Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation disorders.Mitochondrial dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders.Currently,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear.In this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular function.The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration.Therefore,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration.In addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

Stress accumulation in Ni-rich layered oxide cathodes:Origin,impact,and resolution

LiNi_(x)Co_(y)Mn_(z)O_(2)(NCM,x+y+z=1)is one of the most promising cathode candidates for high energy density lithium-ion batteries(LIBs).Due to the potential in enhancing energy density and cyclic life of LIBs,Ni-rich layered NCM(NCM,x≥0.6)have garnered significant research attention.However,improved specific capacity lead to severer expansion and shrinkage of layered lattice,accelerating the stress generation and accumulation even microcracks formation in NCM materials.The microcracks can promote the electrolyte permeation and decomposition,which can consequently reduce cyclic stabilities.Therefore,it is significant to provide an in-depth insight into the origin and impacts of stress accumulation,and the available modification strategies for the future development of NCM materials.In this review,we will first summarize the origin of stress accumulation in NCM materials.Next,we discuss the impact of stress accumulation.The electrolyte permeation along microcracks can enhance the extent of side reaction at the interface,trigger phase transformation and consequential capacity fading.To cushion the impact of stress accumulation,we will review five main strategies.Finally,concise perspectives to reduce stress accumulation and enhance particle strength in further works will be presented.

Effects of helium implantation on mechanical properties of (Al_(0.31)Cr_(0.20)Fe_(0.14)Ni_(0.35)) O high entropy oxide films

It is widely accepted that helium(He) bubbles can prevent dislocations from moving and causing hardening and embrittlement of the material. However, He can affect the mechanical properties of materials in various ways. In this work,ultrafine nanocrystal high entropy oxide(HEO) films with He implantation are prepared by using a radio frequency(RF)reactive magnetron sputtering system to investigate the effects of He bubbles located at grain boundary on the mechanical properties of the films. The mechanical properties of the HEO films are investigated systematically via nanoindentation measurements. The results indicate that the grain boundary cavities induced by He implantation can degrade the hardness,the elastic modulus, and the creep resistance of the HEO films. The mechanical properties of the HEO films are sensitive to the interaction between the He bubbles and the dominating defects.

Effects of Environmental Cadmium on Cadmium Accumulation, Oxidative Response, and Microelements Regulation in the Liver and Kidney of Hexagrammos otakii

The effects of cadmium(Cd)on metal accumulation,microelements contents,and antioxidant responses in Hexagram-mos otakii were studied.The fish were exposed to 0.2,2.5,or 10μg L−1 Cd for 12 or 24 days.Then,the concentration of Cd and mi-croelements(Ca,Fe,Zn,and Se)were determined in the liver and kidney.Moreover,the activities of antioxidant enzymes including superoxide dismutase(SOD),catalase(CAT),and glutathione-S-transferase(GST),and the content of malondialdehyde(MDA)in the liver and kidney were also measured.A continuous accumulation of Cd was observed throughout the experimental period.Cd accumulation was higher in liver than that in the kidney,while Ca and Fe contents were lower in liver than those in the kidney.Cd exposure resulted in a decrease of Ca and Fe concentrations in the kidney,while there was no effect on the liver.Zn and Se remained unaffected with exposure to Cd.Cd exposure induced severe oxidative stress in H.otakii,as indicated by significant induction of the activities of SOD,CAT,and GST,and a simultaneous increase of MDA content.These data show that antioxidant enzymes and mi-croelements contents can be used as potential biomarkers to monitor environmental health in fish.

Effects of Zn Stress on Zn Accumulation and Anti-Oxidant Enzymes Activity in Four Varieties of Ryegrass

We investigated the influence of different content of Zn^2＋（0, 2, 4, 8, 16 mmol·kg^-1） on plant growth, activities of peroxidase （POD） and superoxide dismutase （SOD）, free proline content and Zn accumulation in four varieties of ryegrass （Loliurn perenne L.） hy pot cuhure experiment. The results showed that plant hiomass increased at the ranges of 0-2 （Tuoya）, 0-4 （Yey- ing）, 0-8 mmol·kg^-1（Airuisi and Taide）, respectively, and then decreased under excess Zn. The activities of POD ,SOD and proline content in shoots decreased firstly, and then increased with the in crease of Zn content. The plaut biomass, activities of POD and SOD in Taide were evidently higher than in the other three varie ties. Root tolerance index （RTI） and Zn transport ratio from root to shoot （S/R） in Taide were exceed 1. 0. The maximum of Zn content was 583.9 mg/kg （ at 16 mmol·kg^-1） in Taide＇s shoot.

Salt-induced difference between Glycine cyrtoloba and G.max in anti-oxidative ability and K^+ vs. Na^+ selective accumulation

To characterize differences in soybean resistance to salt stress, two soybean species, the wild salt-tolerant soybean Glycine cyrtoloba(serial number ACC547) and the cultivated salt-sensitive soybean G. max(cv. Melrose) were treated with 0, 50, 100, or 150 mmol L-1Na Cl for 5 days. A series of physiological parameters were determined in both shoots and roots, including content of chlorophyll(Chl) and malondialdehyde(MDA); electrolyte leakage(EL); hydrogen peroxide(H2O2) concentration; superoxide oxygen radical(O2-)production rate; activities of several enzymes including superoxide dismutase(SOD),catalase(CAT), and peroxidase(POD); and selective ion(Na+and K+) accumulation. Our results showed that the relative salt tolerance of ACC547 was associated with lower loss of Chl content; lower MDA content, EL, H2O2 concentration, and O2-production rate in both shoots and roots; higher POD activity caused by new isoforms in roots; and higher K+concentration and K+/Na+ratio in shoots. These results suggested that relative lower membrane injury, efficient K+vs. Na+selective accumulation, and newly induced POD isoenzymes are mechanisms of salt tolerance in soybean.

Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.Mesenchymal stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver diseases.Therefore,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD.

硒暴露对斑马鱼(Danio rerio)组织元素含量及氧化胁迫的影响研究

以斑马鱼为受试材料,研究了Se(Ⅳ)暴露对斑马鱼组织的元素含量及氧化胁迫的影响。试验分4组,分别为对照组,5μg·L^(-1)、50μg·L^(-1)和500μg·L^(-1)暴露组,处理21 d后,对斑马鱼各组织(脑、鳃、肝、肠、肌肉)中的Se、Al、Cr、Cu、Mg和Zn的含量进行测定,同时测定各组织中超氧化物歧化酶(SOD)活性、谷胱甘肽-S-转移酶(GST)活性、还原型谷胱甘肽(GSH)含量和脂质过氧化产物(MDA)含量。结果显示,与对照组相比,硒处理组斑马鱼各组织呈现不同程度的硒累积,肝组织中硒累积量最高,且元素Cu和Zn显著增加。肝组织中SOD和GSH水平呈现先升高后降低的趋势,500μg·L^(-1)处理组肝组织中GST活性显著降低56.5%,而肝和鳃组织中MDA分别显著升高3.1倍和1.6倍。研究结果表明硒暴露破坏斑马鱼组织Cu、Zn元素平衡,引起脂质过氧化,诱导斑马鱼肝鳃组织发生氧化胁迫,试验为进一步从元素平衡和氧化胁迫角度研究硒暴露对水生生物的毒性效应奠定了基础。

铁死亡在类风湿性关节炎中的研究进展

类风湿性关节炎(rheumatoid arthritis,RA)是一种慢性自身免疫性疾病,其特征是关节炎症、进行性软骨破坏、骨侵蚀。最近的研究表明,铁死亡参与自身免疫性肝炎、类风湿性关节炎等自身免疫性疾病的发生和发展。该综述重点围绕铁死亡的机制及其与RA发病机制的关联,探讨靶向铁死亡的疗法为RA患者治疗提供新的理论基础和潜在治疗方法。

不同生物膜附着微塑料对文蛤鳃的毒性效应

近年来,微塑料在海洋环境中的广泛分布及其生物毒性效应与健康风险备受关注。天然海洋环境中,微塑料表面易被多种微生物定殖并形成生物膜,这可能影响微塑料的生物毒性,然而目前对其影响仍知之甚少。以海南典型双壳贝类文蛤(Meretrix lyrata)为受试动物,并以其重要的呼吸和滤食器官鳃为靶器官,研究生物膜对微塑料生物毒性的影响。通过将文蛤暴露在质量浓度为100μg·L^(-1)的不同类型原始和生物膜附着的微塑料(聚苯乙烯PS、聚乙烯PE、聚对苯二甲酸乙二醇酯PET)环境中14 d,研究微塑料在文蛤鳃中的富集特征及其对鳃组织的病理损伤、抗氧化及免疫防御系统相关指标的影响。结果表明,原始和生物膜附着微塑料均能在文蛤鳃组织中富集,富集量随暴露时间延长而增加,且生物膜附着微塑料的生物富集效应更显著;微塑料富集导致鳃组织发生不同程度的机械损伤,出现鳃丝粘连、萎缩及断裂、鳃丝细胞坏死、纤毛脱落等病理现象,其中附着生物膜的微塑料比原始微塑料对鳃显微结构的损伤更为明显;微塑料胁迫造成超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和碱性磷酸酶(ALP)活性升高,谷胱甘肽(GSH)含量下降,丙二醛(MDA)含量无显著变化;不同类型原始和附着生物膜微塑料均诱导了文蛤鳃组织的氧化应激和免疫反应,但未产生脂质过氧化损伤。此外,实验结果表明生物膜附着的微塑料比微塑料单独作用对文蛤鳃的毒性效应更强。该研究为评价海洋环境中附着生物膜的微塑料对水生生物的毒性机制及健康风险提供科学依据。

银氧化镉材料退火状态对氧化物聚集改善效果的研究

通过试验验证内氧化法银氧化镉材料冲制形变前不同退火温度和时间对其晶粒再结晶程度、材料硬度和表层氧化层厚度等的影响以及在不同晶粒再结晶状态和硬度下产品冲制形变和内氧化后对其晶界氧化物聚集改善效果的影响,分析得出内氧化法银氧化镉材料成型前选择合适的退火温度和时间可明显改善其晶界氧化物聚集的结论。

排石汤联合间苯三酚对湿热蕴结证肾结石钬激光碎石术后辅助治疗的临床效果

目的探究排石汤联合间苯三酚对湿热蕴结证肾结石钬激光碎石术后辅助治疗的临床效果。方法前瞻性选取2020年5月—2022年5月行钬激光碎石术治疗的200例湿热蕴结证肾结石为研究对象,采用随机数字表法分为观察组1组、观察组2组、观察组3组和对照组,每组50例。对照组术后行常规治疗,在此基础上观察1组给予排石汤联合间苯三酚,观察2组给予排石汤,观察3组给予间苯三酚。比较4组结石清除效果,并比较治疗前后中医证候评分、肾主动脉血流动力学[收缩期间峰值流速(V_(max))、收缩期峰值流速(S)、舒张末期峰值流速(D)、阻力指数(RI)]、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化脂质(LPO)]、舒适度(导尿管相关性症状评分)及不良反应。结果观察1组结石清除率和结石排净率高于观察2组、观察3组、对照组(P<0.05)。治疗第3、7天,观察1组各中医证候评分、导尿管相关性症状评分、RI以及血清MDA、LPO水平低于观察2组、观察3组、对照组,且观察2组、观察3组低于对照组(P<0.05)。治疗第3、7天,观察1组V_(max)、S/D及血清SOD水平高于观察2组、观察3组、对照组,且观察2组、观察3组高于对照组(P<0.05)。4组不良反应发生率比较差异无统计学意义(P>0.05)。结论湿热蕴结证肾结石行钬激光碎石术后给予排石汤联合间苯三酚能提高结石清除效果,改善肾脏血流动力学,减轻氧化应激反应,缓解患者症状并提高舒适度,且安全性较高。

Inhibiting heme oxygenase-1 attenuates rat liver fibrosis by removing iron accumulation

AIM:To investigate the effects of the heme oxygenase(HO)-1/carbon monoxide system on iron deposition and portal pressure in rats with hepatic fibrosis induced by bile duct ligation(BDL).METHODS:Male Sprague-Dawley rats were divided randomly into a Sham group,BDL group,Fe group,deferoxamine(DFX) group,zinc protoporphyrin(ZnPP) group and cobalt protoporphyrin(CoPP) group.The levels of HO-1 were detected using different methods.The serum carboxyhemoglobin(COHb),iron,and portal vein pressure(PVP) were also quantified.The plasma and mRNA levels of hepcidin were measured.Hepatic fibrosis and its main pathway were assessed using Van Gieson's stain,hydroxyproline,transforming growth factor-β1(TGF-β1),nuclear factor-E2-related factor 2(Nrf2),matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-1(TIMP-1).RESULTS:Serum COHb and protein and mRNA expression levels of HO-1 and Nrf2 were increased in the BDL group compared with the Sham group and were much higher in the CoPP group.The ZnPP group showed lower expression of HO-1 and Nrf2 and lower COHb.The levels of iron and PVP were enhanced in the BDL group but were lower in the ZnPP and DFX groups and were higher in the CoPP and Fe groups.Hepcidin levels were higher,whereas superoxide dismutase levels were increased and malonaldehyde levels were decreased in the ZnPP and DFX groups.The ZnPP group also showed inhibited TGF-β1 expression and regulated TIMP-1/MMP-2 expression,as well as obviously attenuated liver fibrosis.CONCLUSION:Reducing hepatic iron deposition and CO levels by inhibiting HO-1 activity though the Nrf2/Keap pathway could be helpful in improving hepatic fibrosis and regulating PVP.

Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation

AIM: To investigate long-term effects of Garcinia Cambogia (GC), weight-loss supplement, on adiposity and non-alcoholic fatty liver disease in obese mice. METHODS: Obesity-prone C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without GC (1%, w/w) for 16 wk. The HFD contained 45 kcal% fat, 20 kcal% protein and 35 kcal% carbohydrate. They were given free access to food and distilled water, and food consumption and body weight were measured daily and weekly, respectively. Data were expressed as the mean ± SE. Statistical analyses were performed using the statistical package for the social science software program. Student's t test was used to assess the differences between the groups. Statistical significance was considered at P < 0.05. RESULTS: There were no significant changes in body weight and food intake between the groups. However, the supplementation of GC significantly lowered visceral fat accumulation and adipocyte size via inhibition of fatty acid synthase activity and its mRNA expression in visceral adipose tissue, along with enhanced enzymatic activity and gene expression involved in adipose fatty acid β-oxidation. Moreover, GC supplementation resulted in significant reductions in glucose intolerance and the plasma resistin level in the HFD-fed mice. However, we first demonstrated that it increased hepatic collagen accumulation, lipid peroxidation and mRNA levels of genes related to oxidative stress (superoxide dismutase and glutathione peroxidase) and inflammatory responses (tumor necrosis factor-α and monocyte chemoattractant protein-1) as well as plasma alanine transaminase and aspartate transaminase levels, although HFD-induced hepatic steatosis was not altered. CONCLUSION: GC protects against HFD-induced obesity by modulating adipose fatty acid synthesis and β-oxidation but induces hepatic fibrosis, inflammation and oxidative stress.

Variations among rice cultivars on root oxidation and Cd uptake

In order to understand the mechanisms on the variation between rice cultivars in Cd uptake and accumulation, two pot soil experiments were conducted with typical rice cultivars that varied greatly in soil Cd uptake. The experiments with six rice cultivars showed that the root oxidation abilities of rice differed with rice cultivars and also with types of the cultivars, the cultivars with indica consanguinity were significantly higher than the cultivars with japonica consanguinity. Root oxidation abilities of the rice cultivars correlated positively and significantly （P〈0.01） with their Cd concentrations and Cd quantity accumulations in rice plants. The experiments with two rice cultivars showed that significant differences also existed between the two cultivars in pot soil redox potentials, which of Shan you 63 （higher soil Cd accumulator） were significantly higher than that of Wu yun jing 7 （lower soil Cd accumulator） under different soil Cd levels, but the degrees of the differences varied with soil Cd levels. The differences were larger under soil Cd treatments than the control. The results indicate that root oxidation ability, especially in Cd contaminated soil, is one of the main mechanisms which dominate Cd uptake and accumulation by rice plant.

Correction to“Inhibiting heme oxygenase-1 attenuates rat liver fibrosis by removing iron accumulation”

We found a mistake in Figure 6. Panels A (Sham group) and F (DFX group) (180degrees rotated) is same images. We have replaced the incorrect images (Panels F)with the correct Figure. This error does not change the meaning of the picture orthe conclusion of the manuscript. We apologize for our unintentional mistakes,which caused great inconvenience.

铁调素敲除对雄性小鼠铁代谢及骨代谢影响的实验研究

目的利用铁调素基因敲除雄性小鼠构建铁蓄积小鼠模型,观察小鼠铁代谢指标以及骨微结构的改变,探讨慢性铁蓄积对小鼠骨转换、氧化应激指标的动态作用。方法根据基因鉴定将小鼠分为铁调素敲除组(KO组)与野生型组(WT组),正常饮食,分别在7、12、18月龄作为观察点,检测小鼠体重、胫骨铁含量,肝脏铁染色,分析小鼠股骨骨微结构,检测血清铁调素、铁蛋白、骨转换指标骨钙素(OCN)、I型胶原羧基末端肽(CTX)水平以及反映氧化应激水平的血清丙二醛(MDA)、超氧化物歧化酶(SOD)水平。结果比较两组小鼠体重无明显差异,各时间点KO组小鼠的血清铁调素指标均显著低于WT组小鼠,KO组小鼠的血清铁蛋白、肝铁、骨铁含量均显著高于WT组小鼠;KO组小鼠纵向比较提示随着年龄增大,铁蓄积越来越明显。Micro-CT结果显示,与WT组小鼠比较,KO组松质骨BMD、Tb.Th、BV/TV、Tb.N、ConnD均显著下降(P<0.05),Tb.Sp、SMI显著升高(P<0.05)。KO组小鼠皮质骨面积低于WT组小鼠。横向同年龄比较,KO组小鼠的血清OCN、SOD水平均显著低于WT组小鼠(P<0.05),而CTX除7月龄时无明显差异,在12、18月龄时均显著高于WT组小鼠,MDA水平各时间点KO组均高于WT组小鼠(P<0.05)。结论铁调素基因敲除后小鼠出现慢性累积性铁蓄积,铁蓄积可刺激氧化应激水平提高,并通过抑制成骨活性、促进破骨吸收而加重骨量丢失。

泄化浊瘀方对急性痛风性关节炎患者血清炎症因子、氧化应激及相关基质金属蛋白酶表达的影响

目的 观察泄化浊瘀方联合芙黄膏外用治疗急性痛风性关节炎(AGA)(湿热蕴结证)的临床疗效及对血清炎症因子、氧化应激及基质金属蛋白酶的影响。方法 将100例患者随机分为对照组与观察组各50例。对照组口服美洛昔康片联合双氯芬酸二乙胺乳胶外用;观察组给予泄化浊瘀方联合芙黄膏外用;疗程均为5 d。患者每日记录疼痛程度(VAS评分);比较治疗前后关节疼痛、压痛、肿胀和活动障碍评分;记录湿热蕴结证积分;检测治疗前后超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、丙二醇(MDA)、超氧化物歧化酶(SOD)、8-羟基脱氧鸟苷(8-OHdG)、基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-7(MMP-7)、基质金属蛋白酶-9(MMP-9)和金属蛋白酶抑制剂-1(TIMP-1)水平;进行安全性评价。比较两组中医证候疗效。结果 治疗后两组患者VAS评分显著下降(P <0.05),观察组患者在治疗后2~5 d的VAS评分均低于对照组(P <0.05);治疗后观察组患者关节疼痛、压痛、肿胀和活动障碍评分低于对照组(P <0.05);治疗后,两组患者hs-CRP、TNF-α、IL-1β和IL-6水平下降(P <0.05),且观察组低于对照组(P <0.05);治疗后观察组MMP-3、MMP-7、MMP-9水平低于对照组(P <0.05),TIMP-1水平高于对照组(P <0.05);治疗后观察组8-OHdG、MDA低于对照组(P <0.05),SOD高于对照组(P <0.05);治疗后观察组中医证候疗效总有效率高于对照组(P <0.05)。结论 泄化浊瘀方联合芙黄膏外用治疗AGA(湿热蕴结证)患者,具有抗炎、抗氧化和调节MMP作用,能减轻疼痛、肿胀,改善肢体活动范围,疗效优于常规抗炎止痛治疗措施,且使用安全。

山药硒多糖对镉暴露小鼠镉蓄积和氧化应激的缓解作用

为探讨山药硒多糖(Chinese yam selenium polysaccharide,SeY)对镉(Cd)暴露小鼠Cd蓄积和氧化应激的缓解作用,选取100只成年C57BL/6雄性小鼠,适应性饲养1周后,随机分成5组[对照组(CK组),氯化镉处理组(Cd组),山药硒多糖低(L-SeY)、中(M-SeY)、高剂量组(H-SeY)],6周后收集组织器官和血液进行测定。结果显示,Cd在小鼠各器官的蓄积分别为肾脏(47.55μg/g)>肝脏(23.15μg/g)>心脏(13.26μg/g)>小肠(9.31μg/g)>大脑(0.07μg/g),血液中Cd含量为5.17μg/L。此外,Cd组小鼠肝脏指数显著升高,且Cd暴露显著提高了小鼠血清中谷草转氨酶(aspartate transaminase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)、乳酸脱氢酶(lactate dehydrogenase,LDH)和碱性磷酸酶(alkaline phosphatase medicine,ALP)活性,小鼠肝脏中超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)和谷胱甘肽还原酶(glutathione reductase,GR)活性显著降低,而丙二醛(malondialdehyde,MDA)水平显著升高(P<0.05)。而山药硒多糖显著降低了Cd暴露小鼠血液、肾脏、肝脏、小肠和心脏中的Cd含量(P<0.05)。此外,山药硒多糖显著降低了Cd暴露小鼠血清中AST、ALT、LDH和ALP活性(P<0.05),显著升高了小鼠肝脏中SOD、GSH-Px、CAT和GR活性,并降低了MDA水平(P<0.05),且呈剂量依赖性。综上,山药硒多糖可降低Cd在小鼠各组织器官中蓄积并缓解Cd暴露引起的小鼠氧化应激。

Reactivation of PPARαalleviates myocardial lipid accumulation and cardiac dysfunction by improving fatty acidβ-oxidation in Dsg2-deficient arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy(ACM),a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes,accounts for 20%of sudden cardiac death and lacks effective treatment.It is often caused by mutations in desmosome proteins,with Desmoglein-2(DSG2)mutations as a common etiology.However,the mechanism underlying the accumulation of fibrofatty in ACM remains unknown,which impedes the development of curative treatment.Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2(CS-Dsg2^(-/-)).Heart failure and cardiac lipid accumulation were observed in CSDsg2^(-/-)mice.We demonstrated that these phenotypes were caused by decline of fatty acid(FA)β-oxidation resulted from impaired mammalian target of rapamycin(m TOR)signaling.Rapamycin worsened while overexpression of m TOR and 4EBP1 rescued the FAβ-oxidation pathway in CS-Dsg2^(-/-)mice.Reactivation of PPARa by fenofibrate or AAV9-Ppara significantly alleviated the lipid accumulation and restored cardiac function.Our results suggest that impaired m TOR-4EBP1-PPARa-dependent FAβ-oxidation contributes to myocardial lipid accumulation in ACM and PPARa may be a potential target for curative treatment of ACM.