Objective:The frequent consumption of deep-fried foods has been linked to high risk of certain non-communicable diseases.As a consequence,the safety of deep-fried oil(DFO)ingested with fried foods has been called into...Objective:The frequent consumption of deep-fried foods has been linked to high risk of certain non-communicable diseases.As a consequence,the safety of deep-fried oil(DFO)ingested with fried foods has been called into question.This study therefore evaluated the effects of DFO from palm kernel on serum 4-hydroxynonenal protein adduct formation,De Ritis ratio(DRR),liver histology and atherogenicity in Wistar rats and the role of vitamin C intervention.Methods:Deep-fried oil samples were characterized for total antioxidant capacity(TAC),degradation and metal contamination levels and compared against counterpart unused frying oil(UFO).In the animal experiment,both oil samples,sourced from commercial cooks,were orally administered,for 13 weeks,to sixty-two rats randomly divided into six test groups of two exposure levels alongside vitamin C control.After exposure,serum liver enzyme activities and lipoproteins levels were determined using colorimetric methods,while protein adducts levels were determined using enzyme-linked immunosorbent assay(ELISA).Histopathological examinations of liver tissues were also performed.Results:DFO had significantly lower(P=0.021)TAC,significantly higher(P=0.024)volatile acid and Pb concentrations compared to UFO.Exposure to DFO significantly increased(P<0.01)serum protein adduct formation,the De Ritis ratio and caused cytoplasmic vacuolation and pigment deposit on liver tissues compared to the control.Additionally,DFO exposures had an initial negative body weight gain rate that increased at the end of the study.Conclusion:However,co-administration of vitamin C significantly reduced(P<0.05)the De Ritis ratio and reduced the serum protein adducts levels by at least 15%.Concomitant intake of vitamin C and DFO can mitigate probable adverse effects.展开更多
The lipid oxidation product, the toxic 4-hydroxynonenal, was measured for fried chicken in commercial samples from two fast food restaurants and one commercial establishment. The fried chicken samples were breasts, th...The lipid oxidation product, the toxic 4-hydroxynonenal, was measured for fried chicken in commercial samples from two fast food restaurants and one commercial establishment. The fried chicken samples were breasts, thighs, chicken nuggets and popcorn chicken. Fried chicken samples were separated to breast skin and meat, and thigh skin and meat. Chicken nuggets and popcorn chicken were not separated from the coating materials and the meat was analyzed together. Samples were analyzed for total fat, fatty acid distribution, reactivity with thiobarbituric acid (TBAR), measuring the secondary lipid peroxidation products such as aldehydes, ketones and related carbonyl compounds. Samples were analyzed for HNE, a toxic aldehyde using high performance liquid chromatography (HPLC). Fatty acid distribution showed in breast and thigh meats, a higher level of palmitic acid, compared to the breast and thigh skins. TBAR values were significantly higher in all breast meats compared to skins. TBAR values were significantly higher in thigh meat than in skin samples. HNE concentrations (μg HNE/g fat) were significantly very low in breast skins compared to breast meat. HNE concentration was generally higher in thigh meat than skin but not in every sample. In chicken nuggets, both the TBAR value and HNE concentration were much higher from one establishment than from the two others. Chicken nuggets TBAR and HNE concentrations resembled one of the chicken nugget samples. The average toxic HNE concentration for 100 g fried chicken breast (skins + meat) was 12.55 μg and for thighs (skin + meat) was 26.76 μg. The average total HNE concentration was 2.1 times higher in the fried chicken thighs than in the breasts. It is clear that HNE is produced during the heating process of oils and incorporated into the fried meat and skin samples during the frying process. If HNE, a toxic aldehyde, is consumed with the food, over long periods of time it could be related to a number of pathological conditions.展开更多
High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symme...High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symmetric observation error model that differentiates between land and sea for FY-4A/AGRI all-sky assimilation,developed an all-sky assimilation scheme for FY-4A/AGRI based on hydrometeor control variables,and investigated the impacts of all-sky FY-4A/AGRI water vapor channels at different altitudes and rapid-update assimilation at different frequencies on the assimilation and forecasting of a severe convective weather event.Results show that simultaneous assimilation of two water vapor channels can enhance precipitation forecasts compared to single-channel assimilation,which is mainly attributable to a more accurate analysis of water vapor and hydrometeor information.Experiments with different assimilation frequencies demonstrate that the hourly assimilation frequency,compared to other frequencies,incorporates the high-frequency information from AGRI while reducing the impact of spurious oscillations caused by excessively high-frequency assimilation.This hourly assimilation frequency reduces the incoordination among thermal,dynamical,and water vapor conditions caused by excessively fast or slow assimilation frequencies,thus improving the forecast accuracy compared to other frequencies.展开更多
The rapid growth of distributed data-centric applications and AI workloads increases demand for low-latency,high-throughput communication,necessitating frequent and flexible updates to network routing configurations.H...The rapid growth of distributed data-centric applications and AI workloads increases demand for low-latency,high-throughput communication,necessitating frequent and flexible updates to network routing configurations.However,maintaining consistent forwarding states during these updates is challenging,particularly when rerouting multiple flows simultaneously.Existing approaches pay little attention to multi-flow update,where improper update sequences across data plane nodes may construct deadlock dependencies.Moreover,these methods typically involve excessive control-data plane interactions,incurring significant resource overhead and performance degradation.This paper presents P4LoF,an efficient loop-free update approach that enables the controller to reroute multiple flows through minimal interactions.P4LoF first utilizes a greedy-based algorithm to generate the shortest update dependency chain for the single-flow update.These chains are then dynamically merged into a dependency graph and resolved as a Shortest Common Super-sequence(SCS)problem to produce the update sequence of multi-flow update.To address deadlock dependencies in multi-flow updates,P4LoF builds a deadlock-fix forwarding model that leverages the flexible packet processing capabilities of the programmable data plane.Experimental results show that P4LoF reduces control-data plane interactions by at least 32.6%with modest overhead,while effectively guaranteeing loop-free consistency.展开更多
Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a ...Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
文摘Objective:The frequent consumption of deep-fried foods has been linked to high risk of certain non-communicable diseases.As a consequence,the safety of deep-fried oil(DFO)ingested with fried foods has been called into question.This study therefore evaluated the effects of DFO from palm kernel on serum 4-hydroxynonenal protein adduct formation,De Ritis ratio(DRR),liver histology and atherogenicity in Wistar rats and the role of vitamin C intervention.Methods:Deep-fried oil samples were characterized for total antioxidant capacity(TAC),degradation and metal contamination levels and compared against counterpart unused frying oil(UFO).In the animal experiment,both oil samples,sourced from commercial cooks,were orally administered,for 13 weeks,to sixty-two rats randomly divided into six test groups of two exposure levels alongside vitamin C control.After exposure,serum liver enzyme activities and lipoproteins levels were determined using colorimetric methods,while protein adducts levels were determined using enzyme-linked immunosorbent assay(ELISA).Histopathological examinations of liver tissues were also performed.Results:DFO had significantly lower(P=0.021)TAC,significantly higher(P=0.024)volatile acid and Pb concentrations compared to UFO.Exposure to DFO significantly increased(P<0.01)serum protein adduct formation,the De Ritis ratio and caused cytoplasmic vacuolation and pigment deposit on liver tissues compared to the control.Additionally,DFO exposures had an initial negative body weight gain rate that increased at the end of the study.Conclusion:However,co-administration of vitamin C significantly reduced(P<0.05)the De Ritis ratio and reduced the serum protein adducts levels by at least 15%.Concomitant intake of vitamin C and DFO can mitigate probable adverse effects.
文摘The lipid oxidation product, the toxic 4-hydroxynonenal, was measured for fried chicken in commercial samples from two fast food restaurants and one commercial establishment. The fried chicken samples were breasts, thighs, chicken nuggets and popcorn chicken. Fried chicken samples were separated to breast skin and meat, and thigh skin and meat. Chicken nuggets and popcorn chicken were not separated from the coating materials and the meat was analyzed together. Samples were analyzed for total fat, fatty acid distribution, reactivity with thiobarbituric acid (TBAR), measuring the secondary lipid peroxidation products such as aldehydes, ketones and related carbonyl compounds. Samples were analyzed for HNE, a toxic aldehyde using high performance liquid chromatography (HPLC). Fatty acid distribution showed in breast and thigh meats, a higher level of palmitic acid, compared to the breast and thigh skins. TBAR values were significantly higher in all breast meats compared to skins. TBAR values were significantly higher in thigh meat than in skin samples. HNE concentrations (μg HNE/g fat) were significantly very low in breast skins compared to breast meat. HNE concentration was generally higher in thigh meat than skin but not in every sample. In chicken nuggets, both the TBAR value and HNE concentration were much higher from one establishment than from the two others. Chicken nuggets TBAR and HNE concentrations resembled one of the chicken nugget samples. The average toxic HNE concentration for 100 g fried chicken breast (skins + meat) was 12.55 μg and for thighs (skin + meat) was 26.76 μg. The average total HNE concentration was 2.1 times higher in the fried chicken thighs than in the breasts. It is clear that HNE is produced during the heating process of oils and incorporated into the fried meat and skin samples during the frying process. If HNE, a toxic aldehyde, is consumed with the food, over long periods of time it could be related to a number of pathological conditions.
基金supported by the National Key R&D Program of China(Grant No.2022YFC3080500)the National Natural Science Foundation of China(Grant Nos.U2142208,42475158,and 42105149)the High-Performance Computing Center of Nanjing University of Information Science&Technology for supporting this work。
文摘High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symmetric observation error model that differentiates between land and sea for FY-4A/AGRI all-sky assimilation,developed an all-sky assimilation scheme for FY-4A/AGRI based on hydrometeor control variables,and investigated the impacts of all-sky FY-4A/AGRI water vapor channels at different altitudes and rapid-update assimilation at different frequencies on the assimilation and forecasting of a severe convective weather event.Results show that simultaneous assimilation of two water vapor channels can enhance precipitation forecasts compared to single-channel assimilation,which is mainly attributable to a more accurate analysis of water vapor and hydrometeor information.Experiments with different assimilation frequencies demonstrate that the hourly assimilation frequency,compared to other frequencies,incorporates the high-frequency information from AGRI while reducing the impact of spurious oscillations caused by excessively high-frequency assimilation.This hourly assimilation frequency reduces the incoordination among thermal,dynamical,and water vapor conditions caused by excessively fast or slow assimilation frequencies,thus improving the forecast accuracy compared to other frequencies.
基金supported by the National Key Research and Development Program of China under Grant 2022YFB2901501in part by the Science and Technology Innovation leading Talents Subsidy Project of Central Plains under Grant 244200510038.
文摘The rapid growth of distributed data-centric applications and AI workloads increases demand for low-latency,high-throughput communication,necessitating frequent and flexible updates to network routing configurations.However,maintaining consistent forwarding states during these updates is challenging,particularly when rerouting multiple flows simultaneously.Existing approaches pay little attention to multi-flow update,where improper update sequences across data plane nodes may construct deadlock dependencies.Moreover,these methods typically involve excessive control-data plane interactions,incurring significant resource overhead and performance degradation.This paper presents P4LoF,an efficient loop-free update approach that enables the controller to reroute multiple flows through minimal interactions.P4LoF first utilizes a greedy-based algorithm to generate the shortest update dependency chain for the single-flow update.These chains are then dynamically merged into a dependency graph and resolved as a Shortest Common Super-sequence(SCS)problem to produce the update sequence of multi-flow update.To address deadlock dependencies in multi-flow updates,P4LoF builds a deadlock-fix forwarding model that leverages the flexible packet processing capabilities of the programmable data plane.Experimental results show that P4LoF reduces control-data plane interactions by at least 32.6%with modest overhead,while effectively guaranteeing loop-free consistency.
基金supported by the Chinese Medicine"Dual Chain Integration"Young and Middle-aged Scientific Research and Innovation Teams(No.2022-SLRH-YQ-006)the Key R&D Programme Projects of Xianyang Municipality(No.L2023-ZDYF-SF-014)+1 种基金the Shaanxi University of Traditional Chinese Medicine Science,Education and Research Collaborative Educational Achievement Transformation Project(No.2024KC03)the open research topic from the Key Laboratory of Neurological Diseases in Traditional Chinese Medicine,Shaanxi Province(No.KF202315).
文摘Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
