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Single-cell RNA sequencing (scRNA-seq) and its insights into cellular heterogeneity in atherosclerosis
No full textSingle-cell RNA sequencing (scRNA-seq) has transformed our understanding of cellular diversity in human biology, providing novel insights into disease mechanisms. In cardiovascular disease (CVD), scRNA-seq enables precise mapping of complex cell populations, uncovering unique cell types and states that influence disease progression and suggest new therapeutic targets. In atherosclerosis (AS), scRNA-seq has redefined plaque pathology by identifying distinct cell types, including endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, macrophages, T cells, and B cells, each with specific roles in plaque stability, inflammation, and disease progression. In our review, we summarized these major cellular populations and their cellular heterogeneity in non-diseased and atherosclerotic aorta, as identified by scRNA-seq in mice and human tissues. We discussed conserved and species-specific subpopulations, their defining markers, and their functional implications in plaque progression. In addition, we integrated findings from scRNA-seq with experimental studies to highlight key molecular targets with therapeutic potential. In the future, these insights offer a refined cellular and molecular framework of atherosclerosis and may help the development of targeted interventions to promote plaque stabilization and reduce cardiovascular risk
Surveillance of QTc-Interval Prolonging Medications Upon Admission Throughout Hospitalization in a Tertiary Care Geriatric Ward
No full textObjective: Long QT syndrome (LQTS) poses a significant risk of torsade de pointes, particularly in older patients
due to age-related changes in cardiac repolarization and increased susceptibility to medication-induced QTc
interval prolongation. Despite the increased risk, data on medication-related LQTS remain limited, leading to this
study on its prevalence, characteristics, and risk factors, along with QT-prolonging drug use in older patients. The
study aims to identify clinical and medication-related predictors of LQTS and evaluate the burden of co-prescribed
QT-prolonging medications in this population. Subject and Methods: This prospective study at a tertiary care
hospital included initial and follow-up ECGs, with medication details were collected. Statistical analyses compared
variables, including QTc intervals and medication use, between patients with and without LQTS. Results: The
study included 128 adults aged 65 or older, with 27.3% presenting LQTS on admission, increasing to 42.2% after 7
days of hospitalization. Patients with LQTS had a higher prevalence of QTc-interval prolonging medications, List 1
medications, and atrial fibrillation. Laboratory changes and medication use were observed, with significant
increases in QTc interval and List 1 medication administration. Male sex and amiodarone use were identified as
predictors of LQTS during hospitalization. Conclusion: The study report a high prevalence of prolonged QTc
interval and LQTS in older inpatients. Proton pump inhibitors were frequently prescribed despite their QTc-
prolonging potential. This underscores the need of close monitoring and awareness of QTc prolongation risks in
older patients, advocating for routine ECG assessments and vigilant management of modifiable risk factors,
especially the electrolytes.This is peer-reviewed version of the following article: Baralić Knežević, I., Kovačević, M., Stefanović, K., Erceg, P., Mihajlović, G., Aćimović, J.,& Vučićević, K.. (2025). Surveillance of Corrected QT Interval-Prolonging Medications Upon Admission Throughout Hospitalization in a Tertiary Care Geriatric Ward. in Medical Principles and Practice
Karger..
[https://doi.org/10.1159/000544820
Metabolic Dysfunction-Associated Steatotic Liver Disease Is Characterized by Enhanced Endogenous Cholesterol Synthesis and Impaired Synthesis/Absorption Balance
No full textCholesterol accumulation plays a significant role in the pathogenesis of metabolic-dysfunction-associated steatotic liver disease (MASLD), yet changes in cholesterol homeostasis in MASLD remain insufficiently investigated. This study aimed to examine alterations in cholesterol synthesis and absorption by measuring plasma levels of endogenous cholesterol precursors (as markers of synthesis) and phytosterols (as indicators of absorption). A total of 124 MASLD patients and 43 healthy individuals were included. Our results showed higher plasma concentrations of lathosterol in the MASLD group (p = 0.006), in parallel with comparable concentrations of desmosterol (p = 0.472) and all analyzed phytosterols in both groups. Correlation analysis showed that both lathosterol and desmosterol were positively associated with non-invasive hepatic steatosis indices: FLI, HSI, and TyG index (p < 0.01, p < 0.01, and p < 0.05, respectively). Multivariate linear regression further confirmed that these synthesis markers remained significant predictors of FLI (p = 0.010), HSI (p = 0.013), and TyG index (p = 0.002), even after adjusting for other relevant variables. These findings indicate that MASLD is associated with a shift in cholesterol homeostasis towards enhanced endogenous cholesterol synthesis
TechNote - Minimum Preanalytical Information for the Publication of Studies on Circulating Cell-Free microRNA-based Biomarkers
No full textCirculating cell-free microRNAs (miRNAs) are emerging as promising biomarkers with broad potential for clinical
applications. However, pre-analytical variability significantly affects miRNA quantification and hampers reproduc-
ibility across studies. This work aims to define the Minimum Preanalytical Information required for the publication
of studies on circulating cell-free miRNA-based biomarkers. We review key pre-analytical factors that influence circu-
lating miRNA levels quantified using RT-qPCR. Critical variables include blood collection timing, sample type,
centrifugation protocols, transport and storage conditions, hemolysis, lipemia, medication, physical activity and
pathogen inactivation methods. We introduce a standardized checklist to promote methodological transparency and
inter-study comparability. The final aim is to enhance the reliability of miRNA-based biomarker research and support
its successful translation into clinical practice
Low energy nanoemulsions with citrus essential oils: formulation development and antioxidant activity
No full textThe aim of this study was to develop nanoemulsions using an eco-friendly low energy process, as well as to evaluate their stability and suitability as cosmetic products with antioxidant activity
Antibiofilm Effects of N-Acetyl Cysteine on Staphylococcal Biofilm in Patients with Chronic Rhinosinusitis
No full textStaphylococcal bacterial biofilm plays an important role in the pathogenesis and bacterial persistence of chronic rhinosinusitis. N-acetyl cysteine (NAC) has an inhibitory role in biofilm formation, suppressing adhesion and matrix production or favoring dispersal of preformed biofilm. The aim of this study was to examine the in vitro effect of NAC on Staphylococcal biofilm formation by bacterial strains isolated from tissue samples of patients with chronic rhinosinusitis with or without nasal polyps (CRSwNP and CRSsNP). Prospective study included 75 patients with CRS. The biofilm-forming capacity of isolated strains was detected by microtiter-plate method and the effects of sub-inhibitory (1/2x, 1/4x, and 1/8x minimal inhibitory concentration, MIC) and supra-inhibitory minimal concentrations (2x, 4x, and 8xMIC) of NAC on biofilm production were investigated. Staphylococcal bacterial strains were isolated in 54 (72%) patients, and the most frequently isolated species were Staphylococcus aureus (40.7%). Coagulase-negative Staphylococci species were weak producers of biofilm, while S. aureus was a strong biofilm producer. Concentration of 3.1 mg/mL (1/2 MIC) was sufficient to completely prevent biofilm formation in 77.8% of the isolates, where 49.6 mg/mL (8xMIC) led to the complete eradication of formed biofilm in 81.5% of the isolates. The subinhibitory and eradication effects were dose- and strain-dependent. There were no significant differences in MIC values between isolates from patients with CRSwNP and CRSsNP isolates. NAC proved to be effective in inhibiting biofilm formation and reducing formed biofilm by Staphylococcal isolates from patients with CRS. A comparable antibiofilm effect was exhibited in both phenotypes of CRS, indicating that NAC’s antibiofilm activity was independent of the underlying clinical phenotype, and more targeted on biofilm matrix components
From Chemistry to Pharmacology: Exploring the Anti-Inflammatory and Antioxidant Potential of Novel Dexketoprofen Amide Derivatives
No full textIn the present study, five novel dexketoprofen amide derivatives with a free carboxyl group in their side chains were synthesized. The in vivo anti-inflammatory potential of dexketoprofen derivatives was evaluated using a carrageenan-induced paw edema model of acute inflammation. Additionally, the local and systemic redox status in rats following acute administration of the compounds was assessed by measuring levels of pro-oxidative markers and the activity of antioxidant enzymes. Among the analyzed molecules, derivatives 2 and 4 exhibited the most potent in vivo anti-inflammatory activity, showing effects comparable to those of the parent compound dexketoprofen. In vitro results revealed that all newly synthesized compounds exhibited low inhibitory activity toward COX-1, whereas only compound 4 showed significant COX-2 inhibition. The stronger binding affinity of derivative 4 for COX-2 in comparison to other tested compounds is likely attributed to its ability to form multiple electrostatic interactions within the enzyme’s active site. Furthermore, compounds 2 and 5 demonstrated efficacy comparable to the parent drug in restoring redox balance, indicating their potential antioxidant properties under acute inflammatory conditions. The findings of this study underscore the therapeutic potential of the novel dexketoprofen amide derivatives as dual-function agents with the capacity to modulate both inflammatory responses and oxidative stress
Exploring the Potential of Oral Butyrate Supplementation in Metabolic Dysfunction-Associated Steatotic Liver Disease: Subgroup Insights from an Interventional Study
No full textMetabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver disease and is closely associated with metabolic abnormalities and cardiovascular risks. Butyrate, a short-chain fatty acid produced by gut microbiota, has the potential to enhance liver health by modulating inflammation and supporting gut barrier integrity. This study aimed to investigate and compare the effects of sodium butyrate and calcium butyrate in patients with MASLD. In this single-center, randomized clinical trial, 181 patients with MASLD were enrolled and assigned to receive either sodium butyrate (n = 121) or calcium butyrate (n = 60) supplementation at a daily dose of 1000 mg. The primary endpoint was the change in liver steatosis, measured using the Controlled Attenuation Parameter (CAP) via FibroScan®. Secondary endpoints included liver stiffness, biochemical parameters, hepatic steatosis and fatty liver indices, fecal calprotectin levels, stool short-chain fatty acid levels, and microbiome composition. A subgroup analysis compared responders (a ≥ 5% reduction in CAP) to non-responders. There were no significant changes in CAP values for either group (ΔCAP: sodium butyrate, 0.84; calcium butyrate, −0.23; p = 0.70). Sodium butyrate significantly reduced serum trimethylamine N-oxide and fatty liver index, while calcium butyrate led to a decrease in fecal calprotectin levels. Responders demonstrated a lower body mass index, higher levels of high-sensitivity C-reactive protein and HbA1c, and distinct microbiome profiles, characterized by lower abundance of Subdoligranulum and higher abundance of Catenibacterium. Although butyrate supplementation did not significantly improve liver steatosis as measured by CAP, the differing effects on metabolic and inflammatory markers suggest that there may be potential benefits for specific subgroups of patients with MASLD
In vitro release test development for arbutin-loaded chitosan/hyaluronic acid polyelectrolyte complex films for cosmetic use
No full textThis study investigated the release rate of arbutin, a natural skin-brightening agent, from chitosan/hyaluronic acid polyelectrolyte complex films for cosmetic use. ..
Restricted antibiotic use in the clinical center of montenegro
No full textBACKGROUND: In this century, antimicrobial resistance (AMR) presents a major public health problem, because it is a leading cause of death worldwide. Antimicrobial resistance is caused by the overprescription of antibiotics as well as self-medication. In 2010, antibiotics were the most commonly prescribed medications according to the Montenegrin Institute of Public Health. To reduce side effects, improve treatment efficacy, and prevent AMR, it is necessary to have greater control and help formulating national and international level policies over antibiotic prescription and their use.
AIMS: This research focuses on the analysis of requests for the dispensing of reserve antibiotics and the justification of their prescription and use.
MATERIALS AND METHODS: In the Clinical Center of Montenegro, 174 requests for restricted antibiotics were retrospectively analyzed.
RESULTS: Data analysis of 174 requests for restricted antibiotics determined that an antibiogram has been performed in only 21.84% of cases, which means that there were 78.16% of cases of empirical antibiotic use. In 72.25% of cases, restricted antibiotics were included in therapy without prior use of unrestricted antimicrobial therapy.
CONCLUSIONS: Based on data analytics, it can be concluded that using restricted antibiotics in therapy is not completely in line with rational antibiotics implementation. Restricted antibiotics are used without culture sensitivity tests in more than 2/3rd of cases. Similarly, restricted antibiotics were used as first-line therapy