The state of the respiratory system of students in conditions of high-altitude hypoxia

The article presents the results of studies on the influence of mountain hypoxia on the state of the students’ respiratory system. When exposed to oxygen deficiency, only the respiratory capacity of the lungs undergoes significant changes. For instance, the RC level in female students under the influence of hypoxia gradually increased in conditions of medium altitude, reaching the maximum value of 0.64 liters (P ˂ 0.05), and on the plain - 0.44 liters. The RC value in young men reached the highest value of 0.74 liters in mid-altitude conditions, and on the plains, it constitutes 0.56 liters. The highest respiration rate for young men of 18.2 movements per minute was noted at an altitude of 600 meters, and the lowest - 17.4 at an altitude of 170 m. The maximum level of respiratory capacity while inhaling in girls is 1.24 liters, detected at an altitude of 600 meters, and the minimum level of 1.18 liters is noted at 170 m. The value of respiratory capacity while exhaling among young men living in the Sharoi region increased to 2.32 liters, and for those from Grozny - 2.24 liters. The highest VC level in girls - 3.87 liters - was found in the middle mountains, and on the plains, it was 3.58 liters. The VC value in young men, gradually increasing, reaches the highest value under the conditions of the Sharoi region - 4.57 liters, and in Grozny it was 4.28.

Resveratrol-Encapsulated Mitochondria-Targeting Liposome Enhances Mitochondrial Respiratory Capacity in Myocardial Cells

The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic β cells (β-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the β-MEND (β-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells). The β-MEND (RES) was readily taken up by H9c2 cells, as verified by fluorescence-activated cell sorter data, and was observed to be colocalized with intracellular mitochondria by confocal laser scanning microscopy. Myocardial mitochondrial function was evaluated by a Seahorse XF Analyzer and the results showed that the β-MEND (RES) significantly activated cellular maximal respiratory capacity. In addition, the β-MEND (RES) showed no cellular toxicity for H9c2 cells as evidenced by Premix WST-1 assays. This is the first report of the use of a myocardial mitochondria-targeting liposome encapsulating RES for activating mitochondrial function, which was clearly confirmed based on analyses using a Seahorse XF Analyzer.

A Link between Mitochondrial Dysregulation and Idiopathic Autism Spectrum Disorder (ASD): Alterations in Mitochondrial Respiratory Capacity and Membrane Potential

Autism spectrum disorder (ASD) is a neurological disorder triggered by various factors through complex mechanisms. Research has been done to elucidate the potential etiologic mechanisms in ASD, but no single cause has been confirmed. The involvement of oxidative stress is correlated with ASD and possibly affects mitochondrial function. This study aimed to elucidate the link between mitochondrial dysregulation and idiopathic ASD by focusing on mitochondrial respiratory capacity and membrane potential. Our findings showed that mitochondrial function in the energy metabolism pathway was significantly dysregulated in a lymphoblastoid cell line (LCL) derived from an autistic child (ALCL). Respiratory capacities of oxidative phosphorylation (OXPHOS), electron transfer of the Complex I and Complex II linked pathways, membrane potential, and Complex IV activity of the ALCL were analyzed and compared with control cell lines derived from a developmentally normal non-autistic sibling (NALCL). All experiments were performed using high-resolution respirometry. Respiratory capacities of OXPHOS, electron transfer of the Complex I- and Complex II-linked pathways, and Complex IV activity of the ALCL were significantly higher compared to healthy controls. Mitochondrial membrane potential was also significantly higher, measured in the Complex II-linked pathway during LEAK respiration and OXPHOS. These results indicate the abnormalities in mitochondrial respiratory control linking mitochondrial function with autism. Correlating mitochondrial dysfunction and autism is important for a better understanding of ASD pathogenesis in order to produce effective interventions.

Study on cardio-respiratory adaptive mechanisms for performance athletes with physical disabilities

Introduction.Recently, the emphasis has been on the problems faced by performance athletes with physical deficiencies of the spine. The aim of the paper is to train coaches in awareness of physical problems, especially of the spine in swimming athletes aged 10-12 years and the development of kinetic programs on land in order to correct them. Material and method. Research on the effectiveness of kinetic programs as means of correction are very numerous and, in this regard, we aim to select the most effective exercises to correct deficiencies acquired by swimmers and change the functional parameters of the cardio-respiratory system during their training. In order to highlight the need for kinetic correction programs, the coach must work in collaboration with the sports doctor and the physiotherapist in order to prevent possible deviations from normal somatic-functional values. Results and discussions. Regarding the estimation of the adaptive possibilities of the cardio-respiratory capacity, hence the need to apply a complex of tests to assess the effort capacity of athletes. Conclusions. In this sense, we will submit to the study the performance group from the University Sports Club from Suceava, and the recovery programs will take place within the Swimming and Kinesiology Complex, Suceava. Keywords: adaptive mechanisms, performance swimmers, functional physical deficiencies, kinetic means,

Enhanced hepatic respiratory capacity and altered lipid metabolism support metabolic homeostasis during short-term hypoxic stress

Background Tissue hypoxia is a key feature of several endemic hepatic diseases, including alcoholic and non-alcoholic fatty liver disease, and organ failure. Hypoxia imposes a severe metabolic challenge on the liver, potentially disrupting its capacity to carry out essential functions including fuel storage and the integration of lipid metabolism at the whole-body level. Mitochondrial respiratory function is understood to be critical in mediating the hepatic hypoxic response, yet the time-dependent nature of this response and the role of the respiratory chain in this remain unclear. Results Here, we report that hepatic respiratory capacity is enhanced following short-term exposure to hypoxia (2 days, 10% O2) and is associated with increased abundance of the respiratory chain supercomplex III2+IV and increased cardiolipin levels. Suppression of this enhanced respiratory capacity, achieved via mild inhibition of mitochondrial complex III, disrupted metabolic homeostasis. Hypoxic exposure for 2 days led to accumulation of plasma and hepatic long chain acyl-carnitines. This was observed alongside depletion of hepatic triacylglycerol species with total chain lengths of 39-53 carbons, containing palmitic, palmitoleic, stearic, and oleic acids, which are associated with de novo lipogenesis. The changes to hepatic respiratory capacity and lipid metabolism following 2 days hypoxic exposure were transient, becoming resolved after 14 days in line with systemic acclimation to hypoxia and elevated circulating haemoglobin concentrations. Conclusions The liver maintains metabolic homeostasis in response to shorter term hypoxic exposure through transient enhancement of respiratory chain capacity and alterations to lipid metabolism. These findings may have implications in understanding and treating hepatic pathologies associated with hypoxia.

Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity

Sustained ryanodine receptor (RyR) Ca2+ leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training (MICT), triggers RyR1 protein oxidation and nitrosylation leading to calstabin1 dissociation in healthy human muscle and in in vitro SIT models (simulated SIT or S-SIT). This is accompanied by decreased sarcoplasmic reticulum Ca2+ content, increased levels of mitochondrial oxidative phosphorylation proteins, supercomplex formation and enhanced NADH-linked mitochondrial respiratory capacity. Mechanistically, (S-)SIT increases mitochondrial Ca2+ uptake in mouse myotubes and muscle fibres, and decreases pyruvate dehydrogenase phosphorylation in human muscle and mouse myotubes. Countering Ca2+ leak or preventing mitochondrial Ca2+ uptake blunts S-SIT-induced adaptations, a result supported by proteomic analyses. Here we show that triggering acute transient Ca2+ leak through RyR1 in healthy muscle may contribute to the multiple health promoting benefits of exercise.

Homeopathic Medicines Influence Fungal Adhesion and Cellular Oxygen Metabolism of MDCK and MA104 Cell Lines

Background: Fungal and viral infections constitute a serious public health problem, because morbidity and mortality rates of these diseases have been increasing in the last decades [1,2]. The resistance to antifungal and antiviral agents [3,4] currently available in the pharmaceutical market motivates the development of new therapies, including complementary and alternative health practices [5,6]. In this context, our research group has deepened the knowledge about the therapeutic potential of homeopathy using different models [7-9]. Homeopathic medicines undergo a process of serial dilution whereby the final remedy contains extremely low amounts of the active substance, with pharmacological action, and, consequently, cannot be considered merely placebos [10]. Aims: In the present study, we evaluated the potential of two different homeopathic medicines, named Influenzinum RC (compounded with influenza A virus) and Candida albicans RC (compounded with Candida albicans yeasts), which are prepared according to Brazilian homeopathic procedures [11]. Methodology: The biotherapics (12x, 30x) were prepared from Candida albicans yeasts [7, 11] and from influenza A (H3N2) viruses [6,11]. The cellular parameters evaluated after biotherapic treatments were: cytotoxicity by MTT assay; PFK-1 activity; and maximum respiratory capacity. Results: Our results showed that Influenzinum RC did not cause cytotoxic effects but induced morphological alterations, increased (p < 0.05) mitochondrial respiration, and significantly modified (p < 0.05) PFK-1 activity of MDCK cells. Additionally, using high-resolution respirometry we could detect an increase in the maximum respiratory capacity when these cells were treated with Influenzinum RC, despite a well-preserved ultrastructure of their mitochondrial organelles. In contrast, when MA104 cells were treated with Candida albicans RC, a significant decrease in cellular respiratory capacity as well as in yeasts adhesion rate was detected. Conclusions: These results indicate that homeopathic medicines modify important cellular and metabolic aspects of mammalian cells and these alterations should be responsible for the therapeutic potential of these drugs.

Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease

Increased amyloid-beta (Aβ) and amyloid precursor protein (APP) in the brains of Alzheimer’s disease (AD) patients are common pathological hallmarks mediating the disease progression. Growing evidence also suggests that mitochondrial abnormalities are an early feature in the pathogenesis of AD. Intervention with antioxidants has received great interest as a molecular strategy for the manipulation of mitochondrial function. Our previous preliminary study using in vitro cell models expressing different types of APP demonstrated that treatment with alpha-tocopherol (ATF) or gamma-tocopherol (GTF) modulates mitochondrial function by reducing mitochondrial reactive oxygen species (ROS), increasing the production of ATP and preventing apoptosis events, especially in cells expressing the mutant APP form. Thus, we hypothesized that ATF or GTF treatment might also alter mitochondrial metabolic pathways such as oxidative phosphorylation. The present study aimed to investigate the role of ATF and GTF in modulating mitochondrial oxidative metabolism using high-resolution respirometry. Our results showed that both ATF and GTF increased the respiratory capacity and membrane potential in the ROUTINE and OXPHOSCI-LINKED states as well as complex IV enzyme activity in wild-type and mutant APP-overexpressing SH-SY5Y cells. Although preliminary, these findings indicate that ATF and GTF modulate mitochondrial oxidative metabolism in APP-overexpressing cells and, in part, may contribute to the planning of strategies for utilizing vitamin E isomers against mitochondrial-related diseases such as AD.

Dietary Iron Overload and Hfe−/− Related Hemochromatosis Alter Hepatic Mitochondrial Function

Iron is an essential co-factor for many cellular metabolic processes, and mitochondria are main sites of utilization. Iron accumulation promotes production of reactive oxygen species (ROS) via the catalytic activity of iron species. Herein, we investigated the consequences of dietary and genetic iron overload on mitochondrial function. C57BL/6N wildtype and Hfe−/− mice, the latter a genetic hemochromatosis model, received either normal diet (ND) or high iron diet (HI) for two weeks. Liver mitochondrial respiration was measured using high-resolution respirometry along with analysis of expression of specific proteins and ROS production. HI promoted tissue iron accumulation and slightly affected mitochondrial function in wildtype mice. Hepatic mitochondrial function was impaired in Hfe−/− mice on ND and HI. Compared to wildtype mice, Hfe−/− mice on ND showed increased mitochondrial respiratory capacity. Hfe−/− mice on HI showed very high liver iron levels, decreased mitochondrial respiratory capacity and increased ROS production associated with reduced mitochondrial aconitase activity. Although Hfe−/− resulted in increased mitochondrial iron loading, the concentration of metabolically reactive cytoplasmic iron and mitochondrial density remained unchanged. Our data show multiple effects of dietary and genetic iron loading on mitochondrial function and linked metabolic pathways, providing an explanation for fatigue in iron-overloaded hemochromatosis patients, and suggests iron reduction therapy for improvement of mitochondrial function.