| 11. |
- Kaluza, Joanna, et al.
(författare)
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Questionnaire-Based Anti-Inflammatory Diet Index as a Predictor of Low-Grade Systemic Inflammation.
- 2018
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 28:1, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- There is accumulating evidence that diet may be associated with markers of inflammation. We have evaluated if an empirically developed questionnaire-based Anti-Inflammatory Diet Index (AIDI) may predict low-grade systemic chronic inflammation in a Nordic population. The AIDI was developed using a 123-item food frequency questionnaire among 3503 women (56-74 years old) with high-sensitivity C-reactive protein (hsCRP) plasma concentration <20 mg/L. Using Spearman correlations, we identified 20 foods (AIDI-20) statistically significantly related to hsCRP. The median (range) of AIDI-20 was 8 (0-17) scores, and the median concentration of hsCRP in the lowest versus the highest quintile of AIDI-20 (≤6 vs. ≥11 scores) varied by 80% (1.8 vs. 1.0 mg/L, respectively). In a multivariable-adjusted linear regression model, women in the highest quintile of AIDI-20 compared with those in the lowest had a 26% (95% confidence interval [CI] 18-33%; p-trend <0.001) lower hsCRP concentration; each 1-score increment in the AIDI-20 was associated with a 0.06 (95% CI 0.04-0.08) mg/L lower hsCRP. The observed association between the AIDI-20 and hsCRP was robust by all hsCRP levels and in subgroups defined by inflammatory-related factors. Our results lead to the hypothesis that the empirically developed questionnaire-based dietary anti-inflammatory index may predict low-grade systemic inflammation. Antioxid. Redox Signal. 28, 78-84.
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| 12. |
- Kristiansson, Amanda, et al.
(författare)
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Protection of Kidney Function with Human Antioxidation Protein α 1 -Microglobulin in a Mouse 177 Lu-DOTATATE Radiation Therapy Model
- 2019
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 30:14, s. 1746-1759
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Peptide receptor radionuclide therapy (PRRT) is in clinical use today to treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin analog peptides target tumors that are killed by irradiation damage. The peptides, however, are also retained in kidneys due to glomerular filtration, and the administered doses must be limited to avoid kidney damage. The human radical scavenger and antioxidant, α 1 -microglobulin (A1M), has previously been shown to protect bystander tissue against irradiation damage and has pharmacokinetic and biodistribution properties similar to somatostatin analogs. In this study, we have investigated if A1M can be used as a renal protective agent in PRRT. Results: We describe nephroprotective effects of human recombinant A1M on the short- and long-term renal damage observed following lutetium 177 ( 177 Lu)-DOTATATE (150 MBq) exposure in BALB/c mice. After 1, 4, and 8 days (short term), 177 Lu-DOTATATE injections resulted in increased formation of DNA double-strand breaks in the renal cortex, upregulated expression of apoptosis and stress response-related genes, and proteinuria (albumin in urine), all of which were significantly suppressed by coadministration of A1M (7 mg/kg). After 6, 12, and 24 weeks (long term), 177 Lu-DOTATATE injections resulted in increased animal death, kidney lesions, glomerular loss, upregulation of stress genes, proteinuria, and plasma markers of reduced kidney function, all of which were suppressed by coadministration of A1M. Innovation and Conclusion: This study demonstrates that A1M effectively inhibits radiation-induced renal damage. The findings suggest that A1M may be used as a radioprotector during clinical PRRT, potentially facilitating improved tumor control and enabling more patients to receive treatment. © Amanda Kristiansson et al. 2018; Published by Mary Ann Liebert, Inc.
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| 13. |
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| 14. |
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| 15. |
- Papaevgeniou, Nikoletta, et al.
(författare)
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18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures
- 2016
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Ingår i: Antioxidants and Redox Signaling. - New Rochelle, USA : Mary Ann Liebert. - 1523-0864 .- 1557-7716. ; 25:16, s. 855-869
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression.Results: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment.Innovation: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism.Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet.
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| 16. |
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| 17. |
- Sareila, Outi, et al.
(författare)
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Reactive Oxygen Species Regulate Both Priming and Established Arthritis, but with Different Mechanisms
- 2017
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 27:18, s. 1473-1490
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Neutrophil cytosolic factor 1 (NCF1) is a key regulatory component of the phagocytic NOX2 complex, which produces reactive oxygen species (ROS). Polymorphism of the Ncf1 gene is associated with increased arthritis severity. In this study, we generated targeted Ncf1 knock-in mice with inducible Ncf1 expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis.Results: Targeted Ncf1 knock-in mice lacked NOX2-derived ROS, and in vivo allelic conversion of Ncf1 by the CreER(T2) recombinase led to full protein expression and ROS production within 10 days. Mice in which Ncf1 had been activated before immunization with type II collagen (CII) developed only mild clinical symptoms of collagen-induced arthritis (CIA), whereas the ROS-deficient littermates had severe arthritis. The functional Ncf1 restricted the expansion of IL-17A-producing T cells specific for the immunodominant CII peptide. When the Ncf1 gene was activated after the priming phase, Ncf1-dependent protection from autoimmune arthritis was still observed, together with a reduced number of splenic monocytes but it was not associated with alterations in peptide-specific T cell response. The Ncf1-deficient mice expressed pronounced interferon signature, which could be normalized by conditional expression of Ncf1 and was also present in the Ncf1-mutated mouse during arthritis.Innovation and Conclusion: Ncf1 deficiency has been known to predispose to autoimmunity in both humans and rodents. Our in vivo results point to a regulatory role of NOX2-derived ROS not only during priming but also during the effector phase of CIA, most likely via different mechanisms.
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| 18. |
- Shan, Yuexin, et al.
(författare)
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ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation
- 2015
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Ingår i: Antioxidants & Redox Signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 22:8, s. 651-668
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow (BM) transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine BM-derived macrophages from wild-type or ATF3-deficient mice. Results: Absence of ATF3 in myeloid-derived cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased exudative edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased paracellular leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 expression in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest that ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner, opening novel opportunities for cell specific therapy for ALI/VILI. Antioxid. Redox Signal. 22, 651-668.
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| 19. |
- Singh-Mallah, Gagandeep, et al.
(författare)
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The Role of Mitochondrial and Endoplasmic Reticulum Reactive Oxygen Species Production in Models of Perinatal Brain Injury
- 2019
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Ingår i: Antioxidants & Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 31:9, s. 643-663
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Tidskriftsartikel (refereegranskat)abstract
- Recent Advances and Critical Issues: Mechanisms underlying ER stress-associated ROS production have been primarily elucidated using either non-neuronal cells or adult neurodegenerative experimental models. Findings from mature brain cannot be simply transferred to the immature brain. Therefore, age-specific studies investigating ER stress modulators may help investigate ER stress-associated ROS pathways in the immature brain. New therapeutics such as mitochondrial site-specific ROS inhibitors that selectively inhibit superoxide (O-2(center dot-))/hydrogen peroxide (H2O2) production are currently being developed. Future Directions: Because ER stress and oxidative stress accentuate each other, a combinatorial therapy utilizing both antioxidants and ER stress inhibitors may prove to be more protective against perinatal brain injury. Moreover, multiple relevant targets need to be identified for targeting ROS before they are formed. The role of organelle-specific ROS in brain repair needs investigation.
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| 20. |
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