1.Ameliorating effect of betaine on oxygen-glucose deprivation injury in rat brain microvascular endothelial cells and its influence in PI3K/AKT pathway
Min CHEN ; Huiyan ZHU ; Jing TAO ; Yipeng XU
Journal of Jilin University(Medicine Edition) 2025;51(1):96-104
Objective:To investigate the effect of betaine in oxygen-glucose deprivation injury of rat brain microvascular endothelial cells(BMECs),and to clarify the regulatory effect of betaine on phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway.Methods:Five SD rats aged 7 d were selected and the rat BMSEs were obtained.The oxygen-glucose deprivation model of rat BMECs was prepared under hypoxic and hypoglycemic conditions;the experiment was divdided into model group,and low dose,medium dose,and high dose of betaine groups and positive control group,at the same time,blank control group(without modeling)was set up.The BMECs in blank control group and model group were treated with fresh medium,the BMECs in positive control group were given a final concentration of 10 μmnol·L-1 nimodipine,and the BMECs in low,medium and high doses of betaine groups were treated with betaine at final concentration of 0.5,1.0 and 2.0 mmol·L-1,respectively.The survival rates of BMECs in various groups were determined by CCK-8 method at 12,24 and 48 h after culture;the activities of lactate dehydrogenase(LDH)and the levels of adenine ribonucleoside triphosphate(ATP)in the rat BMECs in various groups were determined using kits,and the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,and IL-18 in supernatants of the BMECs in various groups were determined by enzyme-linked immunosorbent assay(ELISA);the activities of superoxide dismutase(SOD)and levels of malondialdehyde(MDA)in the BMECs in various groups were determined by kits;the transendothelial resistance(TEER)values of rat BMSCs in various groups were determined by TEER analyzer,and the horseradish peroxidase(HRP)permeabilities of BMECs in various groups were determined by an insertion cell culture apparatus.TUNEL staining was used to determine the apoptotic rates of rat BMECs in vaisous groups,and Western blotting method was used to determine the ratios of phosphory lated PI3K(p-PI3K)/PI3K and phosphorylated AKT(p-AKT)/AKT in the rat BMECs in various groups.Results:Compared with blank control group,the survival rate of BMECs,activity of SOD,and level of ATP,value of TEER,and ratios of p-PI3K/PI3K and p-AKT/AKT of the rat BMECs in model group were significantly decreased(P<0.05),while the activity of LDH,the levels of TNF-α,IL-6,IL-1β,IL-18,and MDA,the apoptotic rate of the BMECs,and HRP permeability were significantly increased(P<0.05).Compared with model group,the survival rates of the BMECs,activities of SOD,and levels of ATP,values of TEER,and ratios of p-PI3K/PI3K and p-AKT/AKT of the BMECs in low,medium,and high doses of betaine groups and positive control group were significantly increased(P<0.05),while the activities of LDH,the levels of TNF-α,IL-6,IL-1β,IL-18,and MDA,the apoptotic rates of BMECs and HRP permeabilities were significantly decreased(P<0.05).Conclusion:Betaine can significantly repair the oxygen-glucose deprivation/reperfusion injury in the rat BMECs,inhibit the oxidative damage and apoptosis of BMECs,and improve the permeability of the cells;its mechanism may be related to the regulation of the PI3K/AKT pathway.
2.Enriched environment regulates neural stem cell migration in ischemic stroke rats mediated by NT3/p75NTR signaling pathway
Huiyan ZHU ; Min CHEN ; Chunli LI
Chinese Journal of Pathophysiology 2025;41(10):1963-1971
AIM:By establishing ischemic stroke(IS)rats and cell models,this study aimed to investigate the therapeutic effect of an enriched environment(EE)and to explore its impact on the neurotrophin 3(NT3)/p75 neuro-trophin receptor(p75NTR)signaling pathway.METHODS:The study consisted of in vivo and in vitro experiments.In vi-vo,Sprague-Dawley(SD)rats were randomly divided by weight into sham,IS,and IS+EE groups(n=10),with 8 addi-tional rats per group reserved for supplementary analyses.The IS model was established by the Longa suture occlusion method.Neurological and motor function deficits were assessed on days 1,3,7 and 14 post-modeling using the modified neurological severity score(mNSS).On days 3,7 and 14,4 additional rats from each group were sacrificed,and the whole-brain tissue was collected to measure infarct volume via 2,3,5-triphenyltetrazolium chloride(TTC)staining.On day 14,brain tissue was harvested for immunofluorescence staining to evaluate neuronal proliferation markers,while the ischemic penumbra was analyzed by Western blot for NT3/p75NTR pathway protein expression.In vitro,primary neural stem cells(NSCs)were isolated from fetal rats and cultured as neurospheres.These cells were divided into CON group and experimental groups treated with different concentrations of NT3 to evaluate the effects of NT3 on NSC proliferation and migration.Additionally,SH-SY5Y cell lines were used to establish an in vitro model of ischemic stroke through oxy-gen-glucose deprivation(OGD).These cells were treated with varying concentrations of NT3,along with CON and CON+NT3 groups,and a scratch assay was performed to assess the impact of NT3 on cell migration.RESULTS:EE significant-ly reduced neurological function scores in IS rats(P<0.05),prolonged latency in the rotarod test(P<0.05),and de-creased cerebral infarct area(P<0.05).EE further enhanced the protein expression of BrdU and Ki67 in the ischemic penumbra(P<0.05),as well as increased the co-expression of BrdU/DCX and BrdU/NeuN(P<0.05).Additionally,EE further upregulated the protein expression of NT3,p75NTR,PI3K,and Akt in the subventricular zone(SVZ)(P<0.05).In vitro,NT3(1 and 10 μg/L)significantly increased nestin expression(P<0.05)in the primary neural stem cell system.In the neural stem cell sphere system,compared to the CON group,1 μg/L NT3 markedly enhanced tubulin and phalloidin protein expression(P<0.05).In the scratch assay,1 ug/L NT3 significantly promoted the migration of both normal SH-SY5Y cells and OGD-induced SH-SY5Y cells compared to the CON group(P<0.05).CONCLUSION:Enriched envi-ronment activates the NT3/p75NTR signaling pathway,promoting the proliferation of NSCs in the SVZ and their migration to the ischemic penumbra,where they ultimately differentiate into neurons to replace those damaged,thereby contributing to the improvement of neurological function in rats with IS.
3.Prognostic analysis of cardiovascular and cerebrovascular diseases patients with general medicine and family motivation management
Xiaoping DONG ; Jiangfeng ZHU ; Huiyan ZHU ; Li ZHAO
China Modern Doctor 2025;63(26):24-27,32
Objective To explore the influence of general medicine combined with family motivation management on the prognosis of cardiovascular and cerebrovascular disease patients.Methods A total of 120 cardiovascular and cerebrovascular diseases patients who received medical care at the First People's Hospital ofFuyang District from October 2023 to October 2024 were selected as subjects.They were divided into control group(n=60)and study group(n=60)by using a random number table method.Control group received standard nursing interventions,while study group underwent combined general medicine and family motivation management.Psychological status was assessed using the self-rating anxiety scale(SAS)and self-rating depression scale(SDS),with quality of life and self-management ability evaluated using the World Health Organization quality of life brief scale(WHOQOL-BREF)and exercise of self-care agency scale(ESCA).The triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C),readmission rate and average length of stay before and after intervention were compared between two groups.Results After intervention,both groups showed decreased SAS and SDS scores,while WHOQOL-BREF scores and ESCA levels increased.Score of study group were statistically significant better than that of control group(P<0.05).After intervention,HDL-C levels rose in both groups,whereas LDL-C,TG,and TC levels decreased.The improvement of each index in study group was better than that in control group(P<0.05).The rehospitalization rate and average length of stay in study group were significantly lower than those in control group(P<0.05).Conclusion The combination of general medicine and family motivation management can effectively optimize the prognosis of cardiovascular and cerebrovascular disease patients.
4.Effects of enriched environment on glucose metabolism in ischemic penumbra in rats with ischemic stroke
Journal of China Medical University 2025;54(4):328-332
Objective To investigate the effect of an enriched environment on glucose metabolism in the ischemic penumbra of rats with ischemic stroke(IS).Methods SD rats were subjected to middle cerebral artery ischemia to establish an IS model.The rats were ran-domly grouped and housed under different conditions with scheduled drug administration for 21 consecutive days.Neurological function scores and TTC staining were used to assess animal IS symptoms,whereas HPLC and Western blotting were used to detect glucose me-tabolic indicators and related protein expression,respectively.Results Compared to the model group,rats in the enriched envi-ronment group showed significant improvement in IS symptoms,with increased levels of glucose metabolic indicators and related protein expression.Compared to the positive drug group,rats in the positive drug+enriched environment group showed further improvement in IS symptoms,and the levels of glucose metabolic indicators and related protein expression were further enhanced.Conclusion Enriched environment can significantly improve IS symptoms in rats,and its mechanism may be related to an increase in glucose metabolic levels.
5.Organizational Agility in Public Hospitals:Concepts,Core Capabilities,and Development Pathways
Huiyan MAO ; Xuemei WANG ; Jianing WANG ; Yating CHENG ; Yuxuan ZHU ; Tingshan DUAN ; Tao SUN
Chinese Hospital Management 2025;45(3):50-54
In the current era filled with change and challenges,public hospitals,as a crucial part of the national healthcare system,urgently need to enhance their agility to swiftly respond to the ever-changing environment.Current it outlines the origins and connotations of organizational agility,argues for the necessity of organizational agility in public hospitals,and proposes the core competencies required to maintain organizational agility in public hospitals,namely:patient-centeredness,environmental sensitivity,proactive planning,organizational integration capability,flexibility,rapid response,iterative regulation,and continuous learning.Furthermore,it attempts to establish a cultivation pathway for organizational agility in public hospitals,encompassing multiple dimensions such as organizational culture,agile leadership,communication systems,organizational structure,the embedding of new productivity,management systems,partner management,training systems,performance evaluation,and compliance management.
6.Enriched environment regulates neural stem cell migration in ischemic stroke rats mediated by NT3/p75NTR signaling pathway
Huiyan ZHU ; Min CHEN ; Chunli LI
Chinese Journal of Pathophysiology 2025;41(10):1963-1971
AIM:By establishing ischemic stroke(IS)rats and cell models,this study aimed to investigate the therapeutic effect of an enriched environment(EE)and to explore its impact on the neurotrophin 3(NT3)/p75 neuro-trophin receptor(p75NTR)signaling pathway.METHODS:The study consisted of in vivo and in vitro experiments.In vi-vo,Sprague-Dawley(SD)rats were randomly divided by weight into sham,IS,and IS+EE groups(n=10),with 8 addi-tional rats per group reserved for supplementary analyses.The IS model was established by the Longa suture occlusion method.Neurological and motor function deficits were assessed on days 1,3,7 and 14 post-modeling using the modified neurological severity score(mNSS).On days 3,7 and 14,4 additional rats from each group were sacrificed,and the whole-brain tissue was collected to measure infarct volume via 2,3,5-triphenyltetrazolium chloride(TTC)staining.On day 14,brain tissue was harvested for immunofluorescence staining to evaluate neuronal proliferation markers,while the ischemic penumbra was analyzed by Western blot for NT3/p75NTR pathway protein expression.In vitro,primary neural stem cells(NSCs)were isolated from fetal rats and cultured as neurospheres.These cells were divided into CON group and experimental groups treated with different concentrations of NT3 to evaluate the effects of NT3 on NSC proliferation and migration.Additionally,SH-SY5Y cell lines were used to establish an in vitro model of ischemic stroke through oxy-gen-glucose deprivation(OGD).These cells were treated with varying concentrations of NT3,along with CON and CON+NT3 groups,and a scratch assay was performed to assess the impact of NT3 on cell migration.RESULTS:EE significant-ly reduced neurological function scores in IS rats(P<0.05),prolonged latency in the rotarod test(P<0.05),and de-creased cerebral infarct area(P<0.05).EE further enhanced the protein expression of BrdU and Ki67 in the ischemic penumbra(P<0.05),as well as increased the co-expression of BrdU/DCX and BrdU/NeuN(P<0.05).Additionally,EE further upregulated the protein expression of NT3,p75NTR,PI3K,and Akt in the subventricular zone(SVZ)(P<0.05).In vitro,NT3(1 and 10 μg/L)significantly increased nestin expression(P<0.05)in the primary neural stem cell system.In the neural stem cell sphere system,compared to the CON group,1 μg/L NT3 markedly enhanced tubulin and phalloidin protein expression(P<0.05).In the scratch assay,1 ug/L NT3 significantly promoted the migration of both normal SH-SY5Y cells and OGD-induced SH-SY5Y cells compared to the CON group(P<0.05).CONCLUSION:Enriched envi-ronment activates the NT3/p75NTR signaling pathway,promoting the proliferation of NSCs in the SVZ and their migration to the ischemic penumbra,where they ultimately differentiate into neurons to replace those damaged,thereby contributing to the improvement of neurological function in rats with IS.
7.Prognostic analysis of cardiovascular and cerebrovascular diseases patients with general medicine and family motivation management
Xiaoping DONG ; Jiangfeng ZHU ; Huiyan ZHU ; Li ZHAO
China Modern Doctor 2025;63(26):24-27,32
Objective To explore the influence of general medicine combined with family motivation management on the prognosis of cardiovascular and cerebrovascular disease patients.Methods A total of 120 cardiovascular and cerebrovascular diseases patients who received medical care at the First People's Hospital ofFuyang District from October 2023 to October 2024 were selected as subjects.They were divided into control group(n=60)and study group(n=60)by using a random number table method.Control group received standard nursing interventions,while study group underwent combined general medicine and family motivation management.Psychological status was assessed using the self-rating anxiety scale(SAS)and self-rating depression scale(SDS),with quality of life and self-management ability evaluated using the World Health Organization quality of life brief scale(WHOQOL-BREF)and exercise of self-care agency scale(ESCA).The triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C),readmission rate and average length of stay before and after intervention were compared between two groups.Results After intervention,both groups showed decreased SAS and SDS scores,while WHOQOL-BREF scores and ESCA levels increased.Score of study group were statistically significant better than that of control group(P<0.05).After intervention,HDL-C levels rose in both groups,whereas LDL-C,TG,and TC levels decreased.The improvement of each index in study group was better than that in control group(P<0.05).The rehospitalization rate and average length of stay in study group were significantly lower than those in control group(P<0.05).Conclusion The combination of general medicine and family motivation management can effectively optimize the prognosis of cardiovascular and cerebrovascular disease patients.
8.Organizational Agility in Public Hospitals:Concepts,Core Capabilities,and Development Pathways
Huiyan MAO ; Xuemei WANG ; Jianing WANG ; Yating CHENG ; Yuxuan ZHU ; Tingshan DUAN ; Tao SUN
Chinese Hospital Management 2025;45(3):50-54
In the current era filled with change and challenges,public hospitals,as a crucial part of the national healthcare system,urgently need to enhance their agility to swiftly respond to the ever-changing environment.Current it outlines the origins and connotations of organizational agility,argues for the necessity of organizational agility in public hospitals,and proposes the core competencies required to maintain organizational agility in public hospitals,namely:patient-centeredness,environmental sensitivity,proactive planning,organizational integration capability,flexibility,rapid response,iterative regulation,and continuous learning.Furthermore,it attempts to establish a cultivation pathway for organizational agility in public hospitals,encompassing multiple dimensions such as organizational culture,agile leadership,communication systems,organizational structure,the embedding of new productivity,management systems,partner management,training systems,performance evaluation,and compliance management.
9.Effects of enriched environment on glucose metabolism in ischemic penumbra in rats with ischemic stroke
Journal of China Medical University 2025;54(4):328-332
Objective To investigate the effect of an enriched environment on glucose metabolism in the ischemic penumbra of rats with ischemic stroke(IS).Methods SD rats were subjected to middle cerebral artery ischemia to establish an IS model.The rats were ran-domly grouped and housed under different conditions with scheduled drug administration for 21 consecutive days.Neurological function scores and TTC staining were used to assess animal IS symptoms,whereas HPLC and Western blotting were used to detect glucose me-tabolic indicators and related protein expression,respectively.Results Compared to the model group,rats in the enriched envi-ronment group showed significant improvement in IS symptoms,with increased levels of glucose metabolic indicators and related protein expression.Compared to the positive drug group,rats in the positive drug+enriched environment group showed further improvement in IS symptoms,and the levels of glucose metabolic indicators and related protein expression were further enhanced.Conclusion Enriched environment can significantly improve IS symptoms in rats,and its mechanism may be related to an increase in glucose metabolic levels.
10.α-mangostin inhibits LPS/ATP-induced NLRP3 inflammasome activation in microglia via the NF- κB pathway
Min Chen ; Jing Tao ; Huiyan Zhu
Acta Universitatis Medicinalis Anhui 2024;59(4):575-580
Objective :
To investigate the effects and underlying mechanisms of α-mangostin in a spinal cord inj ury model of microglial cell inflammation .
Methods :
Mouse microglial cell line BV-2 was cultured in vitro , and an in- flammation model was established by co-treatment with lipopolysaccharide and adenosine triphosphate (LPS/ATP) . The CCK-8 assay was used to test the influence of different concentrations (0 , 10 , 20 , 40 , 80 μmol/L) of α-man- gostin on cell proliferation vitality under LPS/ATP stimulation to select an appropriate concentration range of α- mangostin; BV-2 cells were divided into Ctrl group , LPS/ATP group , 40 μmol/L α-mangostin group , and inter- vention groups with different concentrations (10 , 20 , 40 μmol/L) of α-mangostin ( designated as LPS/ATP + 10 μmol/L α-mangostin group , LPS/ATP + 20 μmol/L α-mangostin group , and LPS/ATP + 40 μmol/L α-mangostin group , respectively) . ELISA experiments were conducted to detect the levels of pro-inflammatory cytokines inter- leukin -6/1β/18 (IL-6 , IL-1β, IL-18) and tumor necrosis factor (TNF-α) in the supernatants of each group , and Western blot was used to detect the expression of NLRP3 , ASC , cleaved caspase-1 , IL-1β, and the phosphoryla- tion levels of p65 (p-p65/p65) in the NF- κB pathway , as well as the expression of p65 in the nuclei of BV-2 cells .
Results :
Compared with the Ctrl group, cell proliferation vitality in the LPS/ATP group was significantly reduced (P < 0. 05) , but low concentrations (10 , 20 , 40 μmol/L) of α-mangostin significantly improved the inhibi- tory effect of LPS/ATP on microglial cell proliferation vitality (P < 0. 05) , while a high concentration (80 μmol/ L) of α-mangostin exacerbated the damage to microglial cells caused by LPS/ATP (P < 0. 05) . C ompared with the Ctrl group , the levels of inflammatory factors IL-6 , IL-1β, IL-18 , TNF-α, and the expression of NLRP3 , ASC , cleaved caspase-1 , IL-1β, and the p-p65/p65 ratio in the 40 μmol/L α-mangostin group , as well as the expression of p65 protein in the nuclei , showed no significant changes ( P > 0 . 05) , whereas these significantly increased in the LPS/ATP group (P < 0. 05) . Compared with the LPS/ATP group , the levels of IL-6 , IL-1β, IL-18 , TNF-α, and the expression of NLRP3 , ASC , cleaved caspase-1 , IL-1β, and the p-p65/p65 ratio in the intervention groups , as well as the expression of p65 protein in the nuclei , decreased in a concentration-dependent manner with increasing α-mangostin concentration , with the most significant reduction ob served in the LPS/ATP + 40 μmol/L α- mangostin group (P < 0. 01) .
Conclusion
α-mangostin can inhibit the neuroinflammatory response mediated by NLRP3 inflammasome activation in BV-2 cells through the NF- κB pathway .


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