MF FI Fiziologijos ir farmakologijos tyrimų laboratorija (04.04.01)

Įvadas Gliukagono tipo peptidas-1 (GLP-1) yra inkretininis hormonas, kurį išskiria žarnyno L ląstelės kylant gliukozės lygiui organizme. Jis reguliuoja gliukozės homeostazę, skatindamas nuo gliukozės priklausomą insulino sekreciją ir slopindamas gliukagono išsiskyrimą [1]. Nors geriausiai yra išnagrinėtas GLP-1 metabolinis poveikis, tačiau jis veikia ir kitose organizmo vietose [2]. Nustatyta, kad GLP-1 receptorių yra įvairiuose audiniuose: širdyje, kraujagyslių endotelyje bei lygiuosiuose raumenyse. Taip šis hormonas daro įtaką lygiųjų raumenų susitraukimams ir gali tiesiogiai dalyvauti kraujagyslių funkcijos reguliacijoje [1, 2]. Aterosklerozės modelyje pelėse buvo nustatyta, kad GLP-1 didina endotelio azoto sintazės kiekį taip sukeldamas kraujagyslių išsiplėtimą [3]. GLP-1 taip pat padeda atsistatyti kraujagyslių sienelėms po įvairių būklių tokių kaip hiperglikemija ar uždegiminių pokyčių [3]. GLP-1 veikia lygiųjų raumenų ląsteles storajame žarnyne, moduliuodamas jų kontraktiliškumą ir proliferaciją slopindamas jų susitraukimus [4]. GLP-1 biologini aktyvumą reikšmingai riboja dipeptidilpeptidazė-4 (DPP-4). Tai yra serino proteazės fermentas greitai inaktyvuojantis GLP-1 pašalinant N-terminalinius peptidus nuo GLP-1 molekulių. Dėl itin trumpo GLP-1 pusinės eliminacijos laiko (1-2 minutės) DPP-4 aktyvumas yra pagridinis veiksnys, ribojantis GLP-1 veikimo trukmę ir intensyvumą [5]. DPP-4 padidėja nutukimo metu visceraliniame riebaliniame audinyje ir koreliuoja su padidėjusiu adipocitų dydžiu ir metaboliniu ląstelių funkcijų sutrikimu [6]. Tyrimai rodo, kad GLP-1 poveikis endotelio ląstelėms reikšmingai sumažino oksidacinio streso sukeltą endotelio disfunkciją ir autofagiją mažinant reaktyvius deguonies junginius [7]. Tyrimo tikslas Ištirti GLP-1 poveikį žmogaus žarnyno lygiųjų raumenų ląstelių gyvybingumui ir DPP-4 raiškai metabolinio streso sąlygomis. [...]

Background, Objectives: Studies have demonstrated that neo-nates exhibit cortical responses to noxious stimuli, express clear physiological stress reactions. Major challenge – effective pain assessment. There is lack of studies investigating maternal fac-tors influencing neonatal stress and pain responses. This study aimed to identify these factors. Methods: We conducted a prospective quantitative study at the Lithuanian University of Health Sciences Kaunas Clinics (Dec2020–Nov 2021). Term and preterm neonates admitted to the Neonatology Department/NICU were included. Exclusion criteria: neonate endocrine, CNS disorders, treatment with glucocorticoids or analgesics, and dehydration. Data collected: neonate's vitals, demographics, PIPP score, mothers’ medical history. Newborn salivary cortisol and melatonin were measured via ELISA before and 30 minutes after venipuncture or heel prick. Statistical analysis performed with SPSS 29.0. p value < 0.05 considered significant. Results: 98 newborns included in the study, 63.3% born on term. 68.4% of birth – natural. Half of women < 30 y.o. (median29 years, IQR26-33). 73.5% had pathology during pregnancy, 62.2% had medical anesthesia/pain management during labor. Higher melatonin in newborns born via CPO post NICU procedure(p = 0.028). Newborns from mothers who had any pathology during pregnancy were 12.6x more likely to have higher cortisol before heel-lance procedure (p = 0.021). The method of delivery negatively correlated with pre-procedure cortisol concentration(p = 0.035, p = 0.068). Maternal harmful habits increase melatonin concentration 6.319x after the heel-lance prick. Pain relief during labor and harmful maternal habits were associated with difference in melatonin concentration before and after the heel-lance procedure (p = 0.005, p = 0.002). Neonates born via CPO had higher melatonin after NICU procedure (p = 0.028). Conclusion: We observed that neonatal stress and pain responses are significantly influenced by maternal factors, including maternal health, delivery method, and maternal behaviors.

Background, Objectives: Neonates, especially preterm infants in the NICU, undergo numerous procedures that may cause discomfort or pain. There is limited research on factors influencing neonatal stress and pain responses. This study aimed to identify factors in newborns associated with increased neonatal pain. Methods: We conducted a prospective quantitative study at the Lithuanian University of Health Sciences Kaunas Clinics (Dec2020–Nov 2021). Term and preterm neonates admitted to the Neonatology Department/NICU were included. Exclusion criteria: endocrine, and CNS disorders, treatment with glucocorticoids or analgesics, and dehydration. Data collected: neonates’ vitals, demographics, PIPP score, physiological parameters. Salivary cortisol and melatonin were measured via ELISA be-fore and 30 minutes after venipuncture or heel prick. Statistical analysis performed with SPSS 29.0. p value < 0.05 considered significant. Results: In total 98 newborns were included in the study,63.3% were term, 30 – treated in NICU. 68.4% of birth – natural, 9.2% had congenital malformations. Preterm neonates had greater increases in heart and respiratory rates during procedures (p < 0.001, p = 0.005), higher pre-procedural PIPP scores (p < 0.001), it remained similar after procedure. Females tended to have lower SpO2 before and after the procedure(p = 0.059, p = 0.057). Higher RR before, after the procedure associated with congenital abnormalities (p = 0.016, p = 0.050).Cortisol was higher in premature newborns after venipuncture(p = 0.039), also they had higher cortisol difference after NICU procedure (p = 0.039). Females had higher cortisol before procedure in NICU (p = 0.009). Congenital abnormalities associated with greater cortisol difference during heel-lance (B = 29.583,p = 0.039), lower gestational age – with higher cortisol difference in NICU procedures(p = 0.041). Neonatal sepsis was negatively correlated with melatonin concentration (p = 0.025).Conclusion: We observed that prematurity, congenital conditions, and neonatal sepsis are associated with heightened physiological and hormonal stress and pain responses.

Pediatric emergency medicine (PEM) presents unique challenges due to the diverse developmental stages and medical conditions of young patients. The increasing patient load and nonurgent referrals to pediatric emergency departments (PEDs) emphasize the need for personalized decision-making approaches. These approaches must accommodate the complexities of pediatric care while fostering collaboration between healthcare providers and families. Integrating artificial intelligence (AI) into healthcare settings can transform PEM by enhancing diagnostic accuracy, customizing treatments, and optimizing resource allocation. AI technologies leverage vast datasets, including electronic health records and genetic profiles, to generate personalized diagnostic and treatment plans. Machine learning algorithms can identify patterns in complex data, facilitating early disease detection and precise interventions. This literature review analyzes the role of AI in supporting pediatric emergency care through diagnostic assistance, predictive modeling for febrile disease progression, and outcome optimization. It also highlights the challenges of applying AI in PEM, including data limitations and the need for algorithmic transparency. By addressing these challenges, AI has the potential to revolutionize personalized care in pediatric emergency settings, ultimately improving patient outcomes and care delivery.

The use of cardioplegia not only achieves cardiac arrest but also minimizes ischemic/reperfusion (I/R) injury, potentially improving short- or long-term outcomes. The aim of this study was to evaluate the impact of different cardioplegic solutions - del Nido, Custodiol HTK and St. Thomas on genes expression and cytokines response in an immature rat heart model of I/R using the Langendorff preparation. Expression of genes which are involved in cell cycle, proliferation, apoptosis resistance and response to hypoxia were determined in cardiac tissue, as well as levels pro/anti-inflammatory cytokines were measured.

Biomarker search for juvenile idiopathic arthritis (JIA) diagnosis and monitoring remain the focus of research worldwide. Several microRNAs (miRNAs) have been identified as relevant in different rheumatic conditions; however, studies in JIA remain limited. Our study aimed to explore the potential of serum and urine-derived miRNAs for JIA diagnostics and longitudinal JIA monitoring.

Background: Melatonin, widely used for treating insomnia, has potential antiviral effects that remain poorly understood. We aimed to compare its impact on antiviral responses in monolayer and coculture gastrointestinal models. Method: We developed a coculture viral infection model using Caco-2 cells, small intestine fibroblasts (F), and human umbilical vein endothelial cells (E). Caco-2 cells were grown in inserts placed above F+E (3:1 ratio) in 24-well-plates (coculture) or without F+E (monolayer). Cultures were incubated at 37°C with 5% CO2 for 14 days. Caco-2 cells were then pretreated with 50 µM of melatonin for 24 hours and stimulated with 10 μg/ml Poly I:C (TLR3 stimulator) for additional 24 hours or vice versa. The antiviral response was assessed by measuring IFNλ1 (ELISA) and IFNλ receptor-1 (IFNLR1) expression (flow cytometry). Statistical analysis was conducted using SPSS (p<0.05 considered significant). Results: IFNλ1 expression induced by 10 μg/ml of Poly I:C was significantly higher in Caco-2 cells grown in coculture model compared to the monolayer (37.4±1.96 vs. 14.5±0.59 ng/ml, p=0.0006). Pretreatment with melatonin further increased IFNλ1 expression in coculture, while treatment post-infection reduced IFNλ1 by approximately 65% in both models. IFNLR1 expression was also higher in the coculture. In monolayer, melatonin pretreatment reduced IFNLR1 expression, while treatment post-infection increased it; in contrast, the opposite pattern was observed in the coculture. Surprisingly, fibroblasts did not express IFNLR1, whereas epithelial cells showed higher amounts of the receptor in response to melatonin than Caco-2 cells despite lower IFNλ1 levels in F+E supernatant. Conclusions/Learning Points: The findings highlight the critical role of fibroblast-endothelial interaction and synergistic effect with melatonin in modulating antiviral response in Caco-2 cells.

Melatonin is a hormone naturally produced by the body that has recently been found to have antiviral properties. However, its antiviral mechanisms are not entirely understood. Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in the gastrointestinal tract. Melatonin was found to have different effect when applied as a pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin pretreatment after Poly I:C stimulation did not protect organoids from size reduction but enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations were used. On the other hand, treatment with melatonin after the induction of viral inflammation helped to maintain the size of the organoids while reducing cell proliferation. In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, but did not prevent from apoptosis. The findings of this study emphasize the importance of type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light on the antiviral properties of melatonin as a potential therapeutic substance.

Juvenile idiopathic arthritis (JIA) is a group of rare musculoskeletal disorders with chronic inflammation of joints, typically manifesting before the age of 16 years. The assessment of disease activity remains pivotal in JIA treatment decisions, particularly during clinical remission. While musculoskeletal ultrasound (MSUS) has shown promise in detecting subclinical synovitis, longitudinal data on MSUS features in JIA remains limited. The aim of this study was to evaluate the prevalence of subclinical synovitis observed in MSUS over a follow-up period in JIA patients. Additionally, it sought to assess the consistency and correlation between clinical findings, standardized composite clinical score (JADAS10), and MSUS-detected synovitis during 9 months follow-up.

This study aimed to conduct arthroscopic evaluation of cartilage electromechanical properties and establish their correlation with International Cartilage Repair Society (ICRS) grading scores.