| 1. |
- Ehinger, Johannes K., et al.
(författare)
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Mitochondrial function in peripheral blood cells across the human lifespan
- 2024
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Ingår i: npj Aging. - 2731-6068. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction is considered a hallmark of aging. Up to now, a gradual decline of mitochondrial respiration with advancing age has mainly been demonstrated in human muscle tissue. A handful of studies have examined age-related mitochondrial dysfunction in human blood cells, and only with small sample sizes and mainly in platelets. In this study, we analyzed mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and platelets from 308 individuals across the human lifespan (0–86 years). In regression analyses, with adjustment for false discovery rate (FDR), we found age-related changes in respiratory measurements to be either small or absent. The main significant changes were an age-related relative decline in complex I-linked respiration and a corresponding rise of complex II-linked respiration in PBMCs. These results add to the understanding of mitochondrial dysfunction in aging and to its possible role in immune cell and platelet senescence.
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| 2. |
- Mavroudis, Constantine D., et al.
(författare)
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Investigation of Cerebral Mitochondrial Injury in a Porcine Survivor Model of Carbon Monoxide Poisoning
- 2024
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Ingår i: Journal of Medical Toxicology. - 1556-9039. ; 20:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). One of the glaring gaps is the lack of rigorous experimental models that may recapitulate survivors of acute CO poisoning in the early phase. The primary objective of this preliminary study is to use our advanced swine platform of acute CO poisoning to develop a clinically relevant survivor model to perform behavioral assessment and MRI imaging that will allow future development of biomarkers and therapeutics. Methods: Four swine (10 kg) were divided into two groups: control (n = 2) and CO (n = 2). The CO group received CO at 2000 ppm for over 120 min followed by 30 min of re-oxygenation at room air for one swine and 150 min followed by 30 min of re-oxygenation for another swine. The two swine in the sham group received room air for 150 min. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. Following exposures, all surviving animals were observed for a 24-h period with neurobehavioral assessment and imaging. At the end of the 24-h period, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. Results: While a preliminary ongoing study, animals in the CO group showed alterations in cerebral metabolism and cellular function in the acute exposure phase with possible sustained mitochondrial changes 24 h after the CO exposure ended. Conclusions: This preliminary research further establishes a large animal swine model investigating survivors of CO poisoning to measure translational metrics relevant to clinical medicine that includes a basic neurobehavioral assessment and post exposure cellular measures.
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| 3. |
- Piel, Sarah, et al.
(författare)
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Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF’s protective mechanisms and optimize its therapeutic application in post-arrest care.
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| 4. |
- Westerlund, Emil, et al.
(författare)
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Correlation of mitochondrial respiration in platelets, peripheral blood mononuclear cells and muscle fibers
- 2024
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Ingår i: Heliyon. - 2405-8440. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing interest for the possibility of using peripheral blood cells (including platelets) as markers for mitochondrial function in less accessible tissues. Only a few studies have examined the correlation between respiration in blood and muscle tissue, with small sample sizes and conflicting results. This study investigated the correlation of mitochondrial respiration within and across tissues. Additional analyses were performed to elucidate which blood cell type would be most useful for assessing systemic mitochondrial function. There was a significant but weak within tissue correlation between platelets and peripheral blood mononuclear cells (PBMCs). Neither PBMCs nor platelet respiration correlated significantly with muscle respiration. Muscle fibers from a group of athletes had higher mass-specific respiration, due to higher mitochondrial content than non-athlete controls, but this finding was not replicated in either of the blood cell types. In a group of patients with primary mitochondrial diseases, there were significant differences in blood cell respiration compared to healthy controls, particularly in platelets. Platelet respiration generally correlated better with the citrate synthase activity of each sample, in comparison to PBMCs. In conclusion, this study does not support the theory that blood cells can be used as accurate biomarkers to detect minor alterations in muscle respiration. However, in some instances, pronounced mitochondrial abnormalities might be reflected across tissues and detectable in blood cells, with more promising findings for platelets than PBMCs.
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