Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first t...Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.展开更多
Gambogenic acid(GNA),a bioactive compound derived from the resin of Garcinia hanburyi,has demonstrated significant antitumor properties.However,its mechanisms of action in oral squamous cell carcinoma(OSCC)remain larg...Gambogenic acid(GNA),a bioactive compound derived from the resin of Garcinia hanburyi,has demonstrated significant antitumor properties.However,its mechanisms of action in oral squamous cell carcinoma(OSCC)remain largely unclear.This study aimed to elucidate the apoptotic effects of GNA on OSCC cell lines CAL-27 and SCC-15.Our results indicated that GNA induced apoptosis by upregulating the pro-apoptotic protein Noxa.Mechanistic investigations revealed that GNA treatment led to the generation of reactive oxygen species(ROS),which activated endoplasmic reticulum(ER)stress,culminating in cell apoptosis.Inhibition of ROS production and ER stress pathways significantly mitigated GNA-induced Noxa upregulation and subsequent apoptosis.Furthermore,in vivo studies using a murine xenograft model demonstrated that GNA administration effectively inhibited the growth of CAL-27 tumors.Collectively,these findings underscore GNA’s potential as a therapeutic agent for the treatment of OSCC.展开更多
基金supported by the National Natural Science Foundation of China Regional Joint Innovation Fund (No.U22A20524)the Heilongjiang Province Natural Science Foundation Key projects (No.ZD2023C002).
文摘Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
基金supported by the Projects of International Cooperation and Exchanges(No.G2022027012L)the Natural Science Foundation of Hubei Provincial Department of Education(No.T2022021)+2 种基金the Advantages Discipline Group(Medicine)Project in Higher Education of Hubei Province(2021-2025)(Nos.2024XKQY26 and 2023BMXKQY2)the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research of Hubei University of Medicine(No.WDCM2023007)the Innovative Research Program for Graduates of Hubei University of Medicine(No.YC2022033,YC2024003).
文摘Gambogenic acid(GNA),a bioactive compound derived from the resin of Garcinia hanburyi,has demonstrated significant antitumor properties.However,its mechanisms of action in oral squamous cell carcinoma(OSCC)remain largely unclear.This study aimed to elucidate the apoptotic effects of GNA on OSCC cell lines CAL-27 and SCC-15.Our results indicated that GNA induced apoptosis by upregulating the pro-apoptotic protein Noxa.Mechanistic investigations revealed that GNA treatment led to the generation of reactive oxygen species(ROS),which activated endoplasmic reticulum(ER)stress,culminating in cell apoptosis.Inhibition of ROS production and ER stress pathways significantly mitigated GNA-induced Noxa upregulation and subsequent apoptosis.Furthermore,in vivo studies using a murine xenograft model demonstrated that GNA administration effectively inhibited the growth of CAL-27 tumors.Collectively,these findings underscore GNA’s potential as a therapeutic agent for the treatment of OSCC.
