Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relations...Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.展开更多
AIM: To explore the effects of IκBα SUMOylation and NF-κB p65 deacetylation on NF-κB p65 activity induced by high glucose in cultured human lens epithelial cells(HLECs).METHODS: HLECs(SRA01/04) were cultured with ...AIM: To explore the effects of IκBα SUMOylation and NF-κB p65 deacetylation on NF-κB p65 activity induced by high glucose in cultured human lens epithelial cells(HLECs).METHODS: HLECs(SRA01/04) were cultured with 5.5, 25, and 50 mmol/L glucose media for 24 h, and with 50 mmol/L glucose media for 0, 12, and 24 h respectively. SUMO1 and SIRT1 expressions were detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot(WB). IκBα and NF-κB p65 expressions were detected by WB. With NAC, DTT, MG132 or Resveratrol(RSV) treatment, SUMO1 and SIRT1 expressions were detected by WB. Protein expression localizations were examined by immunofluorescence and co-immunofluorescence. The effects of SUMO1 or SIRT1 overexpression, as well as MG132 and RSV, on the nuclear expression and activity of IκBα and NF-κB p65 were analyzed by immunoblot and dual luciferase reporter gene assay.RESULTS: SUMO1 and SIRT1 expressions were influenced by high glucose in mRNA and protein levels, which could be blocked by NAC or DTT. SUMO1 was down-regulated by using MG132, and SIRT1 was up-regulated under RSV treatment. IκBα nuclear expression was attenuated and NF-κB p65 was opposite under high glucose, while IκBα and NF-κB p65 location was transferred to the nucleus. SUMO1 or SIRT1 overexpression and MG132 or RSV treatment affected the nuclear expression and activity of IκBα and NF-κB p65 under high glucose condition.CONCLUSION: IκBα SUMOylation and NF-κB p65 deacetylation affect NF-κB p65 activity in cultured HLECs under high glucose, and presumably play a significant role in controlling diabetic cataract.展开更多
Glial cell line-derived neurotrophic factor(GDNF)plays an important role in the protection of dopaminergic neurons,but there are few reports of the relationship between GDNF and its precursors(α-pro-GDNF andβ-pro-GD...Glial cell line-derived neurotrophic factor(GDNF)plays an important role in the protection of dopaminergic neurons,but there are few reports of the relationship between GDNF and its precursors(α-pro-GDNF andβ-pro-GDNF)and cognitive impairment in Parkinson’s disease.This study aimed to investigate the relationship between the serum levels of GDNF and its precursors and cognitive impairment in Parkinson’s disease,and to assess their potential as a diagnostic marker.Fifty-three primary outpatients and hospitalized patients with Parkinson’s disease(23 men and 30 women)with an average age of 66.58 years were enrolled from the Affiliated Hospital of Xuzhou Medical University of China in this case-control study.The patients were divided into the Parkinson’s disease with cognitive impairment group(n=27)and the Parkinson’s disease with normal cognitive function group(n=26)based on their Mini-Mental State Examination,Montreal Cognitive Assessment,and Clinical Dementia Rating scores.In addition,26 age-and sex-matched healthy subjects were included as the healthy control group.Results demonstrated that serum GDNF levels were significantly higher in the Parkinson’s disease with normal cognitive function group than in the other two groups.There were no significant differences in GDNF precursor levels among the three groups.Correlation analysis revealed that serum GDNF levels,GDNF/α-pro-GDNF ratios,and GDNF/β-pro-GDNF ratios were moderately or highly correlated with the Mini-Mental State Examination,Montreal Cognitive Assessment,and Clinical Dementia Rating scores.To explore the risk factors for cognitive impairment in patients with Parkinson’s disease,logistic regression analysis and stepwise linear regression analysis were performed.Both GDNF levels and Hoehn-Yahr stage were risk factors for cognitive impairment in Parkinson’s disease,and were the common influencing factors for cognitive scale scores.Neitherα-pro-GDNF norβ-pro-GDNF was risk factors for cognitive impairment in Parkinson’s disease.A receiver operating characteristic curve of GDNF was generated to predict cognitive function in Parkinson’s disease(area under the curve=0.859).This result indicates that the possibility that serum GDNF can correctly distinguish whether patients with Parkinson’s disease have cognitive impairment is 0.859.Together,these results suggest that serum GDNF may be an effective diagnostic marker for cognitive impairment in Parkinson’s disease.However,α-pro-GDNF andβ-pro-GDNF are not useful for predicting cognitive impairment in this disease.This study was approved by Ethics Committee of the Affiliated Hospital of Xuzhou Medical University,China(approval No.XYFY2017-KL047-01)on November 30,2017.展开更多
AIM： To compare the results of 25 MHz and 50 MHz ultrasound biomicroscopy（UBM） regarding the image characteristics of the lens and its related diseases and to discuss the application value of 25 MHz UBM in ophthalm...AIM： To compare the results of 25 MHz and 50 MHz ultrasound biomicroscopy（UBM） regarding the image characteristics of the lens and its related diseases and to discuss the application value of 25 MHz UBM in ophthalmology. METHODS： A total of 302 patients（455 eyes） were included in this study from November 2014 to May 2015. Patient ages ranged from 5 to 89 y（mean±SD： 61.0±17.7 y）. Different cross-sectional images of the lens were collected to compare and analyze the image characteristics and anterior segment parameters using 25 MHz and 50 MHz UBM in axial and longitudinal scanning modes, respectively. SPSS 19.0 for Windows, paired t-tests and B＆A plot analysis were used for data analysis, and a value of P〈0.05 was considered statistically significant. RESULTS： The 25 MHz UBM images displayed the lens shape more clearly than 50 MHz UBM images. Particularly for cataracts, the whole opacity of the lens was shown by 25 MHz UBM, but 50 MHz UBM only showed part of the lens. The means of the anterior segment parameters obtained using 25 MHz and 50 MHz UBM were as follows： central corneal thickness： 0.55±0.03 and 0.51±0.04 mm, respectively; central anterior chamber depth： 2.48±0.54 and 2.56±0.56 mm, respectively; and central lens thickness： 4.26±0.62 and 4.15±0.56 mm, respectively. A statistically significant difference was found between the results obtained with 25 MHz UBM and those obtained with 50 MHz UBM. The two devices had a good agreement in measuring the anterior segment parameters. CONCLUSION： The 25 MHz UBM had an obvious advantage in showing the lens shape. It can provide reliable imaging of the lens and its related diseases and has a high application value for ophthalmology.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 81971006 (to DSG), 82101263 (to CXT)Jiangsu Province Science Foundation for Youths,No. BK20210903 (to CXT)+2 种基金Research Foundation for Talented Scholars of Xuzhou Medical University,No. RC20552114 (to CXT)Science&Technology Program of Xuzhou,No. KC19016 (to JC)Project of Xuzhou Medical University,No. 2018KJ06 (to JC)。
文摘Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.
基金Supported by the National Natural Science Foundation of China(No.81170836, No.81570838)
文摘AIM: To explore the effects of IκBα SUMOylation and NF-κB p65 deacetylation on NF-κB p65 activity induced by high glucose in cultured human lens epithelial cells(HLECs).METHODS: HLECs(SRA01/04) were cultured with 5.5, 25, and 50 mmol/L glucose media for 24 h, and with 50 mmol/L glucose media for 0, 12, and 24 h respectively. SUMO1 and SIRT1 expressions were detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot(WB). IκBα and NF-κB p65 expressions were detected by WB. With NAC, DTT, MG132 or Resveratrol(RSV) treatment, SUMO1 and SIRT1 expressions were detected by WB. Protein expression localizations were examined by immunofluorescence and co-immunofluorescence. The effects of SUMO1 or SIRT1 overexpression, as well as MG132 and RSV, on the nuclear expression and activity of IκBα and NF-κB p65 were analyzed by immunoblot and dual luciferase reporter gene assay.RESULTS: SUMO1 and SIRT1 expressions were influenced by high glucose in mRNA and protein levels, which could be blocked by NAC or DTT. SUMO1 was down-regulated by using MG132, and SIRT1 was up-regulated under RSV treatment. IκBα nuclear expression was attenuated and NF-κB p65 was opposite under high glucose, while IκBα and NF-κB p65 location was transferred to the nucleus. SUMO1 or SIRT1 overexpression and MG132 or RSV treatment affected the nuclear expression and activity of IκBα and NF-κB p65 under high glucose condition.CONCLUSION: IκBα SUMOylation and NF-κB p65 deacetylation affect NF-κB p65 activity in cultured HLECs under high glucose, and presumably play a significant role in controlling diabetic cataract.
基金This work was funded by the National Natural Science Foundation of China,No.81971006(to DSG)the Postgraduate Research and Practice Innovation Program of Jiangsu Province of China,Nos.KYCX18_2193(to MYS),KYCX18_2171(to CXT).
文摘Glial cell line-derived neurotrophic factor(GDNF)plays an important role in the protection of dopaminergic neurons,but there are few reports of the relationship between GDNF and its precursors(α-pro-GDNF andβ-pro-GDNF)and cognitive impairment in Parkinson’s disease.This study aimed to investigate the relationship between the serum levels of GDNF and its precursors and cognitive impairment in Parkinson’s disease,and to assess their potential as a diagnostic marker.Fifty-three primary outpatients and hospitalized patients with Parkinson’s disease(23 men and 30 women)with an average age of 66.58 years were enrolled from the Affiliated Hospital of Xuzhou Medical University of China in this case-control study.The patients were divided into the Parkinson’s disease with cognitive impairment group(n=27)and the Parkinson’s disease with normal cognitive function group(n=26)based on their Mini-Mental State Examination,Montreal Cognitive Assessment,and Clinical Dementia Rating scores.In addition,26 age-and sex-matched healthy subjects were included as the healthy control group.Results demonstrated that serum GDNF levels were significantly higher in the Parkinson’s disease with normal cognitive function group than in the other two groups.There were no significant differences in GDNF precursor levels among the three groups.Correlation analysis revealed that serum GDNF levels,GDNF/α-pro-GDNF ratios,and GDNF/β-pro-GDNF ratios were moderately or highly correlated with the Mini-Mental State Examination,Montreal Cognitive Assessment,and Clinical Dementia Rating scores.To explore the risk factors for cognitive impairment in patients with Parkinson’s disease,logistic regression analysis and stepwise linear regression analysis were performed.Both GDNF levels and Hoehn-Yahr stage were risk factors for cognitive impairment in Parkinson’s disease,and were the common influencing factors for cognitive scale scores.Neitherα-pro-GDNF norβ-pro-GDNF was risk factors for cognitive impairment in Parkinson’s disease.A receiver operating characteristic curve of GDNF was generated to predict cognitive function in Parkinson’s disease(area under the curve=0.859).This result indicates that the possibility that serum GDNF can correctly distinguish whether patients with Parkinson’s disease have cognitive impairment is 0.859.Together,these results suggest that serum GDNF may be an effective diagnostic marker for cognitive impairment in Parkinson’s disease.However,α-pro-GDNF andβ-pro-GDNF are not useful for predicting cognitive impairment in this disease.This study was approved by Ethics Committee of the Affiliated Hospital of Xuzhou Medical University,China(approval No.XYFY2017-KL047-01)on November 30,2017.
文摘AIM： To compare the results of 25 MHz and 50 MHz ultrasound biomicroscopy（UBM） regarding the image characteristics of the lens and its related diseases and to discuss the application value of 25 MHz UBM in ophthalmology. METHODS： A total of 302 patients（455 eyes） were included in this study from November 2014 to May 2015. Patient ages ranged from 5 to 89 y（mean±SD： 61.0±17.7 y）. Different cross-sectional images of the lens were collected to compare and analyze the image characteristics and anterior segment parameters using 25 MHz and 50 MHz UBM in axial and longitudinal scanning modes, respectively. SPSS 19.0 for Windows, paired t-tests and B＆A plot analysis were used for data analysis, and a value of P〈0.05 was considered statistically significant. RESULTS： The 25 MHz UBM images displayed the lens shape more clearly than 50 MHz UBM images. Particularly for cataracts, the whole opacity of the lens was shown by 25 MHz UBM, but 50 MHz UBM only showed part of the lens. The means of the anterior segment parameters obtained using 25 MHz and 50 MHz UBM were as follows： central corneal thickness： 0.55±0.03 and 0.51±0.04 mm, respectively; central anterior chamber depth： 2.48±0.54 and 2.56±0.56 mm, respectively; and central lens thickness： 4.26±0.62 and 4.15±0.56 mm, respectively. A statistically significant difference was found between the results obtained with 25 MHz UBM and those obtained with 50 MHz UBM. The two devices had a good agreement in measuring the anterior segment parameters. CONCLUSION： The 25 MHz UBM had an obvious advantage in showing the lens shape. It can provide reliable imaging of the lens and its related diseases and has a high application value for ophthalmology.
