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
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
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
Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial ant...Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.展开更多
Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an imp...Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.展开更多
Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16(CXCL16)in cancer correlates with poor prognosis,as well as tumor cell proliferation,migration,and invasion.While CXCL16 can ...Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16(CXCL16)in cancer correlates with poor prognosis,as well as tumor cell proliferation,migration,and invasion.While CXCL16 can serve as a tumor biomarker,the underlying mechanism in modulating head and neck squamous cell carcinoma(HNSCC)remains unclear.In this study,the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism.Hereby,we determined the high expression of CXCL16 in The Cancer Genome Atlas(TCGA)database,as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines.The results showed that CXCL16 knockdown inhibited the proliferation,migration,and invasion of HNSCC cells.Mechanistically,transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1(GPX1).The reactive oxygen species(ROS)levels were elevated in small interfering CXCL16(si-CXCL16)cells,which may contribute to the inhibition of cell proliferation,migration,and invasion.Moreover,treatment of cells with the GPX1 inhibitor eldecalcitol(ED-71)revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group.In conclusion,CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway.Thus,targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.展开更多
Selenium(Se),an essential micronutrient among the 15 vital elements required for human physiology,exerts its biological functions primarily through its incorporation into selenoproteins.To date,approximately 25 seleno...Selenium(Se),an essential micronutrient among the 15 vital elements required for human physiology,exerts its biological functions primarily through its incorporation into selenoproteins.To date,approximately 25 selenoproteins have been characterized in mammalian systems,including glutathione peroxidase(GPX),thioredoxin reductase(TrxR),and iodothyronine deiodinases(DIOs),all of which exhibit indispensable physiological functions.展开更多
[Objective] The effects of yttrium nitrate （YNO3） on biomass and antioxi- dant systems of paddy rice （Yttrium （Y）; Oxidative stress; Dismutases （SOD）; Per- oxidases （POD）, Catalases （CAT）, Paddy rice （Trit...[Objective] The effects of yttrium nitrate （YNO3） on biomass and antioxi- dant systems of paddy rice （Yttrium （Y）; Oxidative stress; Dismutases （SOD）; Per- oxidases （POD）, Catalases （CAT）, Paddy rice （Triticum aestivum）） together with the occurrences of Y in soils were investigated to assess its ecotoxicological effects on plant. [Method]Y solutions with various concentrations were sprinkled on soil sam- ples, which were well mixed and then put into culture dishes to culture paddy rice seeds for further evaluation. [Result] The results indicated that 25-100 mg/kg Y treatments significantly increased the biomass （total weight, root weight, shoot weight and leaf weight）, chlorophyll （CHL） content and protein content of paddy rice, whereas 200-800 mg/kg Y treatments had a converse effect. Similarly, biomarker for the antioxidant systems including superoxide dismutases （SOD）, peroxidases （POD） and catalases （CAT） all exhibited similar trends in both shoots and roots of paddy rice. At the same time, the malonaldehyde （MDA） content increased at from 25 to 100 mg/kg and decreased with concentrations of Y from 100 to 800 mg/kg in both shoots and roots of paddy rice. This indicated that Y could stimulate the growth of plant at low concentration, but inhibit the growth at relatively high concen- tration. [Conclusion] The levels of Y were 641＋49, 328_＋16 and 473_＋40 mg/kg in soils collected from mining area, farmland and navel orange orchard respectively. The levels of Y in the investigated area were higher than the benefit level （100 mg/kg）, which could cause low biomass as well as low activity of SOD, POD and CAT in paddy rice. Therefore, a more careful use of Y is necessary in crop management.展开更多
Nanozymes,characterized by their stability,cost-effectiveness,and tunable catalytic activity,are promising alternatives to natural enzymes.However,specifically mimicking a single natural enzyme's activity presents...Nanozymes,characterized by their stability,cost-effectiveness,and tunable catalytic activity,are promising alternatives to natural enzymes.However,specifically mimicking a single natural enzyme's activity presents a challenge.By exploiting the catalytic selectivity derived from the valence-band hybridization of noble metal nanoalloys,we introduce an alloying strategy to modulate the reaction specificity of metallic nanozymes.Ag Pd nanoalloy exhibits enhanced peroxidase-like activity and eliminated oxidase-like activity by adjusting the Ag content.The introduction of Ag changes the hybrid d band energy of the alloyed metal and inhibits the O_(2)adsorption and decomposition on Pd,while improving the peroxidase mimicry by allowing for the H_(2)O_(2)activation.By exemplifying the construction of a highly sensitive and selective colorimetric glucose detection platform with its practicality validated in serum samples,this strategy pioneers a multi-noble metal nanozyme with tailored peroxidase activity based on the chemical structure engineering and would advance the development of single-catalytic function nanozymes for building exclusively specific biosensors through reducing substrate competition.展开更多
Objective:Ferroptosis represents a form of cell death characterized by the accumulation of iron dependent lipid peroxidation.This process culminates in membrane damage and cell lysis.One pivotal surveillance mechanism...Objective:Ferroptosis represents a form of cell death characterized by the accumulation of iron dependent lipid peroxidation.This process culminates in membrane damage and cell lysis.One pivotal surveillance mechanism is induced by glutathione peroxidase 4(GPX4).Furthermore,inhibition of GPX4 has been reported to hold a promise effect in cancer therapeutics.Methods:Computer-aided docking and small molecule probe were used for designed compounds.Flow cytometry was used to evaluate the ferroptosis.Animal experiments were taken to evaluate the in vivo effect of two compounds.Results:Based on our prior research,a series of twenty compounds with covalent binding potential was designed and synthesized.Under systematic evaluation,our team identified two small molecules 14 and 16,which significantly stabilized GPX4 thermal denaturation.Further investigations revealed that treatment with compounds14 and 16 led to an increase in lipid peroxidation,oxidative stress,and other markers(C11,Fe^(2+) and ROS)levels also increased.In both in vivo and in vitro experiment,compounds 14 and 16 are found suppression effect on urological cancer cells.Conclusions:Compounds 14 and 16 deserve further works as lead compounds of novel docking models for finally discovering effective anti-tumor drug.Future research is needed to dissect their mechanism and exploits this scaffold for GPX4 inhibitor development.展开更多
Eye depth is an important agronomic trait affecting tubers'appearance,quality,and processing suitability.Hence,cultivating varieties with uniform shapes and shallow eye depth are important goals for potato breedin...Eye depth is an important agronomic trait affecting tubers'appearance,quality,and processing suitability.Hence,cultivating varieties with uniform shapes and shallow eye depth are important goals for potato breeding.In this study,based on the primary mapping of the tuber eyedepth locus using a small primary-segregating population,a large secondary-segregating population with 2100 individuals was used to map the eye-depth locus further.A major quantitative trait locus for eye-depth on chromosome 10 was identified(designated qEyd10.1)using BSAseq and traditional QTL mapping methods.The qEyd10.1 could explain 55.0%of the eye depth phenotypic variation and was further narrowed to a 309.10 kb interval using recombinant analysis.To predict candidate genes,tissue sectioning and RNA-seq of the specific tuber tissues were performed.Genes encoding members of the peroxidase superfamily with likely roles in indole acetic acid regulation were considered the most promising candidates.These results will facilitate marker-assisted selection for the shallow-eye trait in potato breeding and provide a solid basis for eye-depth gene cloning and the analysis of tuber eye-depth regulatory mechanisms.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 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.
文摘Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.
基金supported by the National Natural Science Foundation of China(82270386,82070252,and 8207025)the Zhejiang Provincial Medical and Health Science and Technology Plan(2023RC020)the Zhejiang Provincial Natural Science Foundation(LR21H020001).
文摘Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.
基金supported by the Scientific Research Fund of the National Health Commission-Zhejiang Provincial Health Major Science and Technology Plan Project(No.WKJ-ZJ-2415)the Key Research and Development Program of Zhejiang Province(No.2024C03166)+1 种基金the Traditional Chinese Medicine Science and Technology Project of Zhejiang Province(No.2022ZB020)the Zhejiang Provincial Natural Science Foundation of China(No.LY21H160049).
文摘Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16(CXCL16)in cancer correlates with poor prognosis,as well as tumor cell proliferation,migration,and invasion.While CXCL16 can serve as a tumor biomarker,the underlying mechanism in modulating head and neck squamous cell carcinoma(HNSCC)remains unclear.In this study,the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism.Hereby,we determined the high expression of CXCL16 in The Cancer Genome Atlas(TCGA)database,as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines.The results showed that CXCL16 knockdown inhibited the proliferation,migration,and invasion of HNSCC cells.Mechanistically,transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1(GPX1).The reactive oxygen species(ROS)levels were elevated in small interfering CXCL16(si-CXCL16)cells,which may contribute to the inhibition of cell proliferation,migration,and invasion.Moreover,treatment of cells with the GPX1 inhibitor eldecalcitol(ED-71)revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group.In conclusion,CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway.Thus,targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.
基金Financial support from the Science and Technology Innovation Program of Hunan Province(No.2022RC4044)。
文摘Selenium(Se),an essential micronutrient among the 15 vital elements required for human physiology,exerts its biological functions primarily through its incorporation into selenoproteins.To date,approximately 25 selenoproteins have been characterized in mammalian systems,including glutathione peroxidase(GPX),thioredoxin reductase(TrxR),and iodothyronine deiodinases(DIOs),all of which exhibit indispensable physiological functions.
基金Supported by the National Natural Science Foundation of China(21067003,51364015)the National High-Tech Research and Development Program of China(2012BAC11B07)the Jiangxi Natural Science Foundation(20114BAB203024)~~
文摘[Objective] The effects of yttrium nitrate （YNO3） on biomass and antioxi- dant systems of paddy rice （Yttrium （Y）; Oxidative stress; Dismutases （SOD）; Per- oxidases （POD）, Catalases （CAT）, Paddy rice （Triticum aestivum）） together with the occurrences of Y in soils were investigated to assess its ecotoxicological effects on plant. [Method]Y solutions with various concentrations were sprinkled on soil sam- ples, which were well mixed and then put into culture dishes to culture paddy rice seeds for further evaluation. [Result] The results indicated that 25-100 mg/kg Y treatments significantly increased the biomass （total weight, root weight, shoot weight and leaf weight）, chlorophyll （CHL） content and protein content of paddy rice, whereas 200-800 mg/kg Y treatments had a converse effect. Similarly, biomarker for the antioxidant systems including superoxide dismutases （SOD）, peroxidases （POD） and catalases （CAT） all exhibited similar trends in both shoots and roots of paddy rice. At the same time, the malonaldehyde （MDA） content increased at from 25 to 100 mg/kg and decreased with concentrations of Y from 100 to 800 mg/kg in both shoots and roots of paddy rice. This indicated that Y could stimulate the growth of plant at low concentration, but inhibit the growth at relatively high concen- tration. [Conclusion] The levels of Y were 641＋49, 328_＋16 and 473_＋40 mg/kg in soils collected from mining area, farmland and navel orange orchard respectively. The levels of Y in the investigated area were higher than the benefit level （100 mg/kg）, which could cause low biomass as well as low activity of SOD, POD and CAT in paddy rice. Therefore, a more careful use of Y is necessary in crop management.
基金financially supported by the National Natural Science Foundation of China(No.22074038)the Luoyang Institute of Science and Technology Natural Science General Project(No.21010905)+1 种基金the Fundamental Research Funds for the Central Universitiessponsored by the Domestic Visiting Scholar Program of Shandong University of Science and Technology。
文摘Nanozymes,characterized by their stability,cost-effectiveness,and tunable catalytic activity,are promising alternatives to natural enzymes.However,specifically mimicking a single natural enzyme's activity presents a challenge.By exploiting the catalytic selectivity derived from the valence-band hybridization of noble metal nanoalloys,we introduce an alloying strategy to modulate the reaction specificity of metallic nanozymes.Ag Pd nanoalloy exhibits enhanced peroxidase-like activity and eliminated oxidase-like activity by adjusting the Ag content.The introduction of Ag changes the hybrid d band energy of the alloyed metal and inhibits the O_(2)adsorption and decomposition on Pd,while improving the peroxidase mimicry by allowing for the H_(2)O_(2)activation.By exemplifying the construction of a highly sensitive and selective colorimetric glucose detection platform with its practicality validated in serum samples,this strategy pioneers a multi-noble metal nanozyme with tailored peroxidase activity based on the chemical structure engineering and would advance the development of single-catalytic function nanozymes for building exclusively specific biosensors through reducing substrate competition.
基金supported by the Natural Science Foundation of Hubei Province(No.2023AFB1021)。
文摘Objective:Ferroptosis represents a form of cell death characterized by the accumulation of iron dependent lipid peroxidation.This process culminates in membrane damage and cell lysis.One pivotal surveillance mechanism is induced by glutathione peroxidase 4(GPX4).Furthermore,inhibition of GPX4 has been reported to hold a promise effect in cancer therapeutics.Methods:Computer-aided docking and small molecule probe were used for designed compounds.Flow cytometry was used to evaluate the ferroptosis.Animal experiments were taken to evaluate the in vivo effect of two compounds.Results:Based on our prior research,a series of twenty compounds with covalent binding potential was designed and synthesized.Under systematic evaluation,our team identified two small molecules 14 and 16,which significantly stabilized GPX4 thermal denaturation.Further investigations revealed that treatment with compounds14 and 16 led to an increase in lipid peroxidation,oxidative stress,and other markers(C11,Fe^(2+) and ROS)levels also increased.In both in vivo and in vitro experiment,compounds 14 and 16 are found suppression effect on urological cancer cells.Conclusions:Compounds 14 and 16 deserve further works as lead compounds of novel docking models for finally discovering effective anti-tumor drug.Future research is needed to dissect their mechanism and exploits this scaffold for GPX4 inhibitor development.
基金funded by the National Natural Science Foundation of China(Grant No.31801421)the Chinese Academy of Agricultural Sciences Innovation Project(Grant No.CAAS-ASTIPIVFCAAS).
文摘Eye depth is an important agronomic trait affecting tubers'appearance,quality,and processing suitability.Hence,cultivating varieties with uniform shapes and shallow eye depth are important goals for potato breeding.In this study,based on the primary mapping of the tuber eyedepth locus using a small primary-segregating population,a large secondary-segregating population with 2100 individuals was used to map the eye-depth locus further.A major quantitative trait locus for eye-depth on chromosome 10 was identified(designated qEyd10.1)using BSAseq and traditional QTL mapping methods.The qEyd10.1 could explain 55.0%of the eye depth phenotypic variation and was further narrowed to a 309.10 kb interval using recombinant analysis.To predict candidate genes,tissue sectioning and RNA-seq of the specific tuber tissues were performed.Genes encoding members of the peroxidase superfamily with likely roles in indole acetic acid regulation were considered the most promising candidates.These results will facilitate marker-assisted selection for the shallow-eye trait in potato breeding and provide a solid basis for eye-depth gene cloning and the analysis of tuber eye-depth regulatory mechanisms.
