In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented...In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.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
Oxidative potential(OP)can be used as an indicator of the health risks of particulate matter in the air.To study the variation and sources of OP,we conducted an observation of PM_(2.5) in a megacity in southern China ...Oxidative potential(OP)can be used as an indicator of the health risks of particulate matter in the air.To study the variation and sources of OP,we conducted an observation of PM_(2.5) in a megacity in southern China in winter and spring of 2021.The results show that the average concentration of PM_(2.5) decreased by 47%from winter to spring,while volume-normalized and mass-normalized OP(i.e.,OP_(v) and OP_(m))increased by 6%and 69%,respectively.It suggests that the decline of PM_(2.5) may not necessarily decrease the health risks and the intrinsic toxicity of PM_(2.5).Variations of OP_(v) and OP_(m) among different periods were related to the different source contributions and environmental conditions.The positive matrix factorization model was used to identify the major sources of OP_(v).OP_(v) was mainly contributed by biomass burning/industrial emissions(29%),soil/road dust(20%),secondary sulfate(14%),and coal combustion(13%)in winter.Different major sources were resolved to be secondary sulfate(36%),biological sources(21%),and marine vessels(20%)in spring,presenting the substantial contribution of biological sources.The analysis shows strong associations between OP_(v) and both live and dead bacteria,further confirming the important contribution of bioaerosols to the enhancement of OP.This study highlights the importance of understanding OP in ambient PM_(2.5) in terms of public health impact and provides a new insight into the biological contribution to OP.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
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
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
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
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
Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.I...Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.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
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
Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously...Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].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
This communication looks at the photo-oxidation of polythene and polypropylene plastic bottle tops that are placed on soil in a hot arid environment. The degree of oxidation of the plastic is monitored by FT-IR spectr...This communication looks at the photo-oxidation of polythene and polypropylene plastic bottle tops that are placed on soil in a hot arid environment. The degree of oxidation of the plastic is monitored by FT-IR spectroscopy. It is noted that while different bottle top types photo-oxidize at different rates, all show an appreciable level of oxidation after half a year of exposure to the environment. The oxidation leads to brittleness of the plastic, which leads to fissure formation in bottle tops of little thickness. This leads to fragmentation of the material upon impact, making plastic bottle tops an appreciable source of microplastics.展开更多
T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue ...T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.展开更多
Themanganese-cobalt mixed oxide nanorodswere fabricated using a hydrothermalmethod with different metal precursors(KMnO_(4)and MnSO_(4)·H_(2)O for MnOx and Co(NO3)2>6H_(2)O and CoCl_(2)>6H_(2)O for Co_(3)O_...Themanganese-cobalt mixed oxide nanorodswere fabricated using a hydrothermalmethod with different metal precursors(KMnO_(4)and MnSO_(4)·H_(2)O for MnOx and Co(NO3)2>6H_(2)O and CoCl_(2)>6H_(2)O for Co_(3)O_(4)).Bamboo-like MnO_(2)>Co_(3)O_(4)(B-MnO_(2)>Co_(3)O_(4)(S))was derived from repeated hydrothermal treatments with Co_(3)O_(4)@MnO_(2)and MnSO_(4)>H_(2)O,whereas Co_(3)O_(4)@MnO_(2)nanorods were derived from hydrothermal treatment with Co_(3)O_(4)nanorods and KMnO_(4).The study shows that manganese oxide was tetragonal,while the cobalt oxide was found to be cubic in the crystalline arrangement.Mn surface ions were present in multiple oxidation states(e.g.,Mn^(4+)and Mn^(3+))and surface oxygen deficiencies.The content of adsorbed oxygen species and reducibility at low temperature declined in the sequence of BMnO_(2)>Co_(3)O_(4)(S)>Co_(3)O_(4)@MnO_(2)>MnO_(2)>Co_(3)O_(4),matching the changing trend in activity.Among all the samples,B-MnO_(2)>Co_(3)O_(4)(S)showed the preeminent catalytic performance for the oxidation of toluene(T10%=187℃,T50%=276℃,and T90%=339℃).In addition,the B-MnO_(2)>Co_(3)O_(4)(S)sample also exhibited good H_(2)O^(-),CO_(2)^(-),and SO_(2)^(-)resistant performance.The good catalytic performance of B-MnO_(2)>Co_(3)O_(4)(S)is due to the high concentration of adsorbed oxygen species and good reducibility at low temperature.Toluene oxidation over B-MnO_(2)>Co_(3)O_(4)(S)proceeds through the adsorption of O_(2)and toluene to form O∗,OH∗,and H_(2)C(C6H5)∗species,which then react to produce benzyl alcohol,benzoic acid,and benzaldehyde,ultimately converting to CO_(2)and H_(2)O.The findings suggest that B-MnO_(2)>Co_(3)O_(4)(S)has promising potential for use as an effective catalyst in practical applications.展开更多
Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and e...Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.展开更多
Oocyte cryopreservation is an essential procedure in assisted reproductive technologies,aimed at preserving fertility,particularly for women undergoing IVF treatment or at risk of ovarian damage due to radiation,chemo...Oocyte cryopreservation is an essential procedure in assisted reproductive technologies,aimed at preserving fertility,particularly for women undergoing IVF treatment or at risk of ovarian damage due to radiation,chemotherapy,or surgery.Despite its growing use,the survival and fertilization rates of cryopreserved oocytes remain suboptimal,largely due to cryo-induced oxidative stress.The generation of Reactive Oxygen Species(ROS)during freezing and thawing causes considerable damage to key cellular components,including proteins,lipids,DNA,and mitochondria.This oxidative stress compromises oocyte quality and reduces developmental potential.To address these challenges,the use of additives-especially antioxidants-has shown significant promise in mitigating oxidative damage.Enzymatic antioxidants such as Superoxide Dismutase(SOD)and Catalase(CAT),along with non-enzymatic antioxidants like glutathione,melatonin,and resveratrol,have demonstrated the ability to neutralize ROS and improve oocyte viability and developmental outcomes.Recent studies highlight the potential of Mitoquinone(MitoQ),a mitochondria-targeted antioxidant,to effectively counteract mitochondrial ROS and enhance cellular defense mechanisms during cryopreservation.This review explores the cellular mechanisms of cryodamage,the role of oxidative stress in oocyte cryopreservation,and the potential of various antioxidant strategies to enhance oocyte survival and function.Developing effective antioxidant supplementation approaches may significantly improve the outcomes of cryopreservation in reproductive medicine.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
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
基金Supported by the National Key Research and Development Program of Traditional Chinese Medicine Modernization Project,China(No.2023YFC3504000)the Science and Technology Development Project of Jilin Province,China(No.20240404043ZP)the Science and Technology Innovation Cooperation Project of Changchun Science and Technology Bureau and Chinese Academy of Sciences,China(No.23SH14)。
文摘In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.
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 the National Natural Science Foundation of China(No.41975156)and the Fundamental Research Funds for the Central Universities.
文摘Oxidative potential(OP)can be used as an indicator of the health risks of particulate matter in the air.To study the variation and sources of OP,we conducted an observation of PM_(2.5) in a megacity in southern China in winter and spring of 2021.The results show that the average concentration of PM_(2.5) decreased by 47%from winter to spring,while volume-normalized and mass-normalized OP(i.e.,OP_(v) and OP_(m))increased by 6%and 69%,respectively.It suggests that the decline of PM_(2.5) may not necessarily decrease the health risks and the intrinsic toxicity of PM_(2.5).Variations of OP_(v) and OP_(m) among different periods were related to the different source contributions and environmental conditions.The positive matrix factorization model was used to identify the major sources of OP_(v).OP_(v) was mainly contributed by biomass burning/industrial emissions(29%),soil/road dust(20%),secondary sulfate(14%),and coal combustion(13%)in winter.Different major sources were resolved to be secondary sulfate(36%),biological sources(21%),and marine vessels(20%)in spring,presenting the substantial contribution of biological sources.The analysis shows strong associations between OP_(v) and both live and dead bacteria,further confirming the important contribution of bioaerosols to the enhancement of OP.This study highlights the importance of understanding OP in ambient PM_(2.5) in terms of public health impact and provides a new insight into the biological contribution to OP.
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.
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 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.
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 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 Natural Science Foundation of Liaoning Province(2023-MSBA-020)the Fundamental Research Funds for Central Universities(DUT24MS020)Science and Technology Innovation Fund of Dalian(2022JJ13SN073).
文摘Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.
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 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.
基金supported by the Hyperbaric Med School of the Department of Biomedical Sciences at the University of Padova,the Italian Air Force,and the Institute of Clinical Physiology(Milan)-National Research Council(IFC-CNR).
文摘Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].
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.
文摘This communication looks at the photo-oxidation of polythene and polypropylene plastic bottle tops that are placed on soil in a hot arid environment. The degree of oxidation of the plastic is monitored by FT-IR spectroscopy. It is noted that while different bottle top types photo-oxidize at different rates, all show an appreciable level of oxidation after half a year of exposure to the environment. The oxidation leads to brittleness of the plastic, which leads to fissure formation in bottle tops of little thickness. This leads to fragmentation of the material upon impact, making plastic bottle tops an appreciable source of microplastics.
基金supported by the National Natural Science Foundation of China(No.81872567).
文摘T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
基金supported by the National Natural Science Foundation Committee of China-Liaoning Provincial People’s Government Joint Fund(No.U1908204)the National Natural Science Foundation of China(Nos.21876006 and 21976009)+2 种基金the Natural Science Foundation of Beijing Municipal Commission of Education(No.KM201710005004)the Development Program for the Youth Outstanding-Notch Talent of Beijing Municipal Commission of Education(No.CIT&TCD201904019)the Foundation on the Creative Research Team Construction Promotion Project of Beijing Municipal Institutions(No.IDHT20190503).
文摘Themanganese-cobalt mixed oxide nanorodswere fabricated using a hydrothermalmethod with different metal precursors(KMnO_(4)and MnSO_(4)·H_(2)O for MnOx and Co(NO3)2>6H_(2)O and CoCl_(2)>6H_(2)O for Co_(3)O_(4)).Bamboo-like MnO_(2)>Co_(3)O_(4)(B-MnO_(2)>Co_(3)O_(4)(S))was derived from repeated hydrothermal treatments with Co_(3)O_(4)@MnO_(2)and MnSO_(4)>H_(2)O,whereas Co_(3)O_(4)@MnO_(2)nanorods were derived from hydrothermal treatment with Co_(3)O_(4)nanorods and KMnO_(4).The study shows that manganese oxide was tetragonal,while the cobalt oxide was found to be cubic in the crystalline arrangement.Mn surface ions were present in multiple oxidation states(e.g.,Mn^(4+)and Mn^(3+))and surface oxygen deficiencies.The content of adsorbed oxygen species and reducibility at low temperature declined in the sequence of BMnO_(2)>Co_(3)O_(4)(S)>Co_(3)O_(4)@MnO_(2)>MnO_(2)>Co_(3)O_(4),matching the changing trend in activity.Among all the samples,B-MnO_(2)>Co_(3)O_(4)(S)showed the preeminent catalytic performance for the oxidation of toluene(T10%=187℃,T50%=276℃,and T90%=339℃).In addition,the B-MnO_(2)>Co_(3)O_(4)(S)sample also exhibited good H_(2)O^(-),CO_(2)^(-),and SO_(2)^(-)resistant performance.The good catalytic performance of B-MnO_(2)>Co_(3)O_(4)(S)is due to the high concentration of adsorbed oxygen species and good reducibility at low temperature.Toluene oxidation over B-MnO_(2)>Co_(3)O_(4)(S)proceeds through the adsorption of O_(2)and toluene to form O∗,OH∗,and H_(2)C(C6H5)∗species,which then react to produce benzyl alcohol,benzoic acid,and benzaldehyde,ultimately converting to CO_(2)and H_(2)O.The findings suggest that B-MnO_(2)>Co_(3)O_(4)(S)has promising potential for use as an effective catalyst in practical applications.
基金supported by grants from the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI,JYY2023-6)the R&D Program of Beijing Municipal Education Commission(KZ20231002543).
文摘Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.
基金Anhui Province Clinical Medical Research Translation Special Program(No.2204295107020002).
文摘Oocyte cryopreservation is an essential procedure in assisted reproductive technologies,aimed at preserving fertility,particularly for women undergoing IVF treatment or at risk of ovarian damage due to radiation,chemotherapy,or surgery.Despite its growing use,the survival and fertilization rates of cryopreserved oocytes remain suboptimal,largely due to cryo-induced oxidative stress.The generation of Reactive Oxygen Species(ROS)during freezing and thawing causes considerable damage to key cellular components,including proteins,lipids,DNA,and mitochondria.This oxidative stress compromises oocyte quality and reduces developmental potential.To address these challenges,the use of additives-especially antioxidants-has shown significant promise in mitigating oxidative damage.Enzymatic antioxidants such as Superoxide Dismutase(SOD)and Catalase(CAT),along with non-enzymatic antioxidants like glutathione,melatonin,and resveratrol,have demonstrated the ability to neutralize ROS and improve oocyte viability and developmental outcomes.Recent studies highlight the potential of Mitoquinone(MitoQ),a mitochondria-targeted antioxidant,to effectively counteract mitochondrial ROS and enhance cellular defense mechanisms during cryopreservation.This review explores the cellular mechanisms of cryodamage,the role of oxidative stress in oocyte cryopreservation,and the potential of various antioxidant strategies to enhance oocyte survival and function.Developing effective antioxidant supplementation approaches may significantly improve the outcomes of cryopreservation in reproductive medicine.
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.
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.
