氧化医学和细胞寿命

Circadian clocks regulate metabolic processes in a tissue-specific manner, which deteriorates during aging. Skeletal muscle is the largest metabolic organ in our body, and our previous studies highlight a key role of circadian regulation of skeletal muscle mitochondria in healthy aging. However, a possible circadian regulation of cardiolipin (CL), the signature lipid class in the mitochondrial inner membrane, remains largely unclear. Here, we show that CL levels oscillate during the diurnal cycle in C2C12 myotubes. Disruption of theRor基因，编码ROR核受体在昼夜振荡器的次级回路，在C2C12细胞中发现，以抑制芯昼夜基因表达。重要的是，涉及合成CL的几个基因，包括TazandPtpmt1, displayed rhythmic expression which was disrupted or diminished in Ror-deficient C2C12 cells.In vivostudies using skeletal muscle tissues collected from young and aged mice showed diverse effects of the clock and aging on the oscillatory expression of CL genes, and CL levels in skeletal muscle were enhanced in aged mice relative to young mice. Finally, consistent with a regulatory role of RORs, Nobiletin, a natural agonist of RORs, was found to partially restore transcripts levels of CL synthesis genes in aged muscle under a dietary challenge condition. Together, these observations highlight a rhythmic CL synthesis in skeletal muscle that is dependent on RORs and modifiable by age and diet.

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Microglial inflammatory activity is thought to be a major contributor to the pathology of neurodegenerative conditions such as Alzheimer’s disease (AD), and strategies to restrain their behaviour are under active investigation. Classically, anti-inflammatory approaches are aimed at suppressing proinflammatory mediator production, but exploitation of inflammatory resolution, the endogenous process whereby an inflammatory reaction is terminated, has not been fully investigated as a therapeutic approach in AD. In this study, we sought to provide proof-of-principle that the major proresolving actor, formyl peptide receptor 2, Fpr2, could be targeted to reverse microglial activation induced by the AD-associated proinflammatory stimulus, oligomericββ-淀粉样蛋白（OAβ）。The immortalised murine microglial cell line BV2 was employed as a model system to investigate the proresolving effects of the Fpr2 ligand QC1 upon oAβ-induced inflammatory, oxidative, and metabolic behaviour. Cytotoxic behaviour of BV2 cells was assessed through the use of cocultures with retinoic acid-differentiated human SH-SY5Y cells. Stimulation of BV2 cells with oAβat 100 nM did not induce classical inflammatory marker production but did stimulate production of reactive oxygen species (ROS), an effect that could be reversed by subsequent treatment with the Fpr2 ligand QC1. Further investigation revealed that oAβ-induced ROS production was associated with NADPH oxidase activation and a shift in BV2 cell metabolic phenotype, activating the pentose phosphate pathway and NADPH production, changes that were again reversed by QC1 treatment. Microglial oAβ刺激的ROS产生足以诱导的旁观者SH-SY5Y细胞的细胞凋亡，这可能通过QC1治疗来预防的效果。在这项研究中，我们提供了指示proresolving受体FPR2可以扭转破坏OA的开发验证的概念数据β-induced microglial activation. Future strategies that are aimed at restraining neuroinflammation in conditions such as AD should examine proresolving actors as a mechanism to harness the brain’s endogenous healing pathways and limit neuroinflammatory damage.

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Eucalyptus leaf polyphenols extract (EPE) has been proved to have various bioactivities, but few reports focus on its antioxidant mechanismin vivo。这项研究的目的是阐明的EPE膳食补充剂对鸡的抗氧化能力的影响及机制。总共216个鸡随机选择用于40天的实验。Four treatment groups received diets including the control diet only, the control diet + low EPE (0.6 g/kg), the control diet + moderate EPE (0.9 g/kg), and the control diet + high EPE (1.2 g/kg). Compared with control group, the glutathione peroxidase (GSH-Px) activity and glutathione (GSH) content in the breast muscle of the moderate EPE treatment group was significantly higher ( ）while the malonaldehyde (MDA) content in the moderate EPE group was reduced ( ）。此外，胸肌的蛋白质组和转录组分析表明，谷胱甘肽代谢和过氧化物酶分别负责肌肉的增加抗氧化能力的两个重要的代谢途径。因此，确定了9个候选基因和两个候选蛋白质与由EPE补充剂诱导提高抗氧化状态。这项研究提供了新的见解的抗氧化能力与EPE膳食补充剂治疗鸡的分子机制。

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Asthma is characterized by the elevated level of Th2 immune responses, oxidative stress, and airway inflammation. Bilsaan, an exudate from the stem ofSambucus nigra, has been traditionally used in the treatment of various ailments in Saudi Arabia. Here, we investigated the therapeutic potential of Bilsaan against ovalbumin- (OVA-) induced allergic asthma in a mouse model. In order to induce allergic asthma, mice were intraperitoneally injected with alum-emulsified-OVA (20 μ天0 g /鼠标),紧随其后的是14和21an intranasal OVA exposure from days 22 to 30. During this time, mice were orally administered with Bilsaan at the doses of 5, 10, and 25 mg/kg. The numbers of total and differential inflammatory cells and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) and IgE were determined in bronchoalveolar lavage fluid (BALF). Moreover, the therapeutic effect of Bilsaan was also assessed to analyze the oxidative stress and inflammatory changes in the lung tissues. The results demonstrated that Bilsaan treatment significantly reduced the total and differential inflammatory cell count in the BALF. The BALF from the mice treated with Bilsaan showed significantly lower levels of IL-4, IL-5, IL-13, and IgE. Interestingly, a similar pattern was observed in IL-4, IL-5, and IL-13 secreted by OVA-sensitized splenocytes from the mice of various groups. Bilsaan treatment alleviated the status of oxidative stress by modulating malondialdehyde (MDA), superoxide dismutase (SOD), and catalase levels in the lung. Moreover, Bilsaan treatment reduced the infiltration of inflammatory cells, thickening of alveolar wall, and congestion in the lung tissues. The findings of the present study demonstrated an antiasthmatic effect of Bilsaan through the modulation of Th2 immune responses, inflammation, and the oxidative stress.

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The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (  U/mL vs.  U/mL, ）and exhibited a descending trend across sequential increase of MS component number ( ）。SOD activity is modestly correlated with glucose indicators and insulin sensitivity andβ-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity andβ细胞功能指数。然而，SOD活性与MS之间的关联的统计显着性调整用于松田胰岛素敏感性指数（ISIM）和胰岛素分泌敏感性指数-2（ISSI-2），这表明一个可能的中介作用后衰减。因此，我们进行了调解模式分析，表明降低的ISIM和ISSI-2部分地和协同地降低介导的SOD活性的到MS的贡献。总之，减少SOD活性为MS的风险增加，与胰岛素抵抗和一个独立的预测β细胞功能障碍部分调解降低SOD活性和MS之间的关系。

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氧化应激是炎症的一个重要因素。Piper methysticum，也被称为Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from thekava是已知植物有药用价值。此研究的目的是证明在BALB上脂多糖（LPS-）诱导的炎症由FKA介导的抗氧化剂分子机制/ c小鼠的原代脾细胞。In vitrodata show that the nontoxic concentrations of FKA (2-30 μM）显著抑制促炎细胞因子（TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB（P65）途径，导致iNOS的抑制显著，COX-2，TNF-αα, and IL-1β蛋白的表达。值得注意的是，FKA青睐的Nrf2的核易位导致抗氧化剂蛋白质HO-1，NQO-1的下游表达，并γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA’s potent antioxidant mechanism in these cells. Supporting thein vitrodata, theex vivo从FKA-施与BALB / c小鼠（口服）显示的原代脾细胞中的数据获得的FKA显著抑制促炎细胞因子（TNF-α, IL-1β和IL-6）的分泌在控制 - ，LPS-，或伴刀豆球蛋白A-（续A-）刺激的细胞。在亲和抗炎细胞因子（IL-6 / IL-10的比率甲显著减少; TNF-α/ IL-10）表明，FKA具有较强的抗炎性质。此外，BALB / c小鼠用缩胆囊素（CCK-）8显示出由于FKA预处理降低血清脂肪酶水平与实验性胰腺炎引起的。我们的结论是，其强大的抗氧化和抗炎性质，查耳酮flavokawain A可以是在炎症相关疾病的治疗的新的治疗剂。

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