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 |
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/ |
RESIST-D - Reward-stress interactions as neurobiological substrate for resilience and vulnerability in mental health and depression: A translational large-scale project
Interakcia medzi odmenou a stresom ako neurobiologický podklad odolnosti a rezistencie v duševnom zdraví a depresii: Rozsiahly translačný projekt
Duration: | 1. 1. 2024 - 31. 12. 2026 |
Evidence number: | NEURON_RV-114 |
Program: | ERANET |
Project leader: | MUDr. Riečanský Igor PhD. |
ONTOX - ONTOX - Ontology-driven and artificial intelligence-based repeated dose toxicity testing of chemicals for next generation risk assessment
ONTOX - Testovanie opakovanej toxicity chemických látok na základe ontológie a umelej inteligencie za účelom hodnotenia rizík metódami NGRA
Duration: | 1. 5. 2021 - 30. 12. 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 |
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., FIACS |
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. |
RESCUE - Bridging the gap between cardiac and vascular regeneration
Preklenutie medzery medzi srdcovou a cievnou regeneráciou
Duration: | 1. 1. 2024 - 31. 12. 2026 |
Program: | Horizont Európa |
Project leader: | doc. RNDr. Barteková Monika PhD. |
Annotation: | Our project has the ambition to develop innovative therapies based on RNA to simultaneously induce the regeneration of the muscular and vascular components of the heart after cardiac damage. Toward this goal, we will explore two hypotheses. The first hypothesis is that the regeneration of the muscular component in sufficient to trigger re-vascularization. The second hypothesis is that the two processes, the regeneration of the cardiac muscle and its blood vessels, need to be stimulated in parallel to achieve functional regeneration of the heart. Whatever the mechanism, our project will develop novel RNA drugs, encapsulated into lipid nanoparticles, able to simultaneously trigger the regeneration of the cardiac muscle and its effective vascularisation. |
Exploration of toxicology properties of drug candidates with antimicrobial and antiviral properties.
Skúmanie toxikologických vlastností kandidátov liečiv s antimikrobiálnymi a antivírusovými vlastnosťami
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 |
Annotation: | The project focuses on exploring the toxicological properties of compounds with potential applications in the treatment of COVID-19. In vitro models of lung, nasal, and alveolar tissues will be employed to assess the safety and efficacy of drug candidates. This approach supports the development of novel therapeutic options while adhering to the principles of alternative testing methods. |
Validation of a Vaginal Irritation Protocol for the In Vitro Assessment of Medical Devices
Validácia protokolu vaginálnej iritácie pre hodnotenie zdravotníckych pomôcok in vitro
Duration: | 1. 12. 2024 - 31. 12. 2026 |
Program: | Multilaterálne - iné |
Project leader: | Dr.rer.nat., Ing. Kanďárová Helena ERT |
Annotation: | The project aims to validate a reconstructed human vaginal model for in vitro testing of personal care products intended for use in the vaginal area. The results will be submitted to the ISO committee for potential implementation into the ISO 10993-23 standard, advancing safety assessment methodologies and promoting alternative testing approaches. |
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. |
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. 8. 2024 - 31. 7. 2025 |
Evidence number: | 09I03-03-V06-00047 |
Program: | Plán obnovy EÚ |
Project leader: | RNDr. Bernátová Iveta DrSc. |
Annotation: | The project is a capital booster associated with the APVV-22-0296 project to support infrastructure purchase. |
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. |
Biomarkers of endothelial dysfunction and erythrocyte characteristics in patients with long COVID
Biomarkery endotelovej dysfunkcie a charakteristika erytrocytov u pacientov s dlhým COVID-om
Duration: | 1. 1. 2025 - 31. 12. 2025 |
Program: | Návratová projektová schéma |
Project leader: | MUDr. RNDr. Púzserová Angelika PhD. |
Annotation: | Long COVID (LC) represents the summation of long-term health consequences caused by SARS-CoV-2 infection. Extensive literature supports an association between infection and cardiovascular complications and increased cardiovascular risk after infection. Endothelial dysfunction (ED) is a central mechanism in COVID-19 and has been identified as a key pathogenic mechanism in LC. Although considerable progress has been made in characterizing the epidemiology, clinical course, and biology of LC, many questions remain unanswered. Further research and data are needed to develop effective therapeutic and preventive strategies. It is assumed that the solution of the project will contribute to the clarification of the complex interplay between endothelial cells and erythrocytes, the internal pathomechanisms of ED in LC, and the clarification of many aspects in the relationship between the change in the integrity of the endothelium and inflammation, oxidative stress and the hypercoagulable state. |
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. |
DiPrev - Dimethyl fumarate as a potential tool for the prevention of cardiovascular and hepatic disorders associated with Western diet in borderline hypertensive rats
Dimetylfumarát ako potenciálny nástroj na prevenciu kardiovaskulárnych a hepatálnych porúch spojených so západnou stravou u potkanov s hraničnou hypertenziou
Duration: | 1. 9. 2024 - 31. 8. 2026 |
Evidence number: | 09I03-03-V04-00427 |
Program: | Plán obnovy EÚ |
Project leader: | RNDr. Bernátová Iveta DrSc. |
EXPERIMENTAL STUDY OF THE EFFECTS OF MATERNAL DEPRESSION AND ANTIDEPRESSANTS CITALOPRAM AND SERTRALINE ON POSTNATAL DEVELOPMENT OF RAT 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. |
Annotation: | Depressive disorders affect around 20% of women during pregnancy and breastfeeding. The most frequently prescribed antidepressants during pregnancy are selective serotonin reuptake inhibitors (SSRIs). However, the safety of their use in the treatment of maternal depression is controversial. The US Food and Drug Administration (FDA) classifies these antidepressants as Category C drugs, which means that there are currently no sufficient well-controlled studies to assess the risk of their administration to pregnant and breastfeeding women. In our experimental project, we will focus on researching citalopram and sertraline and their possible adverse (or therapeutic) effects on rat brain development when administered to pregnant rats alone or in combination with induced maternal depression. With this research, we want to contribute to a more comprehensive characterization of both drugs in terms of their safety in the treatment of maternal depression. |
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. |
Targeting SERCA Activation: Therapeutic Strategies for Managing Endoplasmic Reticulum Stress in Chronic Metabolic Diseases
Farmakologická aktivácia SERCA púmp: význam v manažmente stresu endoplazmatického retikula pri chronických metabolických ochoreniach
Duration: | 1. 1. 2025 - 31. 12. 2028 |
Evidence number: | 2/0127/25 |
Program: | VEGA |
Project leader: | RNDr. Lomenová Jana PhD. |
Annotation: | Calcium homeostasis imbalance activates endoplasmic reticulum (ER) stress, leading to the development of chronic metabolic diseases. The dysfunction of Sarco/Endoplasmic Reticulum Ca2+-ATPases (SERCA) has been identified as a major causative factor of ER stress. Pharmacological activation of SERCA appears to be an effective strategy in alleviating ER stress. The project will investigate the activation of SERCA by polyphenolic compounds to mitigate damage to pancreatic cells induced by methylglyoxal, palmitate, and cytokines (experimental diabetic conditions). The efficacy of compounds will be evaluated based on the activation of isolated SERCA1a protein and at the cellular level, focusing on viability, apoptosis, SERCA2b expression, insulin release, intracellular calcium levels, reactive oxygen species formation, SIRT and PPAR activation, among others. The project will contribute to clarifying the mechanisms of hyperglycemia at the cellular level and the effect of new compounds capable of mitigating ER stress. |
Project web page: | https://e-vega.sav.sk/(S(h22jztv2lbh35lvjyssbrer5))/users/Projekt_SAV_0007.aspx |
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. |
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. 2026 |
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 effects of mesenchymal stem cells and HMGB1 inhibitor after experimentally induced myocardial infarction
Kardioprotektívne účinky mezenchymálnych kmeňových buniek a inhibítora HMGB1 po experimentálne vyvolanom infarkte myokardu
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | 2/0131/24 |
Program: | VEGA |
Project leader: | RNDr. Cebová Martina PhD. |
Annotation: | Myocardial infarction is a cardiovascular disease associated with remodeling as a result of ischemia. The absence of oxygen and nutrients during ischemia results in inflammation, oxidative damage, and tissue degeneration. For understanding of the onset and progression of myocardial protection mechanisms during ischemia, it is necessary to monitor signaling molecules that can block or reverse the pathological process. Despite advances in treatment, myocardial infarction still remains the leading cause of death in the world. The aim of the proposed project will be to clarify the initial molecular and morphological changes caused by both stem cell application and glycyrrhizin, an HMGB1 inhibitor, administrated after myocardial infarction with a focus on suppressing pro-inflammatory and pro-fibrotic pathways. The new results may provide information for targeted therapy aimed either at stem cells application or at the application of an HMGB1 inhibitor as an alternative for the myocardial infarction treatment. |
SGLT2 Cardioprot - Cardioprotective effect of SGLT2 inhibition in heart failure: the role of RISK and SAFE pathway
Kardioprotektívne účinky SGLT2 inhibítora pri srdcovom zlyhávaní: úloha RISK a SAFE signálnej dráhy
Duration: | 1. 9. 2024 - 31. 8. 2026 |
Evidence number: | 09I03-03-V04-00389 |
Program: | Plán obnovy EÚ |
Project leader: | Mgr. Farkašová Veronika PhD |
Annotation: | Heart failure (HF) is the final stage in several cardiovascular diseases (CVD) (cardiomyopathies, valvular or ischemic heart disease, acute myocardial infarction and many others). Myocardial infarction (MI) remains the most common cause of HF worldwide. For almost 50 years HF has been recognised as a determinant of adverse prognosis after MI. Although the patients that successfully survive MI live longer, the alteration of the heart muscle will manifest later on by chronic failure of its pumping function. Potential reasons of that may be related to the complexity of mechanisms of HF and the requirement for multitarget effects of optimal cardioprotection. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are the newest class of antidiabetic drugs. Recently, clinical trials reported the cardiovascular benefits of empagliflozin, an SGLT-2 inhibitor, by significantly decreasing the incidence of hospitalization associated with HF and cardiovascular-cause death rate in diabetic patients with CVD and in HF patients. In addition, SGLT2 inhibitors (SGLT2i) exert cardioprotective effects in animal models of acute MI through a reduction of infarct size and a subsequent attenuation of HF development. Chronic treatment with Empagliflozin in mice with type 2 diabetes showed that the drug increased both the phosphorylation and the expression of cardiac signal transducer and activator of transcription 3 (STAT-3) at early reperfusion. STAT-3 is one of the main signaling molecules in the survivor-activating factor enhancement (SAFE) pathway. SAFE, together with the pro-survival reperfusion injury salvage kinase (RISK) pathway, are considered major mediators of cardioprotection against I/R injury, showing potential for SGLT2 inhibition as a cardioprotective drug candidate. The project aims to evaluate the effect of pharmacological conditioning with an SGLT2 inhibitor on cardiac resistance to acute myocardial infarction and subsequent HF and to determine the role of RISK and SAFE pathways in pharmacological conditioning with an SGLT2 inhibitor in hearts subjected to acute myocardial infarction and subsequent heart failure. |
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. 2025 |
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. |
Can the modulation of sarco-endoplasmic Ca2+ - ATPase (SERCA) by selected natural substances be regulated by sirtuins? Importance in supportive treatment of diabetic complications and tumor diseases
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. Rezbáriková Petronela 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. |
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Prepojenie autofágie a redoxnej signalizácie a ich regulácia pri rôznych poškodeniach srdcových buniek.
Duration: | 1. 7. 2024 - 31. 12. 2025 |
Evidence number: | PostdokGrant APD0130 |
Program: | Iné projekty |
Project leader: | Mgr. Svetláková (Boťanská) Barbora PhD. |
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Prepojenie medzi redoxnou signalizáciou, autofágiou a apoptózou pri rôznych typoch poškodenia srdcových buniek
Duration: | 1. 1. 2025 - 31. 12. 2028 |
Evidence number: | VEGA 2/0091/25 |
Program: | VEGA |
Project leader: | Mgr. Svetláková (Boťanská) Barbora PhD. |
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. |
PQC inhalation m - Preparation and quality control of modern dosage forms for alternative administration rout of biologics by inhalation (APVV-23-0508)
Príprava a kontrola kvality moderných liekových foriem pre alternatívne podanie biologík inhalačnou cestou (APVV-23-0508).
Duration: | 1. 7. 2024 - 30. 6. 2028 |
Evidence number: | APVV-23-0508 |
Program: | APVV |
Project leader: | PharmDr. Dráfi František PhD., MPH |
Annotation: | The use of biopharmaceuticals has drastically expanded with the development of recombinant DNA technology. The typical delivery rout of the innovative drugs is based on intra venous, sub cutaneous, or intra muscular application. Pulmonary drug delivery offers rapid and sustained drug delivery, high efficacy, no first-pass metabolism, and achievement of both local and systemic effects. Development of such biologic demands making particles/droplets that are sufficiently small, and nebulization of the solution to be inhaled. Both aspects affect product quality through decreased activity or protein aggregation. It is essential to optimize the drug formulation with the intended delivery system used. The aim of the project is development of reliable and functional formulations of mAbs and peptides for their inhalation application. We expect that our project will bring comprehensive standard operation protocols or guidelines for formulation of such biologics. |
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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. |
MITPROT - Heart mitochondria proteomic mapping: Uncovering potential signaling pathways
Proteomické mapovanie mitochondrií srdca: Odhaľovanie potenciálnych signálnych dráh
Duration: | 1. 9. 2024 - 31. 8. 2026 |
Evidence number: | 09I03-03-V04-00437 |
Program: | Plán obnovy EÚ |
Project leader: | Mgr. Andelová Natália PhD. |
Annotation: | Exposure of the organism to limited access to oxygen is a significant stimulus in inducing cardioprotection effective against mitochondrial dysfunction. From the point of view of possible initiators of endogenous myocardium protection, hypoxia appears as a potential trigger of adaptation processes. Hypoxia-induced stimulation of the adaptive response induced by preconditioning represents an effective tool for maintaining the bioenergetic balance of the myocardium exposed to ischemia/reperfusion injury. Due to the dynamic nature of mitochondria, research attention is increasingly focused on their proteomic changes. Proteins are proving to be promising prognostic and diagnostic biomarkers. Modern analytical methods, such as mass spectrometry, which allows complex mapping of proteins and their changes, have a promising potential. Applying biostatistical approaches offers new concepts for studying protein-protein interactions (PPI) and characterizing signaling pathways involved in mitochondrial cardioprotective processes. Identifying mitochondrial proteome changes, elucidating calcium and reactive oxygen species signaling, regulating mitochondrial permeability transition pore opening, and studying PPI could provide a breakthrough understanding of signaling pathways from mitochondria to overall myocardial physiology. |
Psychophysiological correlates of semantic interference control
Psychofyziologické koreláty kontroly sémantickej interferencie
Duration: | 1. 7. 2024 - 31. 12. 2025 |
Program: | Iné projekty |
Project leader: | Mgr. Michalko Drahomír PhD. |
Annotation: | The human brain integrates vast amounts of information about the world into organised semantic representations, forming a knowledge basis by which we understand and think about objects and events unfolding in our environment. The hallmark of our cognitive system is the ability to flexibly select from this vast pool of knowledge only those bits that suit the current contextual demands, allowing us to adapt our thinking to everchanging conditions. A crucial role in this ability plays the mechanism of inhibitory control, which shapes our thinking to meet the current situational demands by suppressing interfering, contextually irrelevant bits of knowledge. Contemporary findings indicate that the functionality of this mechanism is influenced by catecholamines (dopamine and noradrenaline). These accounts suggest that deviations from optimal catecholaminergic signalling disrupt inhibitory control, hindering the ability to discern relevant from irrelevant bits of knowledge, resulting in aberrant thought patterns and behaviours symptomatic of various neuropsychiatric conditions. In this project, we plan to test these accounts by developing a novel behavioural method capable of indexing the ability to follow contextual demands under different levels of semantic interference. Subsequently, we plan to combine this method with physiological measures of dopaminergic (spontaneous eyeblink rate) and noradrenergic (changes in pupil size) activity to evaluate, in a detailed way, how these systems affect our ability to resolve semantic interference of varying strength. The proposed project may substantially improve our understanding of adaptive cognitive processes with high clinical relevance, particularly for patients with memory and thought control deficits. |
Semantic memory in mental health disorders
Sémantická pamäť pri poruchách mentálneho zdravia
Duration: | 1. 1. 2025 - 31. 12. 2028 |
Evidence number: | VEGA 2/0067/25 |
Program: | VEGA |
Project leader: | MUDr. Riečanský Igor PhD. |
Senogenic effects of environmental stressors in human skin cells and possibilities of senotherapy using natural and synthetic substances
Senogénne účinky environmentálnych stresorov v ľudských bunkách kože a možnosti senoterapie s využitím prírodných a syntetických látok.
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | VEGA 2/0060/24 |
Program: | VEGA |
Project leader: | Ing. Račková Lucia PhD. |
Annotation: | Current knowledge indicates that organism-environment interaction affects rate of aging of the organism. Oxidative stress and inflammation are among the main gerontogenic mechanisms triggered by environmental stressors. These mechanisms are also linked to cellular senescence, process believed to contribute critically to aging.The skin, which is barrier organ of body, is constitutively exposed to various stimuli affecting its morphology and function.Therefore, skin exposome research can be considered paradigmatic,and its implementation can contribute to better understanding of aging in other organs as well. The aim of project is investigation of senogenic effects of various environmental stressors (such as oxidants,pollutants,UV radiation) also using new aging biomarkers. The scope of research also includes therapeutic efficacy of selected plant metabolites and synthetic compounds.The project will provide insight into gerontogenic and senotherapeutic mechanisms of substances studied in cellular skin models. |
Sensory control of postural balance and its changes due to motor, cognitive and anxiety disorders
Senzorická regulácia rovnováhy a jej zmeny vplyvom motorických, kognitívnych a úzkostných porúch
Duration: | 1. 1. 2025 - 31. 12. 2028 |
Evidence number: | 2/0098/25 |
Program: | VEGA |
Project leader: | RNDr. Kimijanová Jana PhD. |
Annotation: | In everyday life, we are constantly confronted with numerous situations in which individual sensory systems provide conflicting or ambiguous information and with new postural tasks to which we must adapt. Sensory integration plays a key role and the research of its mechanisms is very important for the assessment of balance control, especially in populations that are more prone to the risk of falling, i.e., in the elderly and patients with motor, cognitive or anxiety deficits. Appropriate motor or sensory intervention can help these vulnerable groups to improve impaired balance and thus prevent falls, subsequent injuries and loss of independence. The aim of the project is to characterize the mechanisms of sensory control in maintaining balance in various sensory conditions in elderly people with movement and cognitive disorders and to define indicators of postural stability that most sensitively reflect changes in balance control due to physical and sensory training. |
Investigating the involvement of connexin-43 in rat brown and white adipose tissue in mechanisms of cardiovascular risk and cardioprotection.
Skúmanie účasti konexínu-43 v hnedom a bielom tukovom tkanive potkana v mechanizmoch kardiovaskulárneho rizika a kardioprotekcie.
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | VEGA 2/0133/24 |
Program: | VEGA |
Project leader: | RNDr. Egan Beňová Tamara PhD. |
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. |
Annotation: | Bee products are a frequently studied due to their pharmacological properties. However, the identification of substances responsible for their properties is absent. The aimof the project is to characterize the effect of selected peptides and polyphenolic extracts from bee products on the articular manifestations of rheumatoid arthritis, but also on extra-articular manifestations with the aim of optimizing the conventional treatment. Adjuvant arthritis in rats will be used in the project. Polyphenolic extracts of bee pollen and honey will be tested, as well as melittin from bee venom, 10-hydroxydecanoic acid from royal jelly and the bee peptide apisimin. In addition to biometric indicators, markers of inflammation and oxidative stress will be determined in plasma and in relevant tissues. Study of cardioprotective mechanisms and of mitochondrial energetics will be carried out. Finally, the effectiveness of the most effective substance in combination with methotrexate and upadacitinib will be verified. |
Therapeutic potential of natural antioxidants 7,8-dihydroxyflavone and Naringin in animal model of depression
Terapeutický potenciál prírodných antioxidantov 7,8-dihydroxyflavónu a Naringínu v animálnom modeli depresie
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | 2/0122/24 |
Program: | VEGA |
Project leader: | RNDr. Vranková Stanislava PhD. |
Annotation: | Depression is the most common mental disorder in the world. Pathomechanisms involved in the development of depression are mainly associated with the BDNF/TrkB/CREB signaling pathway. Affecting the BDNF/TrkB/CREB signaling pathway is a critical therapeutic target for inducing adult hippocampal neurogenesis and antidepressant therapy. Compounds capable of inducing rapid structural and functional rearrangement of neuronal networks are particularly attractive. Several of these psychoplastogens are naturally occurring antioxidants, such as 7,8-dihydroxyflavone (7,8-DHF) and Naringin. The aim of our study is to investigate the effects of 7,8-DHF and Naringin, as well as their combinations, on the development of depressive-like symptoms in animal model of depression. Results of this project will contribute to elucidating the pathogenesis of depression and their treatment possibilities. |
ToxiGut - ToxiGut: Modeling and Prediction of Drug and Chemical Side Effects in an In Vitro 3D Reconstituted Human Small Intestine Model
ToxiGut: Modelovanie a predikcia vedľajších účinkov liekov a chemických látok na in vitro 3D rekonštituovanom modeli tenkého čreva
Duration: | 1. 1. 2025 - 31. 12. 2028 |
Evidence number: | 2/0123/25 |
Program: | VEGA |
Project leader: | Dr.rer.nat., Ing. Kanďárová Helena ERT |
Annotation: | The ToxiGut project proposes the development and internal validation of an advanced experimental system for studying the side effects of chemicals and pharmaceuticals on a human 3D reconstructed model of the small intestine. The project focuses on comparing static and dynamic methods of cultivating 3D tissue in a microfluidic device (Gut-on-chip concept), achieving a high level of simulation of the physiological conditions of the small intestine. The project will compare the obtained data with experimental results from the CaCo-2 line of human colorectal carcinoma, which is used for screening in preclinical pharmacological studies. However, this model does not reflect the complexity of the human intestinal environment and, like established animal models, provides inaccurate outputs for clinical studies. The project aims to provide a more efficient testing system that will improve the predictive ability of preclinical tests and increase the safety of patients in clinical trials while reducing costs and time. |
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. |
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. 8. 2024 - 31. 7. 2025 |
Evidence number: | 09I03-03-V06-00059 |
Program: | Plán obnovy EÚ |
Project leader: | RNDr. Cebová Martina PhD. |
Edifu - The effect of dimethyl fumarate on nuclear factor erythroid 2-related factor 2 activation and redox balance in chronic stress-exposed female rats with mild hypertension and comorbid hypertriglyceridemia
Účinok dimetylfumarátu na aktiváciu jadrového faktora NRF2 a redoxnú rovnováhu u samíc potkanov vystavených chronickému stresu s miernou hypertenziou a komorbidnou hypertriglyceridémiou
Duration: | 1. 9. 2024 - 31. 8. 2026 |
Evidence number: | 09I03-03-V04-00477 |
Program: | Plán obnovy EÚ |
Project leader: | Mgr. Mičurová Andrea PhD. |
Annotation: | The number of hypertensive adults worldwide has dramatically increased in last 30 years. Hypertension found together with other comorbidities presents a risk factor for development of several diseases. Nowadays, stress is considered to be significant factor involved not only in development, but also progression of cardiovascular, psychological and other diseases. Several studies associated long-lasting stress with disturbances in redox balance in various tissues, mainly with increased reactive oxygen species production or decreased activity of antioxidant enzymes. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the cytoprotection against toxic and oxidative insults through the expression of genes involved in antioxidant defense. Interestingly, recent studies indicate that expression of NRF2 is decreased under chronic stress and leads to significant changes in redox homeostasis. Since hypertension and comorbid hypertriglyceridemia are often found together and many adults are exposed to chronic stressors, the aim of this project is to specify the chronic stress-induced behavioural changes, disturbances in redox balance, expression of NRF2 and its activation with dimethyl fumarate in various tissues of female experimental model of prehypertension with comorbid triglyceridemia. |
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. |
TOXIPRED - A Public Platform for the Prediction of Toxic Substances Short title of the project/Acronym:
Verejná platforma na predikciu toxických látok
Duration: | 1. 5. 2024 - 31. 12. 2025 |
Evidence number: | 09I05-03-V02-00048 |
Program: | Plán obnovy EÚ |
Project leader: | Ing. Šoltésová Prnová Marta PhD. |
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. |
The effect sex and reproductive stage of females on the vasoregulatory role of sulfide and nitroso signaling pathways in metabolic syndrome
Vplyv pohlavia a reprodukčného stavu samíc na vazoregulačnú úlohu sulfidovej a nitrózovej signánej dráhy v podmienkach metabolického syndrómu
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | 2/0153/24 |
Program: | VEGA |
Project leader: | Mgr. Berényiová Andrea PhD. |
Annotation: | Our studies demonstrated a key vasoregulatory role of nitric oxide (NO) and hydrogen sulfide (H2S) signaling in various animal models of cardiovascular complications. In metabolic syndrome (MS) induced by changed diet, we reported that the interaction of these signaling pathways is disrupted, and H2S donor application can alleviate the pathological manifestations of MS. Moreover, in hypertriglyceridemic rats (HTG) we observed an endothelial dysfunction that was not only associated with reduced NO-synthase activity but also with endogenously produced H2S. Previous studies have focused on cardiovascular changes mainly in males, while studies on HTG females are missing. The project will examine the influence of gender and reproductive status of females HTG rats with the aim of revealing possible differences in vasoactive regulatory mechanisms. At the same time, it will investigate the possible beneficial effects of flavonoid administration on cardiovascular complication associated with postmenopausal MS. |
The role of sex hormones in the a1AMPK- mediated vascular protection during the development of the metabolic syndrome
Vplyv pohlavných hormónov pri indukcii vaskulárnej ochrany sprostredkovanej aktiváciou alfa-1 AMPK počas rozvoja metabolického syndrómu
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | 2/0123/24 |
Program: | VEGA |
Project leader: | Ing. Kvandová Miroslava PhD. |
Annotation: | Disruption of vascular homeostasis caused by reduced nitric oxide bioavailability due to oxidative stress and inflammation is the most severe complication of metabolic syndrome (MetS). Therefore, it is essential to identify the key factors that protect the endothelium and improve the primary and secondary prevention of cardiovascular diseases. Such a factor may be a1AMP-dependent protein kinase (a1AMPK), as it may be involved in improving metabolic control. The project focuses on risk factors affecting endothelial function during MetS and a1AMPK as a potential tool to modify these factors in the context of gender differences, as sex hormones can regulate a1AMPK. The project’s originality is based on a comprehensive assessment of changes in endothelial function during MetS with a clear focus on vascular endothelium and gender differences. The results of this study represent a potential tool to increase the quality of life and reduce the economic burden associated with treating this cardiometabolic disease. |
The influence of semantic representation and executive control on the structure and dynamics of idea generation
Vplyv sémantickej reprezentácie a exekutívnej kontroly na reguláciu štruktúry a dynamiky myslenia
Duration: | 1. 7. 2024 - 30. 6. 2028 |
Program: | APVV |
Project leader: | Mgr. Marko Martin PhD. |
Annotation: | Human thinking emerges from a complex interaction of several neurocognitive processes and mechanisms that are yet poorly understood. Following the recent advances in cognitive psychology and neuroscience, in the present project, we introduce an integrative framework where the unfolding “stream of thought” is conceptualized as a dynamic memory process operating upon structured conceptual representations constrained by situational demands (i.e., contexts or goals). To understand how semantic cognition aids adaptive ideation, we will first develop an original memory paradigm, allowing us to deconstruct the complexity of thinking into fundamental and measurable processes and functions. Using these measures in a series of behavioral and psychophysiological experiments implementing a systematic manipulation of cognitive interference and load, we will further investigate the core determinants and predictors of ideational fluency at various levels of analysis. Moreover, we will employ unifocal as well as bifocal non-invasive electrical brain stimulation and rigorous experimentation to evaluate the causal involvement of the prefrontal cortex and the cerebellum in semantic memory retrieval and control, hence shedding light on the mechanisms and circuits supporting both spontaneous and controlled (i.e., goal-oriented) idea generation. Together, the proposed framework and paradigms bear strong potential to bring novel insights into the architecture of human thinking and inspire future diagnostic procedures or non-pharmacological treatments for individuals with neuropsychiatric conditions that manifest in aberrant memory functioning, language, or thinking. |
Research of plants with therapeutic potential in surgery, dermatology, and dentistry: phytochemical analysis, biological effects, and study of mutual interactions of their constituents.
Výskum rastlín s terapeutickým potenciálom v chirurgii, dermatológii a stomatológii: fytochemická analýza, biologické účinky a štúdium vzájomných interakcií ich obsahových látok.
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | VEGA 1/0170/24 |
Program: | VEGA |
Project leader: | Ing. Račková Lucia PhD. |
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? |
The relationship between cytokines and connexin-43 in brown adipose tissue in laboratory rats with increased thermogenesis.
Vzťah cytokínov a konexínu-43 v hnedom tukovom tkanive u laboratórneho potkana so zvýšenou termogenézou.
Duration: | 1. 7. 2024 - 30. 6. 2025 |
Program: | Iné projekty |
Project leader: | RNDr. Egan Beňová Tamara PhD. |
The role of in Wnt signaling in processes associated with effects of doxorubicin.
Wnt signalizácia a jej úloha v procesoch spojených s účinkami doxorubicínu.
Duration: | 1. 1. 2024 - 31. 12. 2027 |
Evidence number: | VEGA 2/0169/24 |
Program: | VEGA |
Project leader: | RNDr. Barančík Miroslav DrSc. |
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: 72