Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2...Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.展开更多
Bud dormancy facilitates the survival of meristems under harsh environmental conditions.To elucidate how molecular responses to chilling accumulation controlling dormancy in peach buds,chromatin immunoprecipitation se...Bud dormancy facilitates the survival of meristems under harsh environmental conditions.To elucidate how molecular responses to chilling accumulation controlling dormancy in peach buds,chromatin immunoprecipitation sequencing to identify the H3K27me3 modifications and RNA sequencing of two peach cultivars with pronounced differences in chilling requirement were carried out,the results showed that genes associated with abscisic acid and gibberellic acid signal pathways play key roles in dormancy regulation.The results demonstrated that peach flower bud differentiation occurred continuously in both cultivars during chilling accumulation,which was correlated with the transcript abundance of key genes involved in phytohormone metabolism and flower bud development under adverse conditions.The more increased strength in high chillingrequirement cultivar along with the chilling accumulation at the genome-wide level.The function of the dormancy-associated MADS-box gene PpDAM6 was identified,which is involved in leaf bud break in peach and flower development in transgenic Nicotiana tabacum(NC89).In addition,PpDAM6 was positively regulated by PpCBF,and the genes of putative dormancy-related and associated with metabolic pathways were proposed.Taken together,these results constituted a theoretical basis for elucidating the regulation of peach bud dormancy transition.展开更多
Flower organ identity in rice is mainly determined by the A-,B-,C-and E-class genes,with the majority encoding MADS-box transcription factors.However,few studies have investigated how the expression of these floral or...Flower organ identity in rice is mainly determined by the A-,B-,C-and E-class genes,with the majority encoding MADS-box transcription factors.However,few studies have investigated how the expression of these floral organ identity genes is regulated during flower development.In this study,we identified a gene named SUPER WOMAN 2(SPW2),which is necessary for spikelet/floret development in rice by participating in the regulation of the expression of pistil identity genes such as OsMADS3,OsMADS13,OsMADS58 and DL.In the spw2 mutant,ectopic stigma/ovary-like tissues were observed in the non-pistil organs,including sterile lemma,lemma,palea,lodicule,and stamen,suggesting that the identities of these organs were severely affected by mutations in SPW2.SPW2 was shown to encode a plant-specific EMF1-like protein that is involved in H3K27me3 modification as an important component of the PRC2 complex.Expression analysis showed that the SPW2 mutation led to the ectopic expression of OsMADS3,OsMADS13,OsMADS58,and DL in non-pistil organs of the spikelet.The ChIP-qPCR results showed significant reductions in the levels of H3K27me3 modification on the chromatin of these genes.Thus,we demonstrated that SPW2 can mediate the process of H3K27me3 modification of pistil-related genes to regulate their expression in non-pistil organs of spikelets in rice.The results of this study expand our understanding of the molecular mechanism by which SPW2 regulates floral organ identity genes through epigenetic regulation.展开更多
Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was...Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.展开更多
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
基金funded by the National Key Research and Development Program of China(2020YFD0900902)Zhejiang Province Public Welfare Technology Application Research Project(LGJ21C20001)Zhejiang Provincial Key Research and Development Project of China(2019C02076 and 2019C02075)。
文摘Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
基金supported by the National Natural Science Foundation of China(Grant No.32001996)Central Publicinterest Scientific Institution Basal Research Fund(Grant No.Y2022QC23)+2 种基金Agricultural Science and Technology Innovation Program(Grant No.CAAS-ASTIP-2021-ZFRI-01)the Crop Germplasm Resources Conservation Project(Grant No.2016NWB041)the Science and Technology Major Project of Yunnan(Gene mining and breeding of peach at highaltitude and low-latitude regions)。
文摘Bud dormancy facilitates the survival of meristems under harsh environmental conditions.To elucidate how molecular responses to chilling accumulation controlling dormancy in peach buds,chromatin immunoprecipitation sequencing to identify the H3K27me3 modifications and RNA sequencing of two peach cultivars with pronounced differences in chilling requirement were carried out,the results showed that genes associated with abscisic acid and gibberellic acid signal pathways play key roles in dormancy regulation.The results demonstrated that peach flower bud differentiation occurred continuously in both cultivars during chilling accumulation,which was correlated with the transcript abundance of key genes involved in phytohormone metabolism and flower bud development under adverse conditions.The more increased strength in high chillingrequirement cultivar along with the chilling accumulation at the genome-wide level.The function of the dormancy-associated MADS-box gene PpDAM6 was identified,which is involved in leaf bud break in peach and flower development in transgenic Nicotiana tabacum(NC89).In addition,PpDAM6 was positively regulated by PpCBF,and the genes of putative dormancy-related and associated with metabolic pathways were proposed.Taken together,these results constituted a theoretical basis for elucidating the regulation of peach bud dormancy transition.
基金supported by the Chongqing Modern Agricultural Industry Technology System,China(CQMAITS202301)the National Natural Science Foundation of China(32100287 and 31971919)+2 种基金the Natural Science Foundation of Chongqing,China(cstc2020jcyj-jq X0020 and cstc2021ycjh-bgzxm0066)the China Postdoctoral Science Foundation Funded Project(2020M683219)the Fundamental Research Funds for the Central Universities,China(SWU-XDJH202315)。
文摘Flower organ identity in rice is mainly determined by the A-,B-,C-and E-class genes,with the majority encoding MADS-box transcription factors.However,few studies have investigated how the expression of these floral organ identity genes is regulated during flower development.In this study,we identified a gene named SUPER WOMAN 2(SPW2),which is necessary for spikelet/floret development in rice by participating in the regulation of the expression of pistil identity genes such as OsMADS3,OsMADS13,OsMADS58 and DL.In the spw2 mutant,ectopic stigma/ovary-like tissues were observed in the non-pistil organs,including sterile lemma,lemma,palea,lodicule,and stamen,suggesting that the identities of these organs were severely affected by mutations in SPW2.SPW2 was shown to encode a plant-specific EMF1-like protein that is involved in H3K27me3 modification as an important component of the PRC2 complex.Expression analysis showed that the SPW2 mutation led to the ectopic expression of OsMADS3,OsMADS13,OsMADS58,and DL in non-pistil organs of the spikelet.The ChIP-qPCR results showed significant reductions in the levels of H3K27me3 modification on the chromatin of these genes.Thus,we demonstrated that SPW2 can mediate the process of H3K27me3 modification of pistil-related genes to regulate their expression in non-pistil organs of spikelets in rice.The results of this study expand our understanding of the molecular mechanism by which SPW2 regulates floral organ identity genes through epigenetic regulation.
基金supported by Medical and Health Research Project of Nanjing Health Science and Technology Development Special Fund(ZKX21040).
文摘Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.
