1.Treadmill exercise attenuates apoptosis of hippocampal neurons in CRS mice through activation of Sirt1/PGC-1α/mitophagy axis
Yang WANG ; Jijia ZHANG ; Siyun LEI ; Ningjuan HE ; Tongxi ZHOU ; Li LI
Chinese Journal of Pathophysiology 2025;41(11):2100-2109
AIM:This study aimed to investigate the mechanisms by which treadmill exercise ameliorates de-pressive-like behaviors and hippocampal neuronal damage in chronic restraint stress(CRS)mice by regulating mitophagy via the Sirt1/PGC-1α signaling axis.METHODS:Forty C57BL/6J mice were randomly assigned to control,CRS,CRS+exercise(EXE)and EXE groups(n=10).The mice in CRS and CRS+EXE groups underwent 4 h of daily restraint for 28 consecutive days to establish a depression model.The mice in CRS+EXE and EXE groups received 8 weeks of treadmill training(6 sessions per week).Depressive-like behaviors were evaluated using the open field test,sucrose preference test,and tail suspension test.Hippocampal neuronal morphology and pathological changes were examined using hematoxy-lin-eosin and Nissl staining,while neuronal apoptosis was assessed through TUNEL staining.Mitochondrial ultrastructure was examined via transmission electron microscopy.Mitochondrial membrane potential and ATP content were measured using JC-1 assay and ATP assay kits,respectively.The expression levels of silent information regulator 1(Sirt1),peroxi-some proliferator-activated receptor γ coactivator-1α(PGC-1α),PTEN-induced kinase 1(PINK1)and parkin were as-sessed at both mRNA and protein levels by RT-qPCR and Western blot assays,as well as key markers of mitophagy[mi-crotubule-associated protein 1 light chain 3(LC3)and P62]and apoptosis(cleaved caspase-9 and cleaved caspase-3).RESULTS:Compared with control group,CRS mice exhibited significantly reduced central zone entries and time(P<0.01),decreased sucrose preference(P<0.01),increased immobility time(P<0.01),severe hippocampal neuronal damage,elevated apoptosis rate(P<0.01),mitochondrial deterioration;reduced membrane potential and ATP content(P<0.01),decreased mRNA expressions of Sirt1,PGC-1α,PINK1,and parkin(P<0.01),reduced protein levels of Sirt1,PGC-1α,PINK1,parkin and LC3(P<0.01),and increased expression of P62,cleaved caspase-9,and cleaved caspase-3(P<0.01).The mice in CRS+EXE group showed significant improvements in all these parameters compared to CRS group(P<0.05 or P<0.01).CONCLUSION:Treadmill exercise mitigates CRS-induced depressive-like behaviors,mi-tochondrial dysfunction,and neuronal apoptosis in mice by activating the hippocampal Sirt1/PGC-1α/mitophagy axis.
2.Treadmill exercise attenuates apoptosis of hippocampal neurons in CRS mice through activation of Sirt1/PGC-1α/mitophagy axis
Yang WANG ; Jijia ZHANG ; Siyun LEI ; Ningjuan HE ; Tongxi ZHOU ; Li LI
Chinese Journal of Pathophysiology 2025;41(11):2100-2109
AIM:This study aimed to investigate the mechanisms by which treadmill exercise ameliorates de-pressive-like behaviors and hippocampal neuronal damage in chronic restraint stress(CRS)mice by regulating mitophagy via the Sirt1/PGC-1α signaling axis.METHODS:Forty C57BL/6J mice were randomly assigned to control,CRS,CRS+exercise(EXE)and EXE groups(n=10).The mice in CRS and CRS+EXE groups underwent 4 h of daily restraint for 28 consecutive days to establish a depression model.The mice in CRS+EXE and EXE groups received 8 weeks of treadmill training(6 sessions per week).Depressive-like behaviors were evaluated using the open field test,sucrose preference test,and tail suspension test.Hippocampal neuronal morphology and pathological changes were examined using hematoxy-lin-eosin and Nissl staining,while neuronal apoptosis was assessed through TUNEL staining.Mitochondrial ultrastructure was examined via transmission electron microscopy.Mitochondrial membrane potential and ATP content were measured using JC-1 assay and ATP assay kits,respectively.The expression levels of silent information regulator 1(Sirt1),peroxi-some proliferator-activated receptor γ coactivator-1α(PGC-1α),PTEN-induced kinase 1(PINK1)and parkin were as-sessed at both mRNA and protein levels by RT-qPCR and Western blot assays,as well as key markers of mitophagy[mi-crotubule-associated protein 1 light chain 3(LC3)and P62]and apoptosis(cleaved caspase-9 and cleaved caspase-3).RESULTS:Compared with control group,CRS mice exhibited significantly reduced central zone entries and time(P<0.01),decreased sucrose preference(P<0.01),increased immobility time(P<0.01),severe hippocampal neuronal damage,elevated apoptosis rate(P<0.01),mitochondrial deterioration;reduced membrane potential and ATP content(P<0.01),decreased mRNA expressions of Sirt1,PGC-1α,PINK1,and parkin(P<0.01),reduced protein levels of Sirt1,PGC-1α,PINK1,parkin and LC3(P<0.01),and increased expression of P62,cleaved caspase-9,and cleaved caspase-3(P<0.01).The mice in CRS+EXE group showed significant improvements in all these parameters compared to CRS group(P<0.05 or P<0.01).CONCLUSION:Treadmill exercise mitigates CRS-induced depressive-like behaviors,mi-tochondrial dysfunction,and neuronal apoptosis in mice by activating the hippocampal Sirt1/PGC-1α/mitophagy axis.
3.Establishment and practice of virtual simulation experimental teaching platform of Health Management
Lianxiang LI ; Hailei ZHAO ; Jijia SUN ; An ZHANG ; Minghan WANG
Chinese Journal of Medical Education Research 2024;23(3):371-377
In order to solve the problems in traditional health management experimental teaching, such as high cost, safety and difficult repeatability, a virtual simulation experimental teaching platform for health management combined with Traditional Chinese Medicine (TCM) characteristics has been constructed by using virtual simulation, multimedia, and human-computer interaction technologies, which comprises TCM constitution identification, TCM health management and health management service process. Through the combination of virtual simulation and reality situation, the platform has formed an online and offline model of experimental teaching, which has improved the innovation and practice ability of students and enhanced the teaching quality.
4.LOXL1 dynamic expression of the liver in mice infected with Schistosomajaponicum
Bingxin Dai ; Li Gong ; Xuhan Yang ; Jijia Shen ; Miao Liu
Acta Universitatis Medicinalis Anhui 2023;58(3):386-391
Objective :
To observe the dynamic expression of recombinant lysyl oxidase like protein 1 ( LOXL1) in the lysine oxidase family in the liver of C57BL/6 mice infected with Schistosomajaponicum and explore its role in hepatic fibrosis.
Methods:
Mice were infected subcutaneously with cercariae of S.japonicum,and sacrificed with euthanasia in 6,9 and 12 weeks after infection.The sera and liver tissues were collected.The levels of liver fibrosis in mice was dynamically evaluated by HE and Sirius red staining,and the serum transaminases were detected.The dynamic expression levels of collagen type Ⅰ ( Col1) ,LOXL1 and α-smooth muscle actin( α-SMA) in liver tissues were determined respectively by Western blot and qPCR. Finally,the dynamic levels of soluble and insoluble collagens were detected.
Results:
The result of HE and Sirius red staining showed that hepatic fibrosis levels increased at 6 weeks,peaked at 9 week,and decreased at 12 week in response to S.japonicum infection.Western blot and q-PCR showed that the expression levels of LOXL1,Col1 α1,Col3 α1 and α-SMA was significantly up regulated and reached maximum at the 9th week in response to S.japonicum infection.Soluble collagen protein levels reached maximum at the 9th week.and decreased at 12 week,however insoluble collagen protein levels continued to increase.
Conclusion
There may be a correlation between LOXL1 and fiber cross-linking in the process of hepatic fibrosis in S.japonicum,and it plays a role in promoting hepatic fibrosis.
5.Expression of UGRP1 in thyroid cells induced by IL-1β and its correlation with Fas/FasL mediated apoptosis
Cuiping Chen ; Anan Li ; Cuiping Ren ; Jijia Shen ; Chunlin Zuo
Acta Universitatis Medicinalis Anhui 2022;57(7):1073-1077
Objective:
To investigate the expression of uteroglobin-related protein 1(UGRP1) in thyroid cells induced by interleukin-1β(IL-1β) and its correlation with Fas/FasL mediated apoptosis.
Methods:
Control group, IL-1β group and IL-1β+anti-FasL antibody group were established, rat thyroid cells(FRTL-5 cells) were culturedin vitro. The expression levels of UGRP1 and Fas mRNA of each group were detected by real-time PCR and the apoptosis rate of each group was detected by flow cytometry.
Results:
Compared with control group, the mRNA expression levels of UGRP1 and Fas in IL-1β group and IL-1β+anti-FasL antibody group increased, and the difference was statistically significant(P<0.05). Compared with control group, the early apoptosis rate of thyroid cells in IL-1β group increased(7.49%±1.91%vs28.46%±3.17%), and the difference was statistically significant(P<0.001). Compared with IL-1β group, the early apoptosis rate of thyroid cells in IL-1β+anti-FasL antibody group decreased(28.46%±3.17%vs19.20%±1.75%), and the difference was statistically significant(P<0.05). Compared with IL-1β group, the expression levels of UGRP1 mRNA(2.22±0.31vs2.66±0.28) and Fas mRNA(2.75±0.18vs3.03±0.16) in IL-1β+anti-FasL antibody group were not significantly different(P>0.05).
Conclusion
IL-1β induces the high expression of UGRP1 and Fas and apoptosis of thyroid cells, the high expression of UGRP1 is not associated with Fas/FasL mediated apoptosis.
6.Efficacy and mechanism of Yudanrongxin pills in acute myocardial infarction
Jingyao LI ; Jijia WANG ; Hua XU ; Xianghong SONG ; Yue ZHAO
Chinese Journal of Biochemical Pharmaceutics 2016;36(6):145-147
Objective To investigate clinical effect and mechanism of Yudanrongxin pills in the treatment of patients with acute myocardial infarction ( AMI) .Methods 86 cases of AMI in our hospital from February 2014 to February 2015 were selected and divided into the observation group and the control group, with 43 cases in each group.The patients in the control group were treated with conventional therapy, while patients in observation group were treated with Yudanrongxin pills on the basis of the control group.The related inflammation factors, indicators of myocardial injury and heart function index were compared between two groups before and after treatment.Results Compared with before treatment, in both two groups after treatment, the serum inflammatory factors including high-sensitivity C-reactive protein(hs-CRP), IL-6,soluble vascular cellular adhesion molecule-1 (sVCAM-1), TNF-αand P-selectin decreased, the myocardial injury criterion including creatine kinase-MB (CK-MB), lactate dehydrogenase (LD), myocardial troponin I (cTnI) and myoglobin (Mb) decreased,the cardiac function indexes of left ventricular end systolic volume (LVESV) and left ventricular end diastolic volume (LVEDV) decreased and left ventricular ejection fraction (LVEF) increased (P<0.05).Compared with control group, the hs-CRP,IL-6,sVCAM-1,TNF-α,P-selectin,CK-MB,LD,cTnI and Mb in observation group were lower(P<0.05).The degree of improvement at cardiac function was better than that in control group (P<0.05).Conclusion Yudanrongxin pills could better improve cardiac function in treatment with AMI, its role was relative to inhibition of inflammatory factors and myocardial protection against injury.
7.Clinical effect and possible mechanism of Yiqi Shuxin pills in the treatment with viral myocarditis
Jijia WANG ; Yue ZHAO ; Jingyao LI ; Hua XU
Chinese Journal of Biochemical Pharmaceutics 2016;36(8):91-93
Objective To investigate the effect and mechanism of Yiqi Shuxin pills in the treatment with viral myocarditis(VMC).Methods 56 cases of VMC in our hospital were randomly divided into the experimental group and the control group,28 cases in each group.The patients in the control group were with routine treatment,and these in the experimental group were treated with Yiqi Shuxin pills based on the control group.The clinical effects between the two groups were compared, and the changes of miR, myocardial enzyme spectrum and immunity were compared before and after treatment.Results The total effective rate was 92.86% in the experimental group and was 72.57% in the control group,there was statistical significance between the two groups(P<0.05);There was no significant difference between the two groups before treatment at miR-1,miR-133,miR-21,CK-MB, cTnI,LDH,CD3 +,CD4 +,CD8 +,NK in serum;The content of miR-1,miR-133,CD3 +,CD4 +,CD8 +,NK after treatment in the two groups were higher than before treatment(P <0.05),miR-21,CK-MB,cTnI and LDH were lower than before(P <0.05);The improvement of these indicators in the experimental group was superior to that in the control group(P<0.05).Conclusion Yiqi Shuxin pills could improve the therapeutic effect of VMC,the mechanism maybe related to improving the circulation of blood miR and enhance cellular immune function.
8.A retrospective study of OSF coexisted with OLK or OLP
Jieying PENG ; Yingfang WU ; Gaoxing WEI ; Jijia LI ; Liwei MA
Journal of Chinese Physician 2015;17(9):1300-1304
Objective To analyze the clinical feature and pathological characteristics of oral submucous fibrosis (OSF) coexisted with oral leukoplakia (OLK) or oral lichen planus (OLP),and summarize both the common and each clinical and pathological characteristics of two kinds of diseases.Methods The clinical and pathological data of 74 patients with OSF coexisted with OLK and 57patients with OSF coexisted with OLP were retrospectively reviewed.Results Most of patients with OSF coexisted with OLK or OLP were mainly young and middle-aged male patients,and all had the habit of eating betel quid chewing.Most of them had the habit of smoking and alcohol drinking; while their limitation of mouth opening were not obvious.Patients coexisted with unilateral OLK or OLP all had a unilateral mastication of chewing betel nut;the prevalence rate of erosive OLP was lower in the patients with OSF coexisted OLP than that of OLP patients never chew betel nut.The pathology of both OSF coexisted with OLK or OLP was with the respective characteristics of OLK or OLP on the basis of OSF,and the epithelium was thickened more than atrophic.No relationship was found between the degree of epithelial hyperplasia and the severity of fibrosis in patients with OSF coexisted with OLK.Conclusions OSF coexisted with OLK and OSF coexisted with OLP were the occurrence of OLK or OLP on the basis of OSF,which were not a simple superposition of two diseases,but combination with their own characteristics of OSF coexisted with OLK or OLP.
9.Preparation of sodium alginate-nanohydroxyapatite composite material for bone repair and its biocompatibility.
Yanmei WANG ; Jiacai HE ; Quanli LI ; Jijia SHEN
West China Journal of Stomatology 2014;32(1):27-31
OBJECTIVETo prepare sodium alginate-nanohydroxyapatite composite material and to explore its feasibility as a bone repair material.
METHODSSodium alginate-nanohydroxyapatite composite material was prepared using chemical cross-linking and freeze-drying technology. The composite was characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM) and its porosity was measured by liquid displacement method. The fifth passage of bone marrow stromal stem cells (BMSCs) were incubated on the composite material and then growth was observed by inverted microscope and SEM. BMSCs were cultured with liquid extracts of the material, methyl thiazolyl tetrazolium (MTT) assay was used to calculate the relative growth rate (RGR) on 1, 3, 5 d and to evaluate the cytotoxicity. Fresh dog blood was added into the liquid extracts to conduct hemolysis test, the spectrophotometer was used to determine the optical density (OD) and to calculate the hemolysis rate.
RESULTSSodium alginate-nanohydroxyapatite composite material displayed porosity, the porous pore rate was (88.6 +/- 4.5)%. BMSCs showed full stretching and vigorous growth under inverted microscope and SEM. BMSCs cultured with liquid extracts of the material had good activities. The toxicity of composite material was graded as 1. Hemolysis test results showed that the hemolysis rate of the composite material was 1.28%, thus meeting the requirement of medical biomaterials.
CONCLUSIONThe composite material fabricated in this study has high porosity and good biocompatibility.
Alginates ; Biocompatible Materials ; Cells, Cultured ; Glucuronic Acid ; Hexuronic Acids ; Humans ; Mesenchymal Stromal Cells ; Porosity ; Tissue Engineering ; Tissue Scaffolds
10.Preparation of sodium alginate-nanohydroxyapatite composite material for bone repair and its biocompatibility
Yanmei WANG ; Jiacai HE ; Quanli LI ; Jijia SHEN
West China Journal of Stomatology 2014;(1):27-31
Objective To prepare sodium alginate-nanohydroxyapatite composite material and to explore its feasibility as a bone repair material. Methods Sodium alginate-nanohydroxyapatite composite material was prepared using chemical cross-linking and freeze-drying technology. The composite was characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM) and its porosity was measured by liquid displacement method. The fifth passage of bone marrow stromal stem cells (BMSCs) were incubated on the composite material and then growth was observed by inverted micros-cope and SEM. BMSCs were cultured with liquid extracts of the material, methyl thiazolyl tetrazolium (MTT) assay was used to calculate the relative growth rate (RGR) on 1, 3, 5 d and to evaluate the cytotoxicity. Fresh dog blood was added into the liquid extracts to conduct hemolysis test, the spectrophotometer was used to determine the optical density (OD) and to calculate the hemolysis rate. Results Sodium alginate-nanohydroxyapatite composite material displayed porosity, the porous pore rate was (88.6±4.5)%. BMSCs showed full stretching and vigorous growth under inverted microscope and SEM. BMSCs cultured with liquid extracts of the material had good activities. The toxicity of composite material was graded as 1. Hemolysis test results showed that the hemolysis rate of the composite material was 1.28%, thus meeting the requirement of medical biomate-rials. Conclusion The composite material fabricated in this study has high porosity and good biocompatibility.


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