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 |
| Evidence number: | CA21139 |
| 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/ |
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 |
| Evidence number: | CA 20121 |
| 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 |
EU-NETVAL International Thyroid Validation Study
EU-NETVAL Medzinárodná validačná štúdia tyroidnej disrupcie
| Duration: | 1. 1. 2021 - 31. 12. 2024 |
| Program: | Multilaterálne - iné |
| Project leader: | Dr.rer.nat., Ing. Kanďárová Helena ERT |
| Annotation: | Characterising, validating and standardising new non-animal methods and approaches are important steps towards their regulatory use and international adoption. Various thyroid methods, targeting different modes of action of thyroid disruption, are currently under validation by EURL ECVAM and its network of validation laboratories EU-NETVAL. Chemicals that disrupt thyroid homeostasis have the potential to be endocrine disruptors and thus associated with several adverse health effects. About EU-NETVAL: EU-NETVAL is a large network of 39 highly qualified test facilities across Europe, coordinated by the JRC to support the in vitro method validation process. It represents a wide range of expertise and competences and includes laboratories experienced in advanced in vitro procedures, biological test systems and measurement techniques. |
| Project web page: | https://ec.europa.eu/jrc/en/eurl/ecvam/alternative-methods-toxicity-testing/eu-netval |
NETSKINMODELS - Engineering novel 3D organotypic skin models
European Network for Skin Engineering and Modeling (NETSKINMODELS)
| Duration: | 15. 9. 2022 - 14. 9. 2026 |
| Evidence number: | CA21108 |
| 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/ |
EURESTOP - European Network for diagnosis and treatment of antibiotic-resistant bacterial infections
Európska sieť na diagnózu a liečbu bakteriálnych ochorení rezistentných voči antibiotikám
| Duration: | 6. 10. 2022 - 5. 10. 2026 |
| Evidence number: | CA21145 |
| Program: | COST |
| Project leader: | RNDr. Májeková Magdaléna PhD. |
| Annotation: | The emergence and spread of drug-resistant bacteria is an important health and socioeconomic threat with global dimensions, which is developing towards an emergency/pandemic crisis. No drugs are available to address the disease, and diagnostic tools are poorly effective. This negatively impacts the treatment and survival of critically ill patients. Current research in this field is highly fragmented and mostly monodisciplinary, thus limiting the development of innovative diagnostic and therapeutic solutions. This COST Action will bring together industrial and academic European scientists with different skills and expertise in a multidisciplinary and concerted initiative. The Action will combine scientific disciplines in understanding the genetic and molecular bases of bacterial drug resistance, developing innovative diagnostic tools, and delivering lead/pre-clinical candidates, antibody-based therapies, and clinical-ready repurposed drugs towards the personalized treatment of drug-resistant bacterial infections. The further challenge of the Action is to enhance networking among European scientists and to train a new generation of young scientists skilled in the multiple aspects related to bacterial drug resistance. |
| Project web page: | https://eurestop.eu/ |
METAHEART - EUropean network to tackle METAbolic alterations in HEART failure
Európska sieť na riešenie metabolických zmien pri zlyhaní srdca
| Duration: | 18. 10. 2023 - 17. 10. 2027 |
| Evidence number: | CA 22169 |
| Program: | COST |
| Project leader: | doc. RNDr. Barteková Monika PhD. |
| Project web page: | https://www.cost.eu/actions/CA22169/ |
Exploration of toxicology properties of drug candidates with antimicrobial and antiviral properties.
Exploration of toxicology properties of drug candidates with antimicrobial and antiviral properties.
| Duration: | 1. 9. 2024 - 31. 12. 2025 |
| Evidence number: | PSCI Grant - 01 2024 |
| Program: | Multilaterálne - iné |
| Project leader: | Dr.rer.nat., Ing. Kanďárová Helena ERT |
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 |
| Evidence number: | NEURON_CV-060, NEURON grant number 964215 |
| 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. |
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 |
| Evidence number: | H2020 |
| 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
Targeted suppression of pro-inflammatory and pro-fibrotic signalling pathways to prevent life-threatening heart failure and malignant arrhythmias
Cielená modulácia pro-zápalových a pro-fibrotických signálnych dráh ako protekcia pred srdcovým zlyhávaním a život ohrozujúcimi arytmiami.
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Program: | VEGA |
| Project leader: | RNDr. Szeiffová Bačová Barbara PhD. |
BIOCARD - -
Bioenergetická a proteomická diagnostika v kardioprotekcii: efektívny nástroj v sledovaní regulácie mitochondriálnych signalizačných dráh.
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0264 |
| Program: | APVV |
| Project leader: | Ing. Ferko Miroslav PhD. |
| Annotation: | Oxygen-limited supply significantly increases the myocardial energy requirements. The onset of compensatory mechanisms against this disorder is associated with regulation at the level of cardiac mitochondria. It is mitochondrial dysfunction that is currently the goal of a therapeutic cardioprotective strategy. This project will combine the latest scientific insights with state-of-the-art methodological approaches. A key aspect of the presented research is to ensure sufficient energy production in the heart in conditions of increased energy requirements caused by reduced oxygen utilization and ischemic heart disease in combination with various types of preconditioning. The use of modern methodology will allow for investigation into the complex structure of mitochondrial protein signaling pathways, their regulations, proteome and metabolome alterations in heart and mitochondria. Description and comprehension of complex system of protein interactions can help identify signaling pathways in cardioprotection processes. Changes at the level of mitochondrial respiratory chain complexes that play an important role in the cellular energy maintenance will also be identified. One of the considered mechanisms of cardioprotection is the inhibition of mitochondrial permeability transition pores (mPTP) opening. Regulation of mPTP in terms of changes of individual proteins has already been presented. We aim to contribute to the understanding of the protein interactions presumably related to the protective modulation of mPTP. In connection with the remodeling of mitochondrial function, calcium homeostasis and signaling of free oxygen radicals will also be monitored. The presented project will deal with the stimulation of adaptation processes in order to contribute to the elimination of mitochondrial dysfunction and ensure the maintenance of dynamic balance under conditions of energy deprivation in diseased heart. |
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 |
| Evidence number: | APVV-21-0410 |
| 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. |
EXPERIMENTAL STUDY OF THE EFFECTS OF MATERIAL DEPRESSION AND ANTIDEPRESSIVES OF CITALOPRAM AND SERTRALINE ON POSTNATAL DEVELOPMENT OF OFFSPRING
EXPERIMENTÁLNA ŠTÚDIA ÚČINKOV MATERSKEJ DEPRESIE A ANTIDEPRESIVNYCH LIEČIV CITALOPRAMU A SETRALINU NA POSTNATÁLNY VÝVIN POTOMSTVA POTKANOV
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0133/23 |
| Program: | VEGA |
| Project leader: | RNDr. Dubovický Michal CSc. |
Experimental real-life risk simulation approach: The effect of long-term exposure to a chemical mixture of pesticides, contaminants and food additives at low doses in extended one-generation reproductive toxicity study
Experimentálny prístup simulácie rizík v reálnom živote: Vplyv dlhodobej expozície chemickej zmesi pesticídov, kontaminantov a potravinových prísad v nízkych dávkach vo viacgeneračnej štúdii na potkanoch
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0163/24 |
| Program: | VEGA |
| Project leader: | RNDr. Mach Mojmír PhD. |
| Annotation: | In real life, mixtures of xenobiotics can lead to a 'cocktail' effect. Studies have shown that these mixtures can lead not only to predictable additive effects but also to unpredictable synergistic, or antagonistic effects. From early intrauterine life till elderly, the individual is continuously exposed to chemicals with beneficial or detrimental effects depending on the doses, windows of exposure and combinations. Many of these exposures are considered risk factors for many diseases. These observations indicate the necessity of using improved hazard-evaluation models, such as the real-life risk simulation (RLRS) scenario. The present project aims to to provide an evaluation of the pre- and postnatal effects of mixture of chemicals (below NOAEL levels) on development as well as a thorough evaluation of systemic toxicity in pregnant and lactating females and young and adult offspring. |
N/A - Pharmacological intervention in the treatment of cachexia by administering natural extracts (Crocus sativus and Ginkgo biloba) and substances (melittin, saffron, crocin, kaempferol and isorhamnetin) in combination with methotrexate and dexamethasone in an
Farmakologická intervencia v liečbe kachexie podávaním prírodných extraktov (Crocus sativus a Ginkgo biloba) a látok (melitín, šafranal, krocín, kempferol a izorhamnetín) v kombinácii s metotrexátom a dexametazónom na zvieracom modeli zápalovej kachexie.
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | VEGA 2/0126/23 |
| Program: | VEGA |
| Project leader: | PharmDr. Poništ Silvester PhD. |
| Annotation: | Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the synovial joints and is also associated with extra-articular manifestations, including cachexia. Standard treatment of RA with methotrexate (MTX) and glucocorticoids (GC) may worsen cachexia. Thus, an important strategy of this project will be the suppression of cachexia using combination therapy, which will be based on the addition of natural anti-inflammatory substances to MTX and GC. In experimental arthritis, we will also investigate the effect of drugs and natural substances on markers of catabolism (myostatin and E3 ubiquitin-protein ligase) and anabolism (IGF-1, ghrelin, and testosterone) of skeletal muscle, on markers of systemic inflammation (IL-1beta, TNF-alpha, IL-6, MCP-1, IL-17A, MMP-9) and oxidative stress (4-hydroxynonenal, protein carbonyls, glutathione peroxidase, catalase) in plasma, which will help us to elucidate the mechanisms of inflammatory cachexia and it’s affecting by monotherapy and combination therapy. |
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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 |
| Evidence number: | 2/0113/21 |
| Program: | VEGA |
| Project leader: | RNDr. Lomenová Jana PhD. |
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 |
| Evidence number: | 2/0153/21 |
| 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. |
ITAGES - Identification of stress-induced alterations in expression of NRF2 target genes in rat models of prehypertension: the effect of comorbid hypertriglyceridemia and dimethyl fumarate treatment
Identifikácia stresom vyvolaných zmien v expresii cieľových génov NRF2 v potkaních modeloch prehypertenzie: vplyv komorbidnej hypertriglyceridémie a liečby dimetylfumarátom
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0296 |
| Program: | APVV |
| Project leader: | RNDr. Bernátová Iveta DrSc. |
| Annotation: | The nuclear transcription factor erythroid 2-related factor 2 (NRF2) is a key molecular link between several noncommunicable diseases, as it regulates the expression of approximately 250 target genes, including those involved in maintenance of redox balance, the development of metabolic disorders, cardiovascular and liver diseases, as well as in immune responses. Borderline elevated blood pressure (prehypertension) is a common cardiovascular disorder in humans, and elevated blood pressure has been found to be positively correlated with triglyceride levels. In addition, chronic stress is an etiological factor in the development of non-communicable diseases, including elevated blood pressure and hypertriglyceridemia (HTG). In experimental studies, borderline hypertensive rats (BHR) and hypertriglyceridemic rats (HTGR) are suitable models of prehypertension without and with comorbid hypertriglyceridemia. These models are relevant for investigating the effects of stress as well as for investigating the role of changes in expression of NRF2 target genes in the development of hypertension associated with metabolic diseases. To understand better the role of NFR2 as well as the impact of chronic social stress on thementioned diseased states, the aims of this project are: 1) to identify differences in expression of NRF2 target genes in two experimental models of prehypertension - without (in BHR) and with (in HTGR) comorbid HTG - in control conditions and during chronic social stress, 2) to determine if NRF2 activator dimethyl fumarate can reduce stress-induced pathologies in prehypertensive rats, especially in those with comorbid HTG, and 3) to specify a set of suitable whole blood RNA biomarkers for evaluation of changes in NRF2 target genes in prehypertension and HTG and those genes altered by chronic social stress. |
In vitro study of antioxidative/antiinflammatory effects of natural and synthetic compounds. In vivo assessment of medicinal effects of selected compounds in experiments of healing skin wounds.
In vitro štúdium antioxidačných/protizápalových účinkov prírodných a syntetických zlúčenín. In vivo dôkaz liečivých účinkov vybraných zlúčenín v experimentoch hojenia kožných rán.
| Duration: | 1. 1. 2023 - 31. 12. 2027 |
| Evidence number: | 2/0008/23 |
| Program: | VEGA |
| Project leader: | RNDr. Valachová Katarína PhD. |
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Inhibícia ACE2 receptorov pri hypertenzii a obezite ako potenciálny model dôsledkov COVID-19: účinol S-nitrózokaptoprilu
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0025/23 |
| Program: | VEGA |
| Project leader: | doc. RNDr. Pecháňová Oľga DrSc. |
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 |
| Evidence number: | 2/0087/22 |
| Program: | VEGA |
| Project leader: | Ing. Šoltésová Prnová Marta PhD. |
| Annotation: | Increased expression of aldo-keto reductases (AKRs) in tumors of lung, breast, prostate, cervix, testes and colon were reported, and the role of AKRs in the etiology of colorectal carcinoma has been confirmed. Although the AKRs have been studied extensively in the context of diabetic complications, studies in the last decade reveal the role of AKRs in the chemoresistance. The project will focus on the exploration of novel specific targets of chemoresistance represented by the AKRs and will comprise a multidisciplinary approach based on recognition of relevant genetic factors, namely specific mutations that cause chemoresistance, and their relationships to the molecular pathways mediated by AKRs. Moreover combination of QSAR and medicinal chemistry approaches will be used to explore the chemical space of AKR inhibitors with the aim to find the chemical entities of the highest efficacy and selectivity. The project is expected to contribute to establishing personalized therapy of cancer. |
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 |
| Evidence number: | APVV-20-0421 |
| 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 |
| Evidence number: | VEGA SR 1/0775/21 |
| Program: | VEGA |
| Project leader: | Mgr. Farkašová Veronika PhD |
CARDIOEND - Cardiovascular protection mediated by alpha 1 AMPK against metabolic syndrome-mediated endothelial dysfunction - identifying new risk factors
Kardiovaskulárna ochrana sprostredkovaná alfa 1 AMPK proti endotelovej dysfunkcii sprostredkovanej metabolickým syndrómom – identifikácia nových rizikových faktorov
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0154 |
| Program: | APVV |
| Project leader: | Ing. Kvandová Miroslava PhD. |
| Annotation: | Disruption of vascular homeostasis caused by decreased nitric oxide bioavailability oxide due to oxidative stress and inflammation is the most serious complication of metabolic syndrome (MetS), leading to increased morbidity and mortality. There is an unmet need to identify key factors that prevent or protect vascular endothelium and thus improve primary and secondary prevention of cardiovascular diseases. It appears that AMP-dependent protein kinase (AMPK) may be such a factor. Its protective properties and positive effect on endothelial function and oxidative stress are already known. These unique properties suggest that AMPK may be involved in improving metabolic control during MetS, but still, the molecular changes due to α1AMPK-related dysregulation during MetS development are poorly understood. The project focuses on risk factors affecting endothelial function during MetS and the AMPK as a potential tool to modify those risk factors resulting in MetS prevention or treatment. The originality of the project is based on a comprehensive evaluation of functional, molecular, and biochemical changes in endothelial function, inflammation, and metabolic senescence during MetS with a detailed focus on vascular endothelium - proliferation, senescence, and apoptosis. The focus will be put on risk factors affecting endothelial function such as the interaction/adhesion of leukocytes with the vascular endothelium and the AMPK-dependent role of erythrocytes during MetS development. The project will be enriched by the study of phenotypic and molecular changes at the level of the CNS, with an emphasis on neuroinflammation and behavioral changes. Importantly, the project has a translation character, as human studies in patients with MetS will also be performed. The obtained results may represent a potential tool for improving the current population’s health and reducing the economic burden associated with the treatment of this cardiometabolic disease. |
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 |
| Evidence number: | 2/0103/22 |
| 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. |
CardCa2+CNS - Molecular mechanisms implicated in corticosteroid-monoamine interaction in stress-related cardio- and neuropathologies
Molekulárne mechanizmy interakcie signálnych dráh kortikosteroidov a monoamínov v kardio- a neuropatológiách vyvolaných stresom
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0061 |
| Program: | APVV |
| Project leader: | RNDr. Mach Mojmír PhD. |
| Annotation: | Stress is defined as an organism’s response to various stressors jeopardizing the homeostasis. Stressors accompany living organisms all through their life, when the first exposure happens even before the birth (e.g., maternal infection during the gestation). Stress is not necessarily harmful; controlled exposure to the certain stressors might be even beneficial (e.g., cognitive behavioral therapy). On the other side, stress can also be involved in certain heart and brain disorders, which are the worldwide leading causes for disability and mortality. Based on our previous results in rats, we hypothesize that interaction between corticosteroids and monoamines is a factor determining whether certain stressor, administered to the organism of the specific sex, will be harmful, neutral, or even beneficial. We aim to perform a further investigation of corticosteroid-monoamine interaction in rat model of prenatal stress (maternal infection during the gestation caused by LPS administration) and to assess a role of Ca2+ signaling, which decodes diverse extracellular signals into specific cellular responses. Particularly, we will focus on investigation of changes caused by prenatal stress at the level of cardiomyocyte contractility and excitability of serotonin and dopamine neurons in the midbrain. Ca2+ signaling as a potential intracellular effector of corticosteroid-monoamine interaction will be monitored at the level of intracellular Ca2+ channels, which are considered as the main components of Ca2+ signaling in cardiomyocytes as well in neurons. We will also test pyridoindoles as the novel treatment strategies for the stress-related cardiovascular and neurological disorders. This will include in silico modeling (computer simulations of drug interactions) and in vivo treatment. |
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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 |
| Evidence number: | 2/0063/22 |
| Program: | VEGA |
| Project leader: | Mgr. Heger Vladimír PhD. |
On the trace of mitochondrial chloride channel identity.
Na stope identity mitochondriálneho chloridového kanálu.
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0085 |
| Program: | APVV |
| Project leader: | Ing. Ferko Miroslav PhD. |
| Annotation: | Mitochondrial chloride channels are involved in the regulation of the mitochondrial membrane potential deltaΨm. In in vitro conditions, it was observed that oxidative stress results in oscillations of deltaΨm, which leads to the shortening of the action potential on the plasma membrane of cardiomyocytes and to the occurrence of arrhythmias, mediated by the production of ATP in the mitochondria. At the level of the whole heart, arrhythmias were observed as a consequence of ischemia-reperfusion. Specific ligands of the translocator protein (TSPO) prevent the occurrence of post-ischemic arrhythmias. The use of a non-specific chloride channel blocker led to the same effect. TSPO ligands inhibit the mitochondrial chloride channels at nanomolar concentrations, suggesting that the TSPO protein mediates the chloride channel block. Thus, TSPO is likely to be in close contact with the chloride channel. Mitochondrial chloride channels are well described at the electrophysiological level, but their molecular identity remains unclear. Recently, two isoforms of chloride intracellular channel family (CLICs) have been shown to be localized in mitochondria. However, CLIC channels have only been described in an artificial system - overexpressed in host cells. Mitochondrial chloride channels from native membranes are assumed to be identical to one of the two mitochondrial CLIC isoforms. The aim of the presented project is to verify the hypothesis that the measured native chloride channels from cardiac mitochondria are members of the CLIC family and whether the given CLIC isoform and TSPO are in close physical contact. We assume that the obtained results will help to clarify the molecular identity of the mitochondrial chloride channel, which represents a significant potential target for preventing the occurrence of post-ischemic arrhythmias. |
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 |
| Evidence number: | APVV-20-0242 |
| 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 |
| Evidence number: | 2/0052/23 |
| 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 |
| Evidence number: | VEGA 2/0018/23 |
| 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. |
Novel antidiabetic/antiobesty drugs as innovative pharmacotherapeutic tools for cardioprotection in experimental model of type 2 diabetes
Nové antidiabetiká/antiobezitiká ako inovatívny farmakoterapeutický nástroj kardioprotekcie v experimentálnom modeli diabetu 2. typu
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | VEGA 2/0159/24 |
| Program: | VEGA |
| Project leader: | doc. RNDr. Barteková Monika PhD. |
| Annotation: | Ischemic heart disease and myocardial infarction represent major diseases associated with myocardial ischemia-reperfusion (I/R) injury. Although several effective pharmacological and non-pharmacological protective interventions against myocardial I/R have been identified, translation of knowledge into clinical practice is uncertain, also due to comorbidities suffered by cardiac I/R patients, including diabetes and obesity. On the other hand, recently described cardioprotective effects of known antidiabetic drugs give hope for a comprehensive solution for therapy of cardiovascular and metabolic diseases in one. The aim of the project will be to investigate the possibilities of cardioprotection against I/R injury using new drugs with antidiabetic and antiobesity effects in an experimental model of type 2 diabetes. Results of the project will contribute to expanding the possibilities of therapy for cardiometabolic diseases, and thus to better management of patients suffering from civilization diseases |
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 |
| Evidence number: | APVV-21-0194 |
| 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 |
| Evidence number: | 2/0092/22 |
| 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 |
| Evidence number: | APVV-20-0420 |
| 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. |
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 |
| Evidence number: | 2/0080/22 |
| 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. |
2/0091/23 - 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 |
| Evidence number: | 2/0091/23 |
| 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. |
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Protekcia kardiovaskulárneho systému pri experimentálnej hypertenzii a zlyhaní srdca inhibítorom sodíkovo-glukózového kontransportéra 2 -dapagliflozínom: efekt na srdce, cievy a obličky. Porovnanie s ACE inhibítorom kaptoprilom.
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 1/0048/23 |
| Program: | VEGA |
| Project leader: | doc. RNDr. Pecháňová Oľga DrSc. |
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 |
| Evidence number: | 2/0141/21 |
| Program: | VEGA |
| Project leader: | RNDr. Bernátová Iveta DrSc. |
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 |
| Evidence number: | 2/0104/22 |
| 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 |
Therapeutic intervention with bioactive compounds from bee products in experimental arthritis: evaluation of both articular and extra-articular complications
Terapeutické ovplyvnenie experimentálnej artritídy bioaktívnymi látkami zo včelích produktov: hodnotenie kĺbových a mimo-kĺbových komplikácií
| Duration: | 1. 1. 2024 - 31. 12. 2027 |
| Evidence number: | 2/0079/24 |
| Program: | VEGA |
| Project leader: | PharmDr. Bauerová Katarína PhD., DrSc. |
HYDMIM - Effects of mesenchymal stem cells and HMGB1 inhibitor on cardiovascular system after experimentally induced myocardial infarction in hypertension and diabetes mellitus
Účinky mezenchymálnych kmeňových buniek a inhibítora HMGB1 na kardiovaskulárny systém po experimentálne vyvolanom infarkte myokardu v hypertenzii a diabettes mellitus
| Duration: | 1. 7. 2023 - 30. 6. 2027 |
| Evidence number: | APVV-22-0271 |
| Program: | APVV |
| Project leader: | RNDr. Cebová Martina PhD. |
| Annotation: | Myocardial infarction is a serious disease of the coronary arteries, when part of the heart muscle dies and cardiac remodeling occurs as a result of persistent ischemia. The lack of oxygen and nutrients during ischemia results in inflammation, oxidative damage, and tissue degeneration. For a comprehensive understanding of the onset and progression of myocardial protection mechanisms during ischemia, it is necessary to monitor protective signaling molecules that can block or reverse the pathological process. Despite significant progress in the treatment of diseases of the cardiovascular system, myocardial infarction still remains the main cause of death in the world, especially in elderly patients with associated diseases such as hypertension and diabetes mellitus. The aim of the proposed project will be to clarify the significance of the nitric oxide signaling pathway after myocardial infarction in conditions of selected comorbidities. We will define the initial molecular and morphological changes that are caused by either the application of stem cells or glycyrrhizin, an HMGB1 inhibitor, applied after myocardial infarction. We will also examine the effectiveness of stem cells and glycyrrhizin to suppress pro-inflammatory and pro-fibrotic pathways with focus on PI3K-Akt-eNOS signaling pathway and JNK / Bax and TLR4 / NF-κB signaling pathway. The new results may provide information for targeted therapy aimed at the application of stem cells after myocardial infarction. In addition, in patients who are not suitable candidates for the given treatment, the application of an HMGB1 inhibitor can be an alternative for the treatment of myocardial infarction. |
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 |
| Evidence number: | 2/0157/21 |
| 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 |
| Evidence number: | SK-CZ-RD-21-0102 |
| 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 |
| Evidence number: | APVV-20-0534 |
| 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 |
| Evidence number: | 1/0193/21 |
| Program: | VEGA |
| Project leader: | RNDr. Vrbjar Norbert CSc. |
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 |
| Evidence number: | 2/0148/22 |
| 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 |
| Evidence number: | 2/0008/22 |
| Program: | VEGA |
| Project leader: | RNDr. Kováčiková Lucia PhD. |
| Annotation: | Aldose reductase inhibitors (ARIs) have been developed as therapeutics for the treatment of diabetic complications, inflammation and some types of cancer associated with chronic inflammation. In our previous projects, we identified derivatives of indol-1-yl acetic acid, 2-(3-thioxo 2H-[1,2,4]triazino[5,6-b]indol-5(3H)-yl)acetic acid (cemtirestat, CMTI) and 2-(3-oxo-2H-[1,2,4]triazino[5,6-b]indol-5(3H)-yl)acetic acid (OTI) as lead structures. Their high inhibitory effect and selectivity, favorable physicochemical parameters and good water solubility render these derivatives as promising candidates for structure optimization. The project focuses on the design and chemical synthesis of new structural analogs by optimizing the 5-carboxymethyltriazinoindole skeleton, in order to increase inhibitory activity, selectivity, bioavailability, antioxidant activity and improve ADME properties. The efficacy of the new derivatives will then be evaluated in vitro and ex vivo by a structure-activity relationship (SAR) study. |
AMVADYMESE - Significance of endothelial alpha 1 AMPK for vascular dysfunction and metabolic senescence in a rat model of metabolic syndrome/diabetes mellitus type II
Význam endotelovej alfa 1 AMPK 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 |
| Evidence number: | 1368/03/02 |
| 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 alpha 1 AMPK? |
Cardiac mitochondrial bioenergetics regulated by reduced oxygen consumption: In-depth proteomic analysis of cardioprotective signaling pathways.
Zníženou spotrebou kyslíka regulovaná bioenergetika srdcových mitochondrií: Hĺbková proteomická analýza signálnych kardioprotektívnych dráh.
| Duration: | 1. 1. 2023 - 31. 12. 2026 |
| Evidence number: | 2/0016/23 |
| Program: | VEGA |
| Project leader: | Ing. Ferko Miroslav PhD. |
| Annotation: | Reduced oxygen utilization significantly increases the myocardial energy requirements. The compensatory mechanisms against this serious metabolic disorder is associated with regulation of cardiac mitochondria. It is mitochondrial dysfunction that is currently the goal of a therapeutic cardioprotective strategy, effective against energy and dynamic imbalance. Part of the identification of preconditioning-induced adaptation processes will be the monitoring of the role of mitochondria on redox equilibrium, signaling of free oxygen radicals, changes in oxidative phosphorylation and energy pathways, mitochondrial dynamics and ion homeostasis. The definition of hypoxic damage, the effect of preconditioning and the identification of a potential cardioprotective signal carrier will be indicated by proteomic and metabolomic analyzes by LC-MS. The comprehensive analysis will provide detailed information on changes of proteins as potential markers as well as the characteristics of their signaling pathways. |
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 |
| Evidence number: | 2/0147/22 |
| 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: 51