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Doxorubicin (DOX), a potent and broad-spectrum antineoplastic agent, causes an irreversible, cumulative and dose-dependent cardiomyopathy that ultimately leads to congestive heart failure. The mechanisms responsible for DOX cardiotoxicity remain poorly understood, but seem to involve mitochondrial dysfunction on several levels. Epigenetics may explain a portion of this effect. Since mitochondrial
Doxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However, treatment with DOX is associated with cumulative cardiotoxicity inducing progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates the activity of proteins involved in apoptosis, autophagy and metabolism. Our hypothesis is that pharmacological modulation by berberine (BER) pre-conditi
This investigation has explored the properties of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BDTA) derivatives with regard to their being prospective inhibitors of hexokinase II (HKII). A pluripotent embryonic carcinoma cell line P19 (ECC), was used as the biological target for newly generated potential inhibitors of HKII. The results obtained from Virtual High-Throughput Screening (VHTS),
BACKGROUND: Cardiovascular diseases (CVDs) are one of the main factors responsible for human morbidity and mortality. Since mitochondria play a critical role in the regulation of cardiac tissue homeostasis, this organelle is a critical target for the protective effects of several pharmaceuticals. Although specific mitochondria-targeted antioxidants and some pharmacological agents are described as
BACKGROUND: The employment of dietary strategies such as ketogenic diets, which force cells to alter their energy source, has shown efficacy in the treatment of several diseases. Ketogenic diets are composed of high fat, moderate protein and low carbohydrates, which favour mitochondrial respiration rather than glycolysis for energy metabolism.DESIGN: This review focuses on how oncological, neurolo
Methylglyoxal (MGO) is an endogenous toxin, mainly produced as a by-product of glycolysis that has been associated to aging, Alzheimer's disease, and inflammation. Cell culture studies reported that MGO could impair the glyoxalase, thioredoxin, and glutathione systems. Thus, we investigated the effect of in vivo MGO administration on these systems, but no major changes were observed in the glyoxal
BACKGROUND: Evidence has revealed an association between familial hypercholesterolemia and cognitive impairment. In this regard, a connection between cognitive deficits and hippocampal blood-brain barrier (BBB) breakdown was found in low-density lipoprotein receptor knockout mice (LDLr-/-), a mouse model of familial hypercholesterolemia.OBJECTIVE: Herein we investigated the impact of a hypercholes
Although the benefits of moderate intake of red wine in decreasing incidence of cardiovascular diseases associated to hypercholesterolemia are well recognized, there are still widespread misconceptions about its effects on the hypercholesterolemia-related cognitive impairments. Herein we investigated the putative benefits of regular red wine consumption on cognitive performance of low-density lipo
Familial hypercholesterolemia (FH) is a genetic disorder caused by dysfunction of low density lipoprotein receptors (LDLr), resulting in elevated plasma cholesterol levels. FH patients frequently exhibit cognitive impairment, a finding recapitulated in LDLr deficient mice (LDLr-/-), an animal model of FH. In addition, LDLr-/- mice are more vulnerable to the deleterious memory impact of amyloid-β (
Leucine is an essential amino acid that has been investigated by its participation in the regulation of whole-body metabolism and mitochondrial function. Here, we evaluated acute leucine effects on mitochondrial respiration of skeletal muscle from male Swiss mice in vitro. Additionally, we further investigated the effects of 4-wk leucine ingestion (2.5% on drinking water) on skeletal muscle mitoch
New Findings: What is the central question of this study? What are the temporal responses of mitochondrial respiration and mitochondrial responsivity to insulin in soleus muscle fibres from mice during the development of obesity and insulin resistance? What is the main finding and its importance? Short- and long-term feeding with a high-fat diet markedly reduced soleus mitochondrial respiration an
Diabetes impacts on brain metabolism, structure and function. Alterations in brain metabolism have been observed in obesity and diabetes models induced by exposure to diets rich in saturated fat and/or sugar and have been linked to memory impairment. However, it remains to be determined whether brain dysfunction induced by obesogenic diets results from permanent brain alterations. We tested the hy
Boken är en rättshistorisk utredning utförd åt Förtjänstutredningen och utgör en bilaga till SOU 2021:74. I texten finns en historisk översikt över statschefens funktion och ställning, särskilt vad gäller övergången från 1809 års till 1974 årsregeringsform. Vidare behandlas kungahuset och några liknande begrepp samt successionsrätten och husmakten. Tyngdpunkten ligger på en analys av den historisk
The new president of the Islamic Republic of Iran, Ebrahim Raisi, has selected cleric Esmail Khatib as Minister of Intelligence. Khatib is a radical Islamist with close ties to both Supreme Leader Ali Khamenei and the Islamic Revolutionary Guard Corps. During his tenure, we can expect a more aggressive approach by the Ministry of Intelligence, meaning more terrorism and violence at the hands of th
Metal oxide shell layers are promising candidates to improve the performance of metal nanoparticles (NPs) in various applications. However, despite a significant amount of experimental work on metal@metal oxide (M@MO) NPs, computational modeling is scarce, particularly on the sintering mechanism, which plays a crucial role in both the synthesis and performance of NPs. Here, we present atomic diffu
