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Current

Biotechnological production and functional characterization of AKR1A1 enzyme for therapeutic applications
Duration:	1. 1. 2026 - 31. 12. 2029
Evidence number:	VEGA 2/0137/26
Program:	VEGA
Project leader:	Ing. Šoltésová Prnová Marta, PhD.
SAS cosolvers:	Mgr. Boďo Pavol, PhD., Mgr. Jahelková Milica, Ing. Lepáček Marek, PhD.
Annotation:	The project is focused on the biotechnological production, purification and functional characterization of recombinant human AKR1A1 enzyme to identify its substrate specificity and potential for therapeutic use. Optimization of expression systems and purification protocols will ensure a stable and functionally active enzyme. Comparison with the rat enzyme will allow evaluation of functional differences. The project uses a combination of biochemical, molecular and computational methods including enzyme kinetics. The results will contribute to the understanding of the role of AKR1A1 in xenobiotic metabolism, redox balance and pathophysiology, opening the way to its use in medicine and biotechnology.

Targeting SERCA Activation: The impact of Novel Derivatives of Cemtirestat on Enhanced Pancreatic Beta-Cell Function in Diabetes Management
Duration:	1. 1. 2026 - 31. 12. 2029
Evidence number:	VEGA 2/0060/26
Program:	VEGA
Project leader:	Ing. Micháliková Silvia, PhD.
SAS cosolvers:	RNDr. Lomenová Jana, PhD., Mgr. Rezbáriková Petronela, PhD., Mgr. Valúchová Barbora
Annotation:	Preserving pancreatic beta-cell function is key in type 2 diabetes mellitus (T2DM) treatment, as endogenous substances contribute to beta-cell damage. This project investigates the effects of indole compounds (cemtirestat, an oxygenated CMTI derivative, and others) on SERCA modulation and beta-cell viability. Structural and functional changes in SERCA1a and INS-1E cells after methylglyoxal, palmitate, and cytokine damage will be assessed. Compound efficacy will be evaluated by SERCA1a activation and effects on cell viability, apoptosis, SERCA2b expression, insulin secretion, Ca2+ levels, ROS production, and SIRT/PPAR pathway activation. The goal is to deepen knowledge of hyperglycemia-related mechanisms and assess novel compounds\' potential to reduce ER stress and glucotoxicity, including polypharmacological effects of aldose reductase inhibitors in diabetic complications.

Modulating SERCA Pump Activity: Biochemical Studies in Isolated SERCA1a Enzyme and Pancreatic Beta-Cells.
Duration:	1. 1. 2026 - 31. 12. 2029
Evidence number:	2/0097/26
Program:	VEGA
Project leader:	Mgr. Rezbáriková Petronela, PhD.
SAS cosolvers:	RNDr. Lomenová Jana, PhD., Ing. Micháliková Silvia, PhD., Mgr. Valúchová Barbora
Annotation:	Disruption of calcium homeostasis is a key trigger of endoplasmic reticulum (ER) stress, which contributes to the development of metabolic disorders such as type 2 diabetes mellitus. Dysfunction of calcium ATPases from the sarco/endoplasmic reticulum (SERCA) plays a central role in this process. The project focuses on evaluating the effects of selected compounds on SERCA activation and the protection of pancreatic ß-cells exposed to diabetogenic stressors (methylglyoxal, palmitate, cytokines). The research combines biochemical analysis of the isolated SERCA1a protein with functional studies in cell models. Emphasis is placed on enzyme activity, cell viability, apoptosis, insulin secretion, SERCA2b expression, and oxidative stress. The project is conducted in collaboration with the University of Michigan (USA), providing access to unique compounds and expertise in SERCA molecular pharmacology. The results will contribute to the development of new therapeutic strategies.

Rational design, synthesis and biological evaluation of novel aldose reductase inhibitors with improved antioxidant properties and bioavailability
Duration:	1. 1. 2026 - 31. 12. 2029
Evidence number:	VEGA 2/0124/26
Program:	VEGA
Project leader:	RNDr. Kováčiková Lucia, PhD.
SAS cosolvers:	RNDr. Májeková Magdaléna, PhD., Mgr. Wetter Erik
Other cosolvers:	Bohá
Annotation:	To date, no specific class of therapeutics aimed at preventing or suppressing severe diabetes-associated complications has been available in Europe or the United States. Chronic exposure to elevated blood glucose levels adversely affects systemic homeostasis and may lead to cardiovascular toxicity, renal failure, cataract formation, and persistent inflammatory states with links to autoimmune and oncological disorders. Building on the prior identification of cemtirestat and its oxygen-containing analogue otirestat as starting structural scaffolds, and guided by rational design and structural optimization, we propose and investigate novel high-potency inhibitors with pronounced selectivity, antioxidant activity, and suitable bioavailability. Our primary scientific objective is the development of a drug candidate based on aldose reductase inhibition that would be attractive for pharmaceutical translation and further development toward a new therapeutic option for patients with diabetes and, potentially, other disorders associated with chronic inflammation.

PAIS-LC - Biomarkers and pathomechanisms of endothelial cell and erythrocyte dysfunction in patients with long COVID and cardiovascular comorbidities
Duration:	1. 9. 2025 - 31. 8. 2029
Evidence number:	APVV-24-0225
Program:	APVV
Project leader:	MUDr. RNDr. Púzserová Angelika, PhD.
SAS cosolvers:	RNDr. Bališ Peter, PhD., Mgr. Kluknavský Michal, PhD., Mgr. Kovačičová Ivona, Mgr. Magyarová Silvia, Mgr. Šnúriková Denisa, Ing. Tarcalová Miroslava, PhD., RNDr. Vlkovičová Jana, PhD., RNDr. Vrbjar Norbert, CSc., Mgr. Zemančíková Anna, PhD.
Other cosolvers:	MUD
Annotation:	COVID-19 is a viral infectious disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many millions of SARS-CoV-2 infection survivors, including both adults and children, live with chronic, systemic, and often disabling conditions commonly known as long COVID (LC). LC denotes a collection of long-term health consequences caused by the infection. The impact of LC is not limited to the health and quality of life of individual patients. Owing to its prevalence and the breadth of its clinical manifestations, it represents a major public health crisis; it strains health systems and national economies and threatens progress in global health, including the Sustainable Development Goals. Extensive literature supports the association between infection and cardiovascular (CV) complications, as well as an increased CV risk following infection. Endothelial dysfunction (ED) is a central pathomechanism in acute COVID-19 and has also been identified as a key pathogenic mechanism in the pathogenesis of LC. A growing number of studies highlight the significance of erythrocyte (Ery) abnormalities, abnormal clotting processes, excessive inflammation, and oxidative stress (OS) in LC patients. Different biomarker profiles may be associated with the variations in the clinical presentation (LC symptoms) and may suggest distinct pathomechanisms that are dominant in different patient subgroups. Although significant progress has been made in recent years in characterizing LC, many questions remain unanswered. Therefore, further studies and data are needed to develop effective and personalized therapeutic and preventive strategies. It is expected that the implementation of this project will contribute to elucidating the complex interplay between endothelial cells and Ery, the underlying pathomechanisms of ED in LC, and various aspects of the relationship between endothelial integrity changes, inflammation, OS, and hypercoagulable states.
Project website:	www.dlhycovid.sk

SERCA-AKTIV - Pharmacological Activation of SERCA: A Therapeutic Target for Chronic Metabolic Diseases
Duration:	1. 9. 2025 - 31. 8. 2029
Evidence number:	APVV-24-0186
Program:	APVV
Project leader:	RNDr. Lomenová Jana, PhD.
SAS cosolvers:	Mgr. Boďo Pavol, PhD., Mgr. Jahelková Milica, RNDr. Kováčiková Lucia, PhD., RNDr. Kura Branislav, PhD., Ing. Lepáček Marek, PhD., RNDr. Májeková Magdaléna, PhD., Ing. Micháliková Silvia, PhD., PharmDr. Poništ Silvester, PhD., Mgr. Rezbáriková Petronela, PhD., Ing. Šoltésová Prnová Marta, PhD., Mgr. Valúchová Barbora, Mgr. Wetter Erik
Annotation:	The proposed project focuses on the pharmacological activation of SERCA (Sarco/Endoplasmic Reticulum Ca²⁺-ATPase) as a therapeutic strategy to address chronic metabolic diseases, particularly type 2 diabetes mellitus. SERCA dysfunction, exacerbated by oxidative stress and post-translational modifications (PTMs), disrupts calcium homeostasis, increases ER stress, and contributes to beta-cell dysfunction and metabolic dysregulation. This multidisciplinary project aims to systematically evaluate SERCA activators and their role in modulating oxidative and ER stress under diabetic conditions. A set of 15–20 natural and synthetic compounds will be investigated for their effects on SERCA1a activity, oxidative modifications, conformational changes, and lipid peroxidation. In silico modeling will predict binding interactions and identify key allosteric sites, while ADME and toxicity evaluations will guide compound selection. The antioxidant capacity of these activators will be assessed, focusing on their ability to protect against MGX, PAL, and CYT-induced oxidative/ER stress and their correlation with SERCA function restoration. Ex vivo studies will evaluate RBC resistance to oxidative damage, while cellular studies will analyze viability, apoptosis, ROS levels, intracellular calcium levels, insulin secretion, SERCA2b expression, and mitochondrial function. Additionally, the ZDF rat model will serve as a comparative tool to examine tissue-specific changes in calcium-regulating proteins and oxidative stress and inflammatory markers in diabetes-related metabolic disturbances. This project aims to validate SERCA as a therapeutic target, investigate PTM involvement and compensatory mechanisms, and evaluate the role of antioxidant protection. The obtained findings will expand knowledge on calcium regulation and the therapeutic potential of SERCA in metabolic diseases.

QueProbio - New approach in post-traumatic stress disorder (PTSD) therapy: quetiapine treatment supplemented by probiotics
Duration:	1. 9. 2025 - 31. 8. 2029
Evidence number:	APVV-24-0213
Program:	APVV
Project leader:	RNDr. Mach Mojmír, PhD.
SAS cosolvers:	Mgr. Bačová Zuzana, PhD., doc. RNDr. Bakoš Ján, PhD., Mgr. Bukatová Stanislava, PhD. , Mgr. Dziewiczová Lila, Mgr. Havránek Tomáš, PhD., Mgr. Horváthová Ľubica, PhD., RNDr. Kiss Alexander, DrSc., Mgr. Mihalj Denisa, PhD., MVDr. Pecinová Romana, PhD., doc. PharmDr. Pirník Zdenko, PhD., Ing. Tillinger Andrej, PhD.
Other cosolvers:	Aleksandra Tomova, Peter Vargovič
Annotation:	Post-traumatic stress disorder (PTSD) is a multifaceted psychological disorder characterized by dysregulated fear and stress response. Its development affects variety of biological mechanisms including alterations in neurogenesis and brain neuroplasticity. Treatment of PTSD predominantly involves psychological interventions and pharmacotherapy comes out as a second option. Atypical antipsychotic quetiapine (QUE) is one of most promising agents used but besides suppressing the negative manifestations of PTSD it exerts also negative side effects. Recently, several studies have been focused on the involvement of intestinal microflora in psychiatric disorders and alterations in gut microbiome have also been connected with PTSD. However, the interconnections between antipsychotic treatment, gut microbiota and brain in PTSD have not been clarified yet. We assume that treatment with atypical antipsychotic QUE combined with probiotics may overcome disbiosis as an unwanted side effects of QUE and also improve the microbiota disbalance induced by PTSD. Combined treatment as suggested in the proposed project will represent a new trend in PTSD therapy. We believe that the proposed treatment may augment QUE therapeutic effect and suppress the negative behavioral manifestations and changes in the neuroplasticity induced by PTSD more effectively than single QUE therapy. This project will contribute to the better understanding of the mechanisms laying behind the development of PTSD pathology and may show a new perspective way of the PTSD treatment.

sulfidmenopau - The impact of menopause on the vasoregulatory role of the sulfide signaling pathway in cardiovascular complications of diabetes II type
Duration:	1. 9. 2025 - 31. 8. 2029
Evidence number:	APVV-24-0150
Program:	APVV
Project leader:	RNDr. Čačányiová Soňa, PhD.
Annotation:	Hydrogen sulfide (H2S) is an important gaseous molecule involved in the regulation of vascular tone, includingvarious pathological conditions such as hypertension, diabetes and obesity. Perivascular adipose tissue (PVAT),along with its pro-inflammatory activities and influence on vasoactive functions are also important in thedevelopment of cardiovascular complications. Interactions occur between these factors, but the exact mechanismremains unknown. It seems that the progression of metabolic disorders can significantly affect the balance betweenthe pathological and compensatory effects of the sulfide signaling pathway. Inflammation and dysregulation ofPVAT are particularly characteristic of advanced stages of diabetes, which could negatively impact thecompensatory vasoactive effects of H2S observed in milder metabolic disorders. Confirming or disproving thisassumption is one of the goals of the proposed project.Currently, increased attention is focused on aspects of personalized medicine that could contribute to moreeffective therapy by precisely targeting specific patient groups. The development of cardiovascular complicationsand diabetes is significantly higher in postmenopausal women, while in women under 40 years of age, the risk is lower than in men of the same age. The project aims to examine the impact of reproductive status in obese femalerats with type II diabetes (ZDF) following surgical ovariectomy. The goal is to identify potential differences in themechanisms underlying cardiovascular disorders, which might help in better specifying therapeutic targets forobese diabetic postmenopausal women with severe dyslipidemia. Selected plasma parameters will be comparedwith those of diabetic female patients of different reproductive ages. In the next phase, the project will investigatethe potential beneficial effects of the natural isothiocyanate and slow-releasing H2S donor erucin, in reducingdeveloped vascular complications in ovariectomized ZD

DruCARI - Development of novel selective aldose reductase inhibitors (ARIs) with antioxidant properties and improved bioavailability as potential drugs in prevention of diabetes and cancer
Duration:	1. 9. 2025 - 31. 8. 2029
Evidence number:	APVV-24-0388
Program:	APVV
Project leader:	RNDr. Kováčiková Lucia, PhD.
SAS cosolvers:	RNDr. Lomenová Jana, PhD., RNDr. Májeková Magdaléna, PhD., Ing. Micháliková Silvia, PhD., Mgr. Rezbáriková Petronela, PhD., Mgr. Wetter Erik
Annotation:	Multifactorial nature of diabetic complications represents a great challenge in the development of efficient therapy. The multitarget directed approach in prevention of diabetic complications is oriented on the rational design of chemical entities able to affect simultaneously multiple key mechanisms of glucose toxicity, namely non-enzymatic glycation, polyol pathway, oxidative stress and impaired calcium signaling, since targeting just one particular mechanism may have a limited effect. 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. No AR inhibitors have been approved in the USA and Europe. In Asia, epalrestat is used as the only one commercially available low selective inhibitor to treat diabetic neuropathy. In our previous study, we identified sulfur derivative cemtirestat (CMTI) and its oxygen analogue otirestat (OTI) as lead structures. Structure optimization by introducing various substituents into the N(2) position of OTI provided new possibilities for explanation of selectivity in related aldehyde reductase enzyme (ALR1). The aim of this project is development of novel selective ARIs with antioxidant properties and improved bioavailability as potential drugs for efficient therapy in diabetic complications and cancer.
Project website:	https://portal.apvv.sk

ARISER - Consequences of combined therapy of maternal depression – experimental study in rat offspring
Duration:	1. 9. 2025 - 30. 8. 2029
Evidence number:	APVV-24-0391
Program:	APVV
Project leader:	RNDr. Dubovický Michal, CSc.
SAS cosolvers:	Mgr. Bögi Eszter, PhD., Mgr. Bukatová Stanislava, PhD. , MMedSc Dremencov Eliyahu, DrSc, RNDr. Gáspárová Zdenka, PhD., MUDr. Grinchii Daniil, PhD., prof. RNDr. Lacinová Ľubica, DrSc., RNDr. Ondáčová Katarína, PhD., MVDr. Pecinová Romana, PhD., Mgr. Račický Matej, Mgr. Rashkivska Inna, PhD, Mgr. Tomko Matúš, PhD.
Annotation:	The lifetime risk of depression is higher in women than in men, and is particularly high during women\'s reproductive years. Untreated maternal depression not only threatens the health and life of the mother, but also increases the risk of impaired functional brain development in the fetus and newborn, which can lead to behavioral, psychosocial, and cognitive disorders later in life. Treatment of maternal depression includes psychotherapy and pharmacotherapy. While psychotherapy may be sufficient for mild to moderate depression, it often it often fails in moderate to severe depression. Antidepressants with well-studied reproductive safety profile, such as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors are commonly considered as a first-line treatment. However, more than 5% of women with peripartum depression do not respond to standard drug treatment. In this case, it is necessary to use a different antidepressant, a combination of antidepressants, or add antipsychotic drugs. The necessity of pharmacotherapy in this case raises questions about the safety of using the combination of drugs and taking into account their possible risks for fetal and neonatal development, with an emphasis on functional brain development and neurobehavioral adaptations in the later period. According to available clinical knowledge, the combination of the selective serotonin reuptake inhibitor sertraline (SER) and the second-generation antipsychotic aripiprazole (ARI) represents the optimal choice for the treatment of maternal/psychotic depression. Our main objective is therefore to evaluate the safety of ARI and ARI+SER administration during pregnancy in an animal model of maternal depression with a focus on offspring development. To achieve this, we will study the effects of prenatal exposure to these drugs on functional brain development and neurobehavioral consequences in rat offspring.

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Duration:	1. 7. 2025 - 30. 6. 2029
Evidence number:	APVV-24-0619
Program:	APVV
Project leader:	Mgr. Ferenczyová Kristína, PhD.
Other cosolvers:	Farmaceutická fakulta UK

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Duration:	1. 7. 2025 - 30. 6. 2029
Evidence number:	APVV-24-0090
Program:	APVV
Project leader:	Dr.rer.nat., Ing. Kanďárová Helena, ERT

Targeting SERCA Activation: Therapeutic Strategies for Managing Endoplasmic Reticulum Stress in Chronic Metabolic Diseases
Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0127/25
Program:	VEGA
Project leader:	RNDr. Lomenová Jana, PhD.
SAS cosolvers:	RNDr. Kura Branislav, PhD., RNDr. Májeková Magdaléna, PhD., Ing. Micháliková Silvia, PhD., Mgr. Rezbáriková Petronela, PhD., Mgr. Valúchová Barbora, Mgr. Wetter Erik
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 website:	https://e-vega.sav.sk/(S(h22jztv2lbh35lvjyssbrer5))/users/Projekt_SAV_0007.aspx

Pharmacological and non­pharmacological interventions to activate endogenous cardioprotection in failing heart.
Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0078/25
Program:	VEGA
Project leader:	Mgr. Farkašová Veronika, PhD
SAS cosolvers:	Mgr. Andelová Natália, PhD., prof., PharmDr. Duriš Adameová Adriana, DrSc., FIACS, Mgr. Janko Dávid, Mgr. Krsteva Katarína, MUDr. Ravingerová Táňa, DrSc., FIACS
Annotation:	Heart failure (HF) is the final stage of several cardiovascular diseases, in particular, myocardial infarction (MI).Although the patients that successfully survive MI live longer, the alteration of the heart muscle will manifest lateron by chronic failure of its pumping function. Potential reasons for that may be related to the complexity of themechanisms of HF and the requirement for multi­targeted effects of optimal cardioprotection. The project aims tostudy the possibility of reactivating adaptive potential in pathologically remodeled failing myocardium bypharmacological and non­pharmacological interventions. We will examine the effects of drugs withcardioprotective properties and intermittent hypoxia applied prior to administration of pathological stimulus and invarious stages of the development of HF. We will focus on characterizing functional and structural changes in themyocardium and the specific signaling pathways associated with the origin and development of HF andcardioprotection.

Model of Western diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) in borderline hypertensive rats: effect of monomethyl fumarate
Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	VEGA 2/0103/25
Program:	VEGA
Project leader:	RNDr. Bernátová Iveta, DrSc.
SAS cosolvers:	MSc. Anjum Anjum, RNDr. Bališ Peter, PhD., MSc. Bozkurt Aybuke, Mgr. Kluknavský Michal, PhD., RNDr. Kopincová Jana, PhD., Mgr. Mičurová Andrea, PhD.
Annotation:	Cardiovascular diseases (CMDs) and liver diseases are two of the leading causes of death worldwide. Primary prehypertension is a condition in which blood pressure is elevated above normal but not yet high enough to be classified as hypertension. It is a common condition, even in children and young adults. Individuals with prehypertension have an increased risk of developing CVDs and cardiometabolic diseases. To simulate the situation of women with prehypertension who consume a Western diet (WD), we will use an experimental model of female borderline hypertensive rats (BHR) fed a WD. We will investigate metabolic and functional changes, as well as changes in transcription of the nuclear factor erythroid 2-related factor 2 (NRF2) and its target genes, to better understand the mechanisms involved in the development of cardiovascular and hepatic disorders. The proposed model can provide a new tool for studying the interaction of mechanisms involved in the development of CVDs (such as hypertension) and cardiometabolic diseases (such as non-alcoholic fatty liver disease) in prehypertensive rats. The model can also be used to investigate whether dimethyl fumarate, an NRF activator, can be used for the prevention of these diseases.

Neuroprotective potential of quercetin in aging diabetic ZDF rats
Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0147/25
Program:	VEGA
Project leader:	RNDr. Vlkovičová Jana, PhD.
SAS cosolvers:	Ing. Frimmel Karel, PhD., Mgr. Kaločayová Barbora, PhD., Ing. Kornieieva Daria, Mgr. Šnúriková Denisa

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Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0051/25
Program:	VEGA
Project leader:	D.h.c., Prof., MUDr. Slezák Ján, DrSc., FIACS

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Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	VEGA 2/0091/25
Program:	VEGA
Project leader:	Mgr. Svetláková (Boťanská) Barbora, PhD.

Semantic memory in mental health disorders
Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	VEGA 2/0067/25
Program:	VEGA
Project leader:	MUDr. Riečanský Igor, DrSc.
SAS cosolvers:	Mgr. Kubinec Adam, Mgr. Marko Martin, PhD., Mgr. Michalko Drahomír, PhD., Mgr. Mitka Milan, PhD.
Other cosolvers:	Dragašek J

Sensory control of postural balance and its changes due to motor, cognitive and anxiety disorders
Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0098/25
Program:	VEGA
Project leader:	RNDr. Kimijanová Jana, PhD.
SAS cosolvers:	RNDr. Bzdúšková Diana, PhD., Mgr. Hirjaková Zuzana, PhD., Mgr. Marko Martin, PhD., Mgr. Rovný Rastislav, Prof. MUDr. Valkovič Peter, 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.

CARTRE - Investigation of factors involved in cardiorenal syndrom and treatment strategies
Duration:	1. 3. 2025 - 31. 12. 2028
Evidence number:	VV-MVP-24-0278
Program:	APVV
Project leader:	RNDr. Sýkora Matúš, PhD.
SAS cosolvers:	Mgr. Andelová Natália, PhD., RNDr. Barančík Miroslav, DrSc., RNDr. Egan Beňová Tamara, PhD., Ing. Ferko Miroslav, PhD., Mgr. Kaločayová Barbora, PhD., RNDr. Kura Branislav, PhD., Ing. Líšková Viktória, Mgr. Martišková Adriana, Mgr. Ondreják Andelová Katarína, PhD., Mgr. Svetláková (Boťanská) Barbora, PhD., RNDr. Szeiffová Bačová Barbara, PhD., Mgr. Šnúriková Denisa, RNDr. Tribulová Narcisa, DrSc., RNDr. Vlkovičová Jana, PhD., RNDr. Vrbjar Norbert, CSc.
Annotation:	The healthy physiological functioning of the body is ensured by the mutual interaction of individual organs, whereby pathological damage to one organ can cause acute or chronic dysfunction in another organ. The heart and kidneys interact through hemodynamic and non-hemodynamic pathways essential for cardiovascular homeostasis. The maladaptive relationship between the heart and kidneys has been defined as cardiorenal syndrome (CRS), contributing to organ dysfunction and failure. A key factor in this process is the activation of profibrotic pathways and subsequent fibrosis of the heart and kidneys. This life-threatening condition remains an unresolved issue in clinical practice. Therefore, new strategies are urgently needed for early diagnosis and targeted intervention in the fibrosis of the heart and kidneys. The aim of the project is to phenotype profibrotic and fibrotic changes in the heart and kidneys in a relevant model of CRS induced by aortocaval fistula (ACF). In addition to determining circulating markers of oxidative stress, inflammation, and profibrotic factors, it is essential to identify the activation of signaling pathways, the extent of fibrosis, and proarrhythmic factors, including profibrotic and proarrhythmic changes in connexin 43 (Cx43) in the heart and its unexplored role in the kidneys. Another aim of the project is to explore the antiinflammatory and antifibrotic effects of selectively targeted substances (SGLT2i and GLP-1RAs) and their potential in reversing profibrotic signaling pathways, including signaling mediated by connexin channels. The results obtained from this project will provide new information for more targeted therapy of the pathogenesis of heart and kidney fibrosis and will present a challenge for the implementation of translational and clinical studies.

ToxiGut - ToxiGut: Modeling and Prediction of Drug and Chemical Side Effects in an In Vitro 3D Reconstituted Human Small Intestine Model
Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0123/25
Program:	VEGA
Project leader:	Dr.rer.nat., Ing. Kanďárová Helena, ERT
SAS cosolvers:	Mgr. Gabrišová Klára, Ing. Mahmood Sirwan Ahmed, Ing. Milasová Tatiana, Ing. Milec Lucia, Ing. Pôbiš Peter, PhD., Mgr. Pružinská-Koch Katarína, PhD, RNDr. Valachová Katarína , PhD.
Annotation:	The ToxiGut project proposes the development and internal validation of an advanced experimental system forstudying the side effects of chemicals and pharmaceuticals on a human 3D reconstructed model of the smallintestine. The project focuses on comparing static and dynamic methods of cultivating 3D tissue in a microfluidicdevice (Gut-on-chip concept), achieving a high level of simulation of the physiological conditions of the smallintestine. The project will compare the obtained data with experimental results from the CaCo-2 line of humancolorectal carcinoma, which is used for screening in preclinical pharmacological studies. However, this modeldoes not reflect the complexity of the human intestinal environment and, like established animal models, providesinaccurate outputs for clinical studies. The project aims to provide a more efficient testing system that will improvethe predictive ability of preclinical tests and increase the safety of patients in clinical trials while reducing costsand time.

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Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0139/25
Program:	VEGA
Project leader:	Mgr. Ferenczyová Kristína, PhD.

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Duration:	1. 1. 2025 - 31. 12. 2028
Evidence number:	2/0068/25
Program:	VEGA
Project leader:	Mgr. Kindernay Lucia, PhD.

PQC inhalation m - Preparation and quality control of modern dosage forms for alternative administration rout of biologics by inhalation (APVV-23-0508)
Duration:	1. 7. 2024 - 30. 6. 2028
Evidence number:	APVV-23-0508
Program:	APVV
Project leader:	PharmDr. Dráfi František, PhD., MPH
SAS cosolvers:	PharmDr. Bauerová Katarína, PhD., DrSc., PharmDr. Fakhermanesh Mohammad, Mgr. Gabrišová Klára, Ing. Mahmood Sirwan Ahmed, MVDr. Neradil Peter, Ing. Pádej Ivan, Ing. Palenčárová Adriena Milana, PharmDr. Poništ Silvester, PhD., Ing. Pôbiš Peter, PhD., Ing. Švík Karol, CSc.
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.

The influence of semantic representation and executive control on the structure and dynamics of idea generation
Duration:	1. 7. 2024 - 30. 6. 2028
Evidence number:
Program:	APVV
Project leader:	Mgr. Marko Martin, PhD.
SAS cosolvers:	Ing. Bendžala Štefan, RNDr. Bzdúšková Diana, PhD., RNDr. Cimrová Barbora, PhD., RNDr. Kimijanová Jana, PhD., Mgr. Kubinec Adam, Mgr. Michalko Drahomír, PhD., Mgr. Mitka Milan, PhD., MUDr. Riečanský Igor, DrSc., Mgr. Rovný Rastislav, PhD., Mgr. Zelenayová Veronika
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.

The Role of Thyroid Hormones and the NRF2–PPARα Signaling Axis in the Regulation of Lipid Metabolism in a Rat Model of Cardiometabolic Comorbidity
Duration:	1. 1. 2026 - 31. 12. 2027
Evidence number:	Open-Mob-2025-03
Program:	Iné projekty
Project leader:	RNDr. Bernátová Iveta, DrSc.
SAS cosolvers:	MSc. Anjum Anjum, Mgr. Mičurová Andrea, PhD.
Other cosolvers:	Assoc. Prof. Gerasimos Sykiotis, MD., PhD, Panos Ziros, PhD, Georgios Psarias, MSc.
Annotation:	Western diet (WD) significantly contributes to the development of cardiometabolic disorders (CMDs), including (pre)hypertension, dyslipidaemia, and metabolic-associated fatty liver disease (MAFLD). Thyroid hormones are key regulators of lipid metabolism, influencing cholesterol synthesis, clearance, and lipolysis. Altered thyroid hormone homeostasis, possibly induced by WD-related metabolic stress, may contribute to dyslipidaemia and increased CMD risk. Thyroid dysfunction can impair PPARα signalling, reduce fatty acid oxidation, and promote hepatic lipid accumulation.In this bilateral project, we aim to elucidate the role of thyroid hormones in WD-induced metabolic dysregulation using borderline hypertensive rats (BHR). Rats will be fed WD with or without dimethyl fumarate (DMF), a known activator of NRF2, a transcription factor involved in mediating antioxidant defences to maintain redox homeostasis and suppress inflammation. We will analyse how WD modulates thyroid hormone status, the expression of genes encoding NRF2 (Nfe2l2), PPARα (Ppara), and other genes involved in lipid metabolism in blood, the liver and heart.Blood pressure and biochemical markers (plasma lipid profile, markers of liver and heart damage and thyroid hormones) will be assessed alongside gene expression profiles in thyroid gland, pituitary, and metabolic tissues. This project will help clarify the molecular link between thyroid hormone signalling, NRF2–PPARα pathways, and lipid homeostasis in a rat model of cardiometabolic comorbidity induced by chronic WD intake, which may be useful to understand the development of CMDs in humans.

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
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	2/0163/24
Program:	VEGA
Project leader:	RNDr. Mach Mojmír, PhD.
SAS cosolvers:	Mgr. Bögi Eszter, PhD., Mgr. Bukatová Stanislava, PhD. , RNDr. Dubovický Michal, CSc. , MVDr. Neradil Peter, MVDr. Pecinová Romana, PhD., Doc. RNDr. Ujházy Eduard, CSc., Mgr. Zvozilová Alexandra
Other cosolvers:	Kršk
Annotation:	In real life, mixtures of xenobiotics can lead to a \'cocktail\' effect. Studies have shown that these mixtures can leadnot only to predictable additive effects but also to unpredictable synergistic, or antagonistic effects. From earlyintrauterine life till elderly, the individual is continuously exposed to chemicals with beneficial or detrimentaleffects depending on the doses, windows of exposure and combinations. Many of these exposures areconsidered risk factors for many diseases. These observations indicate the necessity of using improvedhazard-evaluation models, such as the real-life risk simulation (RLRS) scenario. The present project aims to toprovide an evaluation of the pre- and postnatal effects of mixture of chemicals (below NOAEL levels) ondevelopment as well as a thorough evaluation of systemic toxicity in pregnant and lactating females and youngand adult offspring.

Cardioprotective effects of mesenchymal stem cells and HMGB1 inhibitor after experimentally induced myocardial infarction
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	2/0131/24
Program:	VEGA
Project leader:	RNDr. Cebová Martina, PhD.
SAS cosolvers:	MVDr. Barta Andrej, PhD., Mgr. Berényiová Andrea, PhD., Mgr. Bujnová Katarína, RNDr. Klimentová Jana, PhD., doc. RNDr. Pecháňová Oľga, DrSc.
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.

Novel antidiabetic/antiobesty drugs as innovative pharmacotherapeutic tools for cardioprotection in experimental model of type 2 diabetes
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	VEGA 2/0159/24
Program:	VEGA
Project leader:	doc. RNDr. Barteková Monika, DrSc.
SAS cosolvers:	Mgr. Duľová Ulrika, Mgr. Ferenczyová Kristína, PhD., Mgr. Kindernay Lucia, PhD., Mgr. Strapec Jakub
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

Senogenic effects of environmental stressors in human skin cells and possibilities of senotherapy using natural and synthetic substances
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	VEGA 2/0060/24
Program:	VEGA
Project leader:	Ing. Račková Lucia, PhD.
SAS cosolvers:	Mgr. Kodríková Rebeka, Ing. Nemčovič Marek, 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 environmentalstressors. These mechanisms are also linked to cellular senescence, process believed to contribute critically toaging.The skin, which is barrier organ of body, is constitutively exposed to various stimuli affecting itsmorphology and function.Therefore, skin exposome research can be considered paradigmatic,and itsimplementation 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 asoxidants,pollutants,UV radiation) also using new aging biomarkers. The scope of research also includestherapeutic efficacy of selected plant metabolites and synthetic compounds.The project will provide insight intogerontogenic and senotherapeutic mechanisms of substances studied in cellular skin models.

Investigating the involvement of connexin-43 in rat brown and white adipose tissue in mechanisms of cardiovascular risk and cardioprotection.
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	VEGA 2/0133/24
Program:	VEGA
Project leader:	RNDr. Egan Beňová Tamara, PhD.

Therapeutic intervention with bioactive compounds from bee products in experimental arthritis: evaluation of both articular and extra-articular complications
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	2/0079/24
Program:	VEGA
Project leader:	PharmDr. Bauerová Katarína, PhD., DrSc.
SAS cosolvers:	PharmDr, M.Phil Ahmad Waqar, PharmDr. Bauerová Katarína, PhD., DrSc., RNDr. Bučková Mária, PhD., PharmDr. Dráfi František, PhD., MPH, PharmDr. Fakhermanesh Mohammad, RNDr. Juránek Ivo, PhD., DrSc., PharmDr. Khademnematolahi Sasan , PhD., Ing. Majtán Juraj, DrSc., MBA, FIFST, PharmDr. Poništ Silvester, PhD., Mgr. Šafranek Martin, PhD., Ing. Švík Karol, CSc., Mgr. Umar Mohammad
Other cosolvers:	Lekárska fakulta UK v Bratislave
Annotation:	Bee products are a frequently studied due to their pharmacological properties. However, the identification ofsubstances responsible for their properties  is absent. The aimof the project is to characterize the effect ofselected peptides and polyphenolic extracts from bee products on the articular manifestations of rheumatoidarthritis, 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 asmelittin 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 relevanttissues. Study of cardioprotective mechanisms and of  mitochondrial energetics will be carried out.  Finally, theeffectiveness 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
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	2/0122/24
Program:	VEGA
Project leader:	RNDr. Vranková Stanislava, PhD.
SAS cosolvers:	MVDr. Barta Andrej, PhD., Ing. Bendžala Štefan, RNDr. Klimentová Jana, PhD., MVDr. Ondičová Katarína, PhD., MUDr. Riečanský Igor, DrSc., Mgr. Rovný Rastislav, 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/CREBsignaling pathway is a critical therapeutic target for inducing adult hippocampal neurogenesis and antidepressanttherapy. Compounds capable of inducing rapid structuraland functional rearrangement of neuronal networks are particularly attractive. Several of these psychoplastogensare 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 thepathogenesis of depression and their treatment possibilities.

The effect sex and reproductive stage of females on the vasoregulatory role of sulfide and nitroso signaling pathways in metabolic syndrome
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 invarious animal models of cardiovascular complications. In metabolic syndrome (MS) induced by changed diet, wereported that the interaction of these signaling pathways is disrupted, and H2S donor application can alleviate thepathological manifestations of MS. Moreover, in hypertriglyceridemic rats (HTG) we observed an endothelialdysfunction that was not only associated with reduced NO-synthase activity but also with endogenously producedH2S. Previous studies have focused on cardiovascular changes mainly in males, while studies on HTG femalesare missing. The project will examine the influence of gender and reproductive status of females HTG rats withthe aim of revealing possible differences in vasoactive regulatory mechanisms. At the same time, it willinvestigate the possible beneficial effects of flavonoid administration on cardiovascular complication associatedwith postmenopausal MS.

The role of sex hormones in the a1AMPK- mediated vascular protection during the development of the metabolic syndrome
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	2/0123/24
Program:	VEGA
Project leader:	Ing. Tarcalová Miroslava, PhD.
SAS cosolvers:	RNDr. Vlkovičová Jana, PhD., Mgr. Zemančíková Anna, 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.

Research of plants with therapeutic potential in surgery, dermatology, and dentistry: phytochemical analysis, biological effects, and study of mutual interactions of their constituents.
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	VEGA 1/0170/24
Program:	VEGA
Project leader:	Ing. Račková Lucia, PhD.

The role of in Wnt signaling in processes associated with effects of doxorubicin.
Duration:	1. 1. 2024 - 31. 12. 2027
Evidence number:	VEGA 2/0169/24
Program:	VEGA
Project leader:	RNDr. Barančík Miroslav, DrSc.

BIOCARD - -
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 compensatorymechanisms against this disorder is associated with regulation at the level of cardiac mitochondria. It ismitochondrial dysfunction that is currently the goal of a therapeutic cardioprotective strategy. This project willcombine the latest scientific insights with state-of-the-art methodological approaches. A key aspect of thepresented research is to ensure sufficient energy production in the heart in conditions of increased energyrequirements caused by reduced oxygen utilization and ischemic heart disease in combination with various types ofpreconditioning. The use of modern methodology will allow for investigation into the complex structure ofmitochondrial protein signaling pathways, their regulations, proteome and metabolome alterations in heart andmitochondria. Description and comprehension of complex system of protein interactions can help identify signalingpathways 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 mechanismsof cardioprotection is the inhibition of mitochondrial permeability transition pores (mPTP) opening. Regulation ofmPTP in terms of changes of individual proteins has already been presented. We aim to contribute to theunderstanding of the protein interactions presumably related to the protective modulation of mPTP. In connectionwith the remodeling of mitochondrial function, calcium homeostasis and signaling of free oxygen radicals will alsobe monitored. The presented project will deal with the stimulation of adaptation processes in order to contribute tothe elimination of mitochondrial dysfunction and ensure the maintenance of dynamic balance under conditions ofenergy deprivation in diseased heart.

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
Duration:	1. 7. 2023 - 30. 6. 2027
Evidence number:	APVV-22-0296
Program:	APVV
Project leader:	RNDr. Bernátová Iveta, DrSc.
SAS cosolvers:	MSc. Anjum Anjum, RNDr. Bališ Peter, PhD., MVDr. Barta Andrej, PhD., MSc. Bozkurt Aybuke, RNDr. Cigáň Alexander, CSc., Ing. Dvurečenskij Andrej, PhD., Mgr. Kaločayová Barbora, PhD., Mgr. Kluknavský Michal, PhD., Ing. Kvandová Miroslava, RNDr. Líšková Silvia, PhD., Mgr. Magyarová Silvia, Ing. Majerová Melinda, PhD., Ing. Maňka Ján, CSc., Mgr. Mičurová Andrea, PhD., Mgr. Škrátek Martin, PhD.
Other cosolvers:	L. Laubertová
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.

CARDIOEND - Cardiovascular protection mediated by alpha 1 AMPK against metabolic syndrome-mediated endothelial dysfunction - identifying new risk factors
Duration:	1. 7. 2023 - 30. 6. 2027
Evidence number:	APVV-22-0154
Program:	APVV
Project leader:	Ing. Tarcalová Miroslava, PhD.
SAS cosolvers:	RNDr. Bališ Peter, PhD., doc. RNDr. Barteková Monika, DrSc., RNDr. Bernátová Iveta, DrSc., Mgr. Csicsátková Nikoleta, PhD., Mgr. Duľová Ulrika, Mgr. Ferenczyová Kristína, PhD., Mgr. Grman Marián, PhD., RNDr. Hlaváčová Nataša, PhD., prof. PharmDr. Ježová Daniela, DrSc., RNDr. Karailiev Peter, PhD., Mgr. Kluknavský Michal, PhD., Mgr. Magyarová Silvia, doc. RNDr. Pecháňová Oľga, DrSc., doc. MUDr. Radošinská Jana, PhD., Mgr. Strapec Jakub, Mgr. Suroviaková Katarína, doc. MUDr. Török Jozef, CSc., Mgr. Zemančíková Anna, 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.

CardCa2+CNS - Molecular mechanisms implicated in corticosteroid-monoamine interaction in stress-related cardio- and neuropathologies
Duration:	1. 7. 2023 - 30. 6. 2027
Evidence number:	APVV-22-0061
Program:	APVV
Project leader:	RNDr. Mach Mojmír, PhD.
SAS cosolvers:	Mgr. Bukatová Stanislava, PhD. , RNDr. Májeková Magdaléna, PhD., Mgr. Zvozilová Alexandra
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.

On the trace of mitochondrial chloride channel identity.
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. Inin vitro conditions, it was observed that oxidative stress results in oscillations of deltaΨm, which leads to theshortening of the action potential on the plasma membrane of cardiomyocytes and to the occurrence ofarrhythmias, mediated by the production of ATP in the mitochondria. At the level of the whole heart, arrhythmiaswere 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 thesame effect. TSPO ligands inhibit the mitochondrial chloride channels at nanomolar concentrations, suggesting thatthe TSPO protein mediates the chloride channel block. Thus, TSPO is likely to be in close contact with the chloridechannel. Mitochondrial chloride channels are well described at the electrophysiological level, but their molecularidentity remains unclear. Recently, two isoforms of chloride intracellular channel family (CLICs) have been shownto 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 identicalto one of the two mitochondrial CLIC isoforms. The aim of the presented project is to verify the hypothesis that themeasured 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 forpreventing the occurrence of post-ischemic arrhythmias.

HYDMIM - Effects of mesenchymal stem cells and HMGB1 inhibitor on cardiovascular system after experimentally induced myocardial infarction in hypertension and diabetes mellitus
Duration:	1. 7. 2023 - 30. 6. 2027
Evidence number:	APVV-22-0271
Program:	APVV
Project leader:	RNDr. Cebová Martina, PhD.
SAS cosolvers:	MVDr. Barta Andrej, PhD., Ing. Bendžala Štefan, Mgr. Bujnová Katarína, RNDr. Čačányiová Soňa, PhD., Bc. Dobošová Denisa, RNDr. Klimentová Jana, PhD., RNDr. Vranková Stanislava, PhD.
Other cosolvers:	Vojtková Mária doc. Ing. 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.

Targeted suppression of pro-inflammatory and pro-fibrotic signalling pathways to prevent life-threatening heart failure and malignant arrhythmias
Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:
Program:	VEGA
Project leader:	RNDr. Szeiffová Bačová Barbara, PhD.

EXPERIMENTAL STUDY OF THE EFFECTS OF MATERNAL DEPRESSION AND ANTIDEPRESSANTS CITALOPRAM AND SERTRALINE ON POSTNATAL DEVELOPMENT OF RAT OFFSPRING
Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	2/0133/23
Program:	VEGA
Project leader:	RNDr. Dubovický Michal, CSc.
SAS cosolvers:	Mgr. Bögi Eszter, PhD., Mgr. Bukatová Stanislava, PhD. , RNDr. Mach Mojmír, PhD., MVDr. Pecinová Romana, PhD., Doc. RNDr. Ujházy Eduard, 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.

Targeting SERCA Activation: Therapeutic Strategies for Managing Endoplasmic Reticulum Stress in Diabetic Conditions
Duration:	1. 1. 2025 - 31. 12. 2026
Evidence number:	Open-Mob-2024-11
Program:	Iné projekty
Project leader:	RNDr. Lomenová Jana, PhD.
SAS cosolvers:	Ing. Micháliková Silvia, PhD., Mgr. Rezbáriková Petronela, 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 newly developed small allosteric SERCA activators to mitigate damage to pancreatic cells induced by methylglyoxal, palmitate, and/ or 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, insulin release, SERCA2b expression, intracellular calcium levels, reactive oxygen species formation, and metabolic analysis, 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.

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
Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	VEGA 2/0126/23
Program:	VEGA
Project leader:	PharmDr. Poništ Silvester, PhD.
SAS cosolvers:	PharmDr. Bauerová Katarína, PhD., DrSc., PharmDr. Dráfi František, PhD., MPH, Ing. Mihalová Danica, PharmDr. Taghdisiesfejír Mohsen
Other cosolvers:	Tóth Jaroslav, Mgr., 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.

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.
Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	2/0008/23
Program:	VEGA
Project leader:	RNDr. Valachová Katarína , PhD.
SAS cosolvers:	RNDr. Juránek Ivo, PhD., DrSc., Dr.rer.nat., Ing. Kanďárová Helena, ERT, Ing. Pádej Ivan, Ing. Šoltés Ladislav, DrSc., Ing. Švík Karol, CSc.

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Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	2/0025/23
Program:	VEGA
Project leader:	doc. RNDr. Pecháňová Oľga, DrSc.

Neurocognitive mechanisms of semantic representation and control
Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	2/0052/23
Program:	VEGA
Project leader:	Mgr. Marko Martin, PhD.
SAS cosolvers:	Mgr. Bajzová Barbora, Ing. Bendžala Štefan, RNDr. Cimrová Barbora, PhD., Mgr. Kravárik Peter, Mgr. Kubinec Adam, Mgr. Marko Martin, PhD., Mgr. Michalko Drahomír, PhD., Mgr. Mitka Milan, PhD., MUDr. Riečanský Igor, DrSc., Mgr. Rovný Rastislav
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
Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	VEGA 2/0018/23
Program:	VEGA
Project leader:	RNDr. Gáspárová Zdenka, PhD.
SAS cosolvers:	MVDr. Bezek Štefan, DrSc., RNDr. Dubovický Michal, CSc. , RNDr. Juránek Ivo, PhD., DrSc., RNDr. Knezl Vladimír, PhD., Ing. Lepáček Marek, PhD., Ing. Pádej Ivan, Ing. Švík Karol, CSc.
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.

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)
Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	2/0091/23
Program:	VEGA
Project leader:	PharmDr. Dráfi František, PhD., MPH
SAS cosolvers:	PharmDr, M.Phil Ahmad Waqar, PharmDr. Bauerová Katarína, PhD., DrSc., PharmDr. Fakhermanesh Mohammad, Ing. Mihalová Danica, PharmDr. Poništ Silvester, PhD., Mgr. Umar Mohammad
Annotation:	Based on the scientific literature we hypothesize that an optimal anti-inflammatory effect of a selected naturalsubstance after its oral administration in its new nano-carrier drug delivery systems (NCDDS) might beneficiallymodulate immune processes in inflammatory diseases as in rheumatoid arthritis (RA). Adjuvant arthritis (AA) is used as one of the in vivo RA models to evaluate the pharmacology of molecules tested. High bioavailability will be achieved by the technological adjustment of the molecules into NCDDS (nanoemulsions and liposomes). Along with other parameters evaluated and focused mainly on inflammation, we will analyze the ability to reduce bone erosion and/or synovitis by the RANKL/RANK/osteoprotegerin signalling pathway. The significant benefit will be statistically assessed by their dose-dependency evaluation and possible synergic/additive pharmacological determination of concomitantly applied standards as methotrexate and upadacitinib, administered both in (sub)therapeutic doses.

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Duration:	1. 1. 2023 - 31. 12. 2026
Evidence number:	1/0048/23
Program:	VEGA
Project leader:	doc. RNDr. Pecháňová Oľga, DrSc.

Cardiac mitochondrial bioenergetics regulated by reduced oxygen consumption: In-depth proteomic analysis of cardioprotective signaling pathways.
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.

DiPrev - Dimethyl fumarate as a potential tool for the prevention of cardiovascular and hepatic disorders associated with Western diet in borderline hypertensive rats
Duration:	1. 9. 2024 - 31. 8. 2026
Evidence number:	09I03-03-V04-00427
Program:	Plán obnovy EÚ
Project leader:	RNDr. Bernátová Iveta, DrSc.
SAS cosolvers:	Mgr. Kluknavský Michal, PhD., RNDr. Kopincová Jana, PhD.

SGLT2 Cardioprot - Cardioprotective effect of SGLT2 inhibition in heart failure: the role of RISK and SAFE pathway
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.

MITPROT - Heart mitochondria proteomic mapping: Uncovering potential signaling pathways
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.

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
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.

SUFIBAR - Targeted suppression of pro-inflammatory and pro-fibrotic signaling pathways to prevent heart failure and occurrence of malignant arrhythmias
Duration:	1. 7. 2022 - 30. 6. 2026
Evidence number:	APVV-21-0410
Program:	APVV
Project leader:	RNDr. Szeiffová Bačová Barbara, PhD.
SAS cosolvers:	Mgr. Andelová Natália, PhD., RNDr. Barančík Miroslav, DrSc., RNDr. Egan Beňová Tamara, PhD., Mgr. Farkašová Veronika, PhD, Mgr. Ferenczyová Kristína, PhD., Ing. Ferko Miroslav, PhD., Mgr. Fogarassyová Mária, Mgr. Kaločayová Barbora, PhD., RNDr. Knezl Vladimír, PhD., RNDr. Kura Branislav, PhD., RNDr. Okruhlicová Ľudmila, CSc., Mgr. Ondreják Andelová Katarína, PhD., D.h.c., Prof., MUDr. Slezák Ján, DrSc., FIACS, Mgr. Svetláková (Boťanská) Barbora, PhD., RNDr. Sýkora Matúš, PhD., RNDr. Tribulová Narcisa, DrSc., RNDr. Vlkovičová Jana, 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.

CARDIOPROT - New aspects of cardioprotection by natural antioxidants: role of ageing and lifestyle-related comorbidities
Duration:	1. 7. 2022 - 30. 6. 2026
Evidence number:	APVV-21-0194
Program:	APVV
Project leader:	doc. RNDr. Barteková Monika, DrSc.
SAS cosolvers:	RNDr. Bališ Peter, PhD., RNDr. Barančík Miroslav, DrSc., Mgr. Berényiová Andrea, PhD., Mgr. Farkašová Veronika, PhD, Mgr. Ferenczyová Kristína, PhD., Mgr. Fogarassyová Mária, Mgr. Kaločayová Barbora, PhD., Mgr. Kindernay Lucia, PhD., RNDr. Kura Branislav, PhD., MUDr. RNDr. Púzserová Angelika, PhD., Mgr. Svetláková (Boťanská) Barbora, PhD., RNDr. Sýkora Matúš, PhD., RNDr. Szeiffová Bačová Barbara, PhD., Mgr. Šnúriková Denisa, RNDr. Vlkovičová Jana, PhD.
Other cosolvers:	Radoš
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