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Ammonia Stress Disrupts Intestinal Health in Litopenaeus vannamei Under Seawater and Low-Salinity Environments by Impairing Mucosal Integrity, Antioxidant Capability, Immunity, Energy Metabolism, and Microbial Community. 氨胁迫通过损害粘膜完整性、抗氧化能力、免疫力、能量代谢和微生物群落,破坏海水和低盐度环境下凡纳滨对虾肠道健康。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-20 DOI: 10.3390/antiox14111383
Yafei Duan, Yuxiu Nan, Jitao Li, Meng Xiao, Yun Wang, Ruijie Zhu

Ammonia is a key water quality factor limiting shrimp aquaculture. Intestinal health is closely associated with the nutrition, metabolism and immunity of shrimp. However, the response characteristics of the shrimp intestine to ammonia stress under seawater and low-salinity environments remain unclear. In this study, the shrimp Litopenaeus vannamei reared in seawater (salinity 30) or low-salinity (salinity 3) water were subjected to ammonia stress for 14 days, respectively. The changes in intestinal morphology, antioxidant capacity, immune response, energy metabolism, and microbial community were systematically investigated. The results showed that ammonia stress induced intestinal tissue damage in both seawater and low-salinity cultured shrimp, characterized by epithelial cell detachment and mucosal structural disruption. At the molecular level, ammonia stress triggered intestinal stress responses by interfering with key physiological processes such as antioxidant defense and endoplasmic reticulum stress. This process further led to varying degrees of disorders in physiological functions, including immune regulation, inflammatory response, and autophagic activity. In addition, ammonia stress disrupted the homeostatic balance of intestinal energy metabolism by affecting the expression of genes related to glucose metabolism, the tricarboxylic acid (TCA) cycle, and mitochondrial respiratory chain. In addition, ammonia stress increased the diversity of intestinal microbiota and caused microbial dysbiosis by increasing harmful bacteria (e.g., Vibrio) and decreasing beneficial bacterial groups (e.g., Bacillus). Ammonia stress generally enhanced intestinal microbiota chemotaxis. Specifically, predicted functions of microbiota in seawater-cultured shrimp showed increased carbohydrate, linoleic acid, and cofactor/vitamin metabolism; in low-salinity-cultured shrimp, functions including protein digestion/absorption, flavonoid/steroid hormone biosynthesis, and glycosaminoglycan degradation were reduced. These results revealed that ammonia stress compromised shrimp intestinal health by disrupting mucosal structure, triggering stress responses, and disturbing immune function, energy metabolism, and microbial homeostasis. Notably, low-salinity cultured shrimp exhibited more pronounced intestinal stress responses and greater physiological vulnerability than seawater-cultured counterparts.

氨是制约对虾养殖的关键水质因子。肠道健康与虾的营养、代谢和免疫力密切相关。然而,在海水和低盐度环境下,虾肠对氨胁迫的响应特性尚不清楚。本研究将凡纳滨对虾饲养在盐度为30的海水和盐度为3的低盐度水中,分别进行了14 d的氨胁迫处理。系统研究了肠道形态、抗氧化能力、免疫反应、能量代谢和微生物群落的变化。结果表明,氨胁迫可诱导海水和低盐度养殖对虾肠道组织损伤,表现为上皮细胞脱离和黏膜结构破坏。在分子水平上,氨胁迫通过干扰抗氧化防御和内质网应激等关键生理过程引发肠道应激反应。这一过程进一步导致不同程度的生理功能紊乱,包括免疫调节、炎症反应和自噬活性。此外,氨胁迫通过影响葡萄糖代谢、三羧酸(TCA)循环和线粒体呼吸链相关基因的表达,破坏了肠道能量代谢的稳态平衡。此外,氨胁迫增加了肠道微生物群的多样性,引起微生物生态失调,有害菌群(如弧菌)增加,有益菌群(如芽孢杆菌)减少。氨胁迫一般增强肠道微生物群趋化性。具体而言,海水养殖对虾微生物群的预测功能显示碳水化合物、亚油酸和辅助因子/维生素代谢增加;低盐养殖对虾的蛋白质消化/吸收、类黄酮/类固醇激素生物合成和糖胺聚糖降解等功能降低。这些结果表明,氨胁迫通过破坏粘膜结构、引发应激反应、扰乱免疫功能、能量代谢和微生物稳态等方式损害对虾肠道健康。与海水养殖对虾相比,低盐度养殖对虾表现出更明显的肠道应激反应和更大的生理脆弱性。
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引用次数: 0
Evaluation of Dexamethasone and Swimming Exercise as Complementary Interventions in a Rat Sciatic Nerve Injury Model. 地塞米松与游泳运动互补干预大鼠坐骨神经损伤模型的评价。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-20 DOI: 10.3390/antiox14111382
Meral Karakoç, Hayat Ayaz, Ferhat Çelik, Fırat Aşır

Background: Peripheral nerve injuries frequently result in incomplete recovery despite advances in microsurgical repair. Both pharmacological and rehabilitative strategies have been investigated to enhance regeneration. Dexamethasone, a potent anti-inflammatory corticosteroid, and aerobic exercise, such as swimming, may promote repair through distinct but complementary mechanisms.

Methods: A standardized rat sciatic nerve crush model was used to evaluate the effects of local dexamethasone administration (2 mg/kg/day, perineural for 10 days), swimming exercise (20 min/session, three times per week for 21 days), and their combination. Functional recovery was assessed by the Sciatic Functional Index (SFI), oxidative stress by MDA, GPX, and MPO assays, and structural recovery by histological, MBP immunohistochemical, and TEM analyses.

Results: The injury group exhibited markedly elevated MDA and MPO levels and reduced GPX activity, indicating oxidative stress. Both dexamethasone and swimming exercise significantly improved these parameters, while the combination group showed values approaching controls (p < 0.001 for all comparisons vs. injury). Histological and immunohistochemical findings confirmed greater myelin preservation and higher MBP expression in treated groups, particularly in the combination group, whose g-ratio and myelin thickness were statistically indistinguishable from controls. SFI analysis revealed progressive motor improvement, with the combination therapy achieving near-normal function by day 28.

Conclusions: This study demonstrates that dexamethasone and swimming exercise each contribute to peripheral nerve recovery and that their combined application provides additive benefits in terms of functional, biochemical, and structural regeneration. These results are limited to the specific dose and exercise regimen tested but support the potential of integrating anti-inflammatory pharmacotherapy with controlled physical exercise as a multimodal approach to enhance peripheral nerve repair.

背景:尽管显微外科修复技术有所进步,但周围神经损伤经常导致不完全恢复。药理学和康复策略已被研究以促进再生。地塞米松(一种有效的抗炎皮质类固醇)和有氧运动(如游泳)可能通过不同但互补的机制促进修复。方法:采用标准化大鼠坐骨神经挤压模型,评价地塞米松局部给药(2 mg/kg/d,神经周围,持续10 d)、游泳运动(20 min/次,每周3次,持续21 d)及其联合给药的效果。通过坐骨功能指数(SFI)评估功能恢复,通过MDA、GPX和MPO分析评估氧化应激,通过组织学、MBP免疫组织化学和TEM分析评估结构恢复。结果:损伤组MDA、MPO水平明显升高,GPX活性明显降低,提示氧化应激。地塞米松和游泳运动均显著改善了这些参数,而联合组的数值接近对照组(与损伤组相比,所有比较p < 0.001)。组织学和免疫组织化学结果证实,在治疗组中,特别是在联合治疗组,其g比和髓鞘厚度在统计学上与对照组没有区别,髓鞘保存和MBP表达更高。SFI分析显示渐进式运动改善,联合治疗在第28天达到接近正常的功能。结论:本研究表明,地塞米松和游泳运动都有助于周围神经的恢复,它们的联合应用在功能、生化和结构再生方面提供了附加的好处。这些结果仅限于测试的特定剂量和运动方案,但支持将抗炎药物治疗与有控制的体育锻炼结合起来作为一种多模式方法来增强周围神经修复的潜力。
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引用次数: 0
Anti-Inflammatory and Antioxidant Mechanisms of Dendrobium moschatum Polysaccharide in Intestinal Epithelial Cells via TLR4-NF-κB and Nrf2 Signaling Pathways. 石斛多糖通过TLR4-NF-κB和Nrf2信号通路对肠上皮细胞的抗炎和抗氧化作用机制
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-20 DOI: 10.3390/antiox14111384
Ji Chen, Chunyan Ma, Xu Mo, Linhong Li, Lijuan Wu, Chaowen Zhang, Rui Li, Yuanfeng Zou, Fan Liu, Mengliang Tian

Dendrobium moschatum neutral polysaccharide (DMP-NP) was isolated using a water extraction-ethanol precipitation method, followed by purification with DEAE-cellulose anion-exchange resin and a dextran gel column. The resulting DMP-NP1 exhibited a weight-average molecular weight of 16.23 kDa. The molar ratio of monosaccharides was as follows: glucose-mannose-galactose-fucose-rhamnose = 78.54:19.11:1.59:0.53:0.23, with a glucose-to-mannose ratio of 4.1:1. Infrared spectroscopic analysis revealed characteristic carbohydrate absorption peaks and confirmed the presence of pyranosidic linkages. NMR analysis revealed that DMP-NP1 possesses a backbone mainly formed by 1→4 glycosidic linkages, a small number of 1→6 branches, and O-acetyl substitutions at the C2 and C3 positions of mannose residues. In vitro experiments demonstrated that treatment with 0-20 μg/mL (0-1.23 μM) DMP-NP significantly enhanced the activities of catalase (CAT) and superoxide dismutase (SOD) in IPEC-J2 cells, along with upregulation of the corresponding antioxidant genes. Concurrently, DMP-NP reduced the secretion of key pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, and downregulated the expression of genes associated with both antioxidant and inflammatory signaling pathways. Collectively, these findings indicate that DMP-NP not only prevents but also ameliorates LPS-induced inflammatory injury in intestinal epithelial cells, thereby providing a basis for the application of DMP-NP in intestinal inflammation mitigation.

采用水提-乙醇沉淀法分离石斛中性多糖(DMP-NP),采用deae -纤维素阴离子交换树脂和右旋糖酐凝胶柱进行纯化。得到的DMP-NP1分子量为16.23 kDa。单糖的摩尔比为:葡萄糖-甘露糖-半乳糖-焦糖-鼠李糖= 78.54:19:11:1.59:0.53:0.23,其中葡萄糖-甘露糖的摩尔比为4.1:1。红外光谱分析显示碳水化合物吸收峰特征,并证实了吡喃嘧啶键的存在。核磁共振分析表明,DMP-NP1具有一个主要由1→4个糖苷键组成的主链,少量1→6个支链,甘露糖残基的C2和C3位置有o -乙酰基取代。体外实验表明,0-20 μg/mL (0-1.23 μM)的DMP-NP可显著增强IPEC-J2细胞过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性,并上调相应的抗氧化基因。同时,DMP-NP降低了关键促炎细胞因子TNF-α、IL-1β和IL-6的分泌,下调了抗氧化和炎症信号通路相关基因的表达。综上所述,这些结果表明,DMP-NP不仅可以预防而且可以改善lps诱导的肠上皮细胞炎症损伤,从而为DMP-NP在肠道炎症缓解中的应用提供了基础。
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引用次数: 0
Correlation of Antioxidant and Antibacterial Activities of the Aqueous Pinus pinaster Aiton Bark Extract Within a Cytocompatible Concentration Range. 在细胞相容浓度范围内松皮水提物抗氧化和抗菌活性的相关性研究。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.3390/antiox14111377
Diana Barros, Liliana Grenho, Maria Helena Fernandes, Pedro Sousa Gomes, Élia Fernandes

This study explores the antioxidant, antibacterial, and cytocompatibility properties of aqueous Pinus pinaster bark extract (PBE). PBE was prepared using two solvent systems-100% distilled water and 1% DMSO in aqueous solution-at a solid-to-liquid ratio of 1:20 (w/v), following ISO guidelines. Extract characterization included yield determination, FTIR analysis, quantification of total phenolic (TPC) and flavonoid (TFC) contents, and assessment of antioxidant activity using four complementary methods: free radical scavenging (DPPH and ABTS), metal ion reduction (FRAP), and a competitive reaction assay (ORAC). The phenolic compound profile was further examined by HPLC-DAD. The results indicated that the two extracts exhibited comparable values across all evaluated parameters when expressed per gram of PBE. The TPC and TFC were approximately 400 mg GAE (gallic acid equivalents)/g PBE and 92 mg CE (catechin equivalents)/g PBE, respectively. Antioxidant capacity values were about 880, 1030, 3210, and 585 mg TE (Trolox equivalents)/g PBE for the DPPH, ABTS, ORAC, and FRAP assays, respectively. Furthermore, in both extracts, the phenolic and flavonoid contents exhibited strong positive correlations with antioxidant activity across all four chemical assays. The 100% aqueous extract was additionally evaluated for antibacterial activity and cytocompatibility with eukaryotic cells. Compared to the control, the extract demonstrated IC50 values of 0.304, 0.678, and 0.845 mg/mL PBE for the inhibition of Staphylococcus aureus, Escherichia coli, and fibroblast cells, respectively. Antioxidant and antibacterial activities showed a positive association within concentration ranges that remained non-cytotoxic to fibroblasts. Overall, these findings indicate that the aqueous PBE retains cytocompatibility across a wide concentration range while maintaining both antioxidant and antibacterial activities, underscoring its potential for biological applications involving direct contact with eukaryotic cells.

本研究探讨了水松皮提取物(PBE)的抗氧化、抗菌和细胞相容性。PBE采用两种溶剂体系——100%蒸馏水和1% DMSO水溶液——在1:20 (w/v)的固液比下制备,遵循ISO指南。提取物的表征包括产率测定、FTIR分析、总酚(TPC)和类黄酮(TFC)含量定量,并通过四种互补方法评估其抗氧化活性:自由基清除(DPPH和ABTS)、金属离子还原(FRAP)和竞争反应测定(ORAC)。用HPLC-DAD进一步检测酚类化合物谱。结果表明,当每克PBE表达时,两种提取物在所有评估参数中表现出可比的值。TPC和TFC分别约为400 mg GAE(没食子酸当量)/g PBE和92 mg CE(儿茶素当量)/g PBE。DPPH、ABTS、ORAC和FRAP试验的抗氧化能力值分别为880、1030、3210和585 mg TE (Trolox当量)/g PBE。此外,在这两种提取物中,酚类和类黄酮含量与抗氧化活性在所有四种化学分析中都表现出很强的正相关。100%水提物的抗菌活性和与真核细胞的细胞相容性也被评估。与对照组相比,提取物对金黄色葡萄球菌、大肠杆菌和成纤维细胞的抑制作用IC50值分别为0.304、0.678和0.845 mg/mL PBE。在对成纤维细胞无细胞毒性的浓度范围内,抗氧化和抗菌活性呈正相关。总的来说,这些发现表明,PBE在广泛的浓度范围内保持细胞相容性,同时保持抗氧化和抗菌活性,强调了其与真核细胞直接接触的生物学应用潜力。
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引用次数: 0
Dehydroascorbic Acid Induces Cell Death in Sarcoma Stem Cells Under bFGF-Mediated Stemness-Supporting Conditions. 脱氢抗坏血酸在bfgf介导的干细胞支持条件下诱导肉瘤干细胞死亡。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.3390/antiox14111376
Maja Ledinski, Katarina Caput Mihalić, Marijana Šimić Jovičić, Karla Ostojić, Zara Škibola, Robert Kolundžić, Inga Urlić

The resilience of sarcomas, tumors characterized by resistance to therapy and high metastatic potential, is largely driven by the unique characteristics of a small population known as cancer stem cells (CSC). Although ascorbic acid (AA) and its oxidized form, dehydroascorbic acid (DHA), have shown potential for selectively targeting cancer cells, their effects on sarcoma CSCs remain insufficiently explored. Still, recent research indicates that AA can affect the specific characteristics of CSC and lead to their cytotoxicity. To investigate the sensitivity of sarcoma CSCs to ascorbate, CSCs were isolated from six sarcoma patient-derived samples using a sphere assay, and their stem identity was evaluated through gene expression profiling and dye-efflux assays. Cytotoxicity testing of AA and DHA showed that DHA has a selective cytotoxic effect on cancer stem cells. The presence of basic fibroblast growth factor (bFGF), which is commonly used to support the self-renewal of CSCs, had an influence on the cytotoxic effect of DHA. To evaluate the difference in the effect of AA and DHA, a seven-day treatment of CSCs with these forms of ascorbate was performed. The gene expression analysis revealed that DHA in the presence of bFGF had a stronger impact on response to oxidative stress and cellular metabolism. Also, investigation of somatic mutations of oncogenes and tumor suppressors revealed that in liposarcoma and rhabdomyosarcoma, there are mutations that induce proliferative signals. These proliferative signals, joined with bFGF in the presence of DHA, do not lead to proliferation but instead cause cell death.

肉瘤是一种以抵抗治疗和高转移潜力为特征的肿瘤,其恢复能力在很大程度上是由一个被称为癌症干细胞(CSC)的小群体的独特特征驱动的。尽管抗坏血酸(AA)及其氧化形式脱氢抗坏血酸(DHA)已显示出选择性靶向癌细胞的潜力,但它们对肉瘤CSCs的作用仍未充分探索。然而,最近的研究表明,AA可以影响CSC的特定特性并导致其细胞毒性。为了研究肉瘤CSCs对抗坏血酸的敏感性,使用球法从六个肉瘤患者来源的样本中分离出CSCs,并通过基因表达谱和染料外排法评估其干细胞特性。AA和DHA的细胞毒实验表明,DHA对肿瘤干细胞具有选择性的细胞毒作用。碱性成纤维细胞生长因子(bFGF)的存在对DHA的细胞毒性作用有影响,bFGF通常用于支持csc的自我更新。为了评估AA和DHA作用的差异,用这些形式的抗坏血酸治疗CSCs 7天。基因表达分析显示,DHA在bFGF存在下对氧化应激反应和细胞代谢有更强的影响。此外,对癌基因和肿瘤抑制基因的体细胞突变的研究表明,在脂肪肉瘤和横纹肌肉瘤中,存在诱导增殖信号的突变。这些增殖信号,在DHA存在的情况下与bFGF结合,不会导致增殖,而是导致细胞死亡。
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引用次数: 0
Functional and Metabolomic Analyses of Chamomile Jelly Derived from Gelatin Capsule Waste with Inulin and Polydextrose as Prebiotic Sugar Substitutes. 以菊粉和聚葡萄糖为益生元糖替代品的明胶胶囊废液制备洋甘菊果冻的功能和代谢组学分析。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.3390/antiox14111380
Sasina Sanprasert, Anurak Uchuwittayakul, Pudthaya Kumnerdsiri, Lalitphan Kitsanayanyong, Anusorn Seubsai, Jaksuma Pongsetkul, Kantiya Petsong, Supatra Karnjanapratum, Chalalai Jaisan, Samart Sai-Ut, Saroat Rawdkuen, Passakorn Kingwascharapong

Jelly is a popular confectionery, and research increasingly focuses on nutritionally enhanced formulations. In this study, gelatin capsule waste was valorized as a natural gelling base for chamomile jelly, providing an innovative approach to upcycling food-grade waste into functional products. The effects of replacing sugar with inulin (INU) or polydextrose (PDX) (25-100%) on chemical, physical, and sensory properties were investigated. Sugar replacement decreased carbohydrate content while increasing ash and fat, slightly increased turbidity, and reduced lightness (L*) and yellowness (b*). Gels with inulin and polydextrose exhibited higher gel strength (55.97-81.45 g) and hardness (9.77-10.20 N) than the control, whereas antioxidant activity remained largely unaffected. Among the formulations, 50% inulin (INU-50) received the highest consumer acceptance score (6.88 ± 1.05) and maintained stable quality during 21 days at 4 °C, with decreased free water content and increased gel strength. INU-50 jelly supplied essential nutrients, was cholesterol-free, and promoted Lactobacillus plantarum growth, supported by metabolomic analysis. Overall, this study demonstrates the potential of chamomile jelly with inulin substitution as a functional, health-promoting product and highlights a novel, sustainable approach to valorize gelatin capsule waste for modern health-conscious consumers.

果冻是一种受欢迎的糖果,研究越来越关注营养增强的配方。在本研究中,明胶胶囊废物作为洋甘菊果冻的天然胶凝基地,为将食品级废物升级为功能性产品提供了一种创新方法。研究了用菊粉(INU)或聚葡萄糖(PDX)(25-100%)代替糖对其化学、物理和感官性能的影响。糖替代降低了碳水化合物含量,同时增加了灰分和脂肪,浊度略有增加,亮度(L*)和黄度(b*)降低。菊粉和聚葡萄糖凝胶的凝胶强度(55.97 ~ 81.45 g)和硬度(9.77 ~ 10.20 N)均高于对照,但抗氧化活性基本未受影响。其中,50%菊粉(INU-50)的消费者接受评分最高(6.88±1.05),在4°C条件下保持21天的质量稳定,游离水含量降低,凝胶强度增加。INU-50果冻提供必需营养素,不含胆固醇,促进植物乳杆菌生长,代谢组学分析支持。总的来说,本研究证明了菊粉替代洋甘菊果冻作为一种功能性健康促进产品的潜力,并为现代注重健康的消费者提供了一种新的、可持续的方法来评估明胶胶囊废物。
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引用次数: 0
Superoxide Dismutase 3 Deficiency Disrupts the Regulation of Oxidative Stress Caused by Polystyrene Nanoplastics. 超氧化物歧化酶3缺乏破坏聚苯乙烯纳米塑料引起的氧化应激的调节。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.3390/antiox14111378
Yugyeong Sim, Jin-Hyoung Kim, Jeong-Soo Lee, Jinyoung Jeong, Hyun-Ju Cho

Nanoplastics have been recognized as emerging pollutants posing potential risks to ecosystems and human health. They are now detected ubiquitously in the environment and even human tissues, where their small size allows for tissue accumulation and cellular penetration. Growing evidence links nanoplastics to oxidative stress, yet the specific contribution of extracellular accumulation to toxicity remains poorly understood. To address this, we used zebrafish, a transparent vertebrate model suitable for toxicological studies, to explore the role of extracellular antioxidant defenses in polystyrene nanoplastic (PSNP)-induced oxidative stress. In particular, we focused on superoxide dismutase 3 (SOD3), which is an enzyme that regulates extracellular reactive oxygen species by catalyzing the detoxification of superoxide radicals. Zebrafish Sod3a is a homolog of human SOD3, preserving conserved metal-binding sites critical for enzymatic function. We established sod3a mutant zebrafish and examined their responses following PSNP exposure. In sod3a mutant larvae, tissue accumulation of PSNPs was higher than in wild-type (WT), and this was associated with elevated oxidative stress, enhanced cell death, and abnormalities in intestinal function and immune responses. Collectively, these observations reveal the functional importance of SOD3 during PSNP-induced oxidative stress and provide new insight into extracellular antioxidant mechanisms that mitigate PSNP-induced toxicity.

纳米塑料已被公认为对生态系统和人类健康构成潜在风险的新兴污染物。它们现在在环境甚至人体组织中无处不在,它们的小尺寸允许组织积累和细胞渗透。越来越多的证据表明纳米塑料与氧化应激有关,但细胞外积聚对毒性的具体贡献仍然知之甚少。为了解决这个问题,我们使用斑马鱼(一种适合毒理学研究的透明脊椎动物模型)来探索细胞外抗氧化防御在聚苯乙烯纳米塑料(PSNP)诱导的氧化应激中的作用。我们特别关注了超氧化物歧化酶3 (SOD3),这是一种通过催化超氧化物自由基解毒来调节细胞外活性氧的酶。斑马鱼的Sod3a是人类SOD3的同源物,保留了对酶功能至关重要的保守金属结合位点。我们建立了sod3a突变斑马鱼,并检测了它们在PSNP暴露后的反应。在sod3a突变体幼虫中,PSNPs的组织积累高于野生型(WT),这与氧化应激升高、细胞死亡增加、肠道功能和免疫反应异常有关。总的来说,这些观察结果揭示了SOD3在psnp诱导的氧化应激过程中的功能重要性,并为减轻psnp诱导的毒性的细胞外抗氧化机制提供了新的见解。
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引用次数: 0
Antioxidants Trolox and Methazolamide Protect Microvascular Endothelial Cells from Oxidative Damage Induced by Sporadic and Familial Forms of Oligomeric Amyloid-β. 抗氧化剂Trolox和Methazolamide保护微血管内皮细胞免受散发性和家族性低聚淀粉样蛋白-β诱导的氧化损伤。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.3390/antiox14111375
Maria Luisa Valle, Bitseat Getaneh, Christopher William, Jorge Ghiso, Agueda Rostagno

Cerebral amyloid angiopathy (CAA), present in more than 90% of Alzheimer's disease (AD) cases, associates with focal ischemia and neurovascular dysfunction. Genetic variants at positions 21-23 of amyloid beta (Aβ), among them the Dutch mutation (AβE22Q), are primarily linked to CAA and the development of cerebral hemorrhages. An important contributor to CAA pathogenesis is the dysregulation of mitochondria-mediated pathways with concomitant induction of oxidative stress. Using biochemical assays and immunofluorescence microscopy, this work demonstrates the exacerbated formation of reactive oxygen species (ROS) in human brain microvascular endothelial cells after short exposure to soluble oligomers of synthetic homologues of Aβ1-42 and the Dutch variant, inducing lipid peroxidation and protein carbonylation, both markers of oxidative stress. The heterogeneity of the soluble oligomeric assemblies inducing this oxidative response was highlighted by their reactivity with two conformational antibodies recognizing specific and mutually exclusive epitopes associated with either soluble prefibrillar oligomers or soluble fibrillar oligomers. Treatment with the multitarget antioxidants Trolox and methazolamide significantly attenuated the Aβ-mediated ROS production and reduced oxidative stress markers to basal levels. Our data highlight the damaging role of heterogeneous Aβ oligomers and the preventing effect of antioxidants, suggesting ROS modulation as a complementary therapeutic strategy to preserve neurovascular unit integrity.

超过90%的阿尔茨海默病(AD)病例存在脑淀粉样血管病(CAA),与局灶性缺血和神经血管功能障碍有关。淀粉样蛋白(Aβ) 21-23位的遗传变异,其中包括荷兰突变(Aβ e22q),主要与CAA和脑出血的发生有关。CAA发病机制的一个重要因素是线粒体介导途径的失调,同时诱导氧化应激。利用生化分析和免疫荧光显微镜,这项工作证明了在短时间暴露于Aβ1-42和荷兰变体的合成同源物的可溶性低聚物后,人脑微血管内皮细胞中活性氧(ROS)的形成加剧,诱导脂质过氧化和蛋白质羰基化,这两者都是氧化应激的标志。诱导这种氧化反应的可溶性低聚物组装的异质性突出表现为它们与两种构象抗体的反应性,这些抗体识别与可溶性纤维前低聚物或可溶性纤维低聚物相关的特异性和互排斥的表位。多靶点抗氧化剂Trolox和methazolamide显著降低了a β介导的ROS产生,并将氧化应激标志物降低到基础水平。我们的数据强调了异质a β低聚物的破坏作用和抗氧化剂的预防作用,表明ROS调节是保持神经血管单位完整性的补充治疗策略。
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引用次数: 0
Effect of Long-Term Storage Temperature on the Quality of Extra-Virgin Olive Oil (Coratina cv.): A Multivariate Discriminant Approach. 长期储存温度对特级初榨橄榄油(Coratina cv.)品质的影响:一种多元判别方法。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.3390/antiox14111379
Pasquale Crupi, Maria Lisa Clodoveo, Addolorata Desantis, Roberta Zupo, Filomena Corbo

Kinetic evolution of quality parameters in 21 extra-virgin olive oils (EVOOs) from Coratina cultivar was evaluated during 18 months of dark storage at room temperature (RT) and 4 °C (LT). The aim was to identify the most discriminating variables-fatty acids, peroxide value, spectrophotometric indices, and phenolic compounds-using kinetic analysis and multivariate statistics. Fatty acids remained stable, while peroxide value and ultraviolet absorbance indices increased significantly at RT, following zero-order kinetics. Polyphenols declined markedly after 6 months, especially at RT, with degradation rates influenced by initial concentrations. Hydroxytyrosol and tyrosol followed pseudo-zero-order kinetics, whereas secoiridoids and lignans followed second-order kinetics. Discriminant analysis achieved 90% accuracy (p = 0.000012) in classifying oils by storage condition. The most relevant discriminants were associated with phenolic degradation and oxidative changes. These findings support the importance of low-temperature storage in preserving the biochemical quality and shelf life of EVOOs.

研究了21种特级初榨橄榄油(EVOOs)在室温(RT)和4℃(LT)暗储18个月期间品质参数的动力学演变。目的是利用动力学分析和多变量统计来确定最具鉴别性的变量——脂肪酸、过氧化值、分光光度指数和酚类化合物。脂肪酸保持稳定,而过氧化值和紫外线吸收指数在RT下显著增加,遵循零级动力学。6个月后,多酚明显下降,尤其是在室温下,降解率受初始浓度的影响。羟基酪醇和酪醇遵循准零级动力学,而环烯醚萜和木脂素遵循二级动力学。判别分析对油品贮存条件的分类准确率达到90% (p = 0.000012)。最相关的鉴别因子与酚类降解和氧化变化有关。这些发现支持了低温储存对保持evoo的生化质量和保质期的重要性。
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引用次数: 0
Ferroptosis Enhances T Lymphocyte Infiltration into Glioblastoma Spheroids. 铁下垂增强T淋巴细胞向胶质母细胞瘤球体的浸润。
IF 6.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.3390/antiox14111373
Anna Schwantes, Yara Shadid, Vanesa Maria Guerrero Ruiz, Blerina Aliraj, Anja Wickert, Megan A Palmer, Sofie P Meyer, Andreas Weigert, Bernhard Brüne, Dominik C Fuhrmann

Glioblastoma is one of the most aggressive and therapeutically challenging brain tumors. It is characterized by a highly immunosuppressive tumor microenvironment and poor prognosis, requiring novel treatment strategies. Along this line, ferroptosis has been proposed. To study the impact of ferroptosis on glioblastoma cells and immune cell infiltration, we established a spheroid model using LN229 glioblastoma cells and verified ferroptosis by measuring lipid peroxidation and RNA expression of ferroptosis-related genes. We then co-cultured spheroids with human peripheral blood mononuclear cells to follow the infiltration of distinct immune cell subsets by flow cytometry and immunohistochemistry. T lymphocyte infiltration into ferroptotic spheroids compared to control spheroids became apparent with the notion that ferroptotic cells attracted T cells more efficiently compared to apoptotic or necrotic cells. Mechanistically, ferroptotic glioblastoma spheroids released high amounts of ATP, which caused T cell attraction, while ATP deprivation reduced this effect. Ferroptosis appears to be an interesting therapy approach but might need co-treatments to ensure proper T cell activation.

胶质母细胞瘤是最具侵袭性和治疗挑战性的脑肿瘤之一。其特点是肿瘤微环境高度免疫抑制,预后差,需要新的治疗策略。沿着这条线,已经提出了铁下垂。为了研究铁中毒对胶质母细胞瘤细胞及免疫细胞浸润的影响,我们利用LN229胶质母细胞瘤细胞建立球形模型,通过检测脂质过氧化和铁中毒相关基因RNA表达来验证铁中毒。然后,我们将球体与人外周血单个核细胞共培养,通过流式细胞术和免疫组织化学观察不同免疫细胞亚群的浸润情况。与对照球相比,T淋巴细胞浸润到铁致球体中变得明显,因为铁致细胞比凋亡或坏死细胞更有效地吸引T细胞。从机制上讲,嗜铁胶质母细胞瘤球体释放大量ATP,引起T细胞吸引,而ATP剥夺则降低了这种作用。铁下垂似乎是一种有趣的治疗方法,但可能需要联合治疗以确保适当的T细胞激活。
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引用次数: 0
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