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Project

Centre of Experimental Medicine SAS

International Projects

IMPROVE - 3Rs concepts to improve the quality of biomedical science (IMPROVE)

3Rs koncepty pre zlepšenie kvality biomedicínskych vied (IMPROVE)

Duration: 21. 10. 2022 - 20. 10. 2026
Program: COST
Project leader: Dr.rer.nat., Ing. Kanďárová Helena ERT
Annotation:Awareness of the existence of a reproducibility and predictability crisis in biomedical science has increased in recent years. The reproducibility crisis refers to the problem that researchers struggle to replicate or reproduce scientific studies. There has been many publications reviewing why preclinical research is irreproducible and lack of predictability, pointing this to deficiencies in reporting and statistical practices. Confounding factors, which are part of the laboratory environment and will influence both the dependent and independent variables, continue to be identified, suggesting that our knowledge of their existence is far from complete. Better statistical methodology will play a central role in improving the reproducibility of science to produce robust and reproducible research. Another area of improvement is the development of novel methods to better define and assess replication success and improve predictability. Under this light, the development and introduction of new, powerful concepts for biomedical research is essential to reduce the production of non-reproducible and non-predictive data. This has immense scientific, economic and social significance. In this context, we propose that the findings and concepts from the 3Rs field can greatly help to improve biomedical research on several levels. Therefore, the main aim of the COST Action IMPROVE is: To establish a network which will work to refine, harmonise and promote 3Rs concepts, data and documents, in order to improve the quality of biomedical science.
Project web page:https://www.cost.eu/actions/CA21139/

Arthrohydrogel - Application of bionic hydrogel enriched with selected natural compounds for repair of articular cartilage lesion.

Aplikácia bionického hydrogélu obohateného o vybrané prírodné látky na regeneráciu poškodenej kĺbovej chrupavky.

Duration: 1. 2. 2022 - 31. 12. 2023
Program: Bilaterálne - iné
Project leader: PharmDr. Bauerová Katarína PhD., DrSc.
Annotation:Articular cartilage lesion is a common knee injury often resulting from degeneration during aging, repetitive wear and tear joint stress, or a traumatic event. The replacement of lesion with biocompatible materials is one promising option for repair. Hydrogels have been used as the replacement materials for this purpose. The key issue in this technique is how to fix the implanted hydrogel with the surrounding tissue. Enrichment of this hydrogel with selected natural compounds possessing anti-inflammatory and antioxidative properties could contribute to enhance the effectivity of the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA) as well. We will develop bionic five layers integrated hydrogel with suitable mechanical strength and porous structure to enhance the c ell proliferation and cell interactions with the surrounding tissue. As a result, the implanted hydrogel can form biological fixation and be well integrated with the surround tissue, providing the robust and safe fixation for the hydrogel. We will also study the effect of natural compounds such as D-limonene, astaxanthin, and crocin in treatment of experimental arthritis to determine their anti-inflammatory and antioxidative potential in the treatment of cartilage destruction. After preliminary experiments will be performed in adjuvant arthritis model, the most effective compounds for hydrogel enrichment will be chosen. Finally, the most efficient treatment with enriched hydrogel with the best biocompatibility will be recommended for clinical trials.

BenBedPhar - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases

Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases

Duration: 19. 10. 2021 - 18. 10. 2025
Program: COST
Project leader: RNDr. Bernátová Iveta DrSc.
Annotation:Non-communicable diseases (NCDs) such as cancer, diabetes, cardiovascular, neurodegenerative, respiratory or immune diseases, account for 77% of all deaths in Europe and remain the most prevalent and without effective therapy. Networking among multidisciplinary teams that explore disease from a perspective of causative pathomechanisms rather than clinical symptoms is the most appropriate approach to overcome this problem. Such pathomechanisms imply the loss of homeostatic functions leading to the pathologic formation of reactive oxygen species, chronic inflammation, metabolic unbalance and proteinopathy. The transcription factor NRF2 is a master regulator of multiple cytoprotective responses and a key molecular link among many NCDs. It provides a unique strategy for drug development and repurposing that is now starting to be translated to the pharmacological and clinical arena. This Action build a network of excellence for integrating and spreading the existing knowledge and providing innovative services, drugs and tools related to NRF2-pharmacology, with the final goal of boosting the translation to the European industry sector. To achieve this, the Action has already gathered a wide set of professionals from different disciplines (medical chemistry, pharmacology, clinical research, molecular biology, bioinformatics, etc.) and sectors (universities, research centres, hospitals, biobanks, biotech and pharma companies, etc.). Thanks to COST tools the Action will boost the career of young researchers, wide participation, and spread excellence.
Project web page:Universidad Autónoma de Madrid

NETSKINMODELS - Engineering novel 3D organotypic skin models

European Network for Skin Engineering and Modeling (NETSKINMODELS)

Duration: 15. 9. 2022 - 14. 9. 2026
Program: COST
Project leader: Dr.rer.nat., Ing. Kanďárová Helena ERT
Annotation:Over the past years, investigative and experimental dermatology has developed various approaches, ranging from utilisation of ex-vivo skin tissues to establishment of reconstructed in-vitro and in-silico skin models as tools in both basic and translational skin research. These models have the strong potential to increase the significance of scientific and clinical outcomes and to reduce animal experimentation. Nevertheless, current skin models lack sophistication and standardisation, thereby hampering their wider acceptance by the scientific community and regulatory bodies. This is partly caused by a lack of cross talk between relevant stakeholders — regulatory bodies, basic scientists, clinicians, and industry — whereby advances in new technologies have not delivered their full potential in this field. In the proposed Action, interdisciplinary and intersectoral research and coordinated initiatives will drive the development and validation of standout sophisticated cell-based and computational skin models, including the development of artificial intelligence models for dermatological research. Furthermore, the Action has ambitions to develop ethical and sustainable reagents required for the elaboration of organotypic skin models, based on a strong partnership between network academia and industries. Harmonisation of scientific and technological knowledge and an enduring bottom-up dynamic in the field will be ensured by dissemination of leading-edge know-how among research intensive and research moderate European territories. Moreover, next-generation scientists will be trained for the long-term propagation and continued development of skin models. Action outcomes will turbocharge the field of skin models to meet rising scientific, clinical, economic, environmental and regulatory expectations, making Europe the epicentre of research in this field.
Project web page:https://www.cost.eu/actions/CA21108/

MECACCM2 - Preclinical study targeting mechanosensitive Ca2+channels for Cerebral Cavernous Malformations therapy and early diagnosis.

Predklinická štúdia zameraná na mechanosenzitívne Ca2+ kanály so zámerom terapie cerebrálnych kavernóznych malformácií a ich včasnej diagnostiky.

Duration: 1. 1. 2023 - 31. 12. 2025
Program: Horizont 2020
Project leader: prof., PharmDr. Duriš Adameová Adriana PhD.
Annotation:Cerebral Cavernous Malformations (CCM), a cerebrovascular disease affecting small vessels in 1 out of 200 individuals, are stacks of dilated and haemorrhagic venous capillaries formed by a unique layer of poorly joined endothelial cells. Incompetent blood-brain barrier (BBB) is a major manifestation of CCM leading to headaches, seizures,paralysis, sensory or cognitive deficits. Currently, surgical resection is not always possible and there is no therapeutic alternative. This project will explore molecular events at the onset of CCM and innovative therapeutic strategies. Mysteriously, CCM lesions form only in low flow venous capillaries but not in high flow vessels. Preliminary results from our consortium advocate for a causative role of mechanosensitive calcium channels of the Piezo and TRPV families. Their contributions to CCM onset has however never been explored. This project brings together recognized experts in endothelial mechanotransduction, cell and matrix mechanics and miRNA signalling to investigate the interplay between cell-generated forces, intrinsic molecular pathways and extrinsicmechanical cues. By combining in vitro data with the analysis of patient CCM samples collected in the largest German biobank, the goal of this project is to identify early biomarkers of CCM initiation and to perform preclinical testing of nanoparticles loaded with drugs targeting mechanosensitive calcium channels. In this project, we will be responsible for several experiments evaluating cell fate – intracelullar signaling of cell death, and survival and oxidative stress being associated with Ca2+ regulation through mechanosensitive Ca2+ channels.

Anti-inflammatory effects of natural compounds isolated from Vietnam medicinal plants

Protizápalový účinok prírodných látok izolovaných z vietnamských liečivých rastlín

Duration: 1. 4. 2020 - 30. 6. 2023
Program: Bilaterálne - iné
Project leader: PharmDr. Bauerová Katarína PhD., DrSc.
Annotation:Objectives of this project are as follows: - Screening of selected Vietnamese medicinal plants and natural compounds for in vitro anti-inflammatory activity; - Identification of mechanisms of action of the most bioactive compounds with anti-inflammatory activity using in vitro and in vivo methods (preferably model of adjuvant arthritis in rats).

ONTOX - Ontology-driven and artificial intelligence-based repeated dose toxicity testing of chemicals for next generation risk assessment

Testovanie opakovanej toxicity chemických látok na základe ontológie a umelej inteligencie za účelom hodnotenia rizík metódami NGRA

Duration: 1. 5. 2021 - 30. 4. 2026
Program: Horizont 2020
Project leader: Dr.rer.nat., Ing. Kanďárová Helena ERT
Annotation:The vision of the ONTOX project is to provide a functional and sustainable solution for advancing human risk assessment of chemicals without the use of animals in line with the principles of 21st century toxicity testing and next-generation risk assessment. Specifically, ONTOX will deliver a generic strategy to create innovative new approach methodologies (NAMs) in order to predict systemic repeated dose toxicity effects that, upon the combination with tailored exposure assessment, will enable human risk assessment. This strategy can be applied to any type of chemical and systemic repeated dose toxicity effect. However, for proof-of-concept purposes, focus will be put on 6 specific NAMs addressing adversities in the liver (steatosis and cholestasis), kidneys (tubular necrosis and crystallopathy) and developing brain (neural tube closure and cognitive function defects) induced by a variety of chemicals, including from the pharmaceutical, cosmetics, food and biocide sectors. The 6 NAMs will each consist of a computational system based on cutting-edge artificial intelligence (AI) and will be primarily fed by available biological/mechanistic, toxicological/ epidemiological, physico-chemical and kinetic data. Data will be consecutively integrated in physiological maps, quantitative adverse outcome pathway networks and ontology frameworks. Data gaps, as identified by AI, will be filled by targeted state-of-the-art in vitro and in silico testing. The 6 NAMs will be evaluated and applied in collaboration with industrial and regulatory stakeholders in order to maximise end-user acceptance and regulatory confidence. This is anticipated to expedite implementation in risk assessment practice and to facilitate commercialisation. ONTOX will have a deep and long-lasting impact at many levels, in particular by consolidating Europe's world-leading position regarding the development, exploitation, regulation and application of animal-free methods for human risk assessment of chemicals.
Project web page:www.ontox-project.eu

National Projects

Centre for biomedical research - BIOMEDIRES - II. stage

Centrum pre biomedicínsky výskum – BIOMEDIRES - II. etapa

Duration: 12. 3. 2020 - 11. 3. 2024
Program: Štrukturálne fondy EÚ Výskum a vývoj
Project leader: doc. RNDr. Pecháňová Oľga DrSc.

SUFIBAR - Targeted suppression of pro-inflammatory and pro-fibrotic signaling pathways to prevent heart failure and occurrence of malignant arrhythmias

Cielená supresia pro-zápalových a pro-fibrotických signálnych dráh pre zabránenie život ohrozujúceho zlyhávania srdca a výskytu malígnych arytmií

Duration: 1. 7. 2022 - 30. 6. 2026
Program: APVV
Project leader: RNDr. Szeiffová Bačová Barbara PhD.
Annotation:Heart failure is characterized by a progressive reduction in cardiac output and occurrence of malignant arrhythmias resulting in substantial morbidity and mortality worldwide. Cardiac fibrosis, the key factor contributing to these life-threatening events, is still unresolved problem in clinic. Detection and management of myocardial fibrosis suffer from a lack of precision, therefore, novel approaches are extremely needed. We hypothesize that the determination of myocardial fibrosis phenotypes in a disease-specific way may reveal more precisely molecular targets for efficient prevention and/or treatment. The idea of the project is to differentiate myocardial fibrosis phenotypes via assessment of circulating markers of oxidative stress, inflammation and pro-fibrotic components along with determining the activation of actual signaling pathways and extent of fibrosis. In the same time to explore efficacy of selected compounds, AT1 receptor blocker, ACE inhibitor, melatonin, triiodothyronine, metoprolol, omega-3 fatty acids and molecular hydrogen, to suppress pro-inflammatory and pro-fibrotic signaling pathways including purinergic signaling mediated by connexin-43 hemichannels and panexin-1 channels and to prevent or attenuate adverse structural and electrical remodeling. Novel findings may provide fundamental input to targeted therapy aimed to reduce myocardial fibrosis burden and challenge to realize well designed clinical trials.

DIAMICROBIOTA - Gut microbiota and diabetic peripheral neuropathy: effect of cemtirestat in rat models of diabetes

Črevná mikrobiota a diabetická periferálna neuropatia: účinok cemtirestatu v potkaňom modely diabetu

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: Ing. Šoltésová Prnová Marta PhD.

Experimental therapy of neonatal hypoxic-ischemic encephalopathy (nHIE): potentiation of hypothermic neuroprotection by melatonin in newborn rats

Experimentálna liečba neonatálnej hypoxicko-ischemickej encefalopatie (nHIE): potenciácia hypotermickej neuroprotekcie melatonínom u novorodených potkanov

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Juránek Ivo PhD., DrSc.
Annotation:Neonatal hypoxic-ischemic encephalopathy (nHIE) is among most serious causes of mortality and morbidity in newborns. Efficacy of current nHIE treatment is rather low. Routinely used therapeutic hypothermia (HT) is only partially effective. To augment hypothermic neuroprotection, drugs like erythropoietin, anticonvulsants, antioxidants and inert gases are tested. In this project, using newborn rats, we will study possible augmentation of hypothermia effect by combining HT with melatonin (MEL)-derived antioxidants. We will assess brain damage and efficacy of each intervention by various techniques, including noninvasive in vivo MRI and MRS, histology and neurobehavioral testing. Novelty of the project lies in testing our idea that MEL-derivative possessing antioxidative properties 100 fold higher than MEL will be more effective in potentiating the hypothermic effect than MEL itself. Anticipated results may help understand better nHIE mechanisms and to propose new strategies to treat birth asphyxia effectively.

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Fenolové látky a ich semisyntetické deriváty ako terapeutické nástroje pre ovplyvnenie stresu endoplazmatického retikula prostredníctvom SERCA púmp.

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Lomenová Jana PhD.

Functional and structural evaluation of changes in early and late postnatal myocardium, vasculature and other vital organs in a rat model of intrauterine growth restriction (IUGR).

Funkčné a štrukturálne hodnotenie zmien včasného a neskorého postnatálneho myokardu, vaskulatúry a iných životne dôležitých orgánov na modeli potkana s vnútromaternicovým obmedzením rastu (IUGR).

Duration: 1. 1. 2023 - 31. 12. 2026
Program: VEGA
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS

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Hodnotenie a porovnanie protizápalovej a antioxidačnej účinnosti karotenoidov in vitro a in vivo pomocou modelov chronických zápalových ochorení.

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: PharmDr. Bauerová Katarína PhD., DrSc.

Bio-compatibility assessment of medical devices and novel medical device materials using in vitro methods based on 3D reconstructed human tissue models.

Hodnotenie biologickej kompatibility zdravotníckych pomôcok (ZP) a innovativnych materiálov pre výrobu ZP s využitím in vitro metód založených na 3D rekonštruovaných modeloch ľudského tkaniva.

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Dr.rer.nat., Ing. Kanďárová Helena ERT
Annotation:The project focuses on the development of highly sensitive and reproducible methods for in vitro safety and bio-compatibility assessment of medical devices (MDs) and assessment of bio-compatibility of innovative materials that may come into the direct contact with human tissues, namely oral and vaginal cavity and ocular epithelium. Representative reconstituted human tissue models (i.e., in vitro 3D models of cornea and models of oral and vaginal epithelium) will be exposed to a set of precisely characterized reference samples representing materials and chemicals used in the manufacturing process of MDs, including toxic impurities and irritating monomers, which may result of manufacturing and/or sterilization cycle. Early detection of toxic materials and impurities in MDs that may pose health risk to patients and consumers will help to increase the safety of medical devices. At the same time, in vitro methods will help to reduce or eliminate the need for follow-up tests on animals in selected classes of MDs.

Hyperuricemia in various comorbidities of the metabolic syndrome - mechanisms of the effect of uric acid on endothelial function and erythrocyte deformability.

Hyperurikémia pri rôznych komorbiditách metabolického syndrómu - mechanizmy vplyvu kyseliny močovej na endotelovú funkciu a deformabilitu erytrocytov.

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Bališ Peter PhD.
Annotation:Numerous studies have shown a significant complex relationship between increased concentration of uric acid (UA) in blood (hyperuricemia) and noncommunicable diseases, including arterial hypertension, metabolic syndrome, diabetes mellitus and cardiovascular diseases. Nevertheless, the mechanisms by which hyperuricemia lead to organ damage are not elucidated yet. Higher UA levels in blood are independent predictors of general and cardiovascular mortality. UA may have a direct negative effect on endothelial function. Therefore, we are focusing on relationship between hyperuricemia and endothelial function in macro- and microcircula. The quality of microcirculation is to high extent also determined by erythrocyte properties. The main aim of the project is to bring new information about the mechanisms of hyperuricemia-induced endothelial dysfunction in various comorbidities of the metabolic syndrome, including arterial hypertension, diabetes mellitus, dyslipidemia and obesity, with the focus on microcirculation.

Safe-MDs - In vitro biocompatibility testing of medical devices (MDs) and new generation bio-materials for MDs

In vitro hodnotenie bio-kompatibility zdravotníckych pomôcok (ZP) a inovatívnych bio-materiálov pre ZP

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: Dr.rer.nat., Ing. Kanďárová Helena ERT
Annotation:Medical devices (MDs) have an irreplaceable role in the healthcare of the 21st century. The term ‘medical device’ covers a broad spectrum of products that are crucial in diagnosis and treatment, disease prevention and improving the quality of life of people suffering from disabilities or injuries. MD must not cause adverse effects and must demonstrate bio-compatibility with the tissues in the patient’s body. Most of the MDs' bio-compatibility assessments are still conducted in animals. However, thanks to the advances in cell and 3D tissue engineering and due to the accelerated progress of validation of alternative methods, the MD regulations also utilize in vitro tests, as demonstrated recently by the adoption of the in vitro reconstructed human epidermis (RhE) test for intra-cutaneous testing into the ISO standard 10993-23. The presented research proposal focuses on the development of in vitro methods for biocompatibility assessment of medical devices (MDs) and innovative materials to be used as MDs polymers and that are intended for the use in the oral and vaginal cavities or on/in ocular epithelium.

Aldo-keto reductase inhibitors in the personalized therapy of several types of cancer

Inhibítory aldo-keto reduktáz v personalizovanej liečbe viacerých typov rakoviny

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Ing. Šoltésová Prnová Marta PhD.

TOXINOVAGE - Innovative approaches in toxicology of ageing

Inovatívne prístupy v toxikológii starnutia

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: Ing. Račková Lucia PhD.

ACE2MAS - Cardiometabolic effects of Mas receptor stimulation by modulation of the renin-angiotensin system - the key role of angiotensin-converting enzyme 2

Kardiometabolické účinky stimulácie Mas receptorov modulovaním renín-angiotenzínového systému - klúčová úloha angiotenzínkonvertujúceho enzýmu 2.

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Čačányiová Soňa PhD.
Annotation:The renin-angiotensin system (RAS) is a hormonal cascade whose chronic activation contributes to the development of cardiovascular pathologies caused mainly by remodeling of the heart and blood vessels. It is becoming apparent that the benefit of RAS inhibitors includes, in addition to Ang II inhibition, stimulation of the alternative arm of RAS mediated by the ACE2/Ang1-7/Mas receptor, which has vasodilatory, antiproliferative, antiinflammatory and metabolic effects. The aim of the present project will be to compare the effect of ACE inhibition, AT1 blockade, stimulation of ACE2 (diminazene) and Mas receptor (cyclic Ang1-7, alamandine) in a model of old, obese, diabetic hypertensive Zucker rats with a focus on the potential benefit of Ang1-7/Ang1-5 on glucose utilization, insulin signal transduction, reduction of the inflammatory response and function of the cardiovascular system. Given the potentially key role of RAS and especially ACE2 in the development of acute respiratory distress syndrome (ARDS) and the severe course of COVID-19, the aim of the present project will be to detect changes in membrane and serum ACE2 and expression of other key molecules for viral infection (ADAM17, TMPRSS2, furin and B0AT1 transporter) using various pharmacological interventions. The dependence of the putative alterations on the activity of the Mas receptor will be monitored by its specific antagonist A779. In vitro, following treatment of human alveolar cells and adipocyte cultures with RAS and diminazene inhibitors, the changes in the ability to bind SARS-CoV-2 virus will be assessed using a pseudoviral methodology. The obtained results might contribute to the elucidation of the role of ACE2 and Mas receptor in the pathogenesis of obesity and diabetes. The project might also contribute to the clarification of the choice of an effective RAS inhibitor in the elderly with a combination of hypertension, obesity and diabetes.

Cardioprotective potential of TRP channels: the role in remodelation, inflammation and calcium dysregulation

Kardioprotektívny potenciál TRP kanálov: úloha v remodelácii, zápale a vápnikovej dysregulácii

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: Mgr. Farkašová Veronika PhD

Cognitive and brain mechanisms of semantic processing

Kognitívne a mozgové mechanizmy sémantického spracovania informácií

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: MUDr. Riečanský Igor PhD.
Annotation:Semantic cognition regulates adaptive behavior and its disruption is associated with a number of neuropsychological conditions. Despite recent progress in the field, fundamental cognitive and neurobiological mechanisms of semantic processing remain unknown. This interdisciplinary project introduces a series of experimental studies that are jointly aimed on the rigorous investigation of main neurocognitive mechanisms of semantic cognition and their interactions. For this purpose, we will draw upon original cognitive assessment tools and paradigms, using which we will identify the fundamental semantic processes and determine their relationship with the executive functions and connectivity of semantic memory. Furthermore, by means of electroencephalography (EEG), we will investigate the dynamic of brain activity associated with specific semantic operations and functions. Finally, based on the behavioral and EEG findings, we will use non-invasive transcranial electric brain stimulation (tES) to modulate the excitability and oscillatory activity of the brain regions that support semantic cognition. Such modern and complex experimental approach will shed light on the architecture of the human semantic system and the fundamental cognitive and neuronal mechanisms that govern semantic processing.

Ligand induced modulation of calcium pump SERCA – study of mechanism and design of new compounds

Ligandom podmienená modulácia vápnikovej pumpy - štúdium mechanizmu a návrh nových látok

Duration: 1. 1. 2022 - 31. 12. 2026
Program: VEGA
Project leader: RNDr. Májeková Magdaléna PhD.
Annotation:Calcium signaling plays a crucial role in many physiological processes such as muscle contraction, gene expression, apoptosis and insulin secretion. A primary role in the maintenance of intracellular Ca2+ concentration belongs to SERCA – sarco/endoplasmic reticulum Ca2+-ATPase. As an impaired function of Ca2+-ATPase is associated with various chronic diseases and disorder, the compounds able to restore it are important as potential drugs. Our aim is to elucidate the mechanism of known SERCA activators by means of experimental and theoretical methods and to use this knowledge in design of new compounds, able to maintain SERCA function. In the framework of our research related to diabetes, we plan to include two more targets in our design – inhibition of polyol pathway and oxidation stress.

Mesenteric perivascular fat and its specific role in regulation of intestinal circulation in rats with different feeding regimens

Mezenterický perivaskulárny tuk a jeho špecifická úloha v regulácii črevnej cirkulácie u potkana pri rôznych režimoch príjmu potravy

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: Mgr. Zemančíková Anna PhD.
Annotation:This project will solve questions to what extent and in which way might the different diet and feeding regimens (intermittent, ad libitum, high fat diet) influence the regulation of smooth muscle activity of rat mesenteric arteries by perivascular fat, and which signal mechanisms participate on these processes. Besides healthy individuals, obese rats will be used in which the vascular sympathetic tone is enhanced and its activity is specifically regulated by mesenteric adipose tissue. On isolated conduit and small mesenteric arteries, the effect of mesenteric fat on their reactivity, biochemical processes, and function of perivascular nerves will be measured. The results of this study should be aimed to respond the question how much these processes might be involved in ingestion/utilization of food in subjects under different dietary regimens, and subsequently in regulation of body weight and visceral adiposity in individuals negatively influenced by obesity.

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Môže byť modulácia sarko/endoplazmatickej Ca2+ - ATPázy (SERCA) vybranými prírodnými látkami regulovaná sirtuínmi? Význam v podpornej liečbe diabetických komplikácií a nádorových ochorení.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Mgr. Heger Vladimír PhD.

NEKDIAKAR - Necroptotic and pleiotropic effects of RIP3 kinase acting as a convergent point in cardiac cell loss: understanding the basic mechanisms in the ischemic heart with or without metabolic stress as a tool for designing therapeutic approaches.

Nekroptotické a pleiotropné účinky RIP3 kinázy pôsobiacej ako konvergentný bod pri strate srdcových buniek: pochopenie základných mechanizmov v ischemickom srdci s metabolickým stresom alebo bez neho ako nástroj návrhu terapeutických prístupov.

Duration: 1. 7. 2021 - 30. 6. 2025
Program: APVV
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Necroptosis, which has been found in ischemic heart, seems to be a significant factor in the body's fate. The mechanisms responsible for execution of this cell death are not fully elucidated and the canonical RIP1-RIP3-MLKL pathway does not appear to be the only one responsible for such cell loss. We suggested a dual pronecroptotic and proinflammatory role of RIP3 in the pathogenesis of post-infarction heart failure. In addition, we have indications on other pleiotropic action of RIP3 being associated with oxidative stress, as well as affecting mitochondrial activity and dynamics. Thus, it appears that RIP3, but not RIP1, may be a key node in intracellular signaling. The proposed processes in the heart damaged by ischemia and reperfusion need to be examined in detail and it is also necessary to determine whether RIP3 inhibition is able to limit these processes and thus alleviate cardiac dysfunction and remodeling. A considerable originality of the project is the study of necroptosis in a metabolically-stressed heart due to diabetes and its precursor - prediabetes and its contribution to heart damage. We will investigate the canonical and the newly-proposed RIP3-mediated signaling and evaluate their activation depending on the glucose levels and other biochemical characteristics of these disturbances in glucose metabolism. We hypothesize that antidiabetic therapy is able to mitigate heart damage due to the limitation of necroptosis what is further amplified by antinecroptotic agents. An important concept is the assessment of released markers of necroptosis signaling into the circulation which could be a prognostic and diagnostic approach. Proposed studies and a variety of methodological approaches, employed according to the guideline for the evaluation of necroptosis in the heart, will provide innovative insights into the pathogenesis of prediabetic and diabetic heart and its damage due to ischemia, and thereby indicate a significant pharmacotherapeutic target.

Neurocognitive mechanisms of semantic representation and control

Neurokognitívne mechanizmy sémantickej reprezentácie a kontroly

Duration: 1. 1. 2023 - 31. 12. 2026
Program: VEGA
Project leader: Mgr. Marko Martin PhD.
Annotation:Semantic cognition underpins the processing, organization, and fluid retrieval of knowledge (facts, concepts, and their relations) stored in memory. It regulates mental processes and adaptive behavior, whereas deterioration of this system is present among several neuropsychiatric disorders and diseases. The aim of this project is to identify cognitive and neurobiological mechanisms that support the ability to search and retrieve conceptual representations within semantic memory. For this purpose, we will carry out a set of original experiments that combine systematic manipulation of cognitive interference, the measurement of cognitive load (effort) using pupillometry, and non-invasive (transcranial) electrical brain stimulation. Via such interdisciplinary approach, we intent to characterize key neurocognitive determinants of automatic and control (executive) functions of the human semantic system, which may inspire effective interventions for their enhancement.

Neuroprotective and cardioprotective potential of phenol acids in the prevention of civilization diseases

Neuroprotektívny a kardioprotektívny potenciál fenolových kyselín v prevencii civilizačných ochorení

Duration: 1. 1. 2023 - 31. 12. 2026
Program: VEGA
Project leader: RNDr. Gáspárová Zdenka PhD.
Annotation:The risk of the civilization disease can be reduced by adjusting the lifestyle and a diet low in fat and increasing the intake of vegetables and fruits rich in flavonoids. These include phenolic acids (PA), small molecules with good bioavailability, and beneficial effects on the body. The project is focused on the cardioprotective and neuroprotective effects of PA on the heart and hippocampus of rats in vitro. After selecting the most effective PA from in vitro experiments, this will be tested in vivo in a model of a metabolic syndrome induced by a high fat-fructose diet. A project innovation lies in (i) the use of promising low molecular weight PA, and (ii) the application of magnetic resonance spectroscopy for non-invasive monitoring of the neurochemical profile changes in the rat brain. The determination of inflammation and oxidative stress markers offers to characterize the mechanism of action of the selected PA. The behavioral test (NOR) will provide data on learning and memory improvements.

OffRISK - Novel antidepressant therapy - long term consequencies on offspring

Nová generácia antidepresív - dlhodobé účinky na potomstvo

Duration: 1. 7. 2020 - 28. 6. 2024
Program: APVV
Project leader: RNDr. Dubovický Michal CSc.
Annotation:Maternal depression experienced during pregnancy endangers both mother and her offspring. It may alter brain activity of offspring on multiple systemic level. Behavioral changes observed in offspring are caused not only by depression-altered maternal behavior, but also by biochemical changes in offspring brain occurring during pregnancy and manifested in altered neuronal excitability in relevant brain regions. These alterations may differ between male and female offspring and may recess during adolescence. Antidepressant treatment during pregnancy may relieve maternal depression, but it may also prevent negative effects of maternal depression on offspring. We will focus on consequences of maternal depression on mental and physical status of offspring and on possible prevention of negative consequences by suitable treatment of the mother during pregnancy. We will characterize health status of offspring on multiple systemic levels starting with whole animal level characterized by animal behavior, through altered neuronal excitability on level of neuronal networks, following with excitability of individual neurons, biochemical alterations of neuronal metabolism, up to subcellular regulation of calcium homeostasis. We will investigate health effect and underlying cellular mechanism of antidepressant mirtazapine, which is commonly used in clinics, yet mechanism of its action is still not fully understood. We will use an established model of maternal depression activated by three weeks long pregestational stress. During weaning period we will assess maternal behavior of mirtazapine-treated and mock-treated mothers. Main focus of the project will be on effects of maternal stress on second generation, i.e., on offspring of treated and untreated of depressed mothers. Further, we will differentiate effects on male and female pups.

CARDIOPROT - New aspects of cardioprotection by natural antioxidants: role of ageing and lifestyle-related comorbidities

Nové aspekty kardioprotekcie prírodnými antioxidantami: vplyv starnutia a komorbidít súvisiacich so životným štýlom

Duration: 1. 7. 2022 - 30. 6. 2026
Program: APVV
Project leader: doc. RNDr. Barteková Monika PhD.
Annotation:Despite the important progress in the treatment of cardiovascular disease (CVD), the new therapeutic strategies as well as mechanisms involved are still being extensively studied to reach the optimal efficiency of the therapy. Ischemia/reperfusion (I/R) injury represents a clinically relevant problem associated with CVD (including ischemic heart disease and myocardial infarction) as well as with cardiac surgery. Natural antioxidants including flavonoid quercetin and several catechins have been shown to exert protective effects against cardiac I/R injury. However, most of the experimental studies have been performed in young healthy animals what is not corresponding to the situation in real life where the patients prone to acute ischemic event (myocardial infarction) are usually aged people suffering from some comorbidities such as hypertension or metabolic disorders. Thus the aim of the current project is to reveal the real therapeutic potential of selected natural antioxidants, quercetin and epicatechin against cardiac I/R injury in aged subjects and subjects suffering from selected metabolic comorbidities (type 2 diabetes, hypertriglyceridemia) and hypertension. Another goal of the project is to uncover intra- as well as intercellular mechanisms involved in the action of selected antioxidantss in individuals with comorbidities exposed to cardiac I/R, including their interactions with mechanisms involved in development of selected comorbidities. Meeting the objectives of the project will significantly help to better management of patients suffering from CVD, particularly from acute myocardial infarction

New methods of treating heart failure. Prevention of oxidative stress by molecular hydrogen.

Nové metódy liečby srdcového zlyhania. Prevencia oxidačného stresu molekulárnym vodíkom.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: RNDr. Kura Branislav PhD.
Annotation:Heart failure (HF) globally affects approximately 26 million people worldwide. Despite many therapeutic advances in the symptomatic treatment of HF, the prevalence, mortality and costs associated with treatment in developed countries continue. One of the key mechanisms involved in the development of the pathophysiology of the failing heart is the uncontrolled overproduction of reactive oxygen species, which causes damage to lipids in membranes, mitochondria, proteins and DNA, leading to cell death. Blocking hydroxyl and nitrosyl radicals could therefore prevent the destruction of cellular components and the progression of HF. Recently, it was discovered that molecular hydrogen (H2) has a protective effect in the case of damage to various organs, mainly due to its antioxidant activity. We hypothesize that H2 application could be a new effective treatment for HF patients. The project is aimed at investigating the therapeutic use of H2 and its ability to act cardioprotectively in the isoproterenol-induced HF model in older rats.

StrokeRehab - Novel approach to post-stroke rehabilitation. A basic and translational study, aiming to restore posture control and body symmetry in post-stroke patients by sensory stimulation.

Nový prístup k rehabilitácii pacientov po cievnej mozgovej príhode. Základný a translačný výskum s cieľom zlepšiť funkciu rovnováhy a symetriu tela u pacientov po cievnej mozgovej príhode pomocou senzorickej stimulácie.

Duration: 1. 8. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Bzdúšková Diana PhD.
Annotation:The main goal of this project is to investigate the pathophysiological mechanisms of keeping balance while sitting and standing in post-stroke patients and to define the rationale for interventions based on visual and proprioceptive stimulations for enhancing balance, impaired trunk mobility and trunk asymmetry. To achieve this, we will use the original method for rehabilitation and monitoring of patients as well as specialized devices together with softwares which we developed during our previous project APVV-16-0233. Stroke is a major health problem, especially considering that post-stroke patients typically have residual impairments to their motor and sensory functions directly affecting their postural system. Keeping balance while sitting up in bed or on a chair is with high probability the first thing a therapist addresses to patients. Controlled trunk function is an important and essential component for standing balance, gait and other daily activities. The voluntary movements of the trunk clearly reveal the postural and movement asymmetry of the upper part of the body. The asymmetric position is most often characterized by one-sided tilt of the trunk or its reduced mobility to one side. We aim to advance knowledge on the abnormal posture due to impairment of dynamic balance as a consequence of stroke, and to exploit visual and proprioceptive stimulations in order to improve posture and trunk asymmetry in post-stroke patients. Finally we will evaluate efficiency of rehabilitation procedures using two different approaches: i) by recording of the centre of pressure using force plate and ii) by recording of trunk tilts using inertial sensors.

Are connexin channels involved in extracellular matrix remodeling of overloaded heart?

Podieľajú sa konexinové kanály v preťaženom srdcovom svale na extracelulárnej remodelácii?

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Tribulová Narcisa DrSc.
Annotation:Cardiac connexin (Cx) channels that are localized at the gap junctions in intercalated discs ensure electrical and molecular signals propagation among cardiomyocytes. Such direct intercellular signaling is essential for synchronized heart contraction. Cardiovascular diseases in humans as well as in animal models are accompanied by abnormal Cx43 expression and its enhanced localization to the lateral sides of the cardiomyocytes. Consequently, it deteriorates synchronized heart function and increase a risk for malignant arrhythmias. Based on general knowledge and our studies we hypothesize that laterally localized Cx43 channels might transmit signals from cardiomyocytes into extracellular space and by this way contribute to adverse extracellular matrix remodeling. Intention of the project is to reveal the possible implication of Cx43 channels in modulation of extracellular space in diseased heart. It may stimulate to search novel approaches in protection from cardiac dysfunction and arrhythmias.

Comparison of antidepressant effects of natural psychoplastogen and an mTOR activator in animal model of depression

Porovnanie antidepresívnych účinkov prírodného psychoplastogénu a aktivátora mTOR v animálnom modeli depresie

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Vranková Stanislava PhD.
Annotation:Increasing prevalence of depression presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert potent acute and long-term positive effects. Several of them are naturally occurring compounds, such as 7,8-dihydroxyflavone (7,8-DHF). The aim of our study is to investigate the effects of 7,8-DHF and NV-5138, an mTOR (mammalian target of rapamycin) activator, and their combinations, on the development of depressive-like symptoms in animal model. Results of this project will contribute to elucidating the pathogenesis of depression and their treatment possibilities.

Postural threat in virtual reality in adults with height intolerance

Posturálna hrozba v prostredí virtuálnej reality u ľudí so strachom z výšky

Duration: 1. 1. 2022 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Bzdúšková Diana PhD.
Annotation:Virtual reality (VR) is suitable for evaluating postural and psychophysiological parameters in different situations and different populations. Fear of height and subsequent fall causes limitations in daily living and avoidance of any height, which represents a postural threat. A possible solution to relieve the stress and anxiety is a stance on an elevated platform in VR, which can repeatedly create a real-life experience that the subject gradually becomes accustomed to, but in safe and controlled conditions. Intervention can be enhanced before exposure to height by transcranial stimulation (tDCS) of the cerebellum, which plays a significant role in postural control. The aim of the project is to gain new knowledge about postural and psychophysiological reactivity during the postural threat in VR and to explore it immediately after tDCS. The obtained results may be beneficial for the rehabilitation of patients with balance disorders, people with height intolerance, and the elderly at risk of falls.

The use of mass spectrometry for comparative study of different rats strains glycoprofiles within metabolic disturbances intervention

Použitie hmotnostnej spektrometrie na porovnanie glykoprofilov rôznych kmeňov potkanov v intervencii metabolických porúch

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: Ing. Brnoliaková Zuzana PhD.
Annotation:Metabolic syndrome (MetS) defines a cluster of interrelated risk factors for diabetes mellitus. Glycobiology is helping in search for biomarkers of severe diseases, the bioanalytical metods were patented. We hypothesize: the glycomic profiling of blood sera has the potential in MetS diagnostics. The goals are to acquire glycomic profiles, by means of mass spectrometry, derived from blood sera of different rats strains; to characterize their composition; to correlate with pathophysiology; to evaluate the differences with respect to the glycosylation changes (sialylation, fucosylation). In vivo: to realize the study with nutritional intervention; to evaluate the effect of allimentary habits preferences on the metabolic condition. In vitro: to investigate the impact of key mechanisms of MetS in association with cellular glycoprofile induced changes. As the output: might be the model glycomic tool for basic research appointed to test therap. approaches with perspespective for clinical research recommendations.

Prenatal programming of adult diseases: treatment and prevention of outcomes of gestational hypoxia in rat offspring

Prenatálne programovanie chorôb v dospelosti: možnosti terapie a prevencie následkov prenatálnej hypoxie u potomstva potkanov

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Mach Mojmír PhD.
Annotation:Hypoxia during pregnancy, labor or early life stage is a major determinant of neurological morbidity and mortality in the neonatal period. In the last decade the fetal origin of chronic adult diseases was proposed as the most important factor in genesis of diabetes and hypertension in adulthood. The scientists showed that malnutrition, and inadequate oxygen supply during embryofetal development may lead to the inadequate apoptosis/necrosis, and caused maldevelopment of the organs responsible for regulation blood pressure, glucose, or improper brain wiring. Although the understanding of perinatal asphyxia-related pathophysiology is gradually increasing, limited therapeutic options are available to prevent or even mitigate the devastating process that unfolds after injury. Mitochondria-targeted antioxidants (MTA) are one of the most important therapies for providing neuroprotection in cerebral ischemia. The aim of the project will be to explore the possibilities of using MTA in late gestational hypoxia model.

Crosslinking of some necrosis-like forms of cell death: signaling and a multi-targeting tool to mitigate heart damage due to ischemia?

Prepojenie niektorých foriem bunkovej smrti nekrotického fenotypu: signalizácia a multicieľový nástroj pre zmiernenie poškodenia srdca v dôsledku ischémie?

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Necrosis-like cell death (CD), such as necroptosis and pyroptosis, and autophagy seem to play a more significant role in cardiac damage than apoptosis. Their signaling is complex and involves some common proteins whose activation depending on conditions leads to the certain form of CD. In the ischemic heart, we examine the relationship between these forms of CD and determine whether the necroptotically damaged area of the heart causes propagation of damage to surrounding tissue due to release of pyroptosis-linked molecules. Their analysis, including TNF, is aimed to assess CD induction. Sensitivity of individual heart cells to such molecules and paracrine pro-necroptotic signaling will be examined. We study whether autophagy induced by cardiac ischemia is associated with or converts to necroptosis. We also test whether the simultaneous inhibition of the particular forms of CD is more effective than individual inhibition in limiting cell death and ameliorating cardiac dysfunction and remodeling.

The contribution of new nano-carrier drug delivery systems to the enhancement of the anti-inflammatory effect of D-limonene, phellandrene, isoborneol and chrysophanol studied in vivo (2/0091/23

Prínos nových nanonosičových liekových systémov k zvýšeniu protizápalového účinku D-limonénu, felandrénu, izoborneolu a chryzofanolu skúmaný in vivo (2/0091/23)

Duration: 1. 1. 2023 - 31. 12. 2026
Program: VEGA
Project leader: PharmDr. Dráfi František PhD., MPH
Annotation:Based on the scientific literature we hypothesize that an optimal anti-inflammatory effect of a selected natural substance after its oral administration in its new nano-carrier drug delivery systems (NCDDS) might beneficially modulate immune processes in inflammatory diseases as in rheumatoid arthritis (RA). Adjuvant arthritis (AA) is used as one of the in vivo RA models to evaluate the pharmacology of molecules tested. High bioavailability will be achieved by the technological adjustment of the molecules into NCDDS (nanoemulsions and liposomes). Along with other parameters evaluated and focused mainly on inflammation, we will analyze the ability to reduce bone erosion and/or synovitis by the RANKL/RANK/osteoprotegerin signalling pathway. The significant benefit will be statistically assessed by their dose-dependency evaluation and possible synergic/additive pharmacological determination of concomitantly applied standards as methotrexate and upadacitinib, administered both in (sub)therapeutic doses.

SVBENMKVS - Investigation of endotoxin effects on mechanosensoric complex in the heart of normotensive rats.

Skúmanie vplyvu bakteriálneho endotoxínu na mechanosenzorický komplex v srdci.

Duration: 1. 12. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Okruhlicová Ľudmila CSc.

SQUID magnetometry of nano- and microparticles, nanocolloids and nanostructures in new applications in the field of biomedicine and materials research associated with the development of new measurement methods and procedures

SQUID magnetometria nano- a mikro častíc, nanokoloidov a nanoštruktúr v nových aplikáciách v oblasti biomedicíny a materiálového výskumu spojených s rozvojom nových meracích metód a postupov

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Bernátová Iveta DrSc.

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Systémový program pre komplexné poznanie a kritické myslenie formou zážitkového vzdelávania

Duration: 1. 10. 2022 - 31. 3. 2023
Program: Iné projekty
Project leader: Ing. Ferko Miroslav PhD.

HNOSES - Study of biological effects of H2S/NO/selenium products and molecular mechanisms of their actions

Štúdium biologických účinkov produktov H2S/NO/selénovej interakcie a molekulárne mechanizmy ich pôsobenia

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Čačányiová Soňa PhD.
Annotation:Reactive sulfur (RSS), nitrogen (RNS) and selenium species (RSEs) are groups of simple chemical molecules of radical or non-radical nature, which interact with cellular components and thereby influence various biological processes. The study of biological effects of RSS, RNS and RSeS and their mutual interactions is important for the understanding of their biological roles, moreover for the potential application of these species in medicine. Our studies of the reactive species interaction in the last 3 years showed that: - products of hydrogen sulfide (H2S) and polysulfides (H2Sn, n≥2) interaction with nitric oxide (NO) or selenium compounds (R-Se) significantly affect oxygen radicals concentrations, hydroperoxide cleavage, DNA damage, rat blood pressure and tension/relaxation of isolated aorta.- H2S and H2S2 interact with tetracycline antibiotics, mainly doxycycline (DOXY) and thereby produce/inhibit superoxide and hydroxyl radicals and induce/inhibit DNA damage These findings imply the possibility that reactive oxygen species (ROS) and other H2S/NO/R-Se interaction products affect (patho)physiological functions in living organisms. In the project´s aims we will build on the previous findings and investigate following new hypotheses: 1) Do mixtures (H2Sn/R-Se, H2Sn/R-Se/NO alebo H2Sn/DOXY) produce ROS or other biologically active compounds? 2) Are these products responsible for production/inhibition of radicals, cleavage of hydroperoxides and induction/inhibition of DNA damage? 3) Do interaction products affect ferroptosis or intracellular calcium concentration in cells? 4) Do these products affect rat blood pressure, arterial pulse waveform and tension of isolated arteries? The aim of this project is to investigate the chemical biology, activity and effects of the interaction products on cellular, organ and whole-organism level. These findings may contribute to the development of novel therapeutic interventions based on the modulation of cellular redox biology.

Study of new mechanisms of cardioprotection against ischemia-reperfusion injury of the heart: role of extracellular vesicles, non-coding RNAs and impact of metabolic co-morbidities on these mechanisms

Štúdium nových mechanizmov kardioprotekcie voči ischemicko-reperfúznemu poškodeniu srdca: úloha extracelulárnych vezikúl, nekódujúcich RNA a vplyv metabolických komorbidít na tieto mechanizmy

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: doc. RNDr. Barteková Monika PhD.
Annotation:Ischemic heart disease and myocardial infarction represent major diseases associated with ischemia-reperfusion (I/R) injury of the heart. Despite several powerful cardioprotective interventions against I/R injury including endogenous (e.g. ischemic conditioning) as well as exogenous ones including treatment with natural antioxidants, have been proposed, molecular mechanisms of cardioprotection are not fully clarified so far; moreover, there are serious translational gaps in transferring cardioprotective interventions into clinics due to comorbidities present in real patients suffering from cardiac I/R injury. The aim of the present project is to uncover the role of extracellular vesicles as new players in cardioprotection, to identify particular non-coding RNAs involved in cardioprotection, and to explore the effect of metabolic co-morbidities on molecular mechanisms and efficiency of cardioprotection, altogether in the sake of effective transfer of experimental knowledge to human personalized medicine.

The study of structural changes of complex glycoconjugates in the proces of inherited metabolic and civilization diseases

Štúdium štruktúrnych zmien komplexných glykokonjugátov v procese dedičných metabolických a civilizačných ochorení

Duration: 1. 3. 2021 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Výskum a inovácie
Project leader: Ing. Brnoliaková Zuzana PhD.
Annotation:The project is focused on the improvement of condition and integration capacities of an excellent independent and industrial research within the functional glycomics with preferencies in inherited metabolic and civilization diseases of humans. The research field is oriented towards the identification of clinically and prognostically relevant glyco-biomarkers and diagnostic approaches.

Study of the role of innate cardioprotection in the rat myocardium evoked by non-pharmacological adaptive stimuli under normal and pathological conditions.

Štúdium úlohy endogénnej kardioprotekcie v myokarde potkana evokovanej nefarmakologickými adaptačnými stimulmi za normálnych a patologických podmienok

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Despite advances in pharmacotherapy, interventional cardiology, and surgery, a growth of ischemic heart disease as one of the main reasons for heart failure will not reduce over the next decades. It is due to longer survival after myocardial infarction (IM) but gradual impairment of its function and incidence of comorbidities. Attenuation of IM consequences employing ischemic “preconditioning“ (PC) is not commonly used in clinical praxis due to technical requirements and short-term duration. On the other hand, there are other adaptive interventions such as PC in a distant organ, physical activity, and/or chronic or acute hypoxia. Their advantage over classical IPC is a noninvasive, relatively simple, and safe mode of introduction with a possibility of repeated application that may be a prerequisite of greater efficiency in humane medicine. It is assumed that application of noninvasive forms of PC induces similar effects as IPC – activation of cell signaling cascades of endogenous cardioprotection

The role of macroautophagy and chaperone-mediated autophagy (CMA) in the responses and adaptation of animal cells to doxorubicin-induced effects

Úloha makroautofágie a autofágie sprostredkovanej šaperónmi (CMA) v odpovediach a v adaptácii živočíšnych buniek na účinky vyvolané pôsobením doxorubicínu

Duration: 1. 1. 2021 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Barančík Miroslav DrSc.
Annotation:The project is focused on characterization of the role of macroautophagy and chaperone-mediated autophagy (CMA) in molecular mechanisms involved in responses of animal cells to the effects of doxorubicin (DOX). The aim is also to study the involvement of intracellular (protein kinases) and redox (Nrf2) signaling in regulation of both types of autophagy after DOX effects. The effects of flavonoid quercetin and Nrf2 pathway activator sulphoraphane on modulation of autophagy and autophagy-related signaling after effects of DOX will also be studied.

The role of matrix metalloproteinases in pathophysiology of cardiovascular system diseases and their relation to cellular redox signaling.

Úloha matrixových metaloproteináz v patofyziológii ochorení kardiovaskulárneho systému a ich vzťah k bunkovej redoxnej signalizácii.

Duration: 1. 7. 2019 - 30. 6. 2023
Program: APVV
Project leader: RNDr. Barančík Miroslav DrSc.
Annotation:The aim of the project is to characterize the role of matrix metalloproteinases and Nrf2 signaling in responses of cardiac cells to pathological conditions associated with effects of anthracycline doxorubicin and in conditions of diabetes. The goal will also be to determine the effects of Nrf2 activator sulforaphane and flavonoid quercetin on activation of responses mediated by Nrf2 pathway, on modulation of cellular injury, and on changes in activity/function of matrix metalloproteinases. To clarify the mechanisms connected with Nrf2 signaling, the intracellular (protein kinase pathways) and intercellular (connexin-43) signaling as well as regulation of enzymes involved in protection of cells against stress pathological conditions will be determined.

MIRCVD - The role of miRNAs in the onset and progression of cardiovascular diseases - new approach to the protection of the heart in situations of increased production of reactive oxygen species

Úloha miRNA pri vzniku a priebehu kardiovaskulárnych ochorení - nové prístupy ochrany srdca v situáciách zvýšenej produkcie reaktívnych foriem kyslíka

Duration: 1. 7. 2020 - 30. 6. 2024
Program: APVV
Project leader: RNDr. Kura Branislav PhD.
Annotation:Despite progress in prevention, diagnosis and treatment, cardiovascular disease (CVD) is one of the highest morbidity and mortality rates in the world. World Health Organization statistics suggest that in 2030 approximately 23.6 million people will die of CVD, particularly from heart failure and myocardial infarction. One of the most common causes of many CVDs is excessive production of reactive oxygen species (ROS). These arise naturally in all organisms that gain energy by oxidizing substrates, but are also the result of various exogenous effects, such as radiation or air pollution. ROSs affect all types of cells in the body. By their activity, they cleave electrons from the molecules, making the surrounding molecules unstable and subsequently damaging other surrounding molecules. This damage process leads to cell apoptosis, tissue damage and pathological processes and diseases. At present, many experimental works emphasize the use of microRNAs (miRNAs) in diagnostics and potentially also in CVD therapy. miRNA is a group of short non-coding RNAs that, upon binding to a protein mRNA chain, inhibit its synthesis, greatly affecting many processes in the body. ROS production and the effect of miRNA expression are linked to the development of many CVDs, so it is important to understand the relationship between these factors. Research into new suitable substances and methods that can positively affect the effects of excessive ROS formation on the cardiovascular system can significantly improve the quality of life of cardiological patients. The aim of the project is to look for suitable substances that will prevent toxic effects of excessively formed ROS and positively affect the mechanisms that cause damage. At the same time, elucidation of the role of miRNA involvement in signaling pathways associated with the action of ROS on the development and progression of various CVDs is also be presented.

NEISAD - The role of non-ischemic adaptive stimuli in protection of ischemic myocardium: study of triggering mechanisms and cardioprotective cell signaling

Úloha neischemických adaptačných stimulov v ochrane ischemického myokardu: štúdium spúšťacích mechanizmov a bunkovej kardioprotektívnej signalizácie.

Duration: 1. 7. 2019 - 30. 6. 2024
Program: APVV
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Cardiovascular diseases, especially ischemic heart disease (IHD) as a leading cause of heart failure and mortality worldwide, will not reduce over the coming decades despite the progress in pharmacotherapy, interventional cardiology and surgery. It is due to aging population and longer survival after acute myocardial infarction (MI), gradual decline of its function and incidence of comorbidities (diabetes, hypertension, dyslipidemia). Experimental studies revealed attenuation of MI by adaptive phenomenon of ischemic “conditioning“. However, it is not usually applicable in clinical medicine. In line with translation-oriented research, the project is aimed to: 1. verify the efficiency of cardioprotection induced by non-ischemic stimuli, such as motoric activity, hypoxia and non-invasive remote “conditioning“; 2. identify triggering mechanisms and pathways of signal transduction (“survival” cascades RISK and SAFE) to the target structures involved in heart injury reduction (mitochondrial permeability transition VV 2019 Základný výskum APVV-19-0540 Akronym: NEISAD 06.07.2020 10:48 Strana/Page: 2 pore, MPTP, nuclear PPAR receptors); 3. investigate the impact of comorbidities, age and gender on the adaptive processes considering functional, structural and subcellular cardiac alterations. Special emphasis will be placed on the role of small non-coding RNA (miRNA) regulating cell “survival” pathways and processes of apoptosis and necroptosis associated with cell oxidative state and Ca2+ homeostasis. We will focus on disclosure of the benefits of combination therapy: pleiotropic effects of PPAR agonists, MPTP inhibitors, coupled with noninvasive adaptive interventions not only under normal but also under pathological conditions (hypertension, hyperlipidemia, hyperglycemia). On animal in vivo and ex vivo models, combination of physiological, biochemical, selected biophysical and molecular biology methods will enable to elucidate processes of heart failing/regeneration and gain results that may lead to development of novel/modified strategies of IHD management.

Role of nuclear factor NRF2-mediated signalling in iron metabolism regulation during stress

Úloha signalizácie sprostredkovanej jadrovým faktorom NRF2 v regulácii metabolizmu železa počas stresu

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Bernátová Iveta DrSc.
Annotation:Stress is considered to be an etiological factor associated with the development of various chronic non-communicable diseases. Stress may also alter iron metabolism. Nuclear factor erythroid 2-related factor 2 (NRF2)-regulates several genes involved in iron metabolism. Despite the accelerating information on the roles of NRF2, less is known about the NRF2 signalling in iron metabolism in conditions of stress. Thus, the aim of this project is to investigate the role of NRF2 signalling in iron metabolism in conditions of acute and chronic stress in rats with genetic predisposition to hypertension. In addition, the effects of pharmacological activation of NRF2 signalling and the distinct roles of inducible and endothelial nitric oxide synthases in iron metabolism in stress conditions will be investigated. Thus, we obtain the original results about NO and NRF2-mediated regulation of iron metabolism and about involvement of altered iron metabolism in the development of cardiovascular and metabolic disorders.

HHTgINFL - The role of inflammation in the development of cardiovascular complications associated with metabolic syndrome and prediabetes

Úloha zápalu v rozvoji kardiovaskulárnych komplikácií spojených s metabolickým syndrómom a prediabetom

Duration: 1. 7. 2022 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Čačányiová Soňa PhD.
Annotation:Inflammatory conditions are one of the most important pathophysiological factors in the development of cardiovascular diseases. Perivascular adipose tissue (PVAT), its pro-inflammatory activities and its impact on vasoactive functions may play an important role in the development of cardiovascular complications. Moreover, impaired PVAT function leads to the secretion of proinflammatory factors and endothelial dysfunction which could be associated with unbalance in sulfide signaling. The aim of the proposed project will analyze the vasoactive and inflammatory mechanisms in the vessel wall and PVAT with special attention to sulfide signaling in model of metabolic syndrome. Crosstalk among them occurs, but the exact mechanism is unknown. The pro-inflammatory mechanisms are particularly triggered in the early stage of diabetes and metabolic syndrome, therefore, a unique model of prediabetes and metabolic syndrome, hereditary hypertriglyceridemic rats, will be used. Currently, increased attention is focused on aspects of personalized medicine, which can contribute to more effective therapy through precise targeting of a specifically defined group of patients.The development of cardiovascular complications and diabetes may depend on age, reproductive status, and genetic background. Cardiovascular riskis significantly increased in postmenopausal women, while it is lower in women under 40 than in men of the same age. The project will monitor the effect of gender and reproductive status in female rats after surgical ovariectomy to reveal possible differences in the mechanism of cardiovascular disorders and to help to better specify therapeutic targets appropriate to non-obese prediabetic postmenopausal women. In the next part, the project will investigate the possible beneficial effects of the administration of the bioflavonoid troxerutin in lowering the risk of developing cardiovascular complications associated with postmenopausal metabolic syndrome.

Multi-Glu - Multi-target approach to diverse molecular mechanisms of diabetic complications and other glucose toxicity related diseases

Viac-cieľový prístup k rozličných molekulovým mechanizmom diabetických komplikácií a iných ochorení súvisiacich s toxicitou glukózy

Duration: 1. 8. 2021 - 30. 6. 2025
Program: APVV
Project leader: RNDr. Májeková Magdaléna PhD.
Annotation:Diabetes mellitus and other diseases related to the glucose toxicity have multifactorial character comprised of multiple mechanisms. Besides others, the mechanisms include increased polyol pathway activity, non-enzymatic glycations of proteins, hexosamine pathway, altered protein kinase C activity, oxidation stress and impaired calcium signaling. Targeting individual mechanisms could lead to design of new compounds - potential drugs for a treatment of diabetic complications. Our aim is to elucidate the impact and roles of individual mechanisms. In this endeavor, we will build upon our previous results, which brought a new insight in details of polyols pathway mechanisms by means of the study of cemtirestat and other novel compounds designed by our group.

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Vlastnosti erytrocytov a oxidačný stres za vybraných patológií a po podávaní antioxidantov

Duration: 1. 1. 2021 - 31. 12. 2024
Program: VEGA
Project leader: RNDr. Vrbjar Norbert CSc.

The effect of aging and hypertension on experimental myocardial infarction

Vplyv starnutia a hypertenzie na experimentálny infarkt myokardu

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: RNDr. Cebová Martina PhD.
Annotation:Myocardial infarction is a serious cardiovascular disease associated with cardiac remodeling as a consequence of ischemia. Hypertension and aging aggravate the consequences of heart attack by the formation of oxidative and inflammatory mediators in the heart. Mereover, reperfusion after ischemia creates additional oxidative stress with a negative effect on myocardial tissue. To monitor the signaling molecules that can block or reverse the pathological process of infarction in hypertension is an important hypothesis for successful treatment of myocardial infarction. Therefore, our goal will be to exmine the effect of hypertension and aging on myocardial infarction and to analyze the effect of nitric oxide production, free oxygen radicals, and pleiotropic transcription factor Nrf2. In particular, the activation of Nrf2 and its target genes in elderly individuals may provide a novel mechanism of protection the myocardium from pathological cardiac remodeling.

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Výskum prírodných látok s terapeutickým potenciálom v humánnej medicíne: komplexná analýza, biologické účinky a štúdium synergie.

Duration: 1. 1. 2020 - 31. 12. 2023
Program: VEGA
Project leader: Ing. Račková Lucia PhD.
Annotation:Research work in the field of natural sources of antimicrobial active substances from the last two decades confirms the strong potential of natural substances and extracts, both in the eradication of resistant bacteria and fungi, but also in the prevention of biofilm formation and its destruction. The aim of this project is to test the biological activities of selected plant extracts, their secondary metabolites and their semisynthetic derivatives as potential antimicrobial and antibiofilm, as well as antioxidant, antiphlogistic and immunomodulatory agents. At the same time to exclude their cytotoxic potential on human cells in vitro and to evaluate the fingerprint of plant extracts by modern analytical methods. The target site for the action of these substances should be microbes colonizing skin infections (especially poorly healing, burns, surgical / postoperative wounds) and infections of the oral mucosa (especially the root canals of devital teeth and periradicular tissues). Another aim is to create a combination of active substances / extracts (synergistically acting), which will be adjusted to a gel base, which will be enriched with high-purity micronized beta-glucan in order to eradicate microbes on the skin and mucosa and promote tissue regeneration.

BIOVID-19 - Development of biomodels to improve efficiency assessment of drugs and substances that have the potential to treat COVID-19 (BIOVID-19)

Vývoj biomodelov pre zlepšenie hodnotenia účinnosti liekov a látok, ktoré majú potenciál pri liečbe COVID-19 (BIOVID-19)

Duration: 9. 6. 2021 - 30. 6. 2023
Program: Štrukturálne fondy EÚ Regionálny operačný program
Project leader: doc. RNDr. Pecháňová Oľga DrSc.
Annotation:The aim of the project is to develop an animal model to improve the evaluation of the effectiveness of drugs identified as having potential in the treatment of COVID-19. We will use the current knowledge about this disease, but mainly the findings obtained from samples of patients who died in direct connection with COVID-19 infection. We will currently test the most suitable treatment on the developed model.
Project web page:http://www.esif-cemsav.sk/

Development of diabetic nephropathy and its treatment with nutraceutic in experimental conditions

Vývoj diabetickej nefropatie a jej liečba nutraceutikom v experimentálnych podmienkach

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: Mgr. Kaločayová Barbora PhD.

Development of multifunctional aldose reductase inhibitors based on triazinoindoles: Optimization of their biological activity, selectivity, bioavailability and antioxidant properties.

Vývoj multifunkčných inhibítorov aldózareduktázy na báze triazínoindolov: Optimalizácia ich biologickej aktivity, selektivity, biodostupnosti a antioxidačných vlastností.

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: RNDr. Kováčiková Lucia PhD.

Development of products by modification of natural compounds and study of their multi-modal effects onCOVID-19 disease

Vývoj produktov modifikáciou prírodných látok a štúdium ich multimodálnych účinkov na ochorenie COVID-19

Duration: 1. 7. 2021 - 30. 6. 2023
Program: Európsky fond regionálneho rozvoja (EFRR)
Project leader: RNDr. Májeková Magdaléna PhD.

AMVADYMESE - Significance of endothelial α1AMPK for vascular dysfunction and metabolic senescence in a rat model of metabolic syndrome/diabetes mellitus type II

Význam endotelovej α1AMPK v rozvoji vaskulárnej dysfunkcie a v procese metabolickej senescencie u potkanov s metabolickým syndrómom/diabetes mellitus II. typu

Duration: 1. 7. 2022 - 30. 6. 2025
Program: SASPRO
Project leader: Ing. Kvandová Miroslava PhD.
Annotation:Endothelial dysfunction is an early common feature of many cardiovascular diseases, caused by decreased nitric oxide (NO) production and/or increased NO inactivation due to oxidative stress. This influences a patient's risk of future cardiovascular events1. The overall goal is to improve primary and secondary prevention for cardiovascular diseases. Therefore, analyzing key factors that prevent or positively influence endothelial dysfunction is essential. Working group of prof. Münzel/Daiber (current affiliation) has been focused on the role of AMP-dependent protein kinase (AMPK) for several years. This ubiquitously expressed enzyme is the central energy sensor of cells in the cardiovascular system2. The protective effect of AMPK has been already demonstrated, especially its protective properties on endothelial function, oxidative stress, cell aging, and inflammation3,4. In addition, AMPK regulates many metabolic pathways that are disturbed in the context of diabetes mellitus, such as the activation of glucose transport in skeletal muscle or the inhibition of gluconeogenesis in the liver. These properties suggest that AMPK may improve diabetic metabolic control. It has been shown for diabetes mellitus that vascular changes are prognostically decisive5. Despite enormous research, the molecular changes that lead to endothelial dysfunction and predisposition to cardiovascular diseases due to α1AMPK-related dysregulation are insufficiently known. Therefore, the following questions will be addressed: 1. How do α1AMPK influence endothelial function, formation of reactive oxygen species, and vascular inflammation in the rat model of the metabolic syndrome/diabetes mellitus II type? 2. Exploring the role of α1AMPK expression in endothelial cell death and the development of metabolic senescence in hyperglycemia and diabetes? 3. Are metabolic syndrome/diabetes mellitus II type mediated disorders of the endothelial function associated with the gender-specific regulation of α1AMPK?

Zofenopril and erucin, H2S releasing coumpounds, in therapy of cardiovascular disorder in experimental model of obesity and 2 type diabetes

Zofenopril a erucín, H2S uvoľňujúce látky, v terapii kardiovaskulárnych porúch pri experimentálnom modeli obezity a diabetu 2. typu

Duration: 1. 1. 2022 - 31. 12. 2025
Program: VEGA
Project leader: RNDr. Čačányiová Soňa PhD.
Annotation:Hydrogen sulfide (H2S) represents an important gaseous transmitter involved in the vascular tone regulation, however, its role in pathological stages such diabetes and obesity remains unexplained. In both, arterial hypertension and metabolic disorder without obesity, H2S produced by arterial wall could participate in impaired vascular function, on the other side, sulfide signal pathway can be a part of compensatory vasoactive mechanisms. We suppose that the escalated metabolic disorder and obesity could impair balanced action of sulfide pathway and enhance the injury of vascular system. H2S-releasing compounds could provide the treatment leading to the decrease of detrimental vasoactive and pro-oxidative effects. We will investigate the chronic effect of angiotensin-converting enzyme inhibitor zofenopril and natural isothiocyanate erucin, both acting as H2S donors, on cardiovascular system of obese Zucker diabetic rats to confirm or refuse a beneficial effect of therapy with H2S releasing drugs in obesity.

Projects total: 62