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
Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evoluti...Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.展开更多
BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b...BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.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
In this editorial,we comment on the article by Zhou et al published in a recent issue.We specifically focus on the crucial roles of ferroptosis and pyroptosis in acute liver failure(ALF),a disease with high mortality ...In this editorial,we comment on the article by Zhou et al published in a recent issue.We specifically focus on the crucial roles of ferroptosis and pyroptosis in acute liver failure(ALF),a disease with high mortality rates.Ferroptosis is the result of increased intracellular reactive oxygen species due to iron accumulation,glutathione(GSH)depletion,and decreased GSH peroxidase 4 activity,while pyroptosis is a procedural cell death mediated by gasdermin D which initiates a sustained inflammatory process.In this review,we describe the characteristics of ferroptosis and pyroptosis,and discuss the involvement of the two cell death modes in the onset and development of ALF.Furthermore,we summarize several interfering methods from the perspective of ferroptosis and pyroptosis for the alleviation of ALF.These observations might provide new targets and a theoretical basis for the treatment of ALF,which are also crucial for improving the prognosis of patients with ALF.展开更多
Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox...Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.展开更多
In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid...In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function.Ferroptosis and pyroptosis,cell death forms that can be initiated or blocked concurrently,can play significant roles in developing inflammation and various malignancies.However,their roles in ALF remain unclear.The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF,and revealed that the silent information regulator sirtuin 1(SIRT1)inhibits both pathways through p53,dramatically reducing inflammation and protecting hepatocytes.This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF.Thus,we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms.Additionally,we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways,as well as examples of SIRT1 activators being used as disease treatment strategies,providing new insights into the therapy of ALF.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
In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ d...In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.展开更多
Osmotic stress caused by low-temperature,drought and salinity was a prevalent abiotic stress in plant that severely inhibited plant development and agricultural yield,particularly in tea plant.Jasmonic acid(JA)is an i...Osmotic stress caused by low-temperature,drought and salinity was a prevalent abiotic stress in plant that severely inhibited plant development and agricultural yield,particularly in tea plant.Jasmonic acid(JA)is an important phytohormone involving in plant stress.However,underlying molecular mechanisms of JA modulated osmotic stress response remains unclear.In this study,high concentration of mannitol induced JA accumulation and increase of peroxidase activity in tea plant.Integrated transcriptome mined a JA signaling master,MYC2 transcription factor is shown as a hub regulator that induced by mannitol,expression of which positively correlated with JA biosynthetic genes(LOX and AOS)and peroxidase genes(PER).CsMYC2 was determined as a nuclei-localized transcription activator,furthermore,ProteinDNA interaction analysis indicated that CsMYC2 was positive regulator that activated the transcription of CsLOX7,CsAOS2,CsPER1 and CsPER3via bound with their promoters,respectively.Suppression of CsMYC2 expression resulted in a reduced JA content and peroxidase activity and osmotic stress tolerance of tea plant.Overexpression of CsMYC2 in Arabidopsis improved JA content,peroxidase activity and plants tolerance against mannitol stress.Together,we proposed a positive feedback loop mediated by CsMYC2,CsLOX7 and CsAOS2 which constituted to increase the tolerance of osmotic stress through fine-tuning the accumulation of JA levels and increase of POD activity in tea plant.展开更多
Breast cancer is a critical threat to women around the globe. Current radio- and chemotherapy regimens can induce multiple drug-resistant effects, e.g., anti-apoptosis, anti-pyroptosis, and anti-necroptosis, causing a...Breast cancer is a critical threat to women around the globe. Current radio- and chemotherapy regimens can induce multiple drug-resistant effects, e.g., anti-apoptosis, anti-pyroptosis, and anti-necroptosis, causing a poor clinical response to therapy. Ferroptosis is a newly programmed cell death characterized by iron overload, the massive production of reactive oxygen species (ROS), and membrane lipid peroxidation. The occurrence of ferroptosis results from an imbalance between peroxidation mechanisms (execution systems) and anti- oxidation mechanisms (defense systems), including the iron metabolism pathway, amino acid metabolism pathway, and lipid metabolism pathway. Recently, the vital role of ferroptosis in various diseases, including cancer, hypertension, diabetes, and Alzheimer's, has been identified. Specifically, triggering ferroptosis in breast cancer cells can inhibit their proliferation and invasion, and improve the chemoradiotherapy sensitivity, which makes it a potential strategy for breast cancer therapy. This review summarizes the definition and features of ferroptosis, as well as its role in the treatment of breast cancer, aimed at providing a theoretical basis for future drug development.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
The objective to this work was to evaluate the enzymatic activity in the culture of Solanum lycopersicum L.infected with Fusarium oxysporum after the combined application of Beauveria bassiana and plant extracts.Solan...The objective to this work was to evaluate the enzymatic activity in the culture of Solanum lycopersicum L.infected with Fusarium oxysporum after the combined application of Beauveria bassiana and plant extracts.Solanum lycopersicum plantlets were transplanted 15 days after the emergency.Five days after transplanting,Beauveria bassiana spores were applied at a concentration of 1×10^(7)spores mL^(−1)onto soil(along with A.indica(N)and P.auritum(H)leaf extracts)where S.lycopersicum plants were planted.Eight days after transplanting,spores of F.oxysporum strain were applied at a concentration of 1×10^(6)spores mL^(−1)to soil where S.lycopersicum plants were growing.The development of S.lycopersicum plants was monitored for 114 days,whereby a randomized complete block treatment design was used,the roots of the plants were crushed with liquid nitrogen,after which UV/VIS spectrophotometry was used to determine protein concentration,as well as the activity ofβ-1,3-glucanases,peroxidases(POX,EC1.11.1.7),catalase and chitinases.The treatments combining B.bassiana and A.indica and P.auritum extracts,had a significant difference in enzymatic activity levels,thus contributing to better defense mechanisms and a greater protection to S.lycopersicum plants in the presence of F.oxysporum.The application of B.bassiana and plant extracts to the ground mitigated damage caused by F.oxysporum on S.lycopersicum plants.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 National Natural Science Foundation of China,No.81501106(to CF)Fund of Taishan Scholar Project(to CF)+1 种基金the Natural Science Foundation of Shandong Province,No.ZR2020QH106(to YH)the Medical and Health Science and Technology Development Plan of Shandong Province,No.202203010799(to QS)。
文摘Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.
基金Supported by National Natural Science Foundation of China,No.82060123Doctoral Start-up Fund of Affiliated Hospital of Guizhou Medical University,No.gysybsky-2021-28+1 种基金Fund Project of Guizhou Provincial Science and Technology Department,No.[2020]1Y299Guizhou Provincial Health Commission,No.gzwjk2019-1-082。
文摘BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.
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.
文摘In this editorial,we comment on the article by Zhou et al published in a recent issue.We specifically focus on the crucial roles of ferroptosis and pyroptosis in acute liver failure(ALF),a disease with high mortality rates.Ferroptosis is the result of increased intracellular reactive oxygen species due to iron accumulation,glutathione(GSH)depletion,and decreased GSH peroxidase 4 activity,while pyroptosis is a procedural cell death mediated by gasdermin D which initiates a sustained inflammatory process.In this review,we describe the characteristics of ferroptosis and pyroptosis,and discuss the involvement of the two cell death modes in the onset and development of ALF.Furthermore,we summarize several interfering methods from the perspective of ferroptosis and pyroptosis for the alleviation of ALF.These observations might provide new targets and a theoretical basis for the treatment of ALF,which are also crucial for improving the prognosis of patients with ALF.
文摘Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.
基金Supported by The Hubei Provincial Natural Science Foundation of China,No.2020CFB656.
文摘In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function.Ferroptosis and pyroptosis,cell death forms that can be initiated or blocked concurrently,can play significant roles in developing inflammation and various malignancies.However,their roles in ALF remain unclear.The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF,and revealed that the silent information regulator sirtuin 1(SIRT1)inhibits both pathways through p53,dramatically reducing inflammation and protecting hepatocytes.This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF.Thus,we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms.Additionally,we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways,as well as examples of SIRT1 activators being used as disease treatment strategies,providing new insights into the therapy of ALF.
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.
基金Supported by China Medical University,No.CMU111-MF-10.
文摘In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.
基金supported by the National Natural Science Foundation of China(Grant Nos.32202542 and U20A2045)the Project of Major Science and Technology in Anhui Province(Grant No.202003a06020021)+2 种基金the Project of Science and Technology of Yunnan Province(Grant No.202102AE090038)Anhui Provincial Natural Science Foundation(Grant No.2108085QC121)the Natural Science Projects for Colleges and Universities in the Anhui Province(Grant No.KJ2021A0145)。
文摘Osmotic stress caused by low-temperature,drought and salinity was a prevalent abiotic stress in plant that severely inhibited plant development and agricultural yield,particularly in tea plant.Jasmonic acid(JA)is an important phytohormone involving in plant stress.However,underlying molecular mechanisms of JA modulated osmotic stress response remains unclear.In this study,high concentration of mannitol induced JA accumulation and increase of peroxidase activity in tea plant.Integrated transcriptome mined a JA signaling master,MYC2 transcription factor is shown as a hub regulator that induced by mannitol,expression of which positively correlated with JA biosynthetic genes(LOX and AOS)and peroxidase genes(PER).CsMYC2 was determined as a nuclei-localized transcription activator,furthermore,ProteinDNA interaction analysis indicated that CsMYC2 was positive regulator that activated the transcription of CsLOX7,CsAOS2,CsPER1 and CsPER3via bound with their promoters,respectively.Suppression of CsMYC2 expression resulted in a reduced JA content and peroxidase activity and osmotic stress tolerance of tea plant.Overexpression of CsMYC2 in Arabidopsis improved JA content,peroxidase activity and plants tolerance against mannitol stress.Together,we proposed a positive feedback loop mediated by CsMYC2,CsLOX7 and CsAOS2 which constituted to increase the tolerance of osmotic stress through fine-tuning the accumulation of JA levels and increase of POD activity in tea plant.
基金National Natural Science Foundation of China(No.82203813)。
文摘Breast cancer is a critical threat to women around the globe. Current radio- and chemotherapy regimens can induce multiple drug-resistant effects, e.g., anti-apoptosis, anti-pyroptosis, and anti-necroptosis, causing a poor clinical response to therapy. Ferroptosis is a newly programmed cell death characterized by iron overload, the massive production of reactive oxygen species (ROS), and membrane lipid peroxidation. The occurrence of ferroptosis results from an imbalance between peroxidation mechanisms (execution systems) and anti- oxidation mechanisms (defense systems), including the iron metabolism pathway, amino acid metabolism pathway, and lipid metabolism pathway. Recently, the vital role of ferroptosis in various diseases, including cancer, hypertension, diabetes, and Alzheimer's, has been identified. Specifically, triggering ferroptosis in breast cancer cells can inhibit their proliferation and invasion, and improve the chemoradiotherapy sensitivity, which makes it a potential strategy for breast cancer therapy. This review summarizes the definition and features of ferroptosis, as well as its role in the treatment of breast cancer, aimed at providing a theoretical basis for future drug development.
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funded by the Tecnológico Nacional de México(TECNM):Project No.6602.18-P.
文摘The objective to this work was to evaluate the enzymatic activity in the culture of Solanum lycopersicum L.infected with Fusarium oxysporum after the combined application of Beauveria bassiana and plant extracts.Solanum lycopersicum plantlets were transplanted 15 days after the emergency.Five days after transplanting,Beauveria bassiana spores were applied at a concentration of 1×10^(7)spores mL^(−1)onto soil(along with A.indica(N)and P.auritum(H)leaf extracts)where S.lycopersicum plants were planted.Eight days after transplanting,spores of F.oxysporum strain were applied at a concentration of 1×10^(6)spores mL^(−1)to soil where S.lycopersicum plants were growing.The development of S.lycopersicum plants was monitored for 114 days,whereby a randomized complete block treatment design was used,the roots of the plants were crushed with liquid nitrogen,after which UV/VIS spectrophotometry was used to determine protein concentration,as well as the activity ofβ-1,3-glucanases,peroxidases(POX,EC1.11.1.7),catalase and chitinases.The treatments combining B.bassiana and A.indica and P.auritum extracts,had a significant difference in enzymatic activity levels,thus contributing to better defense mechanisms and a greater protection to S.lycopersicum plants in the presence of F.oxysporum.The application of B.bassiana and plant extracts to the ground mitigated damage caused by F.oxysporum on S.lycopersicum plants.