdown obviously increased Circ-MYOCD expression, decreased MYOCD expression and lowered both ANP and BNP expressions.
CONCLUSIONS
HNRNPH1 regulates Circ-MYOCD back-splicing to influence the progression of myocardial hypertrophy.
Animals
;
Rats
;
RNA, Circular/genetics*
;
Cardiomegaly/metabolism*
;
Myocytes, Cardiac/metabolism*
;
Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism*
;
Cell Line
;
RNA Splicing
;
Angiotensin II
;
RNA-Binding Proteins
2.Tiaozhou Ziyin recipe for treatment of premature ovarian insufficiency: efficacy, safety and mechanism.
Peipei TANG ; Yong TAN ; Yanyun YIN ; Xiaowei NIE ; Jingyu HUANG ; Wenting ZUO ; Yuling LI
Journal of Southern Medical University 2025;45(5):929-941
OBJECTIVES:
To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms.
METHODS:
We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles.
RESULTS:
The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E2 levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH.
CONCLUSIONS
The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female
;
Primary Ovarian Insufficiency/drug therapy*
;
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Animals
;
Rats
;
Molecular Docking Simulation
;
Signal Transduction
;
Sitosterols/therapeutic use*
;
Kaempferols/therapeutic use*
3.Analysis of risk factors of pleural effusion after spinal separation
Keyi WANG ; Hao QU ; Wen WANG ; Zhaonong YAO ; Xiaowei ZHOU ; Yuhong YAO ; Hengyuan LI ; Peng LIN ; Xiumao LI ; Xiaobo YAN ; Meng LIU ; Xin HUANG ; Nong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2024;44(3):169-176
Objective:To investigate the risk factors of pleural effusion after spinal separation surgery for patients with spinal metastatic tumors.Methods:A total of 427 patients with spinal metastatic tumors from January 2014 to January 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. There were 252 males and 175 females, with an average age of 59±12 years (range, 15-87 years). All patients underwent separation surgery. Based on the chest CT within 1 month after surgery, the volume of pleural effusion was measured individually by reconstruction software. Pleural effusion was defined as small volume (0-500 ml), moderate volume (500-1 000 ml), and large volume (above 1 000 ml). Baseline data and perioperative clinical outcomes were compared between the groups, and indicators with statistically significant differences were included in a binary logistic regression analysis to determine the independent risk factors for the development of pleural effusion after isolation of spinal metastatic cancer. Receiver operating characteristic (ROC) curves were conducted to calculate the area under the curve (AUC) for each independent risk factor.Results:All patients successfully completed the operation. Among the 427 patients, there were 35 cases of large pleural effusion, 42 cases of moderate pleural effusion, and 350 cases of small pleural effusion. There were significant differences in tumor size (χ 2=9.485, P=0.013), intraoperative blood loss ( Z=-2.503, P=0.011), blood transfusion ( Z=-2.983, P=0.003), preoperative total protein ( Z=2.681, P=0.007), preoperative albumin ( Z=1.720, P= 0.085), postoperative hemoglobin ( t=2.950, P=0.008), postoperative total protein ( Z=4.192, P<0.001), and postoperative albumin ( t=2.268, P=0.032) in the large pleural effusion group versus the small and moderate pleural effusion group. Logistic regression analysis showed that decreased preoperative albumin ( OR=0.89, P=0.045) and metastases located in the thoracic spine ( OR=4.01, P=0.039) were independent risk factors for the occurrence of large pleural effusion after separation surgery. The ROC curve showed that the AUC and 95% CI for preoperative albumin, lesion location, and the combined model were 0.637 (0.54, 0.74), 0.421 (0.36, 0.48), and 0.883 (0.81, 0.92). The combined predictive model showed good predictive value. Conclusion:The volume of pleural effusion can be measured individually and quantitatively based on chest CT. Decreased preoperative albumin and metastases located in the thoracic spine are independent risk factors for the occurrence of large pleural effusion after separation surgery. The combined prediction of the two factors has better predictive efficacy.
4.A national questionnaire survey on endoscopic treatment for gastroesophageal varices in portal hypertension in China
Xing WANG ; Bing HU ; Yiling LI ; Zhijie FENG ; Yanjing GAO ; Zhining FAN ; Feng JI ; Bingrong LIU ; Jinhai WANG ; Wenhui ZHANG ; Tong DANG ; Hong XU ; Derun KONG ; Lili YUAN ; Liangbi XU ; Shengjuan HU ; Liangzhi WEN ; Ping YAO ; Yunxiao LIANG ; Xiaodong ZHOU ; Huiling XIANG ; Xiaowei LIU ; Xiaoquan HUANG ; Yinglei MIAO ; Xiaoliang ZHU ; De'an TIAN ; Feihu BAI ; Jitao SONG ; Ligang CHEN ; Yingcai MA ; Yifei HUANG ; Bin WU ; Xiaolong QI
Chinese Journal of Digestive Endoscopy 2024;41(1):43-51
Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
5.Effect of chelerythrine on migration,invasion,and epithelial-mesenchymal transition of human ovarian cancer SKOV3 cells
Jia ZHOU ; Zhidong QIU ; Zhe LIN ; Guangfu LYU ; Jiaming XU ; He LIN ; Kexin WANG ; Yuchen WANG ; Xiaowei HUANG
Journal of Jilin University(Medicine Edition) 2024;50(1):25-32
Objective:To discuss the inhibitory effect of chelerythrine(CHE)on the migration,invasion,and epithelial-mesenchymal transition(EMT)of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism.Methods:The SKOV3 cells were cultured in vitro and divided into control group and 2.5,5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT)assay was used to detect the inhibitory rates of proliferation of the cells in various groups.The SKOV3 cells were cultured in vitro and divided into control group,transforming growth factor-β1(TGF-β1)group,TGF-β1+5 μmol·L-1 CHE group,and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,N-cadherin,and Vimentin proteins in the cells in various groups;immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups.Results:The MTT assay results showed that compared with control group,the inhibitory rates of proliferation of the cells in 5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups were significantly increased(P<0.05 or P<0.01).The cell scratch assay results showed that compared with control group,the migration rate of the cells in TGF-β1 group was increased(P<0.01);compared with TGF-β1 group,the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in TGF-β1 group were significantly increased(P<0.05);compared with TGF-β1 group,the numbers of migration and invasion cells in TGF-β1+5 μmo·l L-1 CHE group and TGF-β1+10 μmo·l L-1 CHE group were significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased(P<0.01),while the expression levels of N-cadherin and Vimentin proteins were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased,and the fluorescence intensity of N-cadherin was increased;compared with TGF-β1 group,the fluorescence intensities of E-cadherin in the cells in TGF-β 1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased,and the fluorescence intensities of N-cadherin were decreased.Conclusion:CHE can inhibit the proliferation,migration,invasion,and EMT of the human ovarian cancer SKOV3 cells.
6.Improvement effect of velvet antler polypeptide in osteoporosis model rats and its effect on SIRT1/FOXO1 signaling pathway
Xueting CHI ; Xiaowei HUANG ; Fangyuan CHEN ; Gaofeng ZHOU ; Jinji WANG ; Guangfu LYU ; Zhe LIN ; Qing GONG
Journal of Jilin University(Medicine Edition) 2024;50(1):120-127
Objective:To discuss the protective effect of velvet antler peptide(VAP)in the osteoporosis(OP)model rats,and to clarify the possible mechanism.Methods:Sixty 12-week-old SD rats were randomly divided into control group,model group,positive drug group(treated with 1 mg·kg-1·d-1 of alendronate sodium by gavage),low dose of VAP group(treated with 100 mg·kg-1·d-1 VAP),medium dose of VAP group(treated with 200 mg·kg-1·d-1 VAP),and high dose of VAP group(treated with 300 mg·kg-1·d-1 VAP),and there were ten rats in each group.Except for control group,the rats in the other groups were injected with dexamethasone(2 mg·kg-1)to replicate the OP rat model,while the rats in control group were injected with the equivalent volume of saline twice a week for 11 consecutive weeks.Dual-energy X-ray absorptiometry was used to detect the bone mineral density(BMD)of femur tissue of the rats in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of serum calcium(Ca2+),phosphate(P),osteoprotegerin(OPG),alkaline phosphatase(ALP),and osteocalcin(OCN)in serum of the rats in various groups;biochemical method was used to detect the malondialdehyde(MDA)level and superoxide dismutase(SOD)activity in serum of the rats in various groups;HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups;Western blotting method was used to detect the expression levels of silent information regulator 1(SIRT1),catalase(CAT),Runt-related transcription factor 2(RUNX2),and forkhead box protein O1(FOXO1)proteins in bone tissue of the rats in various groups.Results:Compared with control group,the BMD of femoral tissue of the rats in model group was decreased(P<0.05);compared with model group,the BMD of femur tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were increased(P<0.05 or P<0.01).Compared with control group,the levels of Ca2+,P,OPG,and SOD activities in serum of the rats in model group were decreased(P<0.05),and the levels of ALP,OCN,and MDA were increased(P<0.05);compared with model group,the level of OPG in serum of the rats in low dose of VAP group was significantly increased(P<0.05),the levels of Ca2+,P,OPG,and activities of SOD in serum of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01),and the levels of ALP,OCN,and MDA in serum of the rats in positive drug group and different doses of VAP groups were decreased(P<0.05 or P<0.01).The HE staining results showed that compared with control group,the rats in model group had fewer bone cells and disordered arrangements in the bone tissue,thinner bone trabeculae with large fractures,and an expanded marrow cavity;compared with model group,the rats in positive drug group,medium dose of VAP group,and high dose of VAP group had thicker bone trabeculae arranged more tightly.The Western blotting results showed that compared with control group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in model group were decreased(P<0.05);compared with model group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01).Conclusion:VAP has the protective effect against OP in the rats,and its mechanism may be related to mediating the antioxidant stress action through the SIRT1/FOXO1 signaling pathway.
7.Application effect of multimodal exercise on enteral nutrition during radiotherapy in patients with esophageal cancer complicating diabetes
Jufen FAN ; Xiaoying SHEN ; Xiaowei FU ; Tingting HUANG ; Weihong FANG
Chongqing Medicine 2024;53(5):748-753
Objective To explore the effect of multimodal exercise combined with enteral nutrition dur-ing radiotherapy in the patients with esophageal cancer complicating diabetes.Methods A total of 52 patients with esophageal cancer complicating diabetes in Zhejiang Provincial Tumor Hospital from January to Decem-ber 2021 were selected as the study subjects and divided into the control group(n=27)and intervention group(n=25)by using the random number table method.The control group implemented the routine exercise scheme,while the intervention group was given the multimodal exercise intervention on the basis of routine exercise.The blood glucose metabolism indicators,related biochemical indicators during radiotherapy and the incidence rate of adverse events during exercise were compared between the two groups.Results The levels of fasting blood glucose,random blood glucose and blood glucose before sleep in the intervention group during radiotherapy were(7.79±1.61)mmol/L,(9.47±1.77)mmol/L and(9.97±3.02)mmol/L,which were lower than(11.84±3.47)mmol/L,(14.18±5.42)mmol/L and(14.62±3.83)mmol/L in the control group with statistically significant differences(P<0.05).During the radiotherapy period,the levels of albumin,total protein and prealbumin in the intervention group were(37.96±2.13)g/L,(68.13±5.02)g/L and(232.89±41.11)g/L,which were lower than(36.05±2.89)g/L,(64.96±5.95)g/L and(207.76±47.59)g/L in the control group with statistically significant differences(P<0.05).The incidence rates of adverse e-vents such as falls,hypoglycemia and accidental extubation during multimodal exercise in the intervention group were lower than those in the control group,and the differences were statistically significant(P<0.05).Conclusion The multimodal exercise could significantly improve the nutritional status during radiotherapy in the patients with esophageal cancer complicating diabetes,stabilize the blood glucose level of the patients,and has good feasibility and safety.
8.Trend of gastrointestinal and liver diseases in China: Results of the Global Burden of Disease Study, 2019
Xiaowei TANG ; Ping WANG ; Shu HUANG ; Jieyu PENG ; Wei ZHANG ; Xiaomin SHI ; Lei SHI ; Xiaolin ZHONG ; Muhan LYU ; Xian ZHOU ; Enqiang LINGHU
Chinese Medical Journal 2024;137(19):2358-2368
Background::China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019.Methods::The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported.Results::The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends.Conclusions::The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.
9.Improvement effect of velvet antler polypeptide on postmenopausal osteoporosis in rats and its mechanism
Xueting CHI ; Fangyuan CHEN ; Zifeng PI ; Guangfu LYU ; Yuchen WANG ; Yinqing LI ; Xiaowei HUANG ; Zhe LIN
Journal of Jilin University(Medicine Edition) 2024;50(4):963-969
Objective:To discuss the protective effect of velvet antler peptide(VAP)on the postmenopausal osteoporosis(PMOP)model rats,and to clarify its possible mechanism.Methods:A total of 60 twelve-week-old female SD rats were randomly divided into sham operation group,model group,alendronate sodium group(1 mg·kg 1·d-1 alendronate sodium administered via gavage),low dose of VAP group(100 mg·kg·d-1 VAP administered via gavage),medium dose of VAP group(200 mg·kg 1·d-1 VAP administered via gavage),and high dose of VAP group(300 mg·kg1·d-1 VAP administered via gavage),and there were 10 rats in each group.Except for the sham operation group,the rats in the other groups underwent bilateral ovariectomy to establish the PMOP rat models.Dual-energy X-ray absorptiometry was used to detect the femur bone mineral density(BMD)of the rats in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum calcium(Ca2+),serum phosphorus(P),bone alkaline phosphatase(BALP),and procollagen type Ⅰ N-terminal propeptide(PINP)of the rats in various groups;Kits were used to detect the activities of superoxide dismutase(SOD)and the levels of malondialdehyde(MDA)of the rats in various groups;HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),and phosphorylated AKT(p-AKT)proteins in bone tissue of the rats in various groups.Results:Compared with sham operation group,the BMD in femur of the rats in model group was decreased(P<0.01);compared with model group,the BMD in femur of the rats in alendronate sodium group,medium dose of VAP group,and high dose of VAP group was increased(P<0.05 or P<0.01).Compared with sham operation group,the levels of Ca2+,P,BALP,PINP,and SOD activity in serum of the rats in model group were decreased(P<0.05 or P<0.01),and the MDA level was increased(P<0.01);compared with model group,the level of P in serum of the rats in medium dose of VAP group was increased(P<0.01),and the levels of Ca2+,P,BALP,PINP and the activities of SOD in serum of the rats in alendronate sodium group and high dose of VAP group were increased(P<0.05 or P<0.01),and the level of MDA in serum was decreased(P<0.05).The HE staining results showed that compared with sham operation group,the bone trabeculae in bone tissue of the rats in model group were thin and fractured,and the medullary cavity was enlarged;compared with model group,the bone trabeculae in bone tissue of the rats in alendronate sodium group,medium dose of VAP group,and high dose of VAP group were thick and tightly arranged,and had more osteocytes.The Western blotting results showed that compared with sham operation group,the ratios of p-PI3K/PI3K and p-AKT/AKT in bone tissue of the rats in model group were decreased(P<0.01);compared with model group,the ratios of p-PI3K/PI3K in bone tissue of rats in different doses of VAP groups were increased(P<0.05 or P<0.01),and the ratios of p-AKT/AKT of the rats in alendronate sodium group and high dose of VAP group was increased(P<0.01).Conclusion:VAP can improve PMOP in the rats,and its mechanisms may be related to the regulation of the PI3K/AKT signaling pathway and the reduction of oxidative stress in bone tissue by VAP.
10.Effect of polygonatum odoratum polysaccharide on acute kidney injury in mice induced by cisplatin and its ferroptosis mechanism
Fangyang JIANG ; Jing XIAO ; He CHANG ; Mingyang SUN ; Wenjing ZHANG ; Guangfu LYU ; He LIN ; Zhe LIN ; Xiaowei HUANG ; Yuchen WANG
Journal of Jilin University(Medicine Edition) 2024;50(5):1235-1242
Objective:To discuss the protective effect of polygonatum odoratum polysaccharide(POP)on the mice with cisplatin-induced acute kidney injury(AKI),and to clarify its possible mechanism.Methods:Forty male C57BL/6 mice were randomly divided into control group,model group,POP group,and ferroptosis inducer Erastin combined with POP(Erastin+POP)group,and there were 10 mice in each group.The mice in POP group and Erastin+POP group were given intragastric administration of POP(400 mg·kg-1),and on the 7th day,the mice in model group,POP group,and Erastin+POP group were intraperitoneally injected with cisplatin(20 mg·kg-1)to establish the AKI models,the mice in control group were injected with the same volume of normal saline,and the mice in Erastin+POP group were intraperitoneally injected with Erastin(40 mg·kg-1)one day in advance(on the 6th day of the experiment).After 9 d,the mice were killed and the serum and kidney tissue were collected,and the levels of serum creatinine(Scr)and blood urea nitrogen(BUN)and the levels of malondialdehyde(MDA)and glutathione(GSH)in kidney tissue of the mice in various groups were detected by kit;HE staining was used to observe the pathomorphology of kidney tissue of the mice in various groups;the expression levels of ferroptosis suppressor protein 1(FSP1),ferritin heavy chain 1(FTH1),and glutathione peroxidase 4(GPX4)proteins in kidney tissue of the mice in various groups were detected by immunohistochemistry;Western blotting method was used to detect the expression levels of nuclear factor-E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in kidney tissue of the mice in various groups.Results:Compared with control group,the levels of Scr and BUN of the mice in model group were significantly increased(P<0.01),the level of MDA in kidney tissue was significantly increased(P<0.01),and the level of GSH was significantly decreased(P<0.01);most kidney tubules were dilated,the epithelial cells were swollen,the vacuolar degeneration and epithelial cells fell off,and the protein-like tubules could be seen in the lumen;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were decreased significantly(P<0.05 or P<0.01).Compared with model group,the levels of Scr and BUN of the mice in POP group were significantly decreased(P<0.01),the level of MDA in kidney tissue was significantly decreased(P<0.01),and the level of GSH was significantly increased(P<0.01);the dilatation of kidney tubular lumen,epithelial cell swelling,vacuolar degeneration,and epithelial cell exfoliation were decreased;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue of the mice in POP group were significantly increased(P<0.05 or P<0.01).Compared with POP group,the levels of Scr and BUN of the mice in Erastin+POP group were significantly increased(P<0.01),the level of MDA in kidney tissue was increased(P<0.05),and the level of GSH was significantly decreased(P<0.01);the pathological injury of kidney tissue was aggravated obviously;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were significantly decreased(P<0.05 or P<0.01).Conclusion:POP can reduce the AKI in the mice induced by cisplatin,and its mechanism may be related to the inhibitory effect of POP on the ferroptosis induced by cisplatin.

Result Analysis
Print
Save
E-mail