Occupatio nal n oise is among the most comm on risks associated with the wellbeing of employees. Occupational exposure to noise causes disabling hearing loss in 16% of adults worldwide.It has bee n ack no wledged that...Occupatio nal n oise is among the most comm on risks associated with the wellbeing of employees. Occupational exposure to noise causes disabling hearing loss in 16% of adults worldwide.It has bee n ack no wledged that no ise-induced heari ng loss (NIHL) is a multifactorial disease, having both genetic and environ mental factors. NIHL continues to be permanent as well as irreversible, but NIHL can be preve nted. As dem on strated by the latest research, excessive oxidative stress in the cochlea has a close link with the pathogenesis of NIHL. which highlights the fact that appropriate control of oxidative stress is a productive strategy for preve nting the in crease in prevale nee and progression of NIHL.展开更多
NFE2-like basic leucine zipper transcription factor 2(NFE2L2,also known as NRF2),is a key transcription factor in the cellular defense against oxidative stress,playing a crucial role in cancer cell survival and resist...NFE2-like basic leucine zipper transcription factor 2(NFE2L2,also known as NRF2),is a key transcription factor in the cellular defense against oxidative stress,playing a crucial role in cancer cell survival and resistance to therapies.This review outlines the current knowledge on the link between NFE2L2 and ferroptosis-a form of regulated cell death characterized by iron-dependent lipid peroxidation-within cancer cells.While NFE2L2 activation can protect normal cells from oxidative damage,its overexpression in cancer cells contributes to drug resistance by upregulating antioxidant defenses and inhibiting ferroptosis.We delve into the molecular pathways of ferroptosis,highlighting the involvement of NFE2L2 and its target genes,such as NQO1,HMOX1,FTH1,FTL,HERC2,SLC40A1,ABCB6,FECH,PIR,MT1G,SLC7A11,GCL,GSS,GSR,GPX4,AIFM2,MGST1,ALDH1A1,ALDH3A1,and G6PD,in ferroptosis resistance.Understanding the delicate balance between NFE2L2’s protective and deleterious roles could pave the way for novel therapeutic strategies targeting NFE2L2 to enhance the efficacy of ferroptosis inducers in cancer therapy.展开更多
Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and trans...Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.展开更多
Objective:To evaluate the antidiabetic effects of manool in streptozotocin-induced diabetic rats and HepG2 cells.Methods:Diabetes was induced in Wistar rats using streptozotocin and nicotinamide,and animals were treat...Objective:To evaluate the antidiabetic effects of manool in streptozotocin-induced diabetic rats and HepG2 cells.Methods:Diabetes was induced in Wistar rats using streptozotocin and nicotinamide,and animals were treated with two doses of manool(1 and 2 mg/kg).Biochemical,oxidative stress,apoptotic,and inflammatory parameters were assessed,followed by histopathology of the pancreas.Expression of key marker genes in the liver and pancreas was analyzed via qRT-PCR.Catalase and superoxide dismutase activities,malondialdehyde level,and glucose consumption were examined in vitro.Results:Manool significantly reduced fasting glucose level,improved insulin levels,and restored glucokinase and Ki67 expression in rats with diabetes.It also enhanced antioxidant defense,upregulated insulin signaling,activated the mTOR pathway,and promoted β-cell regeneration via increased expression of Pdx1,MAFA,Ngn3,and Ins1 in a dose-dependent manner.However,manool suppressed JAK/STAT pathway only at a higher dose of 2 mg/kg.Histopathological study showed near-normal islet architecture in manool-treated diabetic rats.Conclusions:Manool exerts antidiabetic effects by modulating oxidative stress,inflammation,β-cell regeneration,and insulin sensitivity in diabetic rats.However,further pharmacological and clinical investigations are required before confirming its therapeutic applicability.展开更多
基金supported by Outstanding Medical Academic Leaders program of Jiangsu Province [LJ201130]Jiangsu Provincial Youth Medical Talent program [QNRC2016536]+2 种基金Six Talent Peaks Project in Jiangsu Province [WSW-017]Preventive Medicine Foundation of Jiangsu [Y2015049]The Fundamental Research Funds for the Central Universities [3225009404]
文摘Occupatio nal n oise is among the most comm on risks associated with the wellbeing of employees. Occupational exposure to noise causes disabling hearing loss in 16% of adults worldwide.It has bee n ack no wledged that no ise-induced heari ng loss (NIHL) is a multifactorial disease, having both genetic and environ mental factors. NIHL continues to be permanent as well as irreversible, but NIHL can be preve nted. As dem on strated by the latest research, excessive oxidative stress in the cochlea has a close link with the pathogenesis of NIHL. which highlights the fact that appropriate control of oxidative stress is a productive strategy for preve nting the in crease in prevale nee and progression of NIHL.
基金supported by grants from the National Institutes of Health of USA(R01CA160417,R01CA229275,and R01CA211070).
文摘NFE2-like basic leucine zipper transcription factor 2(NFE2L2,also known as NRF2),is a key transcription factor in the cellular defense against oxidative stress,playing a crucial role in cancer cell survival and resistance to therapies.This review outlines the current knowledge on the link between NFE2L2 and ferroptosis-a form of regulated cell death characterized by iron-dependent lipid peroxidation-within cancer cells.While NFE2L2 activation can protect normal cells from oxidative damage,its overexpression in cancer cells contributes to drug resistance by upregulating antioxidant defenses and inhibiting ferroptosis.We delve into the molecular pathways of ferroptosis,highlighting the involvement of NFE2L2 and its target genes,such as NQO1,HMOX1,FTH1,FTL,HERC2,SLC40A1,ABCB6,FECH,PIR,MT1G,SLC7A11,GCL,GSS,GSR,GPX4,AIFM2,MGST1,ALDH1A1,ALDH3A1,and G6PD,in ferroptosis resistance.Understanding the delicate balance between NFE2L2’s protective and deleterious roles could pave the way for novel therapeutic strategies targeting NFE2L2 to enhance the efficacy of ferroptosis inducers in cancer therapy.
文摘Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.
文摘Objective:To evaluate the antidiabetic effects of manool in streptozotocin-induced diabetic rats and HepG2 cells.Methods:Diabetes was induced in Wistar rats using streptozotocin and nicotinamide,and animals were treated with two doses of manool(1 and 2 mg/kg).Biochemical,oxidative stress,apoptotic,and inflammatory parameters were assessed,followed by histopathology of the pancreas.Expression of key marker genes in the liver and pancreas was analyzed via qRT-PCR.Catalase and superoxide dismutase activities,malondialdehyde level,and glucose consumption were examined in vitro.Results:Manool significantly reduced fasting glucose level,improved insulin levels,and restored glucokinase and Ki67 expression in rats with diabetes.It also enhanced antioxidant defense,upregulated insulin signaling,activated the mTOR pathway,and promoted β-cell regeneration via increased expression of Pdx1,MAFA,Ngn3,and Ins1 in a dose-dependent manner.However,manool suppressed JAK/STAT pathway only at a higher dose of 2 mg/kg.Histopathological study showed near-normal islet architecture in manool-treated diabetic rats.Conclusions:Manool exerts antidiabetic effects by modulating oxidative stress,inflammation,β-cell regeneration,and insulin sensitivity in diabetic rats.However,further pharmacological and clinical investigations are required before confirming its therapeutic applicability.
