Arsenic-related oxidative stress and resultant diseases have attracted global concern,while longitudinal studies are scarce.To assess the relationship between arsenic exposure and systemic oxidative damage,we performe...Arsenic-related oxidative stress and resultant diseases have attracted global concern,while longitudinal studies are scarce.To assess the relationship between arsenic exposure and systemic oxidative damage,we performed two repeatedmeasures among 5236 observations(4067 participants)in theWuhan-Zhuhai cohort at the baseline and follow-up after 3 years.Urinary total arsenic,biomarkers of DNA oxidative damage(8-hydroxy-2-deoxyguanosine(8-OHdG)),lipid peroxidation(8-isoprostaglandin F2alpha(8-isoPGF2α)),and protein oxidative damage(protein carbonyls(PCO))were detected for all observations.Here we used linearmixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage.Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions.After adjusting for potential confounders,arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners.In cross-sectional analyses,each 1%increase in arsenic levelwas associated with a 0.406%(95%confidence interval(CI):0.379%to 0.433%),0.360%(0.301%to 0.420%),and 0.079%(0.055%to 0.103%)increase in 8-isoPGF2α,8-OHdG,and PCO,respectively.More importantly,arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α(β:0.147;95%CI:0.130 to 0.164),8-OHdG(0.155;0.118 to 0.192),and PCO(0.050;0.035 to 0.064)in the longitudinal analyses.Our study suggested that arsenic exposurewas not only positively related with global oxidative damage to lipid,DNA,and protein in cross-sectional analyses,but also associated with annual increased rates of these biomarkers in dose-dependent manners.展开更多
The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
Fatty acids are the main constituents of vegetable oils.To determine the fatty acid compositions of small trade vegetable oils and some less well studied beneficial vegetable oils,and investigate their relationships w...Fatty acids are the main constituents of vegetable oils.To determine the fatty acid compositions of small trade vegetable oils and some less well studied beneficial vegetable oils,and investigate their relationships with antioxidant activity and oxidative stability,gas chromatography-mass spectrometry was performed to characterize the associated fatty acid profiles.The antioxidant activity of vegetable oils,based on their DPPH-scavenging capacity(expressed as IC_(50) values),was used to assess their impact on human health,and their oxidative stability was characterized by performing lipid oxidation analysis to determine the oxidative induction time of fats and oils.In addition,correlation analyses were performed to examine associations between the fatty acid composition of the oils and DPPH-scavenging capacity and oxidative stability.The results revealed that among the assessed oils,coffee seed oil has the highest saturated fatty acid content(355.10 mg/g),whereas Garddenia jaminoides oil has the highest unsaturated fatty acid content(844.84 mg/g).Coffee seed oil was also found have the lowest DPPH IC_(50) value(2.30 mg/mL)and the longest oxidation induction time(17.09 h).Correlation analysis revealed a significant linear relationship(P<0.05)between oxidative stability and unsaturated fatty acid content,with lower contents tending to be associated with better oxidative stability.The findings of this study provide reference data for the screening of functional edible vegetable oils.展开更多
The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced m...The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.展开更多
Objective:To investigate the protective effects of naringin on doxorubicin(DOX)-induced liver injury.Methods:A total of 50 male rats were allocated into five groups:the control group,the DOX group,the DOX groups treat...Objective:To investigate the protective effects of naringin on doxorubicin(DOX)-induced liver injury.Methods:A total of 50 male rats were allocated into five groups:the control group,the DOX group,the DOX groups treated with 50 mg/kg and 100 mg/kg of naringin by gastric lavage for 10 days,as well as the group treated with 100 mg/kg of naringin alone.Liver and serum samples were collected for biochemical,histopathological,and molecular analyses,including liver enzyme activity,oxidative stress markers,inflammation,apoptosis-related proteins,and DNA damage indicators.Results:Naringin attenuated DOX-induced elevation in liver enzyme activity and inflammation markers while enhancing antioxidant activities.Naringin also activated the Nrf2-HO-1 signaling pathway,with the most pronounced effect in the high-dose naringin group.In addition,naringin modulated apoptotic signaling by downregulating the expression of PI3K-AKT and BAX,and upregulating Bcl-2,as well as reduced the level of 8-OHdG.Histopathological evaluation showed that DOX-induced structural liver alterations,such as cellular degeneration and necrosis,were notably attenuated by naringin treatment.Conclusions:Naringin treatment exerts protective effects against DOX-induced liver injury through its antioxidative,anti-inflammatory,and anti-apoptotic effects.展开更多
The toxicity of PM_(2.5)does not necessarily change synchronously with its mass concentration.In this study,the chemical composition(carbonaceous species,water-soluble ions,and metals)and oxidative potential(dithiothr...The toxicity of PM_(2.5)does not necessarily change synchronously with its mass concentration.In this study,the chemical composition(carbonaceous species,water-soluble ions,and metals)and oxidative potential(dithiothreitol assay,DTT)of PM_(2.5)were investigated in 2017/2018 and 2022 in Xiamen,China.The decrease rate of volume-normalized DTT(DTTv)(38%)was lower than that of PM_(2.5)(55%)between the two sampling periods.However,the mass-normalized DTT(DTTm)increased by 44%.Clear seasonal patterns with higher levels in winter were found for PM_(2.5),most chemical constituents and DTTv but not for DTTm.The large decrease in DTT activity(84%−92%)after the addition of EDTA suggested that watersoluble metals were the main contributors to DTT in Xiamen.The increased gap between the reconstructed and measured DTTv and the stronger correlations between the reconstructed/measured DTT ratio and carbonaceous species in 2022were observed.The decrease rates of the hazard index(32.5%)and lifetime cancer risk(9.1%)differed from those of PM_(2.5)and DTTv due to their different main contributors.The PMF-MLR model showed that the contributions(nmol/(min·m^(3)))of vehicle emission,coal+biomass burning,ship emission and secondary aerosol to DTTv in 2022 decreased by 63.0%,65.2%,66.5%,and 22.2%,respectively,compared to those in 2017/2018,which was consistent with the emission reduction of vehicle exhaust and coal consumption,the adoption of low-sulfur fuel oil used on board ships and the reduced production of WSOC.However,the contributions of dust+sea salt and industrial emission increased.展开更多
Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototox...Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.展开更多
Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals an...Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.展开更多
Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most seve...Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.展开更多
Objective:To investigate the protective effects of Lepidium draba L.(L.draba)on cyclophosphamide(CP)-induced hepatotoxicity and nephrotoxicity in rats.Methods:A total of 36 rats were divided into six groups as follows...Objective:To investigate the protective effects of Lepidium draba L.(L.draba)on cyclophosphamide(CP)-induced hepatotoxicity and nephrotoxicity in rats.Methods:A total of 36 rats were divided into six groups as follows:the sham control group,the CP group(CP 100 mg/kg i.p.on days 1,7,14,21,28,and 35),the CP groups treated with L.draba extract(100,200 and 400 mg/kg of L.draba extract for 28 d),and the L.draba extract alone group(400 mg/kg of L.draba extract for 28 d).Serum parameters of renal and hepatic function,as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured.Moreover,Bax,Bcl-2,and caspase-3 gene expression and histopathological changes were assessed.Results:L.draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide,TBARS,IL-6,TNF-α,and IL-1βlevels,as well as increasing superoxide dismutase,catalase and glutathione peroxidase activities,and FRAP,MIF,and TGF-βlevels.In addition,the extract downregulated the expression of pro-apoptotic genes(Bax and caspase-3)and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes.Conclusions:L.draba extract can protect hepatic and renal structure and function against CP-induced toxicities,and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.展开更多
BACKGROUND Cyclophosphamide(CP)is a potent chemotherapeutic and immunosuppressant agent,but its hepatotoxicity remains a significant concern.Ambroxol(ABX)is a mucolytic agent with emerging beneficial effects against o...BACKGROUND Cyclophosphamide(CP)is a potent chemotherapeutic and immunosuppressant agent,but its hepatotoxicity remains a significant concern.Ambroxol(ABX)is a mucolytic agent with emerging beneficial effects against oxidative stress and inflammation.AIM To investigate the hepatoprotective effects of ABX against CP-induced liver injury,focusing on oxidative stress,inflammation,and the possible role of cytoglobin,thioredoxin reductase 1(TXNRD1)and high-mobility group box 1(HMGB1).METHODS ABX(20 mg/kg)was orally administered for 7 days,and the rats received a single injection of CP(100 mg/kg)on day 5.Blood and liver samples were collected for analyses,and the affinity of ABX towards cytoglobin,TXNRD1,and HMGB1 was evaluated using molecular docking.RESULTS CP administration significantly elevated alanine aminotransferase,aspartate aminotransferase,and alkaline phosphatase,reduced albumin,and caused multiple histopathological alterations in the liver.ABX effectively restored liver function biomarkers and attenuated histopathological alterations.CP-induced oxidative stress was evidenced by increased malondialdehyde and decreased glutathione and antioxidant enzyme activities,all of which were ameliorated by ABX.CP upregulated toll-like receptor 4(TLR-4),nuclear factor-kappaB(NF-κB)p65 and pro-inflammatory cytokines,while downregulating cytoglobin,TXNRD1 and HMGB1.ABX suppressed TLR-4/NF-κB signaling and pro-inflammatory cytokines,and upregulated cytoglobin,TXNRD1 and HMGB1.In silico molecular docking revealed the affinity of ABX to bind with cytoglobin,TXNRD1,and HMGB1.CONCLUSION ABX protects against CP hepatotoxicity by mitigating oxidative stress,suppressing TLR-4/NF-κB signaling,and upregulating cytoglobin,TXNRD1 and HMGB1.ABX showed binding affinity towards cytoglobin,TXNRD1 and HMGB1.These findings suggest that ABX has therapeutic potential in alleviating hepatotoxicity associated with CP treatment.展开更多
Objective:To investigate the effect of cerebrolysin(CBL)on motor impairment,neuroinflammation,oxidative stress,and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s di...Objective:To investigate the effect of cerebrolysin(CBL)on motor impairment,neuroinflammation,oxidative stress,and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease(PD)in zebrafish.Methods:In the current study,zebrafish were treated with CBL at doses of 1.25,2.5,and 5 mL/kg body weight for 7 consecutive days.MPTP(20 mg/kg body weight)was administered on alternative days-1st,3rd,5th,and 7th.On day 7,zebrafish were sacrificed,and their brains were isolated for biochemical,neurochemical,histopathological,IHC,and neurotransmitter analysis.Results:The treatment with CBL significantly increased total distance traveled and the number of entries in the top zone,which was impaired by MPTP.CBL treatment significantly restored the level of glutathione,superoxide dismutase,and catalase while reducing malondialdehyde level.It also reduced the level of pro-inflammatory mediators interleukin-1β,interleukin-6,and tumor necrosis factor-αin the MPTP-induced PD in the zebrafish model.In histopathological evaluation,pyknotic cells and signs of inflammation were significantly reduced in CBL-treated groups.A significant dose-dependent reduction in glutamate,along with elevations in dopamine,gamma-aminobutyric acid,serotonin,and noradrenaline,was observed in zebrafish treated with CBL.An immunohistochemistry analysis demonstrated that Akt was phosphorylated promptly by CBL,which was downregulated in MPTP-induced PD in zebrafish.Conclusions:These findings suggest that CBL exerts a neuroprotective effect through activation of Akt and may hold therapeutic potential for the treatment of this devastating neurological condition.展开更多
Oxidative stress is considered as a critical factor in the process of pathological diseases,and mitochondria are considered as vital target organelles for disease intervention.The purpose of this study was aimed to ev...Oxidative stress is considered as a critical factor in the process of pathological diseases,and mitochondria are considered as vital target organelles for disease intervention.The purpose of this study was aimed to evaluate the antioxidant efficacy of mitochondria-targeted astaxanthin nanoparticle on hydrogen peroxideinduced oxidative damage.As expected,mitochondria-targeted nanoparticle showed excellent mitochondria co-localization ability with higher Pearson's correlation coefficient(r=0.88).In vitro experiments suggested that the mitochondria-targeted astaxanthin nanoparticle could promote cell viability and increase antioxidantrelated enzyme activities.Simultaneously,metabolomics analysis indicated that mitochondria-targeted astaxanthin nanoparticle could alleviate oxidative stress by regulating amino acid metabolism and energy metabolism.Altogether,all these results strongly confirmed the mitochondria-targeted strategy for astaxanthin delivery could relieve oxidative stress and had great promise in the application of disease intervention.展开更多
Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,po...Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,poses a significant risk of mortality in infants,children,and adolescents.However,the impact of maternal EC exposure on PH development in offspring remains unclear.To address this,we established a PH rat model with maternal EC exposure.Methods Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems.Offspring were administered monocrotaline(MCT)at 6 weeks of age(6-wo)to induce PH.Mechanistic experiments were conducted at 10-week-old(10-wo).Protein expression of NADPH oxidases,DNA methyltransferases,and autophagy-related markers was analyzed by Western blot.Morphological changes and the severity of PH were evaluated via hematoxylin and eosin(HE)staining and echocardiography,respectively.Furthermore,the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA,Western blot,HE staining,and echocardiography.Additionally,ATG5 mRNA expression was measured by qRT-PCR.Results Compared with control conditions,maternal EC exposure significantly worsened MCT-induced PH in male offspring.This was associated with increased oxidative stress,DNA hypomethylation,and anomalous autophagy in the offspring.In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC.Furthermore,N-acetylcysteine(NAC),an antioxidant,attenuated maternal EC exposure-induced oxidative stress,DNA hypomethylation,and excessive autophagy,thereby improving PH.DNA hypermethylation also reversed PH development,accompanied by reduced oxidative stress and suppressed autophagy.ATG5,a key regulator of autophagy,was identified as a potential therapeutic target,as its repression mitigated PH in maternal EC-exposed offspring.Conclusion Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring,leading to anomalous autophagy and exacerbation of PH development.Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.Graphical Abstract Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery,with all offspring undergoing PH induction at 6-wo.Offspring exposed to maternal EC presented increased oxidative stress,which in turn affected DNA methylation patterns.The decreased DNA methylation in male offspring led to the activation of autophagy,exacerbating the development of PH.Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.展开更多
Objective:Limb ischemia-reperfusion injury(LIRI)may lead to tissue necrosis and loss of function,even life-threatening.Our previous study found that Tao-Hong-Si-Wu decoction(THSWD)had some efficacy in treating of LIRI...Objective:Limb ischemia-reperfusion injury(LIRI)may lead to tissue necrosis and loss of function,even life-threatening.Our previous study found that Tao-Hong-Si-Wu decoction(THSWD)had some efficacy in treating of LIRI.Quercetin,the major component of THSWD,was selected further to uncover the molecular mechanism underlying its treatment of LIRI.Methods:In this study,myoblasts were isolated fromrat gastrocnemiusmuscle tissue,and an in vitro LIRI model was established.The cell counting kit-8(CCK-8)and colony formation assay were used to evaluate the impact of quercetin on LIRI-induced myoblast viability and proliferation.Lactate dehydrogenase(LDH)activity wasmeasured to detectmyoblast injury in the LIRI model.Theapoptosis ofmyoblasts was evaluated byHoechst staining and flow cytometry.In addition,molecular docking analysis was performed to predict the interaction between quercetin and NADPH oxidase 2(NOX-2).Subsequently,we investigated the molecular mechanism of quercetin in LIRI-induced myoblasts by overexpressing NOX-2.Results:The myogenic marker Desmin was highly expressed in isolatedmyoblasts.In the LIRImodel,myoblast viability and proliferation were decreased,and cell injury and apoptosis levels were increased.In addition,NOX-2 was highly expressed in the LIRI model.At the same time,LIRI induction promoted the up-regulation of oxidative stress and inflammatory response.Quercetin significantly reversed the effects of LIRI treatment on myoblasts in a concentration-dependent manner.Molecular docking suggested an interaction between quercetin and NOX-2.Further overexpression of NOX-2 inhibited the effect of quercetin on LIRI-induced myoblasts.Conclusion:Quercetin could reduce inflammatory response and oxidative stress by inhibiting NOX-2,thus playing a therapeutic role in treating LIRI.展开更多
The direct difunctionalization of alkenes serves as one of the most straightforward strategies toward complex nitrogen-containing compounds.The existing approach is extensively promoted by using C/Xcentered radicals a...The direct difunctionalization of alkenes serves as one of the most straightforward strategies toward complex nitrogen-containing compounds.The existing approach is extensively promoted by using C/Xcentered radicals and N-nucleophiles to conduct 1,2-difunctional amination/azolization of alkenes.In contrast,2,1-difunctional amination/azolization of alkenes by using nitrogen-centered radicals(NCRs) and nucleophiles still remains rarely underexplored.It is possibly due to the highly active electron properties of NCRs and the relatively poor nucleophilicity of aromatic NCRs to be trapped by arylalkenes.Herein,we demonstrate an unprecedented 2,1-hydroxazolization reactions of arylalkenes through electrochemically enabled addition of NCRs from azoles and nucleophiles(NuH) in high yields and with high regioselectivity.This conversion is characterized by the fact that neither metal catalysts nor external chemical oxidants are required.This electrochemical oxidation synthesis method can also be applied for a broad range of NuH including pyridine hydrofluoride,ammonia,water,alcohols,and acids which enables the formation of C-N and C-X(X=F/N/O) bonds in one-pot fashion to furnish efficient fluoroamination,diamination and oxoamination of alkenes.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Background:Cisplatin(CDDP)is a cornerstone chemotherapeutic agent for many solid tumors,but its clinical use is severely limited by dose-dependent nephrotoxicity,which results in acute kidney injury(AKI)in a significa...Background:Cisplatin(CDDP)is a cornerstone chemotherapeutic agent for many solid tumors,but its clinical use is severely limited by dose-dependent nephrotoxicity,which results in acute kidney injury(AKI)in a significant proportion of patients.CDDP-induced AKI involves interconnected mechanisms,including inflammation,oxidative stress,and tubular cell death.In this study,we aimed to investigate the renoprotective effects of esculetin(ES),a natural antioxidant coumarin,in a murine model of CDDP-induced AKI.Methods:Male C57BL/6 mice(8–10 weeks)received a single intraperitoneal injection of CDDP(20 mg/kg)with or without ES(40 mg/kg/day,oral gavage).Renal function,histopathology,and molecular markers of inflammation,oxidative stress,mitogen-activated protein kinase(MAPK)activation,endoplasmic reticulum(ER)stress,apoptosis,and ferroptosis were assessed by standard biochemical,histological,and immunoblotting techniques.Results:ES significantly reduced CDDP-induced elevations in serum creatinine and blood urea nitrogen,preserved renal structure,and decreased histological injury scores.Molecular analyses showed that ES suppressed the production of systemic and renal proinflammatory cytokines and inhibited the expression of chemokines and adhesion molecules.ES also suppressed the phosphorylation of extracellular signal-regulated kinase 1/2 and p38 MAPKs,mitigating stress-induced inflammatory and apoptotic signaling.Additionally,ES treatment reduced the expression of unfolded protein response markers,such as C/EBP homologous protein,which is indicative of alleviated ER stress.Oxidative injury was reduced,as evidenced by lower malondialdehyde and 4-hydroxynonenal levels and restored glutathione content.Importantly,ES mitigated ferroptosis,as demonstrated by decreased expression of pro-ferroptotic markers and preservation of anti-ferroptotic mediators,including glutathione peroxidase 4 and solute carrier family 7member 1.Conclusion:Collectively,our findings provide the first in vivo evidence that ES robustly protects against CDDP-induced AKI by simultaneously targeting oxidative stress,inflammation,MAPK,and ER stress pathways,apoptosis,and ferroptosis.These results highlight ES as a potential candidate for preventing CDDP-induced nephrotoxicity.展开更多
Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects.Our previous study demonstrated tha...Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects.Our previous study demonstrated that Lateolabrax japonicus peptides(LPH),rich in Glu,Gly,and hydrophobic amino acids,exhibited remarkable antioxidant activity in vitro,with though its action mechanism yet to be revealed.Therefore,to assess the in vivo antioxidative properties of LPH,we employed H_(2)O_(2) to generate oxidative stress in Drosophila melanogaster model.Results indicated that LPH significantly prolonged the lifespan of Drosophila subjected to oxidative stress mostly mediated via LPH’s enhancement of the antioxidant defense system and intestinal functions.Antioxidant effects were manifested by a decrease in malondialdehyde(MDA)levels,elevated superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)activities,decreased levels of reactive oxygen species(ROS)in intestinal epithelial cells,and the preservation of intestinal length.LPH effectively controlled the excessive proliferation and differentiation of oxidative stress-induced Drosophila intestinal stem cells.At the gene level,LPH upregulated the expression of antioxidant-related Nrf2 genes while concurrently downregulated mTOR expression level.Furthermore,high-throughput 16S rDNA sequencing revealed that the addition of LPH significantly influenced the diversity and abundance of the intestinal microbiota in H_(2)O_(2)-induced Drosophila.These findings provide a deeper understanding of the antioxidative mechanism of LPH,suggesting its potential applications in food industry and to be assessed using other in vivo oxidative stress models.展开更多
Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investiga...Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm(gestational age ≤ 32 weeks) and their term-born(gestational age ≥ 38 weeks)counterparts.Methods: Resting venous blood was obtained in normoxia(prior to altitude exposure), immediately upon arrival to altitude, and the following 3mornings. Antioxidant(superoxide dismutase(SOD), catalase, glutathione peroxidase(GPx), and ferric reducing antioxidant power(FRAP)),pro-oxidant(xanthine oxidase(XO) and myeloperoxidase(MPO)) enzyme activity, oxidative stress markers(advanced oxidation protein product(AOPP) and malondialdehyde(MDA)), nitric oxide(NO) metabolites(nitrites, nitrates, and total nitrite and nitrate(NOx)), and nitrotyrosine were measured in plasma.Results: SOD increased only in the preterm group(p < 0.05). Catalase increased at arrival in preterm group(p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely(arrival and Day 1) in control group. MPO increased in both groups throughout the3 days(p < 0.05). AOPP only increased at arrival in the preterm(p < 0.05) whereas it decreased at arrival up to Day 3(p < 0.05) for control.MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups(p < 0.05). Nitrites increased on Day 3(p < 0.05)in control group and decreased on Day 1(p < 0.05) in preterm group.Conclusion: These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals.These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82241088 and 82203996)the China Postdoctoral Science Foundation(Nos.2022T150230 and 2021M691131).
文摘Arsenic-related oxidative stress and resultant diseases have attracted global concern,while longitudinal studies are scarce.To assess the relationship between arsenic exposure and systemic oxidative damage,we performed two repeatedmeasures among 5236 observations(4067 participants)in theWuhan-Zhuhai cohort at the baseline and follow-up after 3 years.Urinary total arsenic,biomarkers of DNA oxidative damage(8-hydroxy-2-deoxyguanosine(8-OHdG)),lipid peroxidation(8-isoprostaglandin F2alpha(8-isoPGF2α)),and protein oxidative damage(protein carbonyls(PCO))were detected for all observations.Here we used linearmixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage.Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions.After adjusting for potential confounders,arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners.In cross-sectional analyses,each 1%increase in arsenic levelwas associated with a 0.406%(95%confidence interval(CI):0.379%to 0.433%),0.360%(0.301%to 0.420%),and 0.079%(0.055%to 0.103%)increase in 8-isoPGF2α,8-OHdG,and PCO,respectively.More importantly,arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α(β:0.147;95%CI:0.130 to 0.164),8-OHdG(0.155;0.118 to 0.192),and PCO(0.050;0.035 to 0.064)in the longitudinal analyses.Our study suggested that arsenic exposurewas not only positively related with global oxidative damage to lipid,DNA,and protein in cross-sectional analyses,but also associated with annual increased rates of these biomarkers in dose-dependent manners.
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
文摘Fatty acids are the main constituents of vegetable oils.To determine the fatty acid compositions of small trade vegetable oils and some less well studied beneficial vegetable oils,and investigate their relationships with antioxidant activity and oxidative stability,gas chromatography-mass spectrometry was performed to characterize the associated fatty acid profiles.The antioxidant activity of vegetable oils,based on their DPPH-scavenging capacity(expressed as IC_(50) values),was used to assess their impact on human health,and their oxidative stability was characterized by performing lipid oxidation analysis to determine the oxidative induction time of fats and oils.In addition,correlation analyses were performed to examine associations between the fatty acid composition of the oils and DPPH-scavenging capacity and oxidative stability.The results revealed that among the assessed oils,coffee seed oil has the highest saturated fatty acid content(355.10 mg/g),whereas Garddenia jaminoides oil has the highest unsaturated fatty acid content(844.84 mg/g).Coffee seed oil was also found have the lowest DPPH IC_(50) value(2.30 mg/mL)and the longest oxidation induction time(17.09 h).Correlation analysis revealed a significant linear relationship(P<0.05)between oxidative stability and unsaturated fatty acid content,with lower contents tending to be associated with better oxidative stability.The findings of this study provide reference data for the screening of functional edible vegetable oils.
基金Jiangxi Provincial Department of Education Science and Technology Project(Grant No.GJJ2401615)Jiangxi Provincial Department of Education Teaching Reform Project(Grant No.JXJG-24-15-15).
文摘The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.
基金supported by the Atatürk University Scientific Research Projects Coordinator(Project No:2020/8737)。
文摘Objective:To investigate the protective effects of naringin on doxorubicin(DOX)-induced liver injury.Methods:A total of 50 male rats were allocated into five groups:the control group,the DOX group,the DOX groups treated with 50 mg/kg and 100 mg/kg of naringin by gastric lavage for 10 days,as well as the group treated with 100 mg/kg of naringin alone.Liver and serum samples were collected for biochemical,histopathological,and molecular analyses,including liver enzyme activity,oxidative stress markers,inflammation,apoptosis-related proteins,and DNA damage indicators.Results:Naringin attenuated DOX-induced elevation in liver enzyme activity and inflammation markers while enhancing antioxidant activities.Naringin also activated the Nrf2-HO-1 signaling pathway,with the most pronounced effect in the high-dose naringin group.In addition,naringin modulated apoptotic signaling by downregulating the expression of PI3K-AKT and BAX,and upregulating Bcl-2,as well as reduced the level of 8-OHdG.Histopathological evaluation showed that DOX-induced structural liver alterations,such as cellular degeneration and necrosis,were notably attenuated by naringin treatment.Conclusions:Naringin treatment exerts protective effects against DOX-induced liver injury through its antioxidative,anti-inflammatory,and anti-apoptotic effects.
基金supported by the Science and Technology Program of Fujian Province,China(No.2023R1014002)the National Natural Science Foundation of China(No.41471390).
文摘The toxicity of PM_(2.5)does not necessarily change synchronously with its mass concentration.In this study,the chemical composition(carbonaceous species,water-soluble ions,and metals)and oxidative potential(dithiothreitol assay,DTT)of PM_(2.5)were investigated in 2017/2018 and 2022 in Xiamen,China.The decrease rate of volume-normalized DTT(DTTv)(38%)was lower than that of PM_(2.5)(55%)between the two sampling periods.However,the mass-normalized DTT(DTTm)increased by 44%.Clear seasonal patterns with higher levels in winter were found for PM_(2.5),most chemical constituents and DTTv but not for DTTm.The large decrease in DTT activity(84%−92%)after the addition of EDTA suggested that watersoluble metals were the main contributors to DTT in Xiamen.The increased gap between the reconstructed and measured DTTv and the stronger correlations between the reconstructed/measured DTT ratio and carbonaceous species in 2022were observed.The decrease rates of the hazard index(32.5%)and lifetime cancer risk(9.1%)differed from those of PM_(2.5)and DTTv due to their different main contributors.The PMF-MLR model showed that the contributions(nmol/(min·m^(3)))of vehicle emission,coal+biomass burning,ship emission and secondary aerosol to DTTv in 2022 decreased by 63.0%,65.2%,66.5%,and 22.2%,respectively,compared to those in 2017/2018,which was consistent with the emission reduction of vehicle exhaust and coal consumption,the adoption of low-sulfur fuel oil used on board ships and the reduced production of WSOC.However,the contributions of dust+sea salt and industrial emission increased.
文摘Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.
基金Supported by American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSand NIH ARRA.
文摘Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.
文摘Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.
基金supported by the Basic Research Joint Special General Project of Yunnan Provincial Local Universities(part)(No:202301BA070001-029,202301BA070001-044)Yunnan Province High-level Scientific and Technological Talents and Innovation Team Selection Special Young and Middle-aged Academic and Technical Leaders Reserve Talent Project(No:202405AC350067).
文摘Objective:To investigate the protective effects of Lepidium draba L.(L.draba)on cyclophosphamide(CP)-induced hepatotoxicity and nephrotoxicity in rats.Methods:A total of 36 rats were divided into six groups as follows:the sham control group,the CP group(CP 100 mg/kg i.p.on days 1,7,14,21,28,and 35),the CP groups treated with L.draba extract(100,200 and 400 mg/kg of L.draba extract for 28 d),and the L.draba extract alone group(400 mg/kg of L.draba extract for 28 d).Serum parameters of renal and hepatic function,as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured.Moreover,Bax,Bcl-2,and caspase-3 gene expression and histopathological changes were assessed.Results:L.draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide,TBARS,IL-6,TNF-α,and IL-1βlevels,as well as increasing superoxide dismutase,catalase and glutathione peroxidase activities,and FRAP,MIF,and TGF-βlevels.In addition,the extract downregulated the expression of pro-apoptotic genes(Bax and caspase-3)and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes.Conclusions:L.draba extract can protect hepatic and renal structure and function against CP-induced toxicities,and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.
基金Supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project Number(PNURSP2025R381),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘BACKGROUND Cyclophosphamide(CP)is a potent chemotherapeutic and immunosuppressant agent,but its hepatotoxicity remains a significant concern.Ambroxol(ABX)is a mucolytic agent with emerging beneficial effects against oxidative stress and inflammation.AIM To investigate the hepatoprotective effects of ABX against CP-induced liver injury,focusing on oxidative stress,inflammation,and the possible role of cytoglobin,thioredoxin reductase 1(TXNRD1)and high-mobility group box 1(HMGB1).METHODS ABX(20 mg/kg)was orally administered for 7 days,and the rats received a single injection of CP(100 mg/kg)on day 5.Blood and liver samples were collected for analyses,and the affinity of ABX towards cytoglobin,TXNRD1,and HMGB1 was evaluated using molecular docking.RESULTS CP administration significantly elevated alanine aminotransferase,aspartate aminotransferase,and alkaline phosphatase,reduced albumin,and caused multiple histopathological alterations in the liver.ABX effectively restored liver function biomarkers and attenuated histopathological alterations.CP-induced oxidative stress was evidenced by increased malondialdehyde and decreased glutathione and antioxidant enzyme activities,all of which were ameliorated by ABX.CP upregulated toll-like receptor 4(TLR-4),nuclear factor-kappaB(NF-κB)p65 and pro-inflammatory cytokines,while downregulating cytoglobin,TXNRD1 and HMGB1.ABX suppressed TLR-4/NF-κB signaling and pro-inflammatory cytokines,and upregulated cytoglobin,TXNRD1 and HMGB1.In silico molecular docking revealed the affinity of ABX to bind with cytoglobin,TXNRD1,and HMGB1.CONCLUSION ABX protects against CP hepatotoxicity by mitigating oxidative stress,suppressing TLR-4/NF-κB signaling,and upregulating cytoglobin,TXNRD1 and HMGB1.ABX showed binding affinity towards cytoglobin,TXNRD1 and HMGB1.These findings suggest that ABX has therapeutic potential in alleviating hepatotoxicity associated with CP treatment.
基金funded by ICMR,New Delhi(Grant No.45/29/2022-PHA/BMS).
文摘Objective:To investigate the effect of cerebrolysin(CBL)on motor impairment,neuroinflammation,oxidative stress,and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease(PD)in zebrafish.Methods:In the current study,zebrafish were treated with CBL at doses of 1.25,2.5,and 5 mL/kg body weight for 7 consecutive days.MPTP(20 mg/kg body weight)was administered on alternative days-1st,3rd,5th,and 7th.On day 7,zebrafish were sacrificed,and their brains were isolated for biochemical,neurochemical,histopathological,IHC,and neurotransmitter analysis.Results:The treatment with CBL significantly increased total distance traveled and the number of entries in the top zone,which was impaired by MPTP.CBL treatment significantly restored the level of glutathione,superoxide dismutase,and catalase while reducing malondialdehyde level.It also reduced the level of pro-inflammatory mediators interleukin-1β,interleukin-6,and tumor necrosis factor-αin the MPTP-induced PD in the zebrafish model.In histopathological evaluation,pyknotic cells and signs of inflammation were significantly reduced in CBL-treated groups.A significant dose-dependent reduction in glutamate,along with elevations in dopamine,gamma-aminobutyric acid,serotonin,and noradrenaline,was observed in zebrafish treated with CBL.An immunohistochemistry analysis demonstrated that Akt was phosphorylated promptly by CBL,which was downregulated in MPTP-induced PD in zebrafish.Conclusions:These findings suggest that CBL exerts a neuroprotective effect through activation of Akt and may hold therapeutic potential for the treatment of this devastating neurological condition.
基金supported by the National Science Fund for Distinguished Young Scholars of China(31925031)Mount Tai Industrial Blue Talent Program of Shandong Province(tsls20231209)。
文摘Oxidative stress is considered as a critical factor in the process of pathological diseases,and mitochondria are considered as vital target organelles for disease intervention.The purpose of this study was aimed to evaluate the antioxidant efficacy of mitochondria-targeted astaxanthin nanoparticle on hydrogen peroxideinduced oxidative damage.As expected,mitochondria-targeted nanoparticle showed excellent mitochondria co-localization ability with higher Pearson's correlation coefficient(r=0.88).In vitro experiments suggested that the mitochondria-targeted astaxanthin nanoparticle could promote cell viability and increase antioxidantrelated enzyme activities.Simultaneously,metabolomics analysis indicated that mitochondria-targeted astaxanthin nanoparticle could alleviate oxidative stress by regulating amino acid metabolism and energy metabolism.Altogether,all these results strongly confirmed the mitochondria-targeted strategy for astaxanthin delivery could relieve oxidative stress and had great promise in the application of disease intervention.
基金supported by National Natural Science Foundation of China(No.82300268)Guangzhou Municipal Science and Technology Project(No.2023B03J1255).
文摘Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,poses a significant risk of mortality in infants,children,and adolescents.However,the impact of maternal EC exposure on PH development in offspring remains unclear.To address this,we established a PH rat model with maternal EC exposure.Methods Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems.Offspring were administered monocrotaline(MCT)at 6 weeks of age(6-wo)to induce PH.Mechanistic experiments were conducted at 10-week-old(10-wo).Protein expression of NADPH oxidases,DNA methyltransferases,and autophagy-related markers was analyzed by Western blot.Morphological changes and the severity of PH were evaluated via hematoxylin and eosin(HE)staining and echocardiography,respectively.Furthermore,the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA,Western blot,HE staining,and echocardiography.Additionally,ATG5 mRNA expression was measured by qRT-PCR.Results Compared with control conditions,maternal EC exposure significantly worsened MCT-induced PH in male offspring.This was associated with increased oxidative stress,DNA hypomethylation,and anomalous autophagy in the offspring.In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC.Furthermore,N-acetylcysteine(NAC),an antioxidant,attenuated maternal EC exposure-induced oxidative stress,DNA hypomethylation,and excessive autophagy,thereby improving PH.DNA hypermethylation also reversed PH development,accompanied by reduced oxidative stress and suppressed autophagy.ATG5,a key regulator of autophagy,was identified as a potential therapeutic target,as its repression mitigated PH in maternal EC-exposed offspring.Conclusion Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring,leading to anomalous autophagy and exacerbation of PH development.Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.Graphical Abstract Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery,with all offspring undergoing PH induction at 6-wo.Offspring exposed to maternal EC presented increased oxidative stress,which in turn affected DNA methylation patterns.The decreased DNA methylation in male offspring led to the activation of autophagy,exacerbating the development of PH.Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.
基金supported by National Natural Science Foundation of China(Grant 82274541&81674008)Key Project of Hunan Provincial Health Commission(Grant 202204072465)Natural Science Foundation of Hunan Province(Grant 2020JJ4070).
文摘Objective:Limb ischemia-reperfusion injury(LIRI)may lead to tissue necrosis and loss of function,even life-threatening.Our previous study found that Tao-Hong-Si-Wu decoction(THSWD)had some efficacy in treating of LIRI.Quercetin,the major component of THSWD,was selected further to uncover the molecular mechanism underlying its treatment of LIRI.Methods:In this study,myoblasts were isolated fromrat gastrocnemiusmuscle tissue,and an in vitro LIRI model was established.The cell counting kit-8(CCK-8)and colony formation assay were used to evaluate the impact of quercetin on LIRI-induced myoblast viability and proliferation.Lactate dehydrogenase(LDH)activity wasmeasured to detectmyoblast injury in the LIRI model.Theapoptosis ofmyoblasts was evaluated byHoechst staining and flow cytometry.In addition,molecular docking analysis was performed to predict the interaction between quercetin and NADPH oxidase 2(NOX-2).Subsequently,we investigated the molecular mechanism of quercetin in LIRI-induced myoblasts by overexpressing NOX-2.Results:The myogenic marker Desmin was highly expressed in isolatedmyoblasts.In the LIRImodel,myoblast viability and proliferation were decreased,and cell injury and apoptosis levels were increased.In addition,NOX-2 was highly expressed in the LIRI model.At the same time,LIRI induction promoted the up-regulation of oxidative stress and inflammatory response.Quercetin significantly reversed the effects of LIRI treatment on myoblasts in a concentration-dependent manner.Molecular docking suggested an interaction between quercetin and NOX-2.Further overexpression of NOX-2 inhibited the effect of quercetin on LIRI-induced myoblasts.Conclusion:Quercetin could reduce inflammatory response and oxidative stress by inhibiting NOX-2,thus playing a therapeutic role in treating LIRI.
基金the National Science Foundation of China(No.22071058)the Fundamental Research Funds for the Central Universities for financial support。
文摘The direct difunctionalization of alkenes serves as one of the most straightforward strategies toward complex nitrogen-containing compounds.The existing approach is extensively promoted by using C/Xcentered radicals and N-nucleophiles to conduct 1,2-difunctional amination/azolization of alkenes.In contrast,2,1-difunctional amination/azolization of alkenes by using nitrogen-centered radicals(NCRs) and nucleophiles still remains rarely underexplored.It is possibly due to the highly active electron properties of NCRs and the relatively poor nucleophilicity of aromatic NCRs to be trapped by arylalkenes.Herein,we demonstrate an unprecedented 2,1-hydroxazolization reactions of arylalkenes through electrochemically enabled addition of NCRs from azoles and nucleophiles(NuH) in high yields and with high regioselectivity.This conversion is characterized by the fact that neither metal catalysts nor external chemical oxidants are required.This electrochemical oxidation synthesis method can also be applied for a broad range of NuH including pyridine hydrofluoride,ammonia,water,alcohols,and acids which enables the formation of C-N and C-X(X=F/N/O) bonds in one-pot fashion to furnish efficient fluoroamination,diamination and oxoamination of alkenes.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金supported by research grants from Daegu Catholic University in 2024(No.20245001).
文摘Background:Cisplatin(CDDP)is a cornerstone chemotherapeutic agent for many solid tumors,but its clinical use is severely limited by dose-dependent nephrotoxicity,which results in acute kidney injury(AKI)in a significant proportion of patients.CDDP-induced AKI involves interconnected mechanisms,including inflammation,oxidative stress,and tubular cell death.In this study,we aimed to investigate the renoprotective effects of esculetin(ES),a natural antioxidant coumarin,in a murine model of CDDP-induced AKI.Methods:Male C57BL/6 mice(8–10 weeks)received a single intraperitoneal injection of CDDP(20 mg/kg)with or without ES(40 mg/kg/day,oral gavage).Renal function,histopathology,and molecular markers of inflammation,oxidative stress,mitogen-activated protein kinase(MAPK)activation,endoplasmic reticulum(ER)stress,apoptosis,and ferroptosis were assessed by standard biochemical,histological,and immunoblotting techniques.Results:ES significantly reduced CDDP-induced elevations in serum creatinine and blood urea nitrogen,preserved renal structure,and decreased histological injury scores.Molecular analyses showed that ES suppressed the production of systemic and renal proinflammatory cytokines and inhibited the expression of chemokines and adhesion molecules.ES also suppressed the phosphorylation of extracellular signal-regulated kinase 1/2 and p38 MAPKs,mitigating stress-induced inflammatory and apoptotic signaling.Additionally,ES treatment reduced the expression of unfolded protein response markers,such as C/EBP homologous protein,which is indicative of alleviated ER stress.Oxidative injury was reduced,as evidenced by lower malondialdehyde and 4-hydroxynonenal levels and restored glutathione content.Importantly,ES mitigated ferroptosis,as demonstrated by decreased expression of pro-ferroptotic markers and preservation of anti-ferroptotic mediators,including glutathione peroxidase 4 and solute carrier family 7member 1.Conclusion:Collectively,our findings provide the first in vivo evidence that ES robustly protects against CDDP-induced AKI by simultaneously targeting oxidative stress,inflammation,MAPK,and ER stress pathways,apoptosis,and ferroptosis.These results highlight ES as a potential candidate for preventing CDDP-induced nephrotoxicity.
基金supported by National Key R&D Program of China(2023YFD2100205)Fuzhou Science&Technology Project,China(2022-Y-0022022-P-023).
文摘Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects.Our previous study demonstrated that Lateolabrax japonicus peptides(LPH),rich in Glu,Gly,and hydrophobic amino acids,exhibited remarkable antioxidant activity in vitro,with though its action mechanism yet to be revealed.Therefore,to assess the in vivo antioxidative properties of LPH,we employed H_(2)O_(2) to generate oxidative stress in Drosophila melanogaster model.Results indicated that LPH significantly prolonged the lifespan of Drosophila subjected to oxidative stress mostly mediated via LPH’s enhancement of the antioxidant defense system and intestinal functions.Antioxidant effects were manifested by a decrease in malondialdehyde(MDA)levels,elevated superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)activities,decreased levels of reactive oxygen species(ROS)in intestinal epithelial cells,and the preservation of intestinal length.LPH effectively controlled the excessive proliferation and differentiation of oxidative stress-induced Drosophila intestinal stem cells.At the gene level,LPH upregulated the expression of antioxidant-related Nrf2 genes while concurrently downregulated mTOR expression level.Furthermore,high-throughput 16S rDNA sequencing revealed that the addition of LPH significantly influenced the diversity and abundance of the intestinal microbiota in H_(2)O_(2)-induced Drosophila.These findings provide a deeper understanding of the antioxidative mechanism of LPH,suggesting its potential applications in food industry and to be assessed using other in vivo oxidative stress models.
基金funded by the Swiss National Science Foundation(SNSF Grant No.320030L_192073 to GM)the Slovenian Research Agency(ARRS Grant No.N5-0152 to TD).
文摘Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm(gestational age ≤ 32 weeks) and their term-born(gestational age ≥ 38 weeks)counterparts.Methods: Resting venous blood was obtained in normoxia(prior to altitude exposure), immediately upon arrival to altitude, and the following 3mornings. Antioxidant(superoxide dismutase(SOD), catalase, glutathione peroxidase(GPx), and ferric reducing antioxidant power(FRAP)),pro-oxidant(xanthine oxidase(XO) and myeloperoxidase(MPO)) enzyme activity, oxidative stress markers(advanced oxidation protein product(AOPP) and malondialdehyde(MDA)), nitric oxide(NO) metabolites(nitrites, nitrates, and total nitrite and nitrate(NOx)), and nitrotyrosine were measured in plasma.Results: SOD increased only in the preterm group(p < 0.05). Catalase increased at arrival in preterm group(p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely(arrival and Day 1) in control group. MPO increased in both groups throughout the3 days(p < 0.05). AOPP only increased at arrival in the preterm(p < 0.05) whereas it decreased at arrival up to Day 3(p < 0.05) for control.MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups(p < 0.05). Nitrites increased on Day 3(p < 0.05)in control group and decreased on Day 1(p < 0.05) in preterm group.Conclusion: These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals.These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.
