Metabolic dysfunction-associated fatty liver disease(MASLD)and alcohol-associated liver disease(ALD)are prevalent chronic liver diseases that can progress to steatohepatitis,fibrosis,cirrhosis,and ultimately liver fai...Metabolic dysfunction-associated fatty liver disease(MASLD)and alcohol-associated liver disease(ALD)are prevalent chronic liver diseases that can progress to steatohepatitis,fibrosis,cirrhosis,and ultimately liver failure.Here,we demonstrated that oral administration of GNVs provided substantial protection against liver injury and fibrosis in MASLD and ALD mouse models.In a Western-style high-fat diet-induced MASLD model and a chronic binge alcohol-induced ALD model,GNVs treatment significantly reduced gut leakiness by restoring intestinal junctional complex proteins and rebalancing the gut microbiome.GNVs attenuated hepatic lipid accumulation,oxidative stress and fibrogenicmarkers.GNV treatment downregulated the fibrosis-associated tissue inhibitor of metalloproteinase-2(TIMP2)pathway in hepatic stellate cells,which is linked to enhanced matrix degradation and reduced fibrogenesis.GNVs prevent MASLD-and ALD-associated gut barrier dysfunction and liver fibrosis through modulation of the gut-liver axis and the TIMP2 pathway.Edible GNVs represent a novel,multifaceted therapeutic strategy for managing chronic liver diseases.展开更多
Infectious wound healing remains a significant medical challenge due to chronic inflammation and bacterial colonization.Effective antimicrobial and anti-inflammatory therapies are essential to facilitate wound recover...Infectious wound healing remains a significant medical challenge due to chronic inflammation and bacterial colonization.Effective antimicrobial and anti-inflammatory therapies are essential to facilitate wound recovery.Herein,we introduce a highly biocompatible,ROS-responsive DNA hydrogel(LGAH),modified with aggregationinduced emission luminogens(AIEgen)and incorporating ginseng-derived exosomes(G-Exos)and nitric oxide(NO)donor-L-arginine(L-Arg)to promote healing of infected wounds.The hydrogel degrades in response to elevated ROS levels,releasing therapeutic agents.Upon laser irradiation,AIEgen generates 1O2,which activates L-Arg to produce NO,leading to a synergistic antimicrobial effect.NO is particularly effective at inhibiting bacterial growth and promoting angiogenesis,supporting wound healing.G-Exos modulate immune responses,reduce inflammation,and promote the transition from the inflammatory to the proliferative phase.They also enhance cell proliferation,migration,and collagen production,which are key to tissue regeneration.In vivo experiments demonstrated that LGAH significantly accelerates S.aureus-infected wound healing by modulating the wound microenvironment and promoting tissue regeneration.Transcriptomic analysis revealed that LGAH down-regulates gene expression in inflammation and immune response signaling pathways while up-regulating genes related to energy metabolism.Biosafety evaluations at cellular and animal levels have demonstrated that LGAH possesses excellent biocompatibility and biodegradability,making it ideal for tissue repair and regener-ation.This multifunctional DNA hydrogel system offers a safe and promising strategy for the clinical treatment of infected wounds.展开更多
Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising canc...Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.展开更多
基金supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (project number RS-2024-00340542)supported in part (to B.J.S.) by the Intramural Fund of National Institute of Alcohol Abuse and Alcoholismsupported by the 2022 research grant from the Korean Society of Ginseng
文摘Metabolic dysfunction-associated fatty liver disease(MASLD)and alcohol-associated liver disease(ALD)are prevalent chronic liver diseases that can progress to steatohepatitis,fibrosis,cirrhosis,and ultimately liver failure.Here,we demonstrated that oral administration of GNVs provided substantial protection against liver injury and fibrosis in MASLD and ALD mouse models.In a Western-style high-fat diet-induced MASLD model and a chronic binge alcohol-induced ALD model,GNVs treatment significantly reduced gut leakiness by restoring intestinal junctional complex proteins and rebalancing the gut microbiome.GNVs attenuated hepatic lipid accumulation,oxidative stress and fibrogenicmarkers.GNV treatment downregulated the fibrosis-associated tissue inhibitor of metalloproteinase-2(TIMP2)pathway in hepatic stellate cells,which is linked to enhanced matrix degradation and reduced fibrogenesis.GNVs prevent MASLD-and ALD-associated gut barrier dysfunction and liver fibrosis through modulation of the gut-liver axis and the TIMP2 pathway.Edible GNVs represent a novel,multifaceted therapeutic strategy for managing chronic liver diseases.
基金supported by the National Key R&D Pro-gram of China(2024YFC231103)National Natural Science Foundation of China(82322042,and 82272248)Natural Science Fund of Guangdong Province for Distinguished Young Scholars(2022B1515020089).
文摘Infectious wound healing remains a significant medical challenge due to chronic inflammation and bacterial colonization.Effective antimicrobial and anti-inflammatory therapies are essential to facilitate wound recovery.Herein,we introduce a highly biocompatible,ROS-responsive DNA hydrogel(LGAH),modified with aggregationinduced emission luminogens(AIEgen)and incorporating ginseng-derived exosomes(G-Exos)and nitric oxide(NO)donor-L-arginine(L-Arg)to promote healing of infected wounds.The hydrogel degrades in response to elevated ROS levels,releasing therapeutic agents.Upon laser irradiation,AIEgen generates 1O2,which activates L-Arg to produce NO,leading to a synergistic antimicrobial effect.NO is particularly effective at inhibiting bacterial growth and promoting angiogenesis,supporting wound healing.G-Exos modulate immune responses,reduce inflammation,and promote the transition from the inflammatory to the proliferative phase.They also enhance cell proliferation,migration,and collagen production,which are key to tissue regeneration.In vivo experiments demonstrated that LGAH significantly accelerates S.aureus-infected wound healing by modulating the wound microenvironment and promoting tissue regeneration.Transcriptomic analysis revealed that LGAH down-regulates gene expression in inflammation and immune response signaling pathways while up-regulating genes related to energy metabolism.Biosafety evaluations at cellular and animal levels have demonstrated that LGAH possesses excellent biocompatibility and biodegradability,making it ideal for tissue repair and regener-ation.This multifunctional DNA hydrogel system offers a safe and promising strategy for the clinical treatment of infected wounds.
基金supported by the Liaoning Provincial Department of Education youth project(No.LJKQZ20222355,China).
文摘Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.
