NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes

Alzheimer's disease (AD) is a common dementia affecting a vast number of individuals and significantly impairing quality of life. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for AD. Astrocytes, the most common cell type of the central nervous system, have been shown to play a role in the major AD pathologies, including accumulation of amyloid plaques, neuroinflammation, and oxidative stress. Here, we show that inflammatory stimulation leads to metabolic activation of human astrocytes and reduces amyloid secretion. On the other hand, the activation of oxidative metabolism leads to increased reactive oxygen species production especially in AD astrocytes. While healthy astrocytes increase glutathione (GSH) release to protect the cells, Presenilin-1-mutated AD patient astrocytes do not. Thus, chronic inflammation is likely to induce oxidative damage in AD astrocytes. Activation of NRF2, the major regulator of cellular antioxidant defenses, encoded by the NFE2L2 gene, poses several beneficial effects on AD astrocytes. We report here that the activation of NRF2 pathway reduces amyloid secretion, normalizes cytokine release, and increases GSH secretion in AD astrocytes. NRF2 induction also activates the metabolism of astrocytes and increases the utilization of glycolysis. Taken together, targeting NRF2 in astrocytes could be a potent therapeutic strategy in AD.     

Disparities in Nutritional Adequacy of Diets between Different Socioeconomic Groups of Finnish Adults

Information on dietary adequacy is needed to assess food and nutrition security in a modern society, especially in the transition towards climate-friendly food systems. In this study, differences in the nutritional adequacy of diets among Finnish adults were evaluated in population groups of different education, income and urbanisation levels. The study used data from the FinDiet 2017 Survey (n = 1655, 18–74 years). Modelled usual intakes of foods and nutrients were evaluated relative to food-based dietary guidelines issued by the National Nutrition Council of Finland (FNNC) and with respect to nutrient adequacy following the Nordic Nutrition Recommendations and FNNC. For about half of the nutrients studied, intakes were found to be adequate. Intakes of protein, fat, saturated fatty acids and salt were estimated to be high. By contrast, inadequate intakes were seen in folate and vitamins A, D, B1, B2 and C in almost all groups studied. Groups with a higher education and income, groups that lived in urban areas and, in particular, women adhered more closely to recommended food consumption and nutrient intakes than others. However, major challenges posed by the Finnish diet are common to all groups studied, and only certain dietary features evaluated in view of nutritional adequacy are associated with socioeconomic differences.     

Topography of the auditory evoked potential in humans reflects differences between vowels embedded in pseudo-words

To study the processing of vowels embedded in more complex linguistic structures, we compared cortical responses for pseudo-words. Auditory evoked potentials were recorded in 11 right-handed females using a passive oddball paradigm, with /pemu/ and /pomu/ as standard stimuli, differing only with respect to the first syllable. Topographic differences in the N100 were observed between the standards: /pemu/ had larger amplitudes than /pomu/ at more posterior electrode sites whereas a reverse pattern was found at more anterior positions along the midline. This topographic difference can be explained by different generators for the two stimuli. Different vowels and/or the initial formant transition possibly activate different neural populations in the auditory cortex, also when the vowels are embedded in pseudo-words.     

MGIT 及BacT/Alert MP液体培养基检测分枝杆菌效果的评价

目的 评价 BacT/Alert MP、MGIT 960 7 mL、MGIT 4 mL 3种液体培养基检测分枝杆菌的效果.方法收集肺结核病疑似患者的149份抗酸染色涂阳、188份涂阴痰标本,分别采用BacT/Alert MP、MGIT 960 7 mL、MGIT 4 mL以及罗氏培养基(L-J)进行分离培养效果比对.另...     

M蛋白干扰对血清样本常规生化检测项目的影响

目的 全面评估单克隆蛋白(M蛋白)对24项常规生化检测项目的影响以及可能存在的潜在干扰.建立适用于临床实验室鉴别、验证进而去除M蛋白干扰的可操作流程.方法 观察57例M蛋白阳性样本的检测反应曲线,鉴别出可疑M蛋白干扰样本,再通过强生Vitros 5.1 FS干式生化分析仪的检测结果验证M蛋白干扰.使用生理盐水稀释M蛋白...     

Oncogenic H-Ras V12 promotes anchorage-independent cytokinesis in human fibroblasts

Cell anchorage is required for cell proliferation of untransformed cells, whereas anchorage-independent growth can be induced by oncogenes and is a hallmark of transformation. Whereas anchorage-dependent control of the progression of the G(1) phase of the cell cycle has been extensively studied, it is less clear whether and how anchorage may control other cell cycle phases and whether oncogenes may affect such controls. Here, we found that lack of cell anchorage did not influence progression through the cell cycle S phase, G(2) phase, or most of mitosis of primary human fibroblasts. However, unanchored fibroblasts could not complete cytokinesis. The cleavage furrow and central spindle were still formed in the absence of anchorage, but cells were unable to complete ingression, causing binucleation. Importantly, V12 H-Ras-transformed fibroblasts and two cancer cell lines progressed through the entire cell cycle without anchorage, including through cytokinesis. This indicates that oncogenic signaling may contribute to anchorage-independent growth and tumorigenesis by promoting the final cleavage furrow ingression during cytokinesis.