Background: Hofbauer cells (HBCs) are the only immunocompetent cells within the stroma of chorionic villi and play a key role in immune regulation and placental development throughout gestation. Their phenotype, abundance, and proliferative activity change in accordance with the needs of the fetoplacental unit. Methods: Thirty healthy human placentas across all three trimesters were analyzed. Samples were processed using standard histological protocols and immunohistochemically stained with CD45, CD68, CD86, and Ki-67 markers. Morphometric analysis was performed to determine the following parameters: percentage of HBCs, numerical areal density, and proliferative index. Results: HBCs were immunoreactive for CD45 and CD68, while CD86 immunoreactivity was not observed in any trimester. The proportion of HBCs was highest in the second trimester and lowest in the third. Numerical areal density was highest in the second trimester (22.21 ± 3.86) and lowest in the first (8.27 ± 4.18). The proliferative index was highest in the first trimester (82.45 ± 10.19%), decreased significantly in the second, and was completely absent in the third trimester. Conclusions: During physiological placental development, Hofbauer cells maintain a predominantly non-M1 macrophage phenotype, accompanied by a gradual reduction in proliferative activity.

BackgroundRecent research highlights the pivotal role of gut microbiota and bile acids as modulators of metabolic homeostasis in type 2 diabetes (T2D). The concomitant use of probiotics and ursodeoxycholic acid (UDCA) may potentiate glycemic and lipid control via complementary mechanisms.ObjectiveTo evaluate the metabolic effects of probiotic supplementation and its combination with UDCA in metformin-treated T2D patients.MethodsIn this monocentric, prospective, randomized, double-blind, controlled trial, 90 patients with T2D on metformin therapy were randomized into three groups: metformin-only (MG), metformin plus probiotic (MPG), and metformin plus probiotic plus UDCA (MPUG). The intervention lasted 4 weeks. Primary outcomes included changes in fasting glucose, postprandial glucose and HbA1c. Secondary outcomes included lipid profile, C-reactive protein (CRP), and fecal levels of probiotics and UDCA. Two visits were conducted during the study - at the beginning and at the end. Visits involved patient interviews, clinical data collection, anthropometric measurements, blood biochemical analyses, and stool sample analysis for the presence of probiotic culture and UDCA concentrations.ResultsAfter 4 weeks, the MPUG group showed a significant reduction in fasting glucose (-1.7 mmol/L; 95% CI: -2.2 to -1.2), postprandial glucose (-1.3 mmol/L; 95% CI: -1.8 to -0.7), and HbA1c (-0.49%; 95% CI: -0.66 to -0.31) compared to the MG group. Total cholesterol and LDL cholesterol were also significantly reduced, while HDL increased. The concentration of Lactobacillus rhamnosus GG was highest in the MPUG group. No serious adverse events were reported.ConclusionCo-administration of probiotics and UDCA for four weeks in metformin-treated T2D patients significantly improves short-term glycemic control and lipid profiles. These promising results warrant validation in larger, longer-term clinical trials.

Background/Objectives: The COVID-19 pandemic accelerated the inappropriate use of antibiotics, amplifying the global threat of antimicrobial resistance (AMR), particularly in resource-limited healthcare settings. This study investigated AMR patterns in a tertiary care hospital, focusing on the impact of the COVID-19 pandemic on invasive bacterial pathogens. Methods: This retrospective observational study was conducted at the University Clinical Centre of the Republic of Srpska, analyzing AMR data from invasive bacterial isolates collected between 2015 and 2024, and assessing correlations between antibiotic utilization and resistance patterns during the study periods. Results: Among 4718 invasive bacterial isolates, Acinetobacter spp. (26.7%) and K. pneumoniae (20.8%) were the most prevalent. A significant increase in invasive isolates was observed during the COVID-19 period, particularly for K. pneumoniae (p = 0.003), P. aeruginosa (p = 0.017), Acinetobacter spp. (p = 0.013), and E. faecium (p = 0.028). The highest multidrug-resistant (MDR) rates were observed in Acinetobacter spp. (97% during COVID-19) and K. pneumoniae (>80% post-COVID-19). Resistance increased significantly in K. pneumoniae to cephalosporins, fluoroquinolones, and carbapenems, and in P. aeruginosa and Acinetobacter spp. to carbapenems, while P. aeruginosa resistance to aminoglycosides declined. Strong correlations were found between carbapenems use and Acinetobacter spp. resistance (r = 0.861, p = 0.001), and vancomycin use and E. faecalis resistance (r = 0.798, p = 0.006). Moderate correlations were also observed between carbapenems use and resistance of K. pneumoniae and P. aeruginosa. Conclusions: These findings highlight the profound impact of the COVID-19 pandemic on AMR dynamics, particularly among Gram-negative pathogens, and underscore the urgent need for strengthened antimicrobial stewardship and targeted surveillance to curb the spread of MDR pathogens, especially in resource-limited hospitals.

Background/Objectives: This study investigates the antimicrobial properties of pomegranate peel extract (PoPEx) and its major polyphenolic constituents against Gram-positive and Gram-negative bacteria, employing six clinical isolates of Staphylococcus aureus and five isolates of Escherichia coli. The study further aims to elucidate mechanisms of action through molecular docking and transport studies. Methods: Chemical composition was analyzed using liquid chromatography–mass spectrometry (LC–MS). Antimicrobial activity was determined by the broth microdilution method. Molecular docking was performed with the AutoDock Vina algorithm, and transport studies through porin channels were carried out using Caver software. Results: PoPEx showed stronger activity against Gram-positive (MICs 15.62–500.00 μg/mL) than Gram-negative bacteria (MICs 125.00–500.00 μg/mL). Punicalagin was most active against S. aureus, while gallic acid was most effective against E. coli. Docking revealed high affinities of punicalagin and punicalin, whereas transport studies highlighted the advantage of smaller phenolics like gallic acid in crossing porins. Conclusions: Larger tannins exhibited strong target binding but limited porin permeability, reducing efficacy in Gram-negative bacteria. These findings provide insights into structure–activity relationships of pomegranate polyphenols and support their potential as natural antimicrobial agents.

Acute mesenteric ischemia (AMI) is a life-threatening condition characterised by oxidative stress, inflammation, apoptosis, and necrosis of intestinal epithelial cells. Different drugs with vasoactive, antioxidant, and anti-inflammatory properties have been used to treat AMI. Levosimendan is a drug with proven anti-ischemic effects used in the management of acute congestive heart failure. This study evaluated the protective effects of levosimendan pretreatment on intestinal, as well as lung, heart, and kidney tissue in a rat model of mesenteric artery ischemia/reperfusion (I/R) injury. Male Wistar rats (N = 24) were divided into four groups: control, I/R, levosimendan (LS) 1 mg/kg i.p, and LS + I/R (1 mg/kg i.p. 30 min before injury). I/R by itself caused elevation of oxidative markers (thyobarbituric acid reactive species (TBARS), hydrogen peroxide (H2O2), super oxide anjon radical (O2−), and nitrogen dioxide (NO2−)), induced inflammation (macrophage infiltration and Interleukin-6 (IL-6) production), and apoptosis (nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), cleaved caspase-3 (CC3), and terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL)). Levosimendan pretreatment significantly reduced oxidative stress markers and enhanced antioxidant defences (catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)). Histological analysis revealed reduced mucosal damage and preserved goblet cells in intestinal tissue. Similar protective effects of levosimendan were observed in other organs such as lung, heart, and kidney. Immunohistochemistry showed reduced epithelial apoptosis and upregulation of antioxidant and anti-inflammatory proteins. These findings highlight levosimendan’s ability to protect mesenteric I/R tissue injury and multi-organ damage by suppressing oxidative stress, inflammation, and apoptosis, emphasising its therapeutic potential in clinical settings.

As the leading cause of global mortality, cardiovascular diseases demand improved and innovative strategies for early detection and risk assessment to enhance prevention and timely treatment. This comprehensive review examines the potential of combining high-sensitivity cardiac troponins (hs-cTns) and homocysteine (Hcy) as complementary biomarkers for enhanced cardiovascular risk prediction. hs-cTn assays have revolutionized cardiovascular diagnostics by enabling the detection of minimal myocardial injury, improving early diagnosis of acute coronary syndrome, and providing robust prognostic information in both symptomatic and asymptomatic populations. Hcy, while established as a marker of vascular dysfunction, presents an interpretative challenge due to multiple confounding factors and inconsistent therapeutic responses. Emerging evidence demonstrates significant correlations between elevated Hcy and troponins across various clinical conditions, suggesting that their combined assessment—reflecting both myocardial injury and vascular dysfunction—may improve cardiovascular risk stratification. While initial findings are promising, additional studies are required to validate the clinical value of the combined marker approach. Future development of personalized interpretation algorithms, and multi-marker panels incorporating these biomarkers, may significantly advance cardiovascular medicine and enable more effective population-specific risk management strategies.

Autonomic imbalance is one of the major pathological disturbances in chronic heart failure (CHF). Additionally, enhanced oxidative stress and inflammation are considered to be the main contributors to the disease progression. A growing body of evidence suggests cholinergic stimulation as a potential therapeutic approach in CHF, since it corrects the autonomic imbalance and alters the inflammatory response via the cholinergic anti-inflammatory pathway. Although previous research has provided some insights into the potential mechanisms behind these effects, there is a gap in knowledge regarding different cholinergic stimulation methods and their specific mechanisms of action. In the present study, an isoprenaline model (5 mg/kg/day s.c. for 7 days, followed by 4 weeks of CHF development) was used. Afterwards, rats received pyridostigmine (22 mg/kg/day in tap water for 14 days) or no treatment. Pyridostigmine treatment prevented the progression of CHF, decreasing chamber wall thinning (↑ PWDd, ↑ PWDs) and left ventricle dilatation (↓ LVIDd, ↓ LVIDs), thus improving cardiac contractile function (↑ EF). Additionally, pyridostigmine improved antioxidative status (↓ TBARS, ↓ NO2−; ↑ CAT, ↑ GSH) and significantly reduced cardiac fibrosis development, confirmed by pathohistological findings and biochemical marker reduction (↓ MMP2, ↓ MMP9). However, further investigations are needed to fully understand the exact cellular mechanisms involved in the CHF attenuation via pyridostigmine.

Dissolution of water-insoluble drugs is an important challenge in drug delivery. Adsorbing water-insoluble drugs onto nanoporous carriers such as zeolites can improve drug dissolution.  The drug molecules adsorbed in a thin layer onto nanoporous carriers are fully exposed to the solvent, enhancing the dissolution process. This presentation will give new insights into the adsorption of water-insoluble letrozole drug onto the nanoporous clinoptilolite zeolite from a nanoscale-science point of view based on experimental and theoretical considerations. Adsorption of the letrozole drug on clinoptilolite zeolite will be conducted from the colloidal dispersion state. The amount of letrozole adsorbed in a monolayer will be evidenced by thermogravimetric measurements, while optical spectroscopy techniques will reveal the interactions of the letrozole drug on the nanoporous zeolite framework. Positive adsorption energy at the letrozole-clinoptilolite interface calculated using density functional theory models suggests a small affinity for letrozole adsorption, suggesting the letrozole release is more favorable than the adsorption process. Thus, this presentation will show new possibilities in adsorption and dissolution of water-insoluble drugs.

Background/Objectives: Improper use of systemic antibiotics remains a significant concern in hospital settings, contributing to increased antimicrobial resistance and suboptimal clinical outcomes. The COVID-19 pandemic exacerbated this issue. This study aimed to evaluate long-term trends in antibiotic utilization in low-resource settings at a tertiary care teaching hospital, focusing specifically on the changes before, during, and after the COVID-19 pandemic. Methods: This retrospective observational study analyzed antibiotic utilization data from the University Clinical Centre of the Republic of Srpska over ten years (2015–2024). Antibiotic consumption was expressed in defined daily doses (DDD) per 100 bed-days, and compared across three periods: pre-COVID-19 (2015–2019), COVID-19 (2020–2022), and post-COVID-19 (2023–2024). Additionally, antibiotic use was categorized according to the WHO AWaRe classification. Results: Antibiotic utilization peaked during the COVID-19 period, with the highest rate observed in 2021 (91.5 DDD/100 bed-days), despite a decrease in hospital admissions. The most frequently used antibiotics were cephalosporins, penicillins, and metronidazole. A significant increase in the use of azithromycin, meropenem, piperacillin/tazobactam, vancomycin, and colistin was noted during the COVID-19 and post-COVID-19 periods (p < 0.05), along with a notable decline in penicillin use. Watch and Reserve antibiotic use rose significantly (p < 0.05), while Access group use fell from 67% to 49.2%. Conclusions: These findings underscore the lasting impact of the COVID-19 pandemic on antibiotic prescribing patterns and emphasize the urgent need for strengthened antimicrobial stewardship efforts to ensure rational antibiotic use and combat antimicrobial resistance.