Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are tradition...Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.展开更多
Current mix design practices typically assume total blending and use the white curve of reclaimed asphalt pavement(RAP)to determine the gradation and optimum asphalt content(OAC)of recycled hot mix asphalt(HMA),often ...Current mix design practices typically assume total blending and use the white curve of reclaimed asphalt pavement(RAP)to determine the gradation and optimum asphalt content(OAC)of recycled hot mix asphalt(HMA),often overlooking the effects of RAP agglomeration and partial blending.This oversight can result in unsatisfactory performance,particularly when higher RAP content is used.Therefore,this paper reviews and discusses strategies for adjusting the mix design of recycled HMA to enhance its in-service performance.The discussion begins with RAP particle agglomeration,a significant phenomenon that significantly impacts the aggregate gradation of recycled HMA.Subsequently,detection methods to clarify the blending between virgin and RAP binders are described.Partial blending between RAP and virgin binders is common,and various indexes have been proposed to quantify the blending degree.Finally,the adjusted mix design method of recycled HMA is presented,emphasizing gradation optimization and corrected OAC.Gradation optimization should account for RAP agglomeration,while the corrected OAC should consider particle blending.Recycled HMA using the adjusted mix design exhibits improved crack resistance and fatigue life without substantially impairing rutting performance.This review aims to help both academics and highway agencies maximize the utilization of RAP materials within sustainable pavement frameworks.展开更多
基金supported by the Key Scientific Research Project of Hubei Provincial Department of Education (No.D20232001)。
文摘Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.
基金sponsored by the National Natural Science Foundation of China(52178420,52408476)Special subsidy from Heilongjiang Provincial People's Government(HITTY-20190028)+1 种基金Postdoctoral Fellowship Program of CPSF(GZC20242207)the Fundamental Research Funds for the Central Universities(HIT.DZJJ.2023086).
文摘Current mix design practices typically assume total blending and use the white curve of reclaimed asphalt pavement(RAP)to determine the gradation and optimum asphalt content(OAC)of recycled hot mix asphalt(HMA),often overlooking the effects of RAP agglomeration and partial blending.This oversight can result in unsatisfactory performance,particularly when higher RAP content is used.Therefore,this paper reviews and discusses strategies for adjusting the mix design of recycled HMA to enhance its in-service performance.The discussion begins with RAP particle agglomeration,a significant phenomenon that significantly impacts the aggregate gradation of recycled HMA.Subsequently,detection methods to clarify the blending between virgin and RAP binders are described.Partial blending between RAP and virgin binders is common,and various indexes have been proposed to quantify the blending degree.Finally,the adjusted mix design method of recycled HMA is presented,emphasizing gradation optimization and corrected OAC.Gradation optimization should account for RAP agglomeration,while the corrected OAC should consider particle blending.Recycled HMA using the adjusted mix design exhibits improved crack resistance and fatigue life without substantially impairing rutting performance.This review aims to help both academics and highway agencies maximize the utilization of RAP materials within sustainable pavement frameworks.
