Glutathione peroxidase (GPX1) was the first identified selenium-dependent enzyme, and this enzyme has been most useful as a biochemical indicator of selenium (Se) status and the parameter of choice for determining Se ...Glutathione peroxidase (GPX1) was the first identified selenium-dependent enzyme, and this enzyme has been most useful as a biochemical indicator of selenium (Se) status and the parameter of choice for determining Se requirements. We have continued to study Se regulation of GPX1 to better understand the underlying mechanism and to gain insight into how cells themselves regulate nutrient status. In progressive Se deficiency in rats, GPX1 activity,protein and mRNA all decrease in a dramatic, coordinated and exponential fashion such that Se-deficient GPX1 mRNA levels are 6-15% of Sexadequate levels. mRNA levels for other Sedependent proteins are far less decreased in the same animals. The mRNA levels for a second Se-dependent peroxidase, phospholipid hydroperoxide glutathione peroxidase (GPX4 ), are little affected by Se deficiency, demonstrating that Se regulation of GPX1 is unique. Se regulation of GPX1 activity in growing male and female rats shows that the Se requirernent is 100 ng/g diet, based on liver GPX1 activity; use of GPX1 mRNA as the parameter indicates that the Se requirement is nearer to 50 ng Se/g diet in both male and female rats. This approach will readily detect an altered dietary Se requirement, as shown by the incremental increases in dietary Se requirement by 150, 100 or 50 ng Se/g diet in Seudeficient rat pups repleted with Se for 3, 7 or 14 d, respectively. Studies with CHO cells stably transfected with recombinant GPX1 also show that overexpression of GPX1 does not alter the minimum level of media Se necessary for Se-adequate levels of GPX1 activity or mRNA. We hypothesize that classical GPX1 has an integral biological role in the mechanism used by cells to regulate Se status,making GPX1 an especially useful and effective parameter for determining Se requirements in animals展开更多
Background: Oxidative stress plays a crucial role in the pathogenesis and progression of many diseases, including cardiovascular disease (CVD) and diabetes mellitus. Oxidative stress results from an imbalance between ...Background: Oxidative stress plays a crucial role in the pathogenesis and progression of many diseases, including cardiovascular disease (CVD) and diabetes mellitus. Oxidative stress results from an imbalance between free radical formation and the protective antioxidant mechanisms. The latter mechanisms include superoxide dismutases (SODs) and glutathione peroxidases (GPx) that scavenge excessive ROS and protect cells against excess ROS production. The aim of current study was to determine the serum levels of SOD and serum GPx mRNA as well as the serum prooxidant-antioxidant balance in CVD patients. Method: A total of 103 subjects were recruited, with ≥50% stenosis (Angio+) or –). The expression levels of SOD and GPx in serum were measured using real time PCR. Biochemical-analyses (e.g., triglycerides;high-density lipo-protein cholesterol;low-density lipoprotein cholesterol;fasting-blood-glucose) were determined in all the subjects. Associations of SOD and GPx levels with biochemical and anthropometric characteristics were assessed together with evaluation of the serum pro-oxidant-antioxidant balance (PAB). Results: CVD subjects had a significantly higher level of fasting blood glucose (FBG), TC, LDL-C, TG and hs-CRP levels, as compared to control subjects. The level of serum PAB was significantly higher in the CVD group, 117.92 ± 35.51 and 110.65 ± 27.65 μg/dl in the angio– and angio+ groups, respectively compared to the control group (54.26 + 23.25). Additionally we observed that the SOD-3 level was higher in angio+ group versus control subjects. Conclusion: We have found that patients with CVD had a significantly higher prooxidant-antioxidant and SOD-3 levels. Further studies in larger multi-center setting are warranted to explore the value of emerging biomarker in CVD patients.展开更多
Peroxidases (POXs) are the key extracellular enzymes produced by crude oil degrading microbes. Knowledge of optimum conditions for POXs activity is crucial for providing effective environment for bioremediation. In th...Peroxidases (POXs) are the key extracellular enzymes produced by crude oil degrading microbes. Knowledge of optimum conditions for POXs activity is crucial for providing effective environment for bioremediation. In this study, physicochemical properties of POXs produced by Actinomyces israelii and Actinomyces viscosus during growth on crude oil were studied. The POXs exhibited similarities in activity and stability with striking differences in response to two divalent metal ions. The POXs from both species had optimum pH of 7.0 and were very stable over a narrow pH range (6.0 - 8.0). The POXs demonstrated similar thermostability exhibiting relative residual activity of 62% at 50°C after 30 min incubation and 45% residual activity at the same temperature after 60 min despite the fact that POXs from A. viscosus and A. israelii had optimum temperatures of 50°C and 40°C, respectively. The POXs from A. viscosus and A. israelii were greatly activated by Fe2+ at 5.0 and 10.0 mM. The enzymes were both strongly inhibited by Cu2+, Mg2+ and Hg2+. Surprisingly, these congeneric POXs demonstrated striking differences in their response to Ca2+ and Mn2+. POX from A. viscosus was activated by Ca2+ and Mn2+ exhibiting relative activity of 136% and 106% at 5 mM, respectively. In contrast, POX from A. israelii was strongly inhibited by Ca2+ and Mn2+ exhibiting 62.5% relative activity in the presence of 5 mM of each metal ion. Increasing the concentration of Ca2+ and Mn2+ led to further activation of POX from A. viscosus and inhibition of POX from A. israelii. Results provide deeper insights into functional properties of studied POXs from closely related microbes. The physicochemical properties are very similar;however, notable differences provide a strong basis for structural characterization of these congeneric enzymes.展开更多
Extracellular manganese peroxidases （MnPs） produced by native and mutant strains of Trametes versicolor IBL‐04 （EB‐60, EMS‐90） were purified by ammonium sulphate precipitation and dialysis, followed by ion‐exc...Extracellular manganese peroxidases （MnPs） produced by native and mutant strains of Trametes versicolor IBL‐04 （EB‐60, EMS‐90） were purified by ammonium sulphate precipitation and dialysis, followed by ion‐exchange and gel‐permeation chromatography. The purified enzymes elucidated a single band in the 43‐kDa region on sodium dodecyl sulphate‐polyacrylamide gel electrophoresis. The optimum pH and temperature of the purified enzymes were found to be 5.0 and 40 °C, respec‐tively. Mutant strain MnPs exhibited a broader active pH range and higher thermal stability than native MnP. Purified MnPs from selected mutants showed almost identical properties to native MnP in electrophoresis, steady‐state kinetics, and metal ion and endocrine‐disrupting compound （EDC） degradation efficiency. Although the fastest reaction rates occurred with Mn2＋, MnPs displayed the highest affinity for ABTS, methoxyhydroquinone, 4‐aminophenol and reactive dyes. MnP activity was significantly enhanced by Mn2＋and Cu2＋, and inhibited in the presence of Zn2＋, Fe2＋, ethylene‐diaminetetraacetic acid and cysteine to various extents, with Hg2＋ as the most potent inhibitory agent. MnPs from all sources efficiently catalyzed the degradation of the EDCs, nonylphenol and triclosan, removing over 80%after 3 h of treatment, which was further increased up to 90%in the presence of MnP‐mediator system. The properties of T. versicolor MnPs, such as high pH and ther‐mal stability, as well as unique Michaelis‐Menten kinetic parameters and high EDC elimination effi‐ciency, render them promising candidates for industrial exploitation.展开更多
Superoxide dismutase (SOD) and ascorbate peroxidase (APX) play central roles in the pathway for scavenging reactive oxygen species in plants, thereby contributing to the tolerance against abiotic stress. Here we repor...Superoxide dismutase (SOD) and ascorbate peroxidase (APX) play central roles in the pathway for scavenging reactive oxygen species in plants, thereby contributing to the tolerance against abiotic stress. Here we report the responses of cytosolic SOD (cSOD; sodCc1 and sodCc2) and cytosolic APX (cAPX; OsAPX1 and OsAPX2) genes to oxidative and abiotic stress in rice. RNA blot analyses revealed that methyl viologen treatment caused a more prominent induction of cAPXs compared with cSODs, and hydrogen peroxide treatment induced the expression of cAPXs whereas cSODs were not affected. These results suggest that cAPXs play more important roles in defense against oxidative stress compared with cSODs. It is noted that cSODs and cAPXs showed coordinate response to abscisic acid treatment which induced both sodCc1 and OsAPX2. However, cSODs and cAPXs responded differentially to drought, salt and chilling stress, which indicates that cSOD and cAPX genes are expressed differentially in response to oxidative and abiotic stress in rice.展开更多
Ascorbate peroxidase(APX) plays a key role in scavenging reactive oxygen species(ROS) in higher plants. However, there is very little information available on the APXs in kiwifruit(Actinidia), which is an economically...Ascorbate peroxidase(APX) plays a key role in scavenging reactive oxygen species(ROS) in higher plants. However, there is very little information available on the APXs in kiwifruit(Actinidia), which is an economically and nutritionally important horticultural crop with exceptionally high ascorbic acid(AsA) accumulation. This study aims to identify and characterize two cytosolic APX genes(AcAPX1 and AcAPX2) derived from A. chinensis ‘Hongyang’. The constitutive expression pattern was determined for both AcAPX1 and AcAPX2, and showed relatively higher expression abundances of AcAPX1 in leaf and AcAPX2 in root. Transcript levels of AcAPX1 and AcAPX2 were increased in kiwifruit roots treated with Na Cl. Subcellular localization assays using GFP-fusion proteins in Arabidopsis protoplasts showed that both AcAPX1 and AcAPX2 are targeted to the cytosol. Recombinant AcAPX1 or AcAPX2 proteins were successfully expressed in the prokaryotic expression system and their individual ascorbate peroxidase activities were determined. Finally, constitutive over-expression of AcAPX1 or AcAPX2 could dramatically increase total As A, glutathione level and salinity tolerance under Na Cl stress in Arabidopsis thaliana. Our findings revealed that cytosolic AcAPX1/2 may play an important protective role in the responses to unfavorable environmental stimuli in kiwifruit.展开更多
The article studies the activity of the peroxidase enzyme in cereals and barks of some varieties of soy plants. The soy (plant) samples we studied were obtained in the conditions of the Tashkent region at the experime...The article studies the activity of the peroxidase enzyme in cereals and barks of some varieties of soy plants. The soy (plant) samples we studied were obtained in the conditions of the Tashkent region at the experimental field of the Institute of genetics and plant experimental biology in the village of Durmen. 11 samples out of 40 examined on electrophoregrams did not show the presence of the studied enzymes. Further research is needed to clarify the results.展开更多
Class Ⅲ secretable plant peroxidases occur as a large family of genes in plants with many functions and probable redundancy. In this review we are concentrating on the evidence we have on the catalysis of lignin poly...Class Ⅲ secretable plant peroxidases occur as a large family of genes in plants with many functions and probable redundancy. In this review we are concentrating on the evidence we have on the catalysis of lignin polymerization by class Ⅲ plant peroxidases present in the apoplastic space in the xylem of trees. Some evidence exists on the specificity of peroxidase isozymes in lignin polymerization through substrate specificity studies, from antisense mutants in tobacco and poplar and from tissue and cell culture lines of Norway spruce （Picea abies） and Zinnia elegans. In addition, real time （RT-）PCR results have pointed out that many peroxidases have tissue specific expression patterns in Norway spruce. Through combining information on catalytic properties of the enzymes, on the expression patterns of the corresponding genes, and on the presence of monolignols and hydrogen peroxide in the apoplastic space, we can show that specific peroxidases catalyze lignin polymerization in the apoplastic space of Norway spruce xylem.展开更多
Manganese peroxidases(MnP)from Phanerochaete chrysosporium were adsorbed onto multi-walled carbon nanotubes(MWNT).Four different loadings of MnP on MWNTs were investigated,and the maximum enzyme loading of 47.5µg...Manganese peroxidases(MnP)from Phanerochaete chrysosporium were adsorbed onto multi-walled carbon nanotubes(MWNT).Four different loadings of MnP on MWNTs were investigated,and the maximum enzyme loading of 47.5µg/mg of MWNTs was obtained in 12 h.The adsorbed MnP showed a catalytic activity of up to 0.1 U/mg of the weight of the system of MnP/MWNTs,with 23%of its original activity retained.The AFM image of the adsorbed enzymes indicated that a layer of MnP covered the surface of the MWNTs and retained its original three-dimensional shape.Amino-based nonspecific interactions may play the dominant role in the adsorption of MnP on MWNTs.展开更多
Zearalenone(ZEN),a mycotoxin present in cereals,poses significant health risks to animals and humans due to its estrogenic effects.Numerous studies on the enzymatic detoxification of ZEN have predominantly focused on ...Zearalenone(ZEN),a mycotoxin present in cereals,poses significant health risks to animals and humans due to its estrogenic effects.Numerous studies on the enzymatic detoxification of ZEN have predominantly focused on reducing the parent toxin to assess the enzyme’s efficacy,yet there is limited research on the identification and toxicity evaluation of the enzymatic degradation products.This study investigated the enzymatic degradation mechanisms of ZEN using commercial peroxidase(POD)and laccase(LC),with a focus on identifying degradation products and assessing their hepatotoxicity effects.Molecular docking and dynamics simulations elucidated the binding mechanisms between these enzymes and ZEN,revealing strong interactions that facilitate efficient detoxification.Subsequent analysis employing ultra-high performance liquid chromatography-high resolution mass spectrometry(UHPLC-HRMS)successfully identified crucial degradation products.Hepatic toxicity of the enzymatic degradation products was comprehensively assessed in HepaRG liver cells through systematic measurements of cell viability,oxidative stress,apoptosis,mitochondrial membrane potential,and molecular metabolic profiles.Our findings demonstrate that both POD and LC exhibit significant efficacy in mitigating hepatocyte toxicity induced by ZEN,thereby highlighting their potential utility in enhancing food safety.This research provides essential data for safety evaluation regarding enzymatic detoxification of ZEN while offering theoretical and technical resources for risk assessment related to mycotoxin enzymatic detoxification.展开更多
Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by ...Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy. Dendrobium officinale(D. officinale), a renowned traditional Chinese medicinal herb, is widely used in several Asian countries for its nutritional and therapeutic benefits.Although D. officinale has demonstrated anti-tumor effects, the molecular mechanisms underlying its action against CRC remain incompletely characterized. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4(GPX4), a key suppressor of ferroptosis. In vitro assays were conducted using HCT116 and SW480 CRC cell lines, and in vivo efficacy was evaluated in BALB/c nude mice bearing CRC xenografts. D. officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. Induction of ferroptosis was evidenced by elevated levels of Fe^(2+), malondialdehyde(MDA), and lipid peroxidation, along with a depleted glutathione/oxidized glutathione disulfide(GSH/GSSG) ratio. Notably, these effects were reversed by ferroptosis inhibitors, including ferrostatin-1(Fer-1) and deferoxamine. Consistently, D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, whereas GPX4 silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis,providing a novel, naturally derived therapeutic approach. These findings bridge traditional medicine and modern oncology, establishing a foundation for developing targeted CRC treatments.展开更多
Ferroptosis plays a key role in nerve injury in intracerebral hemorrhage and is associated with the upregulation of murine double minute 2.Investigating the mechanism underlying murine double minute 2-related ferropto...Ferroptosis plays a key role in nerve injury in intracerebral hemorrhage and is associated with the upregulation of murine double minute 2.Investigating the mechanism underlying murine double minute 2-related ferroptosis could help identify new therapies for intracerebral hemorrhage.An in vitro intracerebral hemorrhage model was established by treating BV2 microglial cells with oxygen-glucose deprivation combined with hemin.The role of murine double minute 2 in regulating ferroptosis was investigated via transduction with RNA interference and lentivirus overexpression.Furthermore,intracerebral hemorrhage mouse models were constructed with and without an murine double minute 2 inhibitor(brigimadlin),and behavioral assays were performed to assess the learning ability and cognitive function.Murine double minute 2 dysregulation was associated with oxygen-glucose deprivation combined with hemin-induced BV2 microglial cell ferroptosis and M1/M2 polarization.The results suggested that murine double minute 2 induced glutathione peroxidase 4 ubiquitination and degradation to regulate ferroptosis and inflammatory responses in BV2 microglial cells.Mechanistically,Wilms tumor 1-associated protein induced murine double minute 2 N6-methyladenosine(m6A)modification and regulated ferroptosis and inflammatory responses.In vivo analysis showed that brigimadlin improved neurological deficits and spatial memory in mice with intracerebral hemorrhage.In summary,the results indicate that Wilms tumor 1-associated protein regulates murine double minute 2 m6A modification,and murine double minute 2 induces glutathione peroxidase 4 ubiquitination and degradation.This regulation promotes ferroptosis and inflammatory responses in oxygen-glucose deprivation combined with hemin-induced BV2 microglial cells,suggesting that the murine double minute 2-glutathione peroxidase 4-ferroptosis regulatory axis exerts neurotoxic effects.These findings identify glutathione peroxidase 4 as a potential gene therapy target for intracerebral hemorrhage-related brain injury.展开更多
Objective:Glioblastoma(GB)therapy is challenged by tumor heterogeneity and multidrug resistance(MDR),highlighting the need for effective therapies.This study aimed to explore the combined anticancer effects of Sunitin...Objective:Glioblastoma(GB)therapy is challenged by tumor heterogeneity and multidrug resistance(MDR),highlighting the need for effective therapies.This study aimed to explore the combined anticancer effects of Sunitinib(SNB)and Fenofibrate(FEN)on U87 cells.Methods:U87 cells were exposed to SNB,FEN,or their combination for 24 h,followed by evaluations of cell viability,migration,and clonogenic survival using MTT,scratch,and colony formation assays.Intracellular reactive oxygen species(ROS)were quantified via the 2′,7′-dichlorofluorescein assay,while mitochondrial membrane potential(MMP)was assessed using JC-1 red/green fluorescence.Molecular docking was performed to investigate SNB and FEN interactions with multiple molecular targets,including topoisomerase II(TOP-II),c-Jun N-terminal kinase(JNK),histone deacetylase 2(HDAC2),cyclooxygenase-2(COX-2),matrix metalloproteinase-9(MMP-9),cytochrome P4503A4(CYP3A4),glutathione peroxidase 4(GPX4),glutathione Stransferase(GST),heme oxygenase-1(HO-1),and 5-lipoxygenase(5-LOX).Results:The results demonstrated that both SNB and FEN significantly reduced U87 cell viability,migration,and clonogenic potential,with the combination treatment exhibiting synergistic cytotoxicity.SNB alone markedly increased ROS levels,while FEN,individually or in combination,reduced oxidative stress.Although SNB diminished mitochondrial membrane potential,cotreatment with FEN restored MMP values close to control levels.Docking analyses revealed that SNB displayed strong affinities for TOP-II,JNK,and HDAC2,whereas FEN preferentially interacted with MMP-9,COX-2,CYP3A4,and GPX4,suggesting complementary mechanisms targeting oxidative stress,inflammation,and programmed cell death regulation.Conclusion:The combination of SNB and FEN represents a promising multi-targeted therapeutic approach against GB.SNB and FEN combination capable of modulating and reprogramming key molecular pathways involved in GB progression and MDR.展开更多
Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function.Cystine-glutamate transporter SLC7A11 is essential for ...Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function.Cystine-glutamate transporter SLC7A11 is essential for maintaining cellular redox homeostasis and resisting ferroptosis.However,the mechanisms underlying neuronal ferroptosis caused by SLC7A11 downregulation following spinal cord injury remain unclear.Herein,we provide evidence that tumor protein 53,a negative regulator of SLC7A11,was significantly upregulated post-spinal cord injury.Transcriptomic analysis indicated that tumor protein 53 was associated with injury severity.We subsequently confirmed that tumor protein 53 inhibition restored the expressions of SLC7A11 and glutathione peroxidase 4,alleviated neuronal ferroptosis,and improved neurological function in a contusion spinal cord injury rat model.The regulatory effects of tumor protein 53 on the transcription and ubiquitination of SLC7A11 were further elucidated using chromatin immunoprecipitation polymerase chain reaction and cleavage under targets and tagmentation techniques.Additionally,Kelch-like protein 4,an E3 ubiquitin ligase adaptor,was demonstrated to play an important role in the tumor protein 53-mediated ubiquitination of SLC7A11.In summary,the present study elucidated the possible mechanisms of tumor protein 53-mediated neuronal ferroptosis in spinal cord injury,thereby providing potential targets and insights for clinical translation.展开更多
Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferro...Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.Methods:This systematic review,registered in PROSPERO(CRD420251090058),followed PRISMA 2020 guidelines.Comprehensive research of PubMed,Scopus,and Web of Science was performed for studies published between January 2010 and July 2025 investigating ferroptosis mechanisms,genetic or pharmacological modulation,or molecular profiling in SCLC.Two reviewers independently performed data extraction and quality assessment.Results:Nineteen preclinical studies met the inclusion criteria.Key regulators included solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),ferroptosis suppressor protein 1(FSP1),and acyl-CoA synthetase long chain family member 4(ACSL4).The molecular subtypes of SCLC,achaete-scute homolog 1(ASCL1),neuronal differentiation 1(NEUROD1),POU class 2 homeobox 3(POU2F3),and Yes1 associated transcriptional regulator(YAP1)exhibit differential ferroptosis gene expressions,influencing therapeutic responsiveness.Non-neuroendocrine subtypes are more ferroptosis-prone,whereas neuroendocrine variants display enhanced antioxidant defenses.Ferroptosis induction also promotes immune activation through stimulator of interferon genes(STING)-mediated CD8+T-cell recruitment.Conclusions:Ferroptosis constitutes a promising therapeutic axis in SCLC.Integrating ferroptosis biomarkers into molecular stratification frameworks could refine patient selection and support precision oncology strategies,warranting further translational and clinical validation.展开更多
Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein bet...Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.展开更多
Nanozymes have become attractive in analytical and biomedical fields,mainly because of their low cost,long shelf life,and less environmental sensitivity.Particularly,nanozymes formed from nanomaterials having high sur...Nanozymes have become attractive in analytical and biomedical fields,mainly because of their low cost,long shelf life,and less environmental sensitivity.Particularly,nanozymes formed from nanomaterials having high surface area and rich active sites are interesting since their activities can be tuned through carefully controlling their size,morphology,and surface properties.This review article focuses on preparation of carbon dots(C dots)possessing peroxidase-like activity and their analytical applications.We highlight the important roles of the oxidation states and surface residues of C dots and their nanocomposites with metal,metal oxides,or metal sulfides playing on determining their specificity and sensitivity toward H2O2.Examples of C dot nanozymes(CDzymes)for developing sensitive and selective absorption,fluorescence,and elec-trochemical sensing systems in the presence of substrates are presented to show their potential in analytical applications.For example,CDzymes couple with glucose oxidase and cholesterol oxidase are specific and sensitive for quantitation of glucose and cholesterol,separately,when using 3,3′,5,5′-tetramethylbenzidine(TMB)as the signal probe.This review article concludes with possible strategies for enhancing and tuning the catalytic activity of CDzymes.展开更多
Mycotoxins in grains pose severe threat to human and animal health.Previous studies showed that manganese peroxidases had degradation capability for various mycotoxins.In this work,to effectively detoxify aflatoxin B1...Mycotoxins in grains pose severe threat to human and animal health.Previous studies showed that manganese peroxidases had degradation capability for various mycotoxins.In this work,to effectively detoxify aflatoxin B1(AFB1),zearalenone(ZEN)and deoxynivalenol(DON),the manganese peroxidases PhcMnp and IrlMnp from Phanerochaete chrysosporium and Irpex lacteus were successfully expressed in Pichia pastoris in a food-grade manner,and were used for degradation tests with the three mycotoxins.The fermentation supernatants containing PhcMnp achieved degradation ratios of 76.56%,70.78%and 48.93%for AFB1,ZEN and DON respectively,while that containing IrlMnp achieved degradation ratios of 46.72%,45.13%and 41.64%correspondingly.The inducible expression conditions for the enzymes and the reaction parameters for the mycotoxin degradations were both optimized.Furthermore,the fermentation supernatants of strain Pichia pastoris GS115(pPIC9K-Phcmnp)were used for mycotoxin degradations in contaminated peanut samples(pH 4.5)at 40℃ for 10 h,resulting in apparent detoxification effects.The residual concentrations of AFB1,ZEN and DON in peanut samples after degradations were 9.42,127.68 and 636.71μg/kg respectively,all of which remained below the legal limits.Results in this study demonstrated that the enzymes PhcMnp and IrlMnp have potentials in mycotoxins detoxification in feed industry.展开更多
Small heat shock proteins(sHSPs)act as molecular chaperones that can prevent the accumulation of damaged proteins during abiotic stress,especially heat shock,but the mechanism is not clear.To study the function of sHS...Small heat shock proteins(sHSPs)act as molecular chaperones that can prevent the accumulation of damaged proteins during abiotic stress,especially heat shock,but the mechanism is not clear.To study the function of sHSPs in Lenzites gibbosa,a common polypore in northern temperate forests that causes spongy white rot of broadleaf trees,under temperature stress,L.gibbosa mycelia were grown at 25℃ for 9 d,treated at 33℃ for 15,30,60,and 120 min before sequencing the transcriptomes.From among 32 heat shock protein(HSP)genes found in the screen of the transcriptome data,a highly expressed gene was cloned and named Lghsp17.4.RT-qPCR was used to analyze the expression of the gene Lghsp17.4 under heat shock and dye stress.Both treatments induced higher expression of Lghsp17.4 at the transcriptional level,indicating that Lghsp17.4 might function in the response to heat stress and dye degradation.We previously found that L.gibbosa generally had a heat shock reaction(HSR)during degradation of aromatic compounds,and HSPs were always produced with manganese peroxidases(MnPs)and other lignin-degrading enzymes.Therefore,we measured the activity of MnPs in L.gibbosa after 33℃ heat shock to analyze the relationship between MnPs expression and Lghsp17.4 expression.Heat shocks of 0–30 min increased MnPs activity,and the change in MnPs activity were closely positively correlated with the expression levels of Lghsp17.4 over time,indicating a potential connection and interaction between LgHSP17.4 and MnPs during the HSR in L.gibbosa.Thus,LgHSP17.4 might have a positive regulatory effect on the HSR in L.gibbosa and be a critical component of a stress resistance mechanism.展开更多
Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene g...Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments.展开更多
文摘Glutathione peroxidase (GPX1) was the first identified selenium-dependent enzyme, and this enzyme has been most useful as a biochemical indicator of selenium (Se) status and the parameter of choice for determining Se requirements. We have continued to study Se regulation of GPX1 to better understand the underlying mechanism and to gain insight into how cells themselves regulate nutrient status. In progressive Se deficiency in rats, GPX1 activity,protein and mRNA all decrease in a dramatic, coordinated and exponential fashion such that Se-deficient GPX1 mRNA levels are 6-15% of Sexadequate levels. mRNA levels for other Sedependent proteins are far less decreased in the same animals. The mRNA levels for a second Se-dependent peroxidase, phospholipid hydroperoxide glutathione peroxidase (GPX4 ), are little affected by Se deficiency, demonstrating that Se regulation of GPX1 is unique. Se regulation of GPX1 activity in growing male and female rats shows that the Se requirernent is 100 ng/g diet, based on liver GPX1 activity; use of GPX1 mRNA as the parameter indicates that the Se requirement is nearer to 50 ng Se/g diet in both male and female rats. This approach will readily detect an altered dietary Se requirement, as shown by the incremental increases in dietary Se requirement by 150, 100 or 50 ng Se/g diet in Seudeficient rat pups repleted with Se for 3, 7 or 14 d, respectively. Studies with CHO cells stably transfected with recombinant GPX1 also show that overexpression of GPX1 does not alter the minimum level of media Se necessary for Se-adequate levels of GPX1 activity or mRNA. We hypothesize that classical GPX1 has an integral biological role in the mechanism used by cells to regulate Se status,making GPX1 an especially useful and effective parameter for determining Se requirements in animals
文摘Background: Oxidative stress plays a crucial role in the pathogenesis and progression of many diseases, including cardiovascular disease (CVD) and diabetes mellitus. Oxidative stress results from an imbalance between free radical formation and the protective antioxidant mechanisms. The latter mechanisms include superoxide dismutases (SODs) and glutathione peroxidases (GPx) that scavenge excessive ROS and protect cells against excess ROS production. The aim of current study was to determine the serum levels of SOD and serum GPx mRNA as well as the serum prooxidant-antioxidant balance in CVD patients. Method: A total of 103 subjects were recruited, with ≥50% stenosis (Angio+) or –). The expression levels of SOD and GPx in serum were measured using real time PCR. Biochemical-analyses (e.g., triglycerides;high-density lipo-protein cholesterol;low-density lipoprotein cholesterol;fasting-blood-glucose) were determined in all the subjects. Associations of SOD and GPx levels with biochemical and anthropometric characteristics were assessed together with evaluation of the serum pro-oxidant-antioxidant balance (PAB). Results: CVD subjects had a significantly higher level of fasting blood glucose (FBG), TC, LDL-C, TG and hs-CRP levels, as compared to control subjects. The level of serum PAB was significantly higher in the CVD group, 117.92 ± 35.51 and 110.65 ± 27.65 μg/dl in the angio– and angio+ groups, respectively compared to the control group (54.26 + 23.25). Additionally we observed that the SOD-3 level was higher in angio+ group versus control subjects. Conclusion: We have found that patients with CVD had a significantly higher prooxidant-antioxidant and SOD-3 levels. Further studies in larger multi-center setting are warranted to explore the value of emerging biomarker in CVD patients.
文摘Peroxidases (POXs) are the key extracellular enzymes produced by crude oil degrading microbes. Knowledge of optimum conditions for POXs activity is crucial for providing effective environment for bioremediation. In this study, physicochemical properties of POXs produced by Actinomyces israelii and Actinomyces viscosus during growth on crude oil were studied. The POXs exhibited similarities in activity and stability with striking differences in response to two divalent metal ions. The POXs from both species had optimum pH of 7.0 and were very stable over a narrow pH range (6.0 - 8.0). The POXs demonstrated similar thermostability exhibiting relative residual activity of 62% at 50°C after 30 min incubation and 45% residual activity at the same temperature after 60 min despite the fact that POXs from A. viscosus and A. israelii had optimum temperatures of 50°C and 40°C, respectively. The POXs from A. viscosus and A. israelii were greatly activated by Fe2+ at 5.0 and 10.0 mM. The enzymes were both strongly inhibited by Cu2+, Mg2+ and Hg2+. Surprisingly, these congeneric POXs demonstrated striking differences in their response to Ca2+ and Mn2+. POX from A. viscosus was activated by Ca2+ and Mn2+ exhibiting relative activity of 136% and 106% at 5 mM, respectively. In contrast, POX from A. israelii was strongly inhibited by Ca2+ and Mn2+ exhibiting 62.5% relative activity in the presence of 5 mM of each metal ion. Increasing the concentration of Ca2+ and Mn2+ led to further activation of POX from A. viscosus and inhibition of POX from A. israelii. Results provide deeper insights into functional properties of studied POXs from closely related microbes. The physicochemical properties are very similar;however, notable differences provide a strong basis for structural characterization of these congeneric enzymes.
基金a part of a research project entitled "The development of immobilized ligninolytic enzymes for industrial applications" supported by Higher Education Commission (HEC), Islamabad, Pakistan
文摘Extracellular manganese peroxidases （MnPs） produced by native and mutant strains of Trametes versicolor IBL‐04 （EB‐60, EMS‐90） were purified by ammonium sulphate precipitation and dialysis, followed by ion‐exchange and gel‐permeation chromatography. The purified enzymes elucidated a single band in the 43‐kDa region on sodium dodecyl sulphate‐polyacrylamide gel electrophoresis. The optimum pH and temperature of the purified enzymes were found to be 5.0 and 40 °C, respec‐tively. Mutant strain MnPs exhibited a broader active pH range and higher thermal stability than native MnP. Purified MnPs from selected mutants showed almost identical properties to native MnP in electrophoresis, steady‐state kinetics, and metal ion and endocrine‐disrupting compound （EDC） degradation efficiency. Although the fastest reaction rates occurred with Mn2＋, MnPs displayed the highest affinity for ABTS, methoxyhydroquinone, 4‐aminophenol and reactive dyes. MnP activity was significantly enhanced by Mn2＋and Cu2＋, and inhibited in the presence of Zn2＋, Fe2＋, ethylene‐diaminetetraacetic acid and cysteine to various extents, with Hg2＋ as the most potent inhibitory agent. MnPs from all sources efficiently catalyzed the degradation of the EDCs, nonylphenol and triclosan, removing over 80%after 3 h of treatment, which was further increased up to 90%in the presence of MnP‐mediator system. The properties of T. versicolor MnPs, such as high pH and ther‐mal stability, as well as unique Michaelis‐Menten kinetic parameters and high EDC elimination effi‐ciency, render them promising candidates for industrial exploitation.
基金supported by the Grants-in-Aid for Scientific Research (Grant No. 10460149 to K.T. and Grant No. 11740448 to S.M.) from the Ministry of Education, Culture, Sports, Science and Technology of Japana grant from the Rice Genome Research Program (Grant No. MP2106 to K.T.) from the Ministry of Agriculture, Forestry and Fisheries of Japan
文摘Superoxide dismutase (SOD) and ascorbate peroxidase (APX) play central roles in the pathway for scavenging reactive oxygen species in plants, thereby contributing to the tolerance against abiotic stress. Here we report the responses of cytosolic SOD (cSOD; sodCc1 and sodCc2) and cytosolic APX (cAPX; OsAPX1 and OsAPX2) genes to oxidative and abiotic stress in rice. RNA blot analyses revealed that methyl viologen treatment caused a more prominent induction of cAPXs compared with cSODs, and hydrogen peroxide treatment induced the expression of cAPXs whereas cSODs were not affected. These results suggest that cAPXs play more important roles in defense against oxidative stress compared with cSODs. It is noted that cSODs and cAPXs showed coordinate response to abscisic acid treatment which induced both sodCc1 and OsAPX2. However, cSODs and cAPXs responded differentially to drought, salt and chilling stress, which indicates that cSOD and cAPX genes are expressed differentially in response to oxidative and abiotic stress in rice.
基金funded by the National Natural Science Foundation of China (31972474)the Natural Science Research Program of Universities of Anhui Province, China (K1832004)+2 种基金the Leading Talent Group Funding of Anhui Province, China (WRMR-2020-75)the Natural Science Foundation of Anhui Province, China (19232002)the Anhui Agriculture University Shennong Scholar Project, China (RC321901)。
文摘Ascorbate peroxidase(APX) plays a key role in scavenging reactive oxygen species(ROS) in higher plants. However, there is very little information available on the APXs in kiwifruit(Actinidia), which is an economically and nutritionally important horticultural crop with exceptionally high ascorbic acid(AsA) accumulation. This study aims to identify and characterize two cytosolic APX genes(AcAPX1 and AcAPX2) derived from A. chinensis ‘Hongyang’. The constitutive expression pattern was determined for both AcAPX1 and AcAPX2, and showed relatively higher expression abundances of AcAPX1 in leaf and AcAPX2 in root. Transcript levels of AcAPX1 and AcAPX2 were increased in kiwifruit roots treated with Na Cl. Subcellular localization assays using GFP-fusion proteins in Arabidopsis protoplasts showed that both AcAPX1 and AcAPX2 are targeted to the cytosol. Recombinant AcAPX1 or AcAPX2 proteins were successfully expressed in the prokaryotic expression system and their individual ascorbate peroxidase activities were determined. Finally, constitutive over-expression of AcAPX1 or AcAPX2 could dramatically increase total As A, glutathione level and salinity tolerance under Na Cl stress in Arabidopsis thaliana. Our findings revealed that cytosolic AcAPX1/2 may play an important protective role in the responses to unfavorable environmental stimuli in kiwifruit.
文摘The article studies the activity of the peroxidase enzyme in cereals and barks of some varieties of soy plants. The soy (plant) samples we studied were obtained in the conditions of the Tashkent region at the experimental field of the Institute of genetics and plant experimental biology in the village of Durmen. 11 samples out of 40 examined on electrophoregrams did not show the presence of the studied enzymes. Further research is needed to clarify the results.
基金supported by the Finnish Centre of Excellence in Plant Signal Research granted by the Academy of Finland(grant number 213509)
文摘Class Ⅲ secretable plant peroxidases occur as a large family of genes in plants with many functions and probable redundancy. In this review we are concentrating on the evidence we have on the catalysis of lignin polymerization by class Ⅲ plant peroxidases present in the apoplastic space in the xylem of trees. Some evidence exists on the specificity of peroxidase isozymes in lignin polymerization through substrate specificity studies, from antisense mutants in tobacco and poplar and from tissue and cell culture lines of Norway spruce （Picea abies） and Zinnia elegans. In addition, real time （RT-）PCR results have pointed out that many peroxidases have tissue specific expression patterns in Norway spruce. Through combining information on catalytic properties of the enzymes, on the expression patterns of the corresponding genes, and on the presence of monolignols and hydrogen peroxide in the apoplastic space, we can show that specific peroxidases catalyze lignin polymerization in the apoplastic space of Norway spruce xylem.
基金the National Natural Science Foundation of China(Grant No.20677033)the special fund of State Key Joint Laboratory of Environment Simulation and Pollution Control,China(08Z01ESPCT).
文摘Manganese peroxidases(MnP)from Phanerochaete chrysosporium were adsorbed onto multi-walled carbon nanotubes(MWNT).Four different loadings of MnP on MWNTs were investigated,and the maximum enzyme loading of 47.5µg/mg of MWNTs was obtained in 12 h.The adsorbed MnP showed a catalytic activity of up to 0.1 U/mg of the weight of the system of MnP/MWNTs,with 23%of its original activity retained.The AFM image of the adsorbed enzymes indicated that a layer of MnP covered the surface of the MWNTs and retained its original three-dimensional shape.Amino-based nonspecific interactions may play the dominant role in the adsorption of MnP on MWNTs.
基金financially supported by the National Key Research and Development Program of China(2022YFF1102500)the Key Research and Development Projects in Hubei Province,China(2021BCA113).
文摘Zearalenone(ZEN),a mycotoxin present in cereals,poses significant health risks to animals and humans due to its estrogenic effects.Numerous studies on the enzymatic detoxification of ZEN have predominantly focused on reducing the parent toxin to assess the enzyme’s efficacy,yet there is limited research on the identification and toxicity evaluation of the enzymatic degradation products.This study investigated the enzymatic degradation mechanisms of ZEN using commercial peroxidase(POD)and laccase(LC),with a focus on identifying degradation products and assessing their hepatotoxicity effects.Molecular docking and dynamics simulations elucidated the binding mechanisms between these enzymes and ZEN,revealing strong interactions that facilitate efficient detoxification.Subsequent analysis employing ultra-high performance liquid chromatography-high resolution mass spectrometry(UHPLC-HRMS)successfully identified crucial degradation products.Hepatic toxicity of the enzymatic degradation products was comprehensively assessed in HepaRG liver cells through systematic measurements of cell viability,oxidative stress,apoptosis,mitochondrial membrane potential,and molecular metabolic profiles.Our findings demonstrate that both POD and LC exhibit significant efficacy in mitigating hepatocyte toxicity induced by ZEN,thereby highlighting their potential utility in enhancing food safety.This research provides essential data for safety evaluation regarding enzymatic detoxification of ZEN while offering theoretical and technical resources for risk assessment related to mycotoxin enzymatic detoxification.
基金supported by the Department of Education of Guangdong Province (No.2023KTSCX024)the Project of Traditional Chinese Medicine Bureau of Guangdong Province(No.20251091)+3 种基金the Joint Funds of the National Natural Science Foundation of China (No.U22A20368)the Key-Area Research and Development Program of Guangdong Province (No.2020B1111100004)Guangdong Basic and Applied Basic Research Foundation (No.2020B1515130005)Shenzhen Baoan District Science and Technology Innovation Bureau Project(Nos.2022JD226 and 2023JD252)。
文摘Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy. Dendrobium officinale(D. officinale), a renowned traditional Chinese medicinal herb, is widely used in several Asian countries for its nutritional and therapeutic benefits.Although D. officinale has demonstrated anti-tumor effects, the molecular mechanisms underlying its action against CRC remain incompletely characterized. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4(GPX4), a key suppressor of ferroptosis. In vitro assays were conducted using HCT116 and SW480 CRC cell lines, and in vivo efficacy was evaluated in BALB/c nude mice bearing CRC xenografts. D. officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. Induction of ferroptosis was evidenced by elevated levels of Fe^(2+), malondialdehyde(MDA), and lipid peroxidation, along with a depleted glutathione/oxidized glutathione disulfide(GSH/GSSG) ratio. Notably, these effects were reversed by ferroptosis inhibitors, including ferrostatin-1(Fer-1) and deferoxamine. Consistently, D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, whereas GPX4 silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis,providing a novel, naturally derived therapeutic approach. These findings bridge traditional medicine and modern oncology, establishing a foundation for developing targeted CRC treatments.
基金the National Natural Science Foundation of China,Nos.82311530117(to RJ),82260260(to FC).
文摘Ferroptosis plays a key role in nerve injury in intracerebral hemorrhage and is associated with the upregulation of murine double minute 2.Investigating the mechanism underlying murine double minute 2-related ferroptosis could help identify new therapies for intracerebral hemorrhage.An in vitro intracerebral hemorrhage model was established by treating BV2 microglial cells with oxygen-glucose deprivation combined with hemin.The role of murine double minute 2 in regulating ferroptosis was investigated via transduction with RNA interference and lentivirus overexpression.Furthermore,intracerebral hemorrhage mouse models were constructed with and without an murine double minute 2 inhibitor(brigimadlin),and behavioral assays were performed to assess the learning ability and cognitive function.Murine double minute 2 dysregulation was associated with oxygen-glucose deprivation combined with hemin-induced BV2 microglial cell ferroptosis and M1/M2 polarization.The results suggested that murine double minute 2 induced glutathione peroxidase 4 ubiquitination and degradation to regulate ferroptosis and inflammatory responses in BV2 microglial cells.Mechanistically,Wilms tumor 1-associated protein induced murine double minute 2 N6-methyladenosine(m6A)modification and regulated ferroptosis and inflammatory responses.In vivo analysis showed that brigimadlin improved neurological deficits and spatial memory in mice with intracerebral hemorrhage.In summary,the results indicate that Wilms tumor 1-associated protein regulates murine double minute 2 m6A modification,and murine double minute 2 induces glutathione peroxidase 4 ubiquitination and degradation.This regulation promotes ferroptosis and inflammatory responses in oxygen-glucose deprivation combined with hemin-induced BV2 microglial cells,suggesting that the murine double minute 2-glutathione peroxidase 4-ferroptosis regulatory axis exerts neurotoxic effects.These findings identify glutathione peroxidase 4 as a potential gene therapy target for intracerebral hemorrhage-related brain injury.
基金funding program(ORF-2025-1037)at King Saud University,Riyadh,Saudi Arabia.
文摘Objective:Glioblastoma(GB)therapy is challenged by tumor heterogeneity and multidrug resistance(MDR),highlighting the need for effective therapies.This study aimed to explore the combined anticancer effects of Sunitinib(SNB)and Fenofibrate(FEN)on U87 cells.Methods:U87 cells were exposed to SNB,FEN,or their combination for 24 h,followed by evaluations of cell viability,migration,and clonogenic survival using MTT,scratch,and colony formation assays.Intracellular reactive oxygen species(ROS)were quantified via the 2′,7′-dichlorofluorescein assay,while mitochondrial membrane potential(MMP)was assessed using JC-1 red/green fluorescence.Molecular docking was performed to investigate SNB and FEN interactions with multiple molecular targets,including topoisomerase II(TOP-II),c-Jun N-terminal kinase(JNK),histone deacetylase 2(HDAC2),cyclooxygenase-2(COX-2),matrix metalloproteinase-9(MMP-9),cytochrome P4503A4(CYP3A4),glutathione peroxidase 4(GPX4),glutathione Stransferase(GST),heme oxygenase-1(HO-1),and 5-lipoxygenase(5-LOX).Results:The results demonstrated that both SNB and FEN significantly reduced U87 cell viability,migration,and clonogenic potential,with the combination treatment exhibiting synergistic cytotoxicity.SNB alone markedly increased ROS levels,while FEN,individually or in combination,reduced oxidative stress.Although SNB diminished mitochondrial membrane potential,cotreatment with FEN restored MMP values close to control levels.Docking analyses revealed that SNB displayed strong affinities for TOP-II,JNK,and HDAC2,whereas FEN preferentially interacted with MMP-9,COX-2,CYP3A4,and GPX4,suggesting complementary mechanisms targeting oxidative stress,inflammation,and programmed cell death regulation.Conclusion:The combination of SNB and FEN represents a promising multi-targeted therapeutic approach against GB.SNB and FEN combination capable of modulating and reprogramming key molecular pathways involved in GB progression and MDR.
基金supported by the National Natural Science Foundation of China,Nos.81672161,81871785,82372411(to ZY)the Health Research Project of Health Commission of Anhui Province,No.AHWJ2023A30106(to YX).
文摘Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function.Cystine-glutamate transporter SLC7A11 is essential for maintaining cellular redox homeostasis and resisting ferroptosis.However,the mechanisms underlying neuronal ferroptosis caused by SLC7A11 downregulation following spinal cord injury remain unclear.Herein,we provide evidence that tumor protein 53,a negative regulator of SLC7A11,was significantly upregulated post-spinal cord injury.Transcriptomic analysis indicated that tumor protein 53 was associated with injury severity.We subsequently confirmed that tumor protein 53 inhibition restored the expressions of SLC7A11 and glutathione peroxidase 4,alleviated neuronal ferroptosis,and improved neurological function in a contusion spinal cord injury rat model.The regulatory effects of tumor protein 53 on the transcription and ubiquitination of SLC7A11 were further elucidated using chromatin immunoprecipitation polymerase chain reaction and cleavage under targets and tagmentation techniques.Additionally,Kelch-like protein 4,an E3 ubiquitin ligase adaptor,was demonstrated to play an important role in the tumor protein 53-mediated ubiquitination of SLC7A11.In summary,the present study elucidated the possible mechanisms of tumor protein 53-mediated neuronal ferroptosis in spinal cord injury,thereby providing potential targets and insights for clinical translation.
基金supported by Regione Autonoma della Sardegna,pursuant to Regional Law 07 August 2007,n.7“Promotion of Scientific Research and Technological Innovation in Sardinia—UGOV Project RAS_CRP2023 CARRULilt Nazionale—5 per mille Program for the year 2022,LILT 2023 scientific-health research call,Number:LILT—Protocol number 2024U0001294 of 29.03.2024。
文摘Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.Methods:This systematic review,registered in PROSPERO(CRD420251090058),followed PRISMA 2020 guidelines.Comprehensive research of PubMed,Scopus,and Web of Science was performed for studies published between January 2010 and July 2025 investigating ferroptosis mechanisms,genetic or pharmacological modulation,or molecular profiling in SCLC.Two reviewers independently performed data extraction and quality assessment.Results:Nineteen preclinical studies met the inclusion criteria.Key regulators included solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),ferroptosis suppressor protein 1(FSP1),and acyl-CoA synthetase long chain family member 4(ACSL4).The molecular subtypes of SCLC,achaete-scute homolog 1(ASCL1),neuronal differentiation 1(NEUROD1),POU class 2 homeobox 3(POU2F3),and Yes1 associated transcriptional regulator(YAP1)exhibit differential ferroptosis gene expressions,influencing therapeutic responsiveness.Non-neuroendocrine subtypes are more ferroptosis-prone,whereas neuroendocrine variants display enhanced antioxidant defenses.Ferroptosis induction also promotes immune activation through stimulator of interferon genes(STING)-mediated CD8+T-cell recruitment.Conclusions:Ferroptosis constitutes a promising therapeutic axis in SCLC.Integrating ferroptosis biomarkers into molecular stratification frameworks could refine patient selection and support precision oncology strategies,warranting further translational and clinical validation.
基金“Dawn”Program of Shanghai Education Commission,No.22SG37(to PY)the National Natural Science Foundation of China,Nos.82371313(to PY),82401536(to YongxinZ).
文摘Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.
基金We are grateful to the Ministry of Science and Technology(MOST)of Taiwan for providing financial support for this study under contracts 107-2113-M-002-015-MY3,and MOST 107-2113-M-018-005.
文摘Nanozymes have become attractive in analytical and biomedical fields,mainly because of their low cost,long shelf life,and less environmental sensitivity.Particularly,nanozymes formed from nanomaterials having high surface area and rich active sites are interesting since their activities can be tuned through carefully controlling their size,morphology,and surface properties.This review article focuses on preparation of carbon dots(C dots)possessing peroxidase-like activity and their analytical applications.We highlight the important roles of the oxidation states and surface residues of C dots and their nanocomposites with metal,metal oxides,or metal sulfides playing on determining their specificity and sensitivity toward H2O2.Examples of C dot nanozymes(CDzymes)for developing sensitive and selective absorption,fluorescence,and elec-trochemical sensing systems in the presence of substrates are presented to show their potential in analytical applications.For example,CDzymes couple with glucose oxidase and cholesterol oxidase are specific and sensitive for quantitation of glucose and cholesterol,separately,when using 3,3′,5,5′-tetramethylbenzidine(TMB)as the signal probe.This review article concludes with possible strategies for enhancing and tuning the catalytic activity of CDzymes.
基金supported by the National Key Research and Development Program of China(2021YFE0101800)the S&T Support Program of Jiangsu Province(BE2022324).
文摘Mycotoxins in grains pose severe threat to human and animal health.Previous studies showed that manganese peroxidases had degradation capability for various mycotoxins.In this work,to effectively detoxify aflatoxin B1(AFB1),zearalenone(ZEN)and deoxynivalenol(DON),the manganese peroxidases PhcMnp and IrlMnp from Phanerochaete chrysosporium and Irpex lacteus were successfully expressed in Pichia pastoris in a food-grade manner,and were used for degradation tests with the three mycotoxins.The fermentation supernatants containing PhcMnp achieved degradation ratios of 76.56%,70.78%and 48.93%for AFB1,ZEN and DON respectively,while that containing IrlMnp achieved degradation ratios of 46.72%,45.13%and 41.64%correspondingly.The inducible expression conditions for the enzymes and the reaction parameters for the mycotoxin degradations were both optimized.Furthermore,the fermentation supernatants of strain Pichia pastoris GS115(pPIC9K-Phcmnp)were used for mycotoxin degradations in contaminated peanut samples(pH 4.5)at 40℃ for 10 h,resulting in apparent detoxification effects.The residual concentrations of AFB1,ZEN and DON in peanut samples after degradations were 9.42,127.68 and 636.71μg/kg respectively,all of which remained below the legal limits.Results in this study demonstrated that the enzymes PhcMnp and IrlMnp have potentials in mycotoxins detoxification in feed industry.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.:2572016AA04)Northeast Asia Biodiversity Research Center Double First class Funds(Grant No.:411146030416 and No.:411147021003).
文摘Small heat shock proteins(sHSPs)act as molecular chaperones that can prevent the accumulation of damaged proteins during abiotic stress,especially heat shock,but the mechanism is not clear.To study the function of sHSPs in Lenzites gibbosa,a common polypore in northern temperate forests that causes spongy white rot of broadleaf trees,under temperature stress,L.gibbosa mycelia were grown at 25℃ for 9 d,treated at 33℃ for 15,30,60,and 120 min before sequencing the transcriptomes.From among 32 heat shock protein(HSP)genes found in the screen of the transcriptome data,a highly expressed gene was cloned and named Lghsp17.4.RT-qPCR was used to analyze the expression of the gene Lghsp17.4 under heat shock and dye stress.Both treatments induced higher expression of Lghsp17.4 at the transcriptional level,indicating that Lghsp17.4 might function in the response to heat stress and dye degradation.We previously found that L.gibbosa generally had a heat shock reaction(HSR)during degradation of aromatic compounds,and HSPs were always produced with manganese peroxidases(MnPs)and other lignin-degrading enzymes.Therefore,we measured the activity of MnPs in L.gibbosa after 33℃ heat shock to analyze the relationship between MnPs expression and Lghsp17.4 expression.Heat shocks of 0–30 min increased MnPs activity,and the change in MnPs activity were closely positively correlated with the expression levels of Lghsp17.4 over time,indicating a potential connection and interaction between LgHSP17.4 and MnPs during the HSR in L.gibbosa.Thus,LgHSP17.4 might have a positive regulatory effect on the HSR in L.gibbosa and be a critical component of a stress resistance mechanism.
基金supported by the Department of Defense AFIRMⅢW81XWH-20-2-0029 grant subcontractLone Star Paralysis gift,UT POC19-1774-13 grant+1 种基金Neuraptive Therapeutics Inc.26-7724-56 grantNational Institutes of Health R01-NS128086(all to GDB)。
文摘Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically poor.We used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor recovery.Furthermore,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles.In this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve.Young adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of PEG.Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site.The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively.At 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase.PEG-fusion repair reestablished axonal continuity.Compared to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal areas.Unexpectedly,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair.This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair,supporting the use of this novel repair methodology over currently available treatments.
