Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the ...Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD.In this paper,we systematically evaluated potential biomarkers,including proteins,metabolites,epigenetic markers,and exosomes,in the peripheral blood of PD patients.Protein markers are one of the main directions of biomarker research in PD.In particular,α‑synuclein and its phosphorylated form play a key role in the pathological process of PD.It has been shown that aggregation ofα-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD.In terms of metabolites,uric acid,as a metabolite,plays an important role in oxidative stress and neuroprotection in PD.It has been found that changes in uric acid levels may be associated with the onset and progression of PD,showing its potential as an early diagnostic marker.Epigenetic markers,such as DNA methylation modifications and miRNAs,have also attracted much attention in Parkinson’s disease research.Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease,providing new research perspectives for the early diagnosis of PD.In addition,exosomes,as a potential biomarker carrier for PD,are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation.Studies have shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide a new breakthrough for early diagnosis.It has been shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide new breakthroughs in early diagnosis.In summary,through in-depth evaluation of biomarkers in the peripheral blood of PD patients,this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms.Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.展开更多
Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes.Macrophages and lymphocytes are involved in the pathogenesis of diabetes,diabetic atherosclerosis,formation of insu...Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes.Macrophages and lymphocytes are involved in the pathogenesis of diabetes,diabetic atherosclerosis,formation of insulin resistance as well as immune response to cancer and tumor maintenance.The aim of the study was to determine the Akt activation by mTORC2 in peripheral blood mononuclear cell(PBMC)of patients with type 2 diabetes and cancer.The following groups were studied:control group,patients with type 2 diabetes,cancer patients and patients with both cancer and diabetes.The amounts of phospho-Akt(р-S473)and phospho-p70S6K1(p-T389)were determined using ELISA kits.The amount of phosphorylated Akt significantly increases in PBMC of patients with cancer.There was no effect in PBMC from patients with type 2 diabetes and significant decrease in the amount of phospho-Akt in PBMC of the patients group both with cancer and diabetes.p70S6K1 activation was observed in PBMC of the groups 2 and 3 patients.Thus,chronic diseases such as type 2 diabetes and cancer can affect the signaling mechanisms in blood cells.The state of Akt phosphorylation in leukocytes can indicate the activity of mTORC1 and its substrates,which may be important for the evaluation of the pathological process and the efficacy of the drugs.展开更多
Objective To study correlations of polychlorinated biphenyls （PCBs）, DIOXIN, and polybrominated diphenyl ethers （PBDE） with thyroid stimulating hormone（TSH） in children, and assess the impact on children＇s heal...Objective To study correlations of polychlorinated biphenyls （PCBs）, DIOXIN, and polybrominated diphenyl ethers （PBDE） with thyroid stimulating hormone（TSH） in children, and assess the impact on children＇s health. Methods Three hundred and sixty nine children aged from 6 to 8, including 195 from Luqiao, the computer E‐waste recycling area, and 174 from Longyou, the control area, were selected for this investigation to elucidate the correlation of PCBs, DIOXIN, and PBDE with TSH in children’s blood samples. The children had a physical examination and their blood levels of PCBs, DIOXIN, PBDE, and TSH were detected after sample collection. Results In the E‐waste recycling area, the contents of PCBs, PBDE, DIOXIN, and TSH in the blood samples of children were 484.00±84.86 ng·g ‐1 lipid weight, 664.28±262.38 ng·g ‐1 lipid weight, 26.00±19.58 ng·g ‐1 lipid weight and 1.88±0.42 μIU/mL （serum） respectively, while in the control area, the PCBs, PBDE, DIOXIN, and TSH contents were 255.38±95 ng·g ‐1 lipid weight, 375.81±262.43 ng·g ‐1 lipid weight, 39.64±31.86 ng·g ‐1 lipid weight, and 3.31±1.04 μIU/mL respectively. Conclusion The health status of children in the control area are better than that in the contaminated area. Among children who are exposed to persistent organic pollutants, the pollutant content increases significantly in their serum, and the distribution of TSH levels in their bodies are also affected.展开更多
Laboratory and clinical experience with PBSCT is reviewed.At.the University of Tokushima,a total of 314 aphoresis were performed by a CS 3000 cell separator in 77 children aged 7 months to 17 years with various types ...Laboratory and clinical experience with PBSCT is reviewed.At.the University of Tokushima,a total of 314 aphoresis were performed by a CS 3000 cell separator in 77 children aged 7 months to 17 years with various types of cancer.Mobidity related to the collection was negligible and a larger number of CFU-GM was collected in younger children than in展开更多
目的:探究外周血单个核细胞G_(2)/S期应答相关蛋白1(G_(2)and S phase-expressed-1,GTSE1)水平与上皮性卵巢癌(epithelial ovarian cancer,EOC)预后的关系。方法:GEPIA和Kaplan-Meier Plotter分析GTSE1在卵巢癌组织中的表达及其与预后...目的:探究外周血单个核细胞G_(2)/S期应答相关蛋白1(G_(2)and S phase-expressed-1,GTSE1)水平与上皮性卵巢癌(epithelial ovarian cancer,EOC)预后的关系。方法:GEPIA和Kaplan-Meier Plotter分析GTSE1在卵巢癌组织中的表达及其与预后的关系。选择2017年04月至2020年10月本院126例EOC患者(EOC组)和40例同期无EOC的健康体检者(对照组)作为研究对象。Ficoll密度梯度离心法分离外周血中单个核细胞,蛋白质免疫印迹法检测GTSE1水平。Spearman相关分析EOC组织和外周血单个核细胞中GTSE1水平的关系。随访了解EOC预后,用COX回归分析EOC预后的风险因素。结果:GEPIA和Kaplan-Meier Plotter分析结果显示,卵巢癌组织中GTSE1水平高于正常卵巢组织(P<0.05),GTSE1低水平卵巢癌患者的中位无进展生存时间高于GTSE1高水平卵巢癌患者(P<0.05)。随访期间复发98例(77.8%),其中铂类敏感型65例,铂类耐药型33例;死亡41例(32.5%)。EOC组的外周血单个核细胞中GTSE1 mRNA和GTSE1蛋白水平均高于对照组(P<0.001)。EOC患者癌组织和外周血单个核细胞中GTSE1水平呈正相关关系(r_(s)=0.225,P=0.011)。国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)Ⅰ-Ⅱ期患者的GTSE1水平低于Ⅲ-Ⅳ期的患者(P<0.001);未复发患者的GTSE1水平低于铂类敏感型和铂类耐药型的患者(P<0.05);生存患者的GTSE1水平低于死亡患者(P<0.001)。GTSE1高水平患者的无复发生存时间和总生存时间均低于GTSE1低水平患者(P<0.001)。COX回归分析结果显示,FIGO分期高(HR=2.110,95%CI:1.465~3.038,P<0.001;HR=2.261,95%CI:1.212~4.216,P=0.011)、初次手术残存灶>1 cm(HR=1.724,95%CI:1.130~2.631,P=0.012;HR=2.465,95%CI:1.246~4.874,P=0.010)和GTSE1>1.29(HR=2.071,95%CI:1.304~3.291,P=0.002;HR=5.634,95%CI:2.410~13.169,P<0.001)是EOC预后(复发和生存)的独立危险因素,应用贝伐单抗(HR=0.293,95%CI:0.116~0.738,P=0.010;HR=0.141,95%CI:0.056~0.357,P<0.001)是EOC预后的独立保护因素。结论:EOC患者外周血单个核细胞中GTSE1水平高提示预后不良风险高。展开更多
Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels r...Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.展开更多
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD.In this paper,we systematically evaluated potential biomarkers,including proteins,metabolites,epigenetic markers,and exosomes,in the peripheral blood of PD patients.Protein markers are one of the main directions of biomarker research in PD.In particular,α‑synuclein and its phosphorylated form play a key role in the pathological process of PD.It has been shown that aggregation ofα-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD.In terms of metabolites,uric acid,as a metabolite,plays an important role in oxidative stress and neuroprotection in PD.It has been found that changes in uric acid levels may be associated with the onset and progression of PD,showing its potential as an early diagnostic marker.Epigenetic markers,such as DNA methylation modifications and miRNAs,have also attracted much attention in Parkinson’s disease research.Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease,providing new research perspectives for the early diagnosis of PD.In addition,exosomes,as a potential biomarker carrier for PD,are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation.Studies have shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide a new breakthrough for early diagnosis.It has been shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide new breakthroughs in early diagnosis.In summary,through in-depth evaluation of biomarkers in the peripheral blood of PD patients,this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms.Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.
文摘Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes.Macrophages and lymphocytes are involved in the pathogenesis of diabetes,diabetic atherosclerosis,formation of insulin resistance as well as immune response to cancer and tumor maintenance.The aim of the study was to determine the Akt activation by mTORC2 in peripheral blood mononuclear cell(PBMC)of patients with type 2 diabetes and cancer.The following groups were studied:control group,patients with type 2 diabetes,cancer patients and patients with both cancer and diabetes.The amounts of phospho-Akt(р-S473)and phospho-p70S6K1(p-T389)were determined using ELISA kits.The amount of phosphorylated Akt significantly increases in PBMC of patients with cancer.There was no effect in PBMC from patients with type 2 diabetes and significant decrease in the amount of phospho-Akt in PBMC of the patients group both with cancer and diabetes.p70S6K1 activation was observed in PBMC of the groups 2 and 3 patients.Thus,chronic diseases such as type 2 diabetes and cancer can affect the signaling mechanisms in blood cells.The state of Akt phosphorylation in leukocytes can indicate the activity of mTORC1 and its substrates,which may be important for the evaluation of the pathological process and the efficacy of the drugs.
基金Funded by the Ministry of Health and Science and Technology (WKJ2007‐2‐006), China
文摘Objective To study correlations of polychlorinated biphenyls （PCBs）, DIOXIN, and polybrominated diphenyl ethers （PBDE） with thyroid stimulating hormone（TSH） in children, and assess the impact on children＇s health. Methods Three hundred and sixty nine children aged from 6 to 8, including 195 from Luqiao, the computer E‐waste recycling area, and 174 from Longyou, the control area, were selected for this investigation to elucidate the correlation of PCBs, DIOXIN, and PBDE with TSH in children’s blood samples. The children had a physical examination and their blood levels of PCBs, DIOXIN, PBDE, and TSH were detected after sample collection. Results In the E‐waste recycling area, the contents of PCBs, PBDE, DIOXIN, and TSH in the blood samples of children were 484.00±84.86 ng·g ‐1 lipid weight, 664.28±262.38 ng·g ‐1 lipid weight, 26.00±19.58 ng·g ‐1 lipid weight and 1.88±0.42 μIU/mL （serum） respectively, while in the control area, the PCBs, PBDE, DIOXIN, and TSH contents were 255.38±95 ng·g ‐1 lipid weight, 375.81±262.43 ng·g ‐1 lipid weight, 39.64±31.86 ng·g ‐1 lipid weight, and 3.31±1.04 μIU/mL respectively. Conclusion The health status of children in the control area are better than that in the contaminated area. Among children who are exposed to persistent organic pollutants, the pollutant content increases significantly in their serum, and the distribution of TSH levels in their bodies are also affected.
文摘Laboratory and clinical experience with PBSCT is reviewed.At.the University of Tokushima,a total of 314 aphoresis were performed by a CS 3000 cell separator in 77 children aged 7 months to 17 years with various types of cancer.Mobidity related to the collection was negligible and a larger number of CFU-GM was collected in younger children than in
基金funded by Key Programme of Chongqing Science and Technology Commision(No.CSTC2007BA5013)National Nature Science Foundation of China(No.30470760)Program for New Century Excellent Talents in University(No.NCET-06-0775)
文摘目的:探究外周血单个核细胞G_(2)/S期应答相关蛋白1(G_(2)and S phase-expressed-1,GTSE1)水平与上皮性卵巢癌(epithelial ovarian cancer,EOC)预后的关系。方法:GEPIA和Kaplan-Meier Plotter分析GTSE1在卵巢癌组织中的表达及其与预后的关系。选择2017年04月至2020年10月本院126例EOC患者(EOC组)和40例同期无EOC的健康体检者(对照组)作为研究对象。Ficoll密度梯度离心法分离外周血中单个核细胞,蛋白质免疫印迹法检测GTSE1水平。Spearman相关分析EOC组织和外周血单个核细胞中GTSE1水平的关系。随访了解EOC预后,用COX回归分析EOC预后的风险因素。结果:GEPIA和Kaplan-Meier Plotter分析结果显示,卵巢癌组织中GTSE1水平高于正常卵巢组织(P<0.05),GTSE1低水平卵巢癌患者的中位无进展生存时间高于GTSE1高水平卵巢癌患者(P<0.05)。随访期间复发98例(77.8%),其中铂类敏感型65例,铂类耐药型33例;死亡41例(32.5%)。EOC组的外周血单个核细胞中GTSE1 mRNA和GTSE1蛋白水平均高于对照组(P<0.001)。EOC患者癌组织和外周血单个核细胞中GTSE1水平呈正相关关系(r_(s)=0.225,P=0.011)。国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)Ⅰ-Ⅱ期患者的GTSE1水平低于Ⅲ-Ⅳ期的患者(P<0.001);未复发患者的GTSE1水平低于铂类敏感型和铂类耐药型的患者(P<0.05);生存患者的GTSE1水平低于死亡患者(P<0.001)。GTSE1高水平患者的无复发生存时间和总生存时间均低于GTSE1低水平患者(P<0.001)。COX回归分析结果显示,FIGO分期高(HR=2.110,95%CI:1.465~3.038,P<0.001;HR=2.261,95%CI:1.212~4.216,P=0.011)、初次手术残存灶>1 cm(HR=1.724,95%CI:1.130~2.631,P=0.012;HR=2.465,95%CI:1.246~4.874,P=0.010)和GTSE1>1.29(HR=2.071,95%CI:1.304~3.291,P=0.002;HR=5.634,95%CI:2.410~13.169,P<0.001)是EOC预后(复发和生存)的独立危险因素,应用贝伐单抗(HR=0.293,95%CI:0.116~0.738,P=0.010;HR=0.141,95%CI:0.056~0.357,P<0.001)是EOC预后的独立保护因素。结论:EOC患者外周血单个核细胞中GTSE1水平高提示预后不良风险高。
基金supported by the National Natural Science Foundation of China,No.81571046(to KZ)Key Project of Educational Department of Liaoning Province,No.LJKZ0755(to KZ)+2 种基金Project of Department of Science&Technology of Liaoning Province,No.2023JH2/20200116(to KZ)Shenyang Young and Middleaged Innovative Talents Support Program,No.RC210240(to KZ)the 345 Talent Project of Shengjing Hospital of China Medical University(to LH)。
文摘Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.
