Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active comp...Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.展开更多
Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as...Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.展开更多
基金supported by the study on the material basis and mechanism of action of American ginseng in the treatment of myocardial ischaemia comorbid depression(2024JH2/102500059).
文摘Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.
基金supported by grants from the National Natural Science Foundation of China(82204428,U24A20815,82304526,82204427,82201001,82430108,82293681(82293680),82273941)the National High-level Personnelof Special Support Program(to Dongmei Zhang and Minfeng Chen)+5 种基金the Natural Science Foundation of Guangdong Province(2023A1515010361 and 2022A1515011813)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020098)the Science and Technology Program of Guangzhou(SL2024A04J00410,SL2024A04J00374,SL2024A04J00280)the Fundamental Research Funds for The Central Universities(21624103)the Science and Technology Projects in Guangzhou(2023A03J1030,202201010173,202102070001)the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(JNU1AF-CFTP-2022-a01210).
文摘Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.
