The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed...The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.展开更多
To evaluate the combined effect of temperature and cadmium on the molecular responses of heat shock protein 70(hsp70)and P-glycoprotein(P-gp)in mantle,digestive gland and gills of Crassostrea gigas,oysters were expose...To evaluate the combined effect of temperature and cadmium on the molecular responses of heat shock protein 70(hsp70)and P-glycoprotein(P-gp)in mantle,digestive gland and gills of Crassostrea gigas,oysters were exposed to combinations of five temperature levels(10,15,20,25,and 30℃)and 10μg L^(-1)cadmium for 21 days.Oysters were sampled for mRNA quantification by qPCR,and the results showed that the P-gp gene expression changed significantly after treatment at different temperatures and different treatment times.The P-gp gene expression was the highest in the digestive gland.Compared with the control group,the P-gp gene expression in cadmium treatment groups at all the different temperatures were significantly higher than the control group.The control oysters(kept at 10℃during the whole experiment without cadmium)expressed low levels of hsp70,but the groups treated with cadmium displayed somewhat higher levels.The present study demonstrated hsp70 and P-gp played an important role in the detoxification of Cd in C.gigas,and confirmed temperature should be considered for the assessment of Cd-induced toxicity in oysters.展开更多
BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood ...BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood UL16-binding protein 2(ULBP2)and human fibrinogen degradation products(DR-70)are the main indicators for the diagnosis of malignant tumors.AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference.METHODS This study involved 60 patients with early-stage CRC(CRC group),50 patients with benign colorectal tumors(benign group),and 50 healthy patients(control group)enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January,2020 and January,2022.ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined.Patients with CRC were divided into the good prognosis and poor prognosis groups,and ULBP2 and DR-70 levels in the blood and diagnostic values were compared.RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups(P<0.05);however,no significant differences were observed between the benign and control groups(P>0.05).Among the 60 patients with CRC followed up for two years,two died(3.33%)and 15 exhibited tumor metastasis,progression,or recurrence(25.00%).ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group(P<0.05).A receiver operating characteristic curve was plotted.Area under the curve,sensitivity,and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices(P<0.05)in both the good and poor prognosis groups.CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC.They improved the diagnostic rate of early-stage CRC and predicted patient prognosis,thereby showing clinical application potential.展开更多
基金supported by the National Natural Science Foundation of China,Nos.91849115 and U1904207(to YX),81974211 and 82171247(to CS)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No.2020-PT310-01(to YX).
文摘The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.
基金supported by the earmarked fund for the Modern Agroindustry Technology Research System in Shandong Province (No.SDAIT-14)。
文摘To evaluate the combined effect of temperature and cadmium on the molecular responses of heat shock protein 70(hsp70)and P-glycoprotein(P-gp)in mantle,digestive gland and gills of Crassostrea gigas,oysters were exposed to combinations of five temperature levels(10,15,20,25,and 30℃)and 10μg L^(-1)cadmium for 21 days.Oysters were sampled for mRNA quantification by qPCR,and the results showed that the P-gp gene expression changed significantly after treatment at different temperatures and different treatment times.The P-gp gene expression was the highest in the digestive gland.Compared with the control group,the P-gp gene expression in cadmium treatment groups at all the different temperatures were significantly higher than the control group.The control oysters(kept at 10℃during the whole experiment without cadmium)expressed low levels of hsp70,but the groups treated with cadmium displayed somewhat higher levels.The present study demonstrated hsp70 and P-gp played an important role in the detoxification of Cd in C.gigas,and confirmed temperature should be considered for the assessment of Cd-induced toxicity in oysters.
文摘BACKGROUND Early diagnosis of colorectal cancer(CRC)is of great significance to improve the survival rate and quality of life of patients,but early diagnosis of CRC requires more sensitive techniques.Peripheral blood UL16-binding protein 2(ULBP2)and human fibrinogen degradation products(DR-70)are the main indicators for the diagnosis of malignant tumors.AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference.METHODS This study involved 60 patients with early-stage CRC(CRC group),50 patients with benign colorectal tumors(benign group),and 50 healthy patients(control group)enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January,2020 and January,2022.ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined.Patients with CRC were divided into the good prognosis and poor prognosis groups,and ULBP2 and DR-70 levels in the blood and diagnostic values were compared.RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups(P<0.05);however,no significant differences were observed between the benign and control groups(P>0.05).Among the 60 patients with CRC followed up for two years,two died(3.33%)and 15 exhibited tumor metastasis,progression,or recurrence(25.00%).ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group(P<0.05).A receiver operating characteristic curve was plotted.Area under the curve,sensitivity,and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices(P<0.05)in both the good and poor prognosis groups.CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC.They improved the diagnostic rate of early-stage CRC and predicted patient prognosis,thereby showing clinical application potential.
