We investigated the anti-angiogenic effects of the water extract of HangAmDan (WEHAD),which is a crude extract of nine Korean medicinal substances of animal and plant origin.In human umbilical vein endothelial cells,W...We investigated the anti-angiogenic effects of the water extract of HangAmDan (WEHAD),which is a crude extract of nine Korean medicinal substances of animal and plant origin.In human umbilical vein endothelial cells,WEHAD significantly inhibited bFGF-induced proliferation,adhesion,migration,and capillary tube formation.We used an antibody array to perform an analysis of signaling proteins,which showed up-regulated expression of various proteins including RAD51,RAD52,and p73,and down-regulated expression of pFAK.Blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD was markedly reduced in length compared with a PBS-treated control group.These results suggest that inhibition of angiogenesis by WEHAD may be the mechanism of action for the anti-cancer effects of HAD.展开更多
Background The clinical presentations of frontotemporal dementia(FTD)are diverse and overlap with other neurological disorders.There are,as of today,no biomarkers in clinical practice for diagnosing the disorders.Here...Background The clinical presentations of frontotemporal dementia(FTD)are diverse and overlap with other neurological disorders.There are,as of today,no biomarkers in clinical practice for diagnosing the disorders.Here,we aimed to find protein markers in cerebrospinal fluid(CSF)from patients with FTD,presymptomatic mutation carriers and non-carriers.Methods Antibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD(bvFTD,n=16)and progressive primary aphasia(PPA,n=13),as well as presymptomatic mutation carriers(PMC,n=16)and non-carriers(NC,n=8).A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples.The findings were further examined in an independent cohort including 13 FTD patients,79 patients with Alzheimer’s disease and 18 healthy controls.Results We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals(PMC and NC)for 26 proteins.The analysis show patterns of separation between unaffected individuals and FTD patients,especially for those with a clinical diagnosis of bvFTD.The most statistically significant differences in protein levels were found for VGF,TN-R,NPTXR,TMEM132D,PDYN and NF-M.Patients with FTD were found to have higher levels of TN-R and NF-M,and lower levels of VGF,NPTXR,TMEM132D and PDYN,compared to unaffected individuals.The main findings were reproduced in the independent cohort.Conclusion In this pilot study,we show a separation of FTD patients from unaffected individuals based on protein levels in CSF.Further investigation is required to explore the CSF profiles in larger cohorts,but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.展开更多
文摘We investigated the anti-angiogenic effects of the water extract of HangAmDan (WEHAD),which is a crude extract of nine Korean medicinal substances of animal and plant origin.In human umbilical vein endothelial cells,WEHAD significantly inhibited bFGF-induced proliferation,adhesion,migration,and capillary tube formation.We used an antibody array to perform an analysis of signaling proteins,which showed up-regulated expression of various proteins including RAD51,RAD52,and p73,and down-regulated expression of pFAK.Blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD was markedly reduced in length compared with a PBS-treated control group.These results suggest that inhibition of angiogenesis by WEHAD may be the mechanism of action for the anti-cancer effects of HAD.
基金This study was supported by grants from the Swedish FTD initiative funded by the Schörling Family Foundation and the KTH Center for Applied Precision Medicine(KCAP)funded by the Erling-Persson Family Foundation.CG,LO and AU were further supported by grants from JPND Prefrontals Swedish Research Council(VR)529-2014-7504,Swedish Research Council(VR)2015-02926,Swedish Research Council(VR)2018-02754,Swedish Brain Foundation,Swedish Alzheimer Foundation,Stockholm County Council ALF,Karolinska Institutet Doctoral Funding and StratNeuro,Swedish Demensfonden.The authors acknowledge support from the National Genomics Infrastructure in Stockholm/Uppsala funded by Science for Life Laboratory,the Knut and Alice Wallenberg Foundation and the Swedish Research Council,and SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure.Open access funding provided by Royal Institute of Technology.
文摘Background The clinical presentations of frontotemporal dementia(FTD)are diverse and overlap with other neurological disorders.There are,as of today,no biomarkers in clinical practice for diagnosing the disorders.Here,we aimed to find protein markers in cerebrospinal fluid(CSF)from patients with FTD,presymptomatic mutation carriers and non-carriers.Methods Antibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD(bvFTD,n=16)and progressive primary aphasia(PPA,n=13),as well as presymptomatic mutation carriers(PMC,n=16)and non-carriers(NC,n=8).A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples.The findings were further examined in an independent cohort including 13 FTD patients,79 patients with Alzheimer’s disease and 18 healthy controls.Results We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals(PMC and NC)for 26 proteins.The analysis show patterns of separation between unaffected individuals and FTD patients,especially for those with a clinical diagnosis of bvFTD.The most statistically significant differences in protein levels were found for VGF,TN-R,NPTXR,TMEM132D,PDYN and NF-M.Patients with FTD were found to have higher levels of TN-R and NF-M,and lower levels of VGF,NPTXR,TMEM132D and PDYN,compared to unaffected individuals.The main findings were reproduced in the independent cohort.Conclusion In this pilot study,we show a separation of FTD patients from unaffected individuals based on protein levels in CSF.Further investigation is required to explore the CSF profiles in larger cohorts,but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.