Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human or...Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.展开更多
Background:The patterns of leukemia burden have dramatically changed in recent years.This study aimed to estimate the global trends of leukemiarelated death and disability-adjusted life-years(DALYs)from 1990 to 2017.M...Background:The patterns of leukemia burden have dramatically changed in recent years.This study aimed to estimate the global trends of leukemiarelated death and disability-adjusted life-years(DALYs)from 1990 to 2017.Methods:The data was acquired from the latest version of the Global Burden of Disease(GBD)study.Estimated annual percentage changes(EAPCs)were calculated to estimate the trend of age-standardized rate(ASR)of death and DALYs due to leukemia and its main subtypes from 1990 to 2017.Results:Globally,the numbers of death and DALYs due to leukemia were 347.58×10^(3)(95%uncertainty interval[UI]=317.26×10^(3)-364.88×10^(3))and 11975.35×10^(3)(95%UI=10749.15×10^(3)-12793.58×10^(3))in 2017,with a 31.22% and 0.03% increase in absolute numbers from 1990 to 2017,respectively.Both of their ASR showed decreasing trends from 1990 to 2017 with the EAPCs being−1.04(95%confidence interval[CI]=(−1.10-−0.99)and−1.52(95%CI=−1.59-−1.44),respectively.Globally,the most pronounced decreasing trend of death and DALYs occurred in chronic myeloid leukemia with EAPCs of−2.76(95%CI=−2.88-−2.64)and−2.84(95%CI=−2.97-−2.70),respectively,while the trend increased in acute myeloid leukemia.The death and DALYs of leukemia decreased in most areas and countries with high socio-demographic index(SDI)including Bahrain,Finland,and Australia.Conclusions:The disease burden of death and DALYs due to leukemia decreased globally,and for most regions and countries from 1990 to 2017.However,the leukemia burden is still a substantial challenge globally and required adequate and affordable medical resources to improve the survival and quality of life of leukemia patients.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.81874496,82374530)the Clinical Medical Technology Innovation Guide Project of Hunan Province(No.2020SK53206)+3 种基金the Natural Science Foundation of Hunan Province(No.2021JJ70062)the Changsha Natural Science Foundation Project(No.kq2014019)the Health Special Fund Research Project of Hunan Province(No.B2020-07)the Clinical Pharmaceutical Research Fund of Hunan Medical Association(No.B202012).
文摘Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.
文摘Background:The patterns of leukemia burden have dramatically changed in recent years.This study aimed to estimate the global trends of leukemiarelated death and disability-adjusted life-years(DALYs)from 1990 to 2017.Methods:The data was acquired from the latest version of the Global Burden of Disease(GBD)study.Estimated annual percentage changes(EAPCs)were calculated to estimate the trend of age-standardized rate(ASR)of death and DALYs due to leukemia and its main subtypes from 1990 to 2017.Results:Globally,the numbers of death and DALYs due to leukemia were 347.58×10^(3)(95%uncertainty interval[UI]=317.26×10^(3)-364.88×10^(3))and 11975.35×10^(3)(95%UI=10749.15×10^(3)-12793.58×10^(3))in 2017,with a 31.22% and 0.03% increase in absolute numbers from 1990 to 2017,respectively.Both of their ASR showed decreasing trends from 1990 to 2017 with the EAPCs being−1.04(95%confidence interval[CI]=(−1.10-−0.99)and−1.52(95%CI=−1.59-−1.44),respectively.Globally,the most pronounced decreasing trend of death and DALYs occurred in chronic myeloid leukemia with EAPCs of−2.76(95%CI=−2.88-−2.64)and−2.84(95%CI=−2.97-−2.70),respectively,while the trend increased in acute myeloid leukemia.The death and DALYs of leukemia decreased in most areas and countries with high socio-demographic index(SDI)including Bahrain,Finland,and Australia.Conclusions:The disease burden of death and DALYs due to leukemia decreased globally,and for most regions and countries from 1990 to 2017.However,the leukemia burden is still a substantial challenge globally and required adequate and affordable medical resources to improve the survival and quality of life of leukemia patients.