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
OBJECTIVE Galangin,apotent scavenger of free radicals,is used as herbal medicine for various ailments for centuries in Asia.With complex pathophysiology,ischemic stroke is one of the most frequent causes of death and ...OBJECTIVE Galangin,apotent scavenger of free radicals,is used as herbal medicine for various ailments for centuries in Asia.With complex pathophysiology,ischemic stroke is one of the most frequent causes of death and disability worldwide.We have reported that galangin provides a direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids for ischemic stroke;however,its mechanism on changes of amino acids in the ischemic brain tissue has not yet been clarified.METHODS In this paper,we explored the amino acid biomarkers of brain tissue in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers with a rapid,sensitive and accurate methodology of simultaneous quantification of 12 AAs in rat brain tissue by the RRLC/QQQ.RESULTS we identified that glutamic acid,alanine and aspartic acid all showed significant change in galangin-treated groups compared to vehicle-treated rats and four pathway-related enzymes were identified by multiplex interactions with the three amino acids.With metabolite-protein network analysis and molecule docking,six of 28 proteins were identified and may become the potential biomarkers of galangin for acute ischemic stroke.CONCLUSION All data in our study provide thought for exploring the mechanism of disease,discovering new targets for drug candidates and elucidating the related regulatory signal network.展开更多
OBJECTIVE To have a systematic pathomechanism view of three chest impediment.syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn.drome(QSBS),Cold Obstruction and Qi Stagnation...OBJECTIVE To have a systematic pathomechanism view of three chest impediment.syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn.drome(QSBS),Cold Obstruction and Qi Stagnation syndrome(COQS) and further investigate the changed metabolome and related pathways for screening potential biomarkers in rat plasma.METHODS According to clinical pathogeny,three kinds of syndrome models were established to simulate the disease of chest impediment.Plasma metabonomics based on UPLC-Q-TOF/MS was applied in this research to detected small molecule metabolites for identifyingthe special potential biomarkers of three chest impediment syndromes,respectively.RESULTS Significant metabolic differences were observed between thecontrol group and three syndrome groups.Furthermore,three syndrome groups were distinguished clearly by pattern recognition method.The particular metabolites contributing most to the classification of three chest impediment syndromes were identified.In the QSBS group,the potential biomarkers could include 2-keto-glutaramic acid,L-methionine,L-homocysteic acid,octadecanamide,stearoylglycine,behenic acid,linoleylcarnitine,lysoPC(14:1(9 Z)),indoxyl sulfate and cholic acid.In the COQS group,they could be aminoadipic acid,palmitic amide,oleamide,lysoPC(P-16:0),lysoPC(P-18:0),lysoPC(20:2(11 Z,14 Z)),9-HETE and tauroursodeoxycholic acid.Moreover,4-pyridoxic acid,L-palmi.toylcarnitine,lysoPC(20:0),lysoPC(22:5(4 Z,7 Z,10 Z,13 Z,16 Z)),3-hydroxyhexadecanoic acid and arachidonic acid could be the potential biomarkers for the QDBS group.CONCLUSION Three chest impediment syndromes have their own potential biomarkers.Each special metabolite has its owndifferent metabolic pathway.Both metabolismof cysteine and methionine,and metabolism of alanine,aspartate and glutamate are the main pathways in regulation of metabolic disorders in QSBS syndrome.Lysine biosynthesis and degradation,fatty acid metabolism,and glycerophospholipid metabolism are the main pathways in regulation of metabolic disorders in COQS syndrome.Arachidonic acid metabolism,fatty acid metabolism,fatty acid elongation in mitochondria,and vitamin B6 metabolism are the main pathways in regulation of metabolic disorders in QDBS syndrome.These endogenous substances were indicated as the special potential biomarkers for three chest impediment syndromes and worth studying in depth.展开更多
Background:The Early Detection Research Network (EDRN), NCI funded and investigator driven, has the mission to evaluate biomarkers for their clinical utilities in cancer risk prediction, diagnosis, early detection,
目的本研究旨在探讨涎液化糖链抗原-6(krebs von den lungen-6,KL-6)在特发性肺含铁血黄素沉着症(idiopathic pulmonary hemosiderosis,IPH)患儿辅助诊断中的临床应用价值。方法收集2014年6月至2024年7月期间于广州医科大学附属第一医...目的本研究旨在探讨涎液化糖链抗原-6(krebs von den lungen-6,KL-6)在特发性肺含铁血黄素沉着症(idiopathic pulmonary hemosiderosis,IPH)患儿辅助诊断中的临床应用价值。方法收集2014年6月至2024年7月期间于广州医科大学附属第一医院就诊的140例患儿,分为病例组与对照组,其中病例组根据疾病类型细分为IPH组(32例)、间质性肺炎(interstitial lung disease,ILD)组(22例)、肺炎(pneumonia,PN)组(60例),对照组为非肺部疾病(non-pulmonary disease,NPD)组(26例)。以上患儿检测血清KL-6水平,分析KL-6在各组患儿中的表达差异。结果KL-6阳性率在各组患儿中从高到低分别为IPH(68.75%)、ILD(45.45%)、PN(1.69%)和NPD(0.00%),组间阳性率差异有统计学意义(χ^(2)=66.10,P<0.001)。IPH组患儿血清KL-6平均水平高于PN组患儿(Ζ=-6.92,P<0.001)。诊断试验结果显示ROC曲线下面积为0.940(95%CI:0.89~1.00,P<0.001),截断值为392.00 U/mL,灵敏度为81.30%,特异度为95.00%。结论KL-6在鉴别IPH患儿与PN和NPD患儿中具有较高的诊断价值,可作为IPH辅助诊断的血液生物标志物。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.
基金The project supported by National Natural Science Foundation of China(81303261,81274133)the Major Scientific and Technological Special Project for″Significant New Drugs Creation″(2012ZX09103-201-055)the Fundamental Research Funds for the Central public welfare research institutes of China(ZZ2014005,ZZ2014060)
文摘OBJECTIVE Galangin,apotent scavenger of free radicals,is used as herbal medicine for various ailments for centuries in Asia.With complex pathophysiology,ischemic stroke is one of the most frequent causes of death and disability worldwide.We have reported that galangin provides a direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids for ischemic stroke;however,its mechanism on changes of amino acids in the ischemic brain tissue has not yet been clarified.METHODS In this paper,we explored the amino acid biomarkers of brain tissue in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers with a rapid,sensitive and accurate methodology of simultaneous quantification of 12 AAs in rat brain tissue by the RRLC/QQQ.RESULTS we identified that glutamic acid,alanine and aspartic acid all showed significant change in galangin-treated groups compared to vehicle-treated rats and four pathway-related enzymes were identified by multiplex interactions with the three amino acids.With metabolite-protein network analysis and molecule docking,six of 28 proteins were identified and may become the potential biomarkers of galangin for acute ischemic stroke.CONCLUSION All data in our study provide thought for exploring the mechanism of disease,discovering new targets for drug candidates and elucidating the related regulatory signal network.
基金supported by National Natural Science Foundation of China(8147357981273654+2 种基金81102879) Beijing Natural Science Foundation(7173267) National Science and Technology Major Projects for ＂Major New Drugs Innovation and Development＂(2013ZX09103002-022)
文摘OBJECTIVE To have a systematic pathomechanism view of three chest impediment.syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn.drome(QSBS),Cold Obstruction and Qi Stagnation syndrome(COQS) and further investigate the changed metabolome and related pathways for screening potential biomarkers in rat plasma.METHODS According to clinical pathogeny,three kinds of syndrome models were established to simulate the disease of chest impediment.Plasma metabonomics based on UPLC-Q-TOF/MS was applied in this research to detected small molecule metabolites for identifyingthe special potential biomarkers of three chest impediment syndromes,respectively.RESULTS Significant metabolic differences were observed between thecontrol group and three syndrome groups.Furthermore,three syndrome groups were distinguished clearly by pattern recognition method.The particular metabolites contributing most to the classification of three chest impediment syndromes were identified.In the QSBS group,the potential biomarkers could include 2-keto-glutaramic acid,L-methionine,L-homocysteic acid,octadecanamide,stearoylglycine,behenic acid,linoleylcarnitine,lysoPC(14:1(9 Z)),indoxyl sulfate and cholic acid.In the COQS group,they could be aminoadipic acid,palmitic amide,oleamide,lysoPC(P-16:0),lysoPC(P-18:0),lysoPC(20:2(11 Z,14 Z)),9-HETE and tauroursodeoxycholic acid.Moreover,4-pyridoxic acid,L-palmi.toylcarnitine,lysoPC(20:0),lysoPC(22:5(4 Z,7 Z,10 Z,13 Z,16 Z)),3-hydroxyhexadecanoic acid and arachidonic acid could be the potential biomarkers for the QDBS group.CONCLUSION Three chest impediment syndromes have their own potential biomarkers.Each special metabolite has its owndifferent metabolic pathway.Both metabolismof cysteine and methionine,and metabolism of alanine,aspartate and glutamate are the main pathways in regulation of metabolic disorders in QSBS syndrome.Lysine biosynthesis and degradation,fatty acid metabolism,and glycerophospholipid metabolism are the main pathways in regulation of metabolic disorders in COQS syndrome.Arachidonic acid metabolism,fatty acid metabolism,fatty acid elongation in mitochondria,and vitamin B6 metabolism are the main pathways in regulation of metabolic disorders in QDBS syndrome.These endogenous substances were indicated as the special potential biomarkers for three chest impediment syndromes and worth studying in depth.
文摘Background:The Early Detection Research Network (EDRN), NCI funded and investigator driven, has the mission to evaluate biomarkers for their clinical utilities in cancer risk prediction, diagnosis, early detection,
文摘目的本研究旨在探讨涎液化糖链抗原-6(krebs von den lungen-6,KL-6)在特发性肺含铁血黄素沉着症(idiopathic pulmonary hemosiderosis,IPH)患儿辅助诊断中的临床应用价值。方法收集2014年6月至2024年7月期间于广州医科大学附属第一医院就诊的140例患儿,分为病例组与对照组,其中病例组根据疾病类型细分为IPH组(32例)、间质性肺炎(interstitial lung disease,ILD)组(22例)、肺炎(pneumonia,PN)组(60例),对照组为非肺部疾病(non-pulmonary disease,NPD)组(26例)。以上患儿检测血清KL-6水平,分析KL-6在各组患儿中的表达差异。结果KL-6阳性率在各组患儿中从高到低分别为IPH(68.75%)、ILD(45.45%)、PN(1.69%)和NPD(0.00%),组间阳性率差异有统计学意义(χ^(2)=66.10,P<0.001)。IPH组患儿血清KL-6平均水平高于PN组患儿(Ζ=-6.92,P<0.001)。诊断试验结果显示ROC曲线下面积为0.940(95%CI:0.89~1.00,P<0.001),截断值为392.00 U/mL,灵敏度为81.30%,特异度为95.00%。结论KL-6在鉴别IPH患儿与PN和NPD患儿中具有较高的诊断价值,可作为IPH辅助诊断的血液生物标志物。
