Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to r...Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis.The only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial effects.The difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis pathogenesis.Among mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious circle.Sharpening the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and inflammation.We here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Sin...Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.展开更多
In this study,we investigated the effects of different concentrations of 5-azacytidine(AZA),a DNA methyltransferase in-hibitor,on the growth,antioxidant activities and germination of pellicle cysts of Scrippsiella acu...In this study,we investigated the effects of different concentrations of 5-azacytidine(AZA),a DNA methyltransferase in-hibitor,on the growth,antioxidant activities and germination of pellicle cysts of Scrippsiella acuminata.The purpose of this study is to understand the toxic effects of AZA on marine microalgae,and to demonstrate the effect of DNA methyltransferase inhibitors on the germination of pellicle cysts.Results showed that AZA inhibited the growth of S.acuminata significantly,and displaced a clear dose-dependent inhibition trend with the 96h EC50 of 146.77μmolL^(-1)(35.84mgL^(-1)).Pellicle cysts of S.acuminata were less sensitive to AZA than the vegetative cells,and the EC50 value of AZA to the germination of pellicle cysts of S.acuminata was 8.08mmolL^(-1)(1.97g L^(-1)).After exposed to AZA,the antioxidant activities in S.acuminata responded rapidly and significantly.Among them,soluble pro-tein and superoxide dismutase(SOD)were more sensitive to AZA,and significant promotions occurred after exposed to 10μmolL^(-1)AZA for 24h.Meanwhile,malondialdehyde(MDA)contents in algal cells did not change significantly after exposed to low concen-trations of AZA,but increased firstly and then decreased under high concentration of AZA.The glutathione(GSH)levels in S.acu-minata increased significantly under high concentrations of AZA,and remained unchanged at low concentrations of AZA.The results suggested that the enhanced protein level and SOD activity of S.acuminata eliminated reactive oxygen species(ROS)to a certain ex-tent,and thus protected algal cells against damages of ROS caused by AZA.展开更多
Objective:The imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer(BC).This study aimed to evaluate serum antioxidant status in patients with BC and determine its pot...Objective:The imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer(BC).This study aimed to evaluate serum antioxidant status in patients with BC and determine its potential use in the diagnosis and progression potential considerations following histopathological assessment.Methods:A cross-sectional study included 90 patients with BC,divided into Ta,T1,and T2eT4 stage subgroups,and according to cancer progression potential,into low-grade(LG)and highgrade(HG)subgroups.The control group(CG)included 30 healthy volunteers.Antioxidant status was determined using the spectrophotometric method and standard laboratory tests.Results:Serum superoxide dismutase activity was significantly higher in BC patients regarding cancer stage in comparison to the CG(p<0.001).Catalase activity was highest in T2eT4 subgroup and was significantly higher compared to the Ta(p<0.01)and T1(p<0.05)subgroups.Serum albumin level was significantly lower in the BC group compared to the CG(p<0.001).In addition,it was significantly lower in T2eT4 subgroup compared to T1 and Ta subgroups(p<0.01).A significant negative correlation was found between tumor size and serum albumin level only(r=0.386,p<0.01).Catalase activity was higher in HG subgroup(p=0.009),while bilirubin level was higher in LG subgroup(p=0.035).The optimal cut-off value of catalase activity in differentiating patients with LG and HG BC subgroups was 11.96 IU/L,and the specificity and sensitivity were 51.1% and 82.2%,respectively.Bilirubin level,for a calculated optimal cut-off value of 11.95 mmol/L,had a specificity of 44.1%and sensitivity of 80.0%.Conclusion:More invasive stages of BC with greater progression potential are associated with an increase in enzymatic antioxidant activity and a decrease in non-enzymatic antioxidant capacity.It may suggest a possible role of antioxidants in the prediction and monitoring of illness trajectory.展开更多
BACKGROUND Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori(H.pylori)infections.Therefore,there is an urgent need to develop new antimicrobial agents to r...BACKGROUND Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori(H.pylori)infections.Therefore,there is an urgent need to develop new antimicrobial agents to replace antibiotics.Our previous study found that linolenic acid-metronidazole(Lla-Met)has a good antibacterial effect against H.pylori,both antibiotic-resistant and sensitive H.pylori.Also,H.pylori does not develop resistance to Lla-Met.Therefore,it could be used for preparing broad-spectrum antibacterial agents.However,since the antibacterial mechanism of Lla-Met is not well understood,we explored this phenomenon in the present study.AIM To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections.METHODS H.pylori cells were treated with the Lla-Met compound,and the effect of the compound on the cell morphology,cell membrane permeability,and oxidation of the bacteria cell was assessed.Meanwhile,the differently expressed genes in H.pylori in response to Lla-Met treatment were identified.RESULTS Lla-Met treatment induced several changes in H.pylori cells,including roughening and swelling.In vivo experiments revealed that Lla-Met induced oxidation,DNA fragmentation,and phosphatidylserine ectropionation in H.pylori cells.Inhibiting Lla-Met with L-cysteine abrogated the above phenomena.Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes,both anti-oxidation-related genes.CONCLUSION Lla-Met kills H.pylori mainly by inducing oxidative stress,DNA damage,phosphatidylserine ectropionation,and changes on cell morphology.展开更多
Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a signifi...Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge.Inspired by metalloenzymes with well-defined coordination structures,a series of MOFs containing halogen-coordinated copper nodes(Cu-X MOFs,X=Cl,Br,I)are employed to elucidate their structure–activity relationship.Intriguingly,experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center.The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes.More importantly,by performing enzyme-mimicking catalysis,the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress,thus effectively relieving ocular chemical burns.Mechanistically,the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways.Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and,more significantly,demonstrating their potential therapeutic effect in ophthalmic disease.展开更多
Wheat embryo globulin(WEG)has been proven to possess multiple biological activities,including antioxidative properties,immunomodulatory,and so on.Aged mouse model were established by subcutaneous injection of D-galact...Wheat embryo globulin(WEG)has been proven to possess multiple biological activities,including antioxidative properties,immunomodulatory,and so on.Aged mouse model were established by subcutaneous injection of D-galactose(D-gal),and the effects of WEG on learning,memory,and antioxidant capacity in aging mice were explored through behavioural tests and antioxidant enzyme activities determination.Compared with the Model group,WEG improved the percentage of the platform quadrant,increased the number of crossing platforms,and enhanced the identification indexs.WEG also increased total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)activities in the liver and brains of aging mice,and reduced malondialdehyde(MDA)content.Pathological observations indicated that WEG protected against damage to brain in D-gal-induced aging mice.These results effectively revealed that WEG not only improved the abilities of learning and memory,and the cognitive impairment,but also delayed the aging process of the D-gal-induced mice.展开更多
We reviewed recent major clinical trials with investigational drugs for the treatment of subjects with neurodegenerative diseases caused by inheritance of gene mutations or associated with genetic risk factors.Specifi...We reviewed recent major clinical trials with investigational drugs for the treatment of subjects with neurodegenerative diseases caused by inheritance of gene mutations or associated with genetic risk factors.Specifically,we discussed randomized clinical trials in subjects with Alzheimer's disease,Huntington's disease and amyotrophic lateral sclerosis bearing pathogenic gene mutations,and glucocerebrosidase-associated Parkinson's disease.Learning potential lessons to improve future therapeutic approaches is the aim of this review.Two long-term,controlled trials on three anti-β-amyloid monoclonal antibodies(solanezumab,gantenerumab and crenezumab)in subjects carrying Alzheimer's disease-linked mutated genes encoding for amyloid precursor protein or presenilin 1 or presenilin 2 failed to show cognitive or functional benefits.A major trial on tominersen,an antisense oligonucleotide designed to reduce the production of the huntingtin protein in subjects with Huntington's disease,was prematurely interrupted because the drug failed to show higher efficacy than placebo and,at highest doses,led to worsened outcomes.A 28-week trial of tofersen,an antisense oligonucleotide for superoxide dismutase 1 in patients with amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutations failed to show significant beneficial effects but the 1-year open label extension of this study indicated better clinical and functional outcomes in the group with early tofersen therapy.A trial of venglustat,a potent and brain-penetrant glucosylceramide synthase inhibitor,in Parkinson's disease subjects with heterozygous glucocerebrosidase gene mutations revealed worsened clinical and cognitive performance of patients on the enzyme inhibitor compared to placebo.We concluded that clinical trials in neurodegenerative diseases with a genetic basis should test monoclonal antibodies,antisense oligonucleotides or gene editing directed against the mutated enzyme or the mutated substrate without dramatically affecting physiological wild-type variants.展开更多
Lime-induced iron chlorosis is a major nutritional disorder causing severe plant growth and yield reduction in the calcareous soils of Tunisia.The understanding the behavior of key metabolic functions of peas on calca...Lime-induced iron chlorosis is a major nutritional disorder causing severe plant growth and yield reduction in the calcareous soils of Tunisia.The understanding the behavior of key metabolic functions of peas on calcareous soils,the identification of useful traits of tolerance,and the exploration of the genotypic differences in response to this constraint remain the most efficient approaches due to their coast,environmental benefits,and sustainability.For this purpose,a greenhouse experiment was conducted on three pea genotypes(Alexandra:Alex,Douce de provence:DP,and Merveille de Kelvedon:MK)cultivated on calcareous soil(Fe-deficient)and fertile soil(control).Plant growth,SPAD index,iron nutrition and distribution,photosynthesis,and antioxidant enzymes were deeply analyzed to discriminate genotypic differences.Calcareous-induced iron deficiency reduced SPAD index,plant growth,net photosynthesis,and tissue Fe content against a significant stimulation of the oxidative stress indicators,H2O2 and Malondialdehyde(MDA).Moreover,we reported a significant induction of SOD and CAT activity in shoots and roots of the Alexandra genotype.Fe use efficiency increased on calcareous soil and clearly discriminated the studied genotypes.Alexandra genotype was found to be the most tolerant to lime-induced iron chlorosis.This genotype protects its tissues against oxidative stress by stimulating enzyme activities(SOD and CAT)and develops significant efficiency of Fe uptake,translocation to shoots and use when cultivated on calcareous soil.展开更多
Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammo...Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammonium citrate was added to the macrophage cell line(RAW264.7)to establish an iron-overloaded macrophage model.Cell counting kit 8 assay was used to detect cell viability.Superoxide dismutase,reactive oxygen species,malondialdehyde,and apoptosis were performed to analyze the severity of cellular oxidative damage.In addition,quantitative real-time polymerase chain reaction and western blot were used to detect the expression of nuclear factor erythroid 2-related factor 2.Results:The result showed that iron overload of macrophage was visualized by incubating in 40μM ferric ammonium citrate for 24 h.The curcumin significantly reversed the iron overload-induced apoptotic cells at low(10μM)and middle(20μM)concentrations.Additionally,the levels of malondialdehyde and reactive oxygen species activity in the groups of curcumin at low(10μM)and middle(20μM)concentrations were significantly decreased,while superoxide dismutase activity was obviously increased compared with that of the ferric ammonium citrate group alone.Finally,we found that low(10μM)and middle(20μM)dose curcumin up-regulated nuclear factor erythroid 2-related factor 2 expression at mRNA and protein levels compared with the ferric ammonium citrate group alone.Conclusion:Curcumin reduces iron-overloaded stress in macrophages by activating nuclear factor erythroid 2-related factor 2 and enhancing the superoxide dismutase activity,thereby protecting cell apoptosis.展开更多
Background:The prime objective of the current research was to evaluate the whole plant hydroalcoholic extract of Ludwigia octovalvis(HLO)against hyperglycemia,and oxidative stress biomarkers in rats induced with diabe...Background:The prime objective of the current research was to evaluate the whole plant hydroalcoholic extract of Ludwigia octovalvis(HLO)against hyperglycemia,and oxidative stress biomarkers in rats induced with diabetes comorbid depression,diabetes comorbid depression(streptozotocin-nicotinamide+electric footshocks).Methods:2,2-Diphenyl-1-picrylhydrazyl assay of HLO versus ascorbic acid was done.Effects of 200 and 400 mg/kg body weight/day HLO doses versus 25 mg/kg body weight/day metformin was studied through insulin,glucose,superoxide dismutase,lipid peroxidation,catalase,and behavioral assessment(forced swim and open field tests).Results:IC50 values of HLO and ascorbic acid were 33.52 and 27.86μg/mL respectively.Both the HLO doses showed intended results with respect to oxidative stress biomarkers in diabetes comorbid depression rats in comparison to metformin.Open field test showed better results for HLO in diabetes comorbid depression rats.However,hypoglycemic effects,and forced swim test performance of metformin was slightly higher than the 400 mg dose,followed by the 200 mg dose of HLO.Ethyl gallate,gallic acid,β-sitosterol,and quercetin in HLO might resulted in attenuating diabetic as well as depression biomarkers.Conclusion:Inhibition of glucosidase and lipase activity,and AMP-activated protein kinase phosphorylation might be the possible biochemical changes occurred in HLO treated rats.展开更多
Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur(TG)amyotrophic lateral sclerosis mouse model.However,most studies have only examined heterogenous nuclear ribonucl...Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur(TG)amyotrophic lateral sclerosis mouse model.However,most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown.In this study,we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis.Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting,and cell proliferation and proteins(TAR DNA binding protein 43,superoxide dismutase 1,and Bax)were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells.We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins.Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons.Amyotrophic lateral sclerosis mice were examined at three stages:preonset(60-70 days),onset(90-100 days)and progression(120-130 days).The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage.The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group,whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage.The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group.The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage.The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage,significantly decreased at the onset stage,and significantly increased at the progression stage compared with the control group.heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage.After heterogenous nuclear ribonucleoprotein G gene silencing,PC12 cell survival was lower than that of control cells.Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells.Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.展开更多
[Objective] This work was aimed to explore the mechanism of Hg2+ toxicity on plants.[Method]Activities of peroxidase(POD),catalase(CAT)and superoxide dismutase(SOD)were investigated in wheat(Triticum aestivum L.)seedl...[Objective] This work was aimed to explore the mechanism of Hg2+ toxicity on plants.[Method]Activities of peroxidase(POD),catalase(CAT)and superoxide dismutase(SOD)were investigated in wheat(Triticum aestivum L.)seedlings under Hg2+ stress at different concentrations.[Result]① There were no obvious effects on the growth of seedlings when the concentration of Hg2+ was lower than 0.10 mmol/L.However,toxic effects on the growth of seedling were observed when the concentration of Hg2+ was higher than 0.10 mmol/L.② Different tissues showed different resistant ability in response to Hg2+ stress.The leaves and roots of wheat seedlings were more insensitive to Hg2+ toxicity.③ CAT was more sensitive to Hg2+ stress compared to POD and SOD.[Conclusion]The toxic effect was related to the concentration of Hg2+(0.10 mmol/L).The higher concentration of Hg2+ could affect the expression of POD,CAT,and SOD isozymes in the leaves,roots of wheat seedlings and germinated seeds,which further affect the normal metabolism of membrane lipid and inhibit the growth of wheat seedlings at last.展开更多
[Objective] The aim of the study is to compare the activities of superoxide dismutase(SOD) isoenzymes in three species of shrimps Penaeus japonicus, Procambarus clarkia and Litopenaeus vannamei. [Method] The experimen...[Objective] The aim of the study is to compare the activities of superoxide dismutase(SOD) isoenzymes in three species of shrimps Penaeus japonicus, Procambarus clarkia and Litopenaeus vannamei. [Method] The experimental materials were used to measure SOD activities after pretreatment, meanwhile the differences in SOD isoenzymes from different materials were assayed by polyacrylamide gel electrophoresis (PAGE). [Result] There are specific and histological differences in SOD activities of shrimps. With a similar electrophoresis pattern and migration rate, Penaeus japonicus and Litopenaeus vannamei showed remarkable differences with that of Procambarus clarkia. [Conclusion] The result showed the differences of cognation and origin of three shrimps.展开更多
基金supported by a grant from the Association Française contre les Myopathies(AFM Téléthongrant 23667,to JCL).
文摘Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis.The only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial effects.The difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis pathogenesis.Among mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious circle.Sharpening the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and inflammation.We here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
文摘Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.
基金supported by the National Natural Science Foundation of China(No.42076141).
文摘In this study,we investigated the effects of different concentrations of 5-azacytidine(AZA),a DNA methyltransferase in-hibitor,on the growth,antioxidant activities and germination of pellicle cysts of Scrippsiella acuminata.The purpose of this study is to understand the toxic effects of AZA on marine microalgae,and to demonstrate the effect of DNA methyltransferase inhibitors on the germination of pellicle cysts.Results showed that AZA inhibited the growth of S.acuminata significantly,and displaced a clear dose-dependent inhibition trend with the 96h EC50 of 146.77μmolL^(-1)(35.84mgL^(-1)).Pellicle cysts of S.acuminata were less sensitive to AZA than the vegetative cells,and the EC50 value of AZA to the germination of pellicle cysts of S.acuminata was 8.08mmolL^(-1)(1.97g L^(-1)).After exposed to AZA,the antioxidant activities in S.acuminata responded rapidly and significantly.Among them,soluble pro-tein and superoxide dismutase(SOD)were more sensitive to AZA,and significant promotions occurred after exposed to 10μmolL^(-1)AZA for 24h.Meanwhile,malondialdehyde(MDA)contents in algal cells did not change significantly after exposed to low concen-trations of AZA,but increased firstly and then decreased under high concentration of AZA.The glutathione(GSH)levels in S.acu-minata increased significantly under high concentrations of AZA,and remained unchanged at low concentrations of AZA.The results suggested that the enhanced protein level and SOD activity of S.acuminata eliminated reactive oxygen species(ROS)to a certain ex-tent,and thus protected algal cells against damages of ROS caused by AZA.
文摘Objective:The imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer(BC).This study aimed to evaluate serum antioxidant status in patients with BC and determine its potential use in the diagnosis and progression potential considerations following histopathological assessment.Methods:A cross-sectional study included 90 patients with BC,divided into Ta,T1,and T2eT4 stage subgroups,and according to cancer progression potential,into low-grade(LG)and highgrade(HG)subgroups.The control group(CG)included 30 healthy volunteers.Antioxidant status was determined using the spectrophotometric method and standard laboratory tests.Results:Serum superoxide dismutase activity was significantly higher in BC patients regarding cancer stage in comparison to the CG(p<0.001).Catalase activity was highest in T2eT4 subgroup and was significantly higher compared to the Ta(p<0.01)and T1(p<0.05)subgroups.Serum albumin level was significantly lower in the BC group compared to the CG(p<0.001).In addition,it was significantly lower in T2eT4 subgroup compared to T1 and Ta subgroups(p<0.01).A significant negative correlation was found between tumor size and serum albumin level only(r=0.386,p<0.01).Catalase activity was higher in HG subgroup(p=0.009),while bilirubin level was higher in LG subgroup(p=0.035).The optimal cut-off value of catalase activity in differentiating patients with LG and HG BC subgroups was 11.96 IU/L,and the specificity and sensitivity were 51.1% and 82.2%,respectively.Bilirubin level,for a calculated optimal cut-off value of 11.95 mmol/L,had a specificity of 44.1%and sensitivity of 80.0%.Conclusion:More invasive stages of BC with greater progression potential are associated with an increase in enzymatic antioxidant activity and a decrease in non-enzymatic antioxidant capacity.It may suggest a possible role of antioxidants in the prediction and monitoring of illness trajectory.
文摘BACKGROUND Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori(H.pylori)infections.Therefore,there is an urgent need to develop new antimicrobial agents to replace antibiotics.Our previous study found that linolenic acid-metronidazole(Lla-Met)has a good antibacterial effect against H.pylori,both antibiotic-resistant and sensitive H.pylori.Also,H.pylori does not develop resistance to Lla-Met.Therefore,it could be used for preparing broad-spectrum antibacterial agents.However,since the antibacterial mechanism of Lla-Met is not well understood,we explored this phenomenon in the present study.AIM To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections.METHODS H.pylori cells were treated with the Lla-Met compound,and the effect of the compound on the cell morphology,cell membrane permeability,and oxidation of the bacteria cell was assessed.Meanwhile,the differently expressed genes in H.pylori in response to Lla-Met treatment were identified.RESULTS Lla-Met treatment induced several changes in H.pylori cells,including roughening and swelling.In vivo experiments revealed that Lla-Met induced oxidation,DNA fragmentation,and phosphatidylserine ectropionation in H.pylori cells.Inhibiting Lla-Met with L-cysteine abrogated the above phenomena.Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes,both anti-oxidation-related genes.CONCLUSION Lla-Met kills H.pylori mainly by inducing oxidative stress,DNA damage,phosphatidylserine ectropionation,and changes on cell morphology.
基金the National Key R&D Program of China(Grant No.2020YFA0908100)the National Nature Science Foundation(Grant Nos.12274356,82070931,and 82271045)+1 种基金Fundamental Research Funds for the Central Universities(20720220022)the 111 Project(B16029)。
文摘Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge.Inspired by metalloenzymes with well-defined coordination structures,a series of MOFs containing halogen-coordinated copper nodes(Cu-X MOFs,X=Cl,Br,I)are employed to elucidate their structure–activity relationship.Intriguingly,experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center.The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes.More importantly,by performing enzyme-mimicking catalysis,the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress,thus effectively relieving ocular chemical burns.Mechanistically,the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways.Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and,more significantly,demonstrating their potential therapeutic effect in ophthalmic disease.
基金funded by Zhongyuan Scholars in Henan Province(192101510004)Major Science and Technology Projects for Public Welfare of Henan Province(201300110300)+2 种基金Innovation Demonstration Special Project of Henan Province(201111110100)financially supported by Key Project Foundation of Natural Science Research of Universities of Henan Province in China(20A550004)Fundamental Research Funds for the Henan Provincial Colleges and Universities in Henan University of Technology(HAUT)and High-Level Talents Research Fund of HAUT(2018QNJH13,and 2018BS012)。
文摘Wheat embryo globulin(WEG)has been proven to possess multiple biological activities,including antioxidative properties,immunomodulatory,and so on.Aged mouse model were established by subcutaneous injection of D-galactose(D-gal),and the effects of WEG on learning,memory,and antioxidant capacity in aging mice were explored through behavioural tests and antioxidant enzyme activities determination.Compared with the Model group,WEG improved the percentage of the platform quadrant,increased the number of crossing platforms,and enhanced the identification indexs.WEG also increased total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)activities in the liver and brains of aging mice,and reduced malondialdehyde(MDA)content.Pathological observations indicated that WEG protected against damage to brain in D-gal-induced aging mice.These results effectively revealed that WEG not only improved the abilities of learning and memory,and the cognitive impairment,but also delayed the aging process of the D-gal-induced mice.
文摘We reviewed recent major clinical trials with investigational drugs for the treatment of subjects with neurodegenerative diseases caused by inheritance of gene mutations or associated with genetic risk factors.Specifically,we discussed randomized clinical trials in subjects with Alzheimer's disease,Huntington's disease and amyotrophic lateral sclerosis bearing pathogenic gene mutations,and glucocerebrosidase-associated Parkinson's disease.Learning potential lessons to improve future therapeutic approaches is the aim of this review.Two long-term,controlled trials on three anti-β-amyloid monoclonal antibodies(solanezumab,gantenerumab and crenezumab)in subjects carrying Alzheimer's disease-linked mutated genes encoding for amyloid precursor protein or presenilin 1 or presenilin 2 failed to show cognitive or functional benefits.A major trial on tominersen,an antisense oligonucleotide designed to reduce the production of the huntingtin protein in subjects with Huntington's disease,was prematurely interrupted because the drug failed to show higher efficacy than placebo and,at highest doses,led to worsened outcomes.A 28-week trial of tofersen,an antisense oligonucleotide for superoxide dismutase 1 in patients with amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutations failed to show significant beneficial effects but the 1-year open label extension of this study indicated better clinical and functional outcomes in the group with early tofersen therapy.A trial of venglustat,a potent and brain-penetrant glucosylceramide synthase inhibitor,in Parkinson's disease subjects with heterozygous glucocerebrosidase gene mutations revealed worsened clinical and cognitive performance of patients on the enzyme inhibitor compared to placebo.We concluded that clinical trials in neurodegenerative diseases with a genetic basis should test monoclonal antibodies,antisense oligonucleotides or gene editing directed against the mutated enzyme or the mutated substrate without dramatically affecting physiological wild-type variants.
基金supported by the Ministry of Higher Education and Scientific Research and conducted within the framework of the Partnership for Research and Innovation in the Mediterranean Area(PRIMA)Project DiVicia:Use and management of Vicia species for sustainability and resilience in biodiversity-based farming systems.
文摘Lime-induced iron chlorosis is a major nutritional disorder causing severe plant growth and yield reduction in the calcareous soils of Tunisia.The understanding the behavior of key metabolic functions of peas on calcareous soils,the identification of useful traits of tolerance,and the exploration of the genotypic differences in response to this constraint remain the most efficient approaches due to their coast,environmental benefits,and sustainability.For this purpose,a greenhouse experiment was conducted on three pea genotypes(Alexandra:Alex,Douce de provence:DP,and Merveille de Kelvedon:MK)cultivated on calcareous soil(Fe-deficient)and fertile soil(control).Plant growth,SPAD index,iron nutrition and distribution,photosynthesis,and antioxidant enzymes were deeply analyzed to discriminate genotypic differences.Calcareous-induced iron deficiency reduced SPAD index,plant growth,net photosynthesis,and tissue Fe content against a significant stimulation of the oxidative stress indicators,H2O2 and Malondialdehyde(MDA).Moreover,we reported a significant induction of SOD and CAT activity in shoots and roots of the Alexandra genotype.Fe use efficiency increased on calcareous soil and clearly discriminated the studied genotypes.Alexandra genotype was found to be the most tolerant to lime-induced iron chlorosis.This genotype protects its tissues against oxidative stress by stimulating enzyme activities(SOD and CAT)and develops significant efficiency of Fe uptake,translocation to shoots and use when cultivated on calcareous soil.
文摘Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammonium citrate was added to the macrophage cell line(RAW264.7)to establish an iron-overloaded macrophage model.Cell counting kit 8 assay was used to detect cell viability.Superoxide dismutase,reactive oxygen species,malondialdehyde,and apoptosis were performed to analyze the severity of cellular oxidative damage.In addition,quantitative real-time polymerase chain reaction and western blot were used to detect the expression of nuclear factor erythroid 2-related factor 2.Results:The result showed that iron overload of macrophage was visualized by incubating in 40μM ferric ammonium citrate for 24 h.The curcumin significantly reversed the iron overload-induced apoptotic cells at low(10μM)and middle(20μM)concentrations.Additionally,the levels of malondialdehyde and reactive oxygen species activity in the groups of curcumin at low(10μM)and middle(20μM)concentrations were significantly decreased,while superoxide dismutase activity was obviously increased compared with that of the ferric ammonium citrate group alone.Finally,we found that low(10μM)and middle(20μM)dose curcumin up-regulated nuclear factor erythroid 2-related factor 2 expression at mRNA and protein levels compared with the ferric ammonium citrate group alone.Conclusion:Curcumin reduces iron-overloaded stress in macrophages by activating nuclear factor erythroid 2-related factor 2 and enhancing the superoxide dismutase activity,thereby protecting cell apoptosis.
文摘Background:The prime objective of the current research was to evaluate the whole plant hydroalcoholic extract of Ludwigia octovalvis(HLO)against hyperglycemia,and oxidative stress biomarkers in rats induced with diabetes comorbid depression,diabetes comorbid depression(streptozotocin-nicotinamide+electric footshocks).Methods:2,2-Diphenyl-1-picrylhydrazyl assay of HLO versus ascorbic acid was done.Effects of 200 and 400 mg/kg body weight/day HLO doses versus 25 mg/kg body weight/day metformin was studied through insulin,glucose,superoxide dismutase,lipid peroxidation,catalase,and behavioral assessment(forced swim and open field tests).Results:IC50 values of HLO and ascorbic acid were 33.52 and 27.86μg/mL respectively.Both the HLO doses showed intended results with respect to oxidative stress biomarkers in diabetes comorbid depression rats in comparison to metformin.Open field test showed better results for HLO in diabetes comorbid depression rats.However,hypoglycemic effects,and forced swim test performance of metformin was slightly higher than the 400 mg dose,followed by the 200 mg dose of HLO.Ethyl gallate,gallic acid,β-sitosterol,and quercetin in HLO might resulted in attenuating diabetic as well as depression biomarkers.Conclusion:Inhibition of glucosidase and lipase activity,and AMP-activated protein kinase phosphorylation might be the possible biochemical changes occurred in HLO treated rats.
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,Nos.[2014]-47,20142BBG70062,20171BAB215022,20192BAB205043Health and Family Planning Commission of Jiangxi Province,No.20181019(all to RSX).
文摘Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur(TG)amyotrophic lateral sclerosis mouse model.However,most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown.In this study,we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis.Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting,and cell proliferation and proteins(TAR DNA binding protein 43,superoxide dismutase 1,and Bax)were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells.We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins.Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons.Amyotrophic lateral sclerosis mice were examined at three stages:preonset(60-70 days),onset(90-100 days)and progression(120-130 days).The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage.The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group,whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage.The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group.The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage.The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage,significantly decreased at the onset stage,and significantly increased at the progression stage compared with the control group.heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage.After heterogenous nuclear ribonucleoprotein G gene silencing,PC12 cell survival was lower than that of control cells.Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells.Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.
文摘[Objective] This work was aimed to explore the mechanism of Hg2+ toxicity on plants.[Method]Activities of peroxidase(POD),catalase(CAT)and superoxide dismutase(SOD)were investigated in wheat(Triticum aestivum L.)seedlings under Hg2+ stress at different concentrations.[Result]① There were no obvious effects on the growth of seedlings when the concentration of Hg2+ was lower than 0.10 mmol/L.However,toxic effects on the growth of seedling were observed when the concentration of Hg2+ was higher than 0.10 mmol/L.② Different tissues showed different resistant ability in response to Hg2+ stress.The leaves and roots of wheat seedlings were more insensitive to Hg2+ toxicity.③ CAT was more sensitive to Hg2+ stress compared to POD and SOD.[Conclusion]The toxic effect was related to the concentration of Hg2+(0.10 mmol/L).The higher concentration of Hg2+ could affect the expression of POD,CAT,and SOD isozymes in the leaves,roots of wheat seedlings and germinated seeds,which further affect the normal metabolism of membrane lipid and inhibit the growth of wheat seedlings at last.
文摘[Objective] The aim of the study is to compare the activities of superoxide dismutase(SOD) isoenzymes in three species of shrimps Penaeus japonicus, Procambarus clarkia and Litopenaeus vannamei. [Method] The experimental materials were used to measure SOD activities after pretreatment, meanwhile the differences in SOD isoenzymes from different materials were assayed by polyacrylamide gel electrophoresis (PAGE). [Result] There are specific and histological differences in SOD activities of shrimps. With a similar electrophoresis pattern and migration rate, Penaeus japonicus and Litopenaeus vannamei showed remarkable differences with that of Procambarus clarkia. [Conclusion] The result showed the differences of cognation and origin of three shrimps.
基金Supported by National Science Foundation of China ( GrantNo.30460085, 30960233)Open Foundation of Provincial Key Laboratory for Fruit and Vegetable Preservation of Hainan ( GrantNo. CH001)National Non-profit Institute Grant (ITBBZD2007-3-1)~~
基金Supported by Natural Science Foundation of Shanghai(10ZR1400300 )Central University Special Foundation of Basic Research and Operating expenses+1 种基金Creative Group Foundation of the National Natural Science Foundation of China (50721006)Key Discipline construction Project of Shanghai (B604)~~
基金Supported by National Natural Science Foundation of China(30700071 )Natural Science Foundation of Shandong Province(Y2008D03 )Science and Technology Program of Qingdao City(08-1-27-jch)~~
