Chronic,unresolved inflammation correlates with persistent hepatic injury and fibrosis,ultimately progressing to hepatocellular carcinoma(HCC).Bisdemethoxycurcumin(BDMC)demonstrates therapeutic potential against HCC,y...Chronic,unresolved inflammation correlates with persistent hepatic injury and fibrosis,ultimately progressing to hepatocellular carcinoma(HCC).Bisdemethoxycurcumin(BDMC)demonstrates therapeutic potential against HCC,yet its mechanism in preventing hepatic"inflammation-carcinoma transformation"remains incompletely understood.In the current research,clinical HCC specimens underwent analysis using hematoxylin-eosin(H&E)staining and immunohistochemistry(IHC)to evaluate the expression of fibrosis markers,M2 macrophage markers,and CXCL12.In vitro,transforming growth factor-β1(TGF-β1)-induced LX-2 cells and a co-culture system of LX-2,THP-1,and HCC cells were established.Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT),flow cytometry,and Transwell assays.Reverse transcription-quantitative polymerase chain reaction(RT-qPCR),Western blotting and immunofluorescence evaluated the differential expression of molecules.The interaction betweenβ-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation(Co-IP),dual luciferase,and chromatin immunoprecipitation(ChIP)assays.A DEN-induced rat model was developed to investigate BDMC’s role in liver fibrosis-associated HCC(LFAHCC)development in vivo.Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages.BDMC delayed liver fibrosis progression to HCC in vivo.BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells(HSCs).Furthermore,BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis.Mechanistically,BDMC repressed TCF4/β-catenin complex formation,thereby reducing CXCL12 transcription in LX-2 cells.Moreover,CXCL12 overexpression reversed BDMC’s inhibitory effect on macrophage M2 polarization and its mediation of fibrosis,as well as HCC proliferation and metastasis.BDMC significantly suppressed LFAHCC development through CXCL12 in rats.In conclusion,BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressingβ-catenin/TCF4-mediated CXCL12 transcription.展开更多
A kind of core(SBR)-shell(PS)particles was synthesized by using SBR latex and grafting with St under gammairradiation.The influences of absorbed dose and dose rate on the grafting yield of PS on SBR seed latex have be...A kind of core(SBR)-shell(PS)particles was synthesized by using SBR latex and grafting with St under gammairradiation.The influences of absorbed dose and dose rate on the grafting yield of PS on SBR seed latex have beeninvestigated.Results show there was a transition layer which contained the SBR/PS graft copolymer between the SBR coreand PS shell.Dynamic laser scattering(DLS)and differential scanning calorimetry(DSC)results confirm the existence ofgrafted polystyrene,and transmission electron microscope(TEM)observation verifies the core-shell structure of SBR-g-PSlatex.Such SBR/PS core-shell latex could be processed easily to ultrafine rubber powders by using spray drying andexpected to be used as an impact modifier for PS.展开更多
基金supported by the National Natural Science Foundation of China(No.81904182)the Training Program for Excellent Young Innovators of Changsha(No.kq2209020)+1 种基金the Excellent Youth Project of Hunan University of Chinese Medicine(No.2022XJB006)the Excellent Youth Project of Natural Science Foundation of Heilongjiang Province(No.YQ2022H015).
文摘Chronic,unresolved inflammation correlates with persistent hepatic injury and fibrosis,ultimately progressing to hepatocellular carcinoma(HCC).Bisdemethoxycurcumin(BDMC)demonstrates therapeutic potential against HCC,yet its mechanism in preventing hepatic"inflammation-carcinoma transformation"remains incompletely understood.In the current research,clinical HCC specimens underwent analysis using hematoxylin-eosin(H&E)staining and immunohistochemistry(IHC)to evaluate the expression of fibrosis markers,M2 macrophage markers,and CXCL12.In vitro,transforming growth factor-β1(TGF-β1)-induced LX-2 cells and a co-culture system of LX-2,THP-1,and HCC cells were established.Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT),flow cytometry,and Transwell assays.Reverse transcription-quantitative polymerase chain reaction(RT-qPCR),Western blotting and immunofluorescence evaluated the differential expression of molecules.The interaction betweenβ-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation(Co-IP),dual luciferase,and chromatin immunoprecipitation(ChIP)assays.A DEN-induced rat model was developed to investigate BDMC’s role in liver fibrosis-associated HCC(LFAHCC)development in vivo.Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages.BDMC delayed liver fibrosis progression to HCC in vivo.BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells(HSCs).Furthermore,BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis.Mechanistically,BDMC repressed TCF4/β-catenin complex formation,thereby reducing CXCL12 transcription in LX-2 cells.Moreover,CXCL12 overexpression reversed BDMC’s inhibitory effect on macrophage M2 polarization and its mediation of fibrosis,as well as HCC proliferation and metastasis.BDMC significantly suppressed LFAHCC development through CXCL12 in rats.In conclusion,BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressingβ-catenin/TCF4-mediated CXCL12 transcription.
基金This work was supported by the National High Technology ResearchDevelopment Program of China(863 Program)(No.2002AA302510).
文摘A kind of core(SBR)-shell(PS)particles was synthesized by using SBR latex and grafting with St under gammairradiation.The influences of absorbed dose and dose rate on the grafting yield of PS on SBR seed latex have beeninvestigated.Results show there was a transition layer which contained the SBR/PS graft copolymer between the SBR coreand PS shell.Dynamic laser scattering(DLS)and differential scanning calorimetry(DSC)results confirm the existence ofgrafted polystyrene,and transmission electron microscope(TEM)observation verifies the core-shell structure of SBR-g-PSlatex.Such SBR/PS core-shell latex could be processed easily to ultrafine rubber powders by using spray drying andexpected to be used as an impact modifier for PS.
