The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our socie...The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our society.Among a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of PD.However,the method for detecting mitochondrial abnormalities-associated early PD has not been fully developed.We herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress.The probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design guidelines.Our research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative charge.After intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high sensitivity.Taken together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.展开更多
Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized child...Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95(5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1(8.6%), 30 HAdV-3(37.0%), two HAdV-6(2.5%), and 42 HAdV-7(51.9%). More HAdV-positive samples were collected in August(4.7%, 12/255), September(15.0%, 41/274) and October(6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases(4.2%, 77/1840;81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.展开更多
Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity....Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity.This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction.Methods:Levels of interleukin(IL)-6,IL-1βand intracellular reactive oxygen species(ROS)were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide(LPS).Subsequently,the m RNA and protein levels of inducible nitric oxide synthase(i NOS),vascular endothelial growth factor(VEGF),cyclooxygenase(COX)-2,tumor necrosis factor(TNF)-a and the phosphorylation expression levels of the MAPK signal pathway were also evaluated.A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway.And then MAPK inhibitors were used to reveal the expression level of i NOS,VEGF,COX-2 and TNF-a in RAW264.7 cells.Results:It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin.Then,the m RNA and protein levels of i NOS,VEGF,COX-2 and TNF-a were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well.In silico analysis,taxifolin could form a relatively stable combination with MAPK signal pathway.MAPK inhibitors showed increasing or decreasing effect in the m RNA levels of i NOS,VEGF,COX-2 and TNF-a,which suggesting that taxifolin down-regulated i NOS,VEGF,COX-2 and TNF-a expressions were not entirely through the MAPK pathway.Conclusion:This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:82241058,31922045,31771031Natural Science Foundation of Tianjin Province of China,Grant/Award Number:21JCZDJC00290+2 种基金State Key Laboratory of Medicinal Chemical Biology in Nankai University,Grant/Award Number:2020017State Key Laboratory of Biochemical EngineeringOpen Funding Project of State Key Laboratory of Biochemical Engineering,Grant/Award Number:2021KF-01。
文摘The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our society.Among a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of PD.However,the method for detecting mitochondrial abnormalities-associated early PD has not been fully developed.We herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress.The probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design guidelines.Our research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative charge.After intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high sensitivity.Taken together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.
基金supported by grants from Beijing Municipal Commission of Health and Family (No. 2060399 PXM2017_026268_00005_ 00254486)The Pediatric Medical Coordinated Development Center of the Beijing Hospitals Authority (No. XTZD20180505)。
文摘Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95(5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1(8.6%), 30 HAdV-3(37.0%), two HAdV-6(2.5%), and 42 HAdV-7(51.9%). More HAdV-positive samples were collected in August(4.7%, 12/255), September(15.0%, 41/274) and October(6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases(4.2%, 77/1840;81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.
基金supported by Open and Selective Project of National Major New Drug Development Science and Technology Major Project in Tianjin,China(No.2017ZX09031062)National Major New Drug Innovation Project of China(No.2017ZX09101001)+4 种基金National Key Research and Development Project in Tianjin,China(No.2019YFA09005600)Open Research fund of State Key Laboratory of Drug Delivery Technology and Pharmacokinetics in TianjinChina(No.010161003)CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-020)Tianjin Key Training Project for‘Project+Team’(No.XC202030)。
文摘Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity.This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction.Methods:Levels of interleukin(IL)-6,IL-1βand intracellular reactive oxygen species(ROS)were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide(LPS).Subsequently,the m RNA and protein levels of inducible nitric oxide synthase(i NOS),vascular endothelial growth factor(VEGF),cyclooxygenase(COX)-2,tumor necrosis factor(TNF)-a and the phosphorylation expression levels of the MAPK signal pathway were also evaluated.A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway.And then MAPK inhibitors were used to reveal the expression level of i NOS,VEGF,COX-2 and TNF-a in RAW264.7 cells.Results:It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin.Then,the m RNA and protein levels of i NOS,VEGF,COX-2 and TNF-a were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well.In silico analysis,taxifolin could form a relatively stable combination with MAPK signal pathway.MAPK inhibitors showed increasing or decreasing effect in the m RNA levels of i NOS,VEGF,COX-2 and TNF-a,which suggesting that taxifolin down-regulated i NOS,VEGF,COX-2 and TNF-a expressions were not entirely through the MAPK pathway.Conclusion:This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.