Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, despite significant advances in diagnostics and pharmacotherapy. This persistent burden has shifted attention toward adjunct therapeutic strategies targeting key mechanisms of myocardial and vascular injury, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, apoptosis, inflammation, endothelial dysfunction, and metabolic dysregulation. A particular interest of contemporary research is focused on bile acid (BA) signaling through nuclear and membrane receptors, primarily the Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), as central regulators of metabolic, inflammatory, and vascular responses. Ursodeoxycholic acid (UDCA), a hydrophilic BA widely used to treat hepatobiliary disorders, has emerged as a potential modulator of cardiometabolic processes. UDCA exerts direct effects through low-affinity but functionally relevant activation of the TGR5 receptor, as well as indirect effects through alterations in BA pool composition, thereby influencing FXR/TGR5 signaling pathways. Experimental studies suggest that UDCA reduces oxidative stress, stabilizes mitochondrial function, alleviates ER stress, suppresses apoptosis and inflammation, and improves endothelial function and nitric oxide (NO) bioavailability. Despite promising mechanistic evidence, currently available clinical data remain limited and are largely based on small studies and surrogate biomarkers, without confirmation of benefits in terms of major cardiovascular outcomes. This review summarizes current knowledge regarding the role of UDCA in the modulation of BA receptor signaling and its potential relevance for cardiovascular protection.

The mechanisms linking chronic hyperglycemia to intestinal inflammation and epithelial dysfunction remain incompletely understood, highlighting an important gap in our understanding of diabetes-associated gastrointestinal pathology. In this study, we investigated the effects of sustained hyperglycemia on intestinal inflammation, endoplasmic reticulum (ER) stress, and autophagy in a translational porcine model of diabetes. Diabetes was induced in Yucatan mini pigs using a high-fat, high-carbohydrate/fructose diet (HFHFD) followed by streptozotocin administration. Intestinal tissues from the terminal ileum and sigmoid colon were analyzed using histological evaluation, quantitative real-time PCR, and immunohistochemistry. Histological analysis revealed structural alterations in diabetic animals, including villous degeneration, crypt depletion, goblet-cell loss, and increased inflammatory-cell infiltration. Gene expression analysis revealed significant upregulation of inflammatory mediators (NF-κB, TNF-α, IL-6, IL-1β), inflammasome components (NLRP3), and macrophage markers (CD68, CD86, CD163). In parallel, ER stress-related genes (ORMDL3, ATF6) and autophagy-associated genes (NOD2, ULK1, ATG4a) were significantly elevated in diabetic pigs. At the protein level, increased expression of ER stress markers was confirmed in both intestinal regions, while autophagy-related proteins showed less consistent changes and did not fully reflect the observed transcriptional patterns, suggesting a potential disconnect between transcriptional activation and downstream autophagy-related protein expression under diabetic conditions. Chronic hyperglycemia is associated with intestinal inflammation and disruption of cellular stress pathways, including ER stress and autophagy, in a porcine model. These findings provide mechanistic insight into how chronic hyperglycemia contributes to intestinal dysfunction through coordinated alterations in inflammatory signaling, ER stress, and autophagy pathways, identifying these processes as potential targets for therapeutic intervention in diabetes-associated gastrointestinal disease.

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.

Pomegranate peel, an abundant agro-industrial by-product, represents a sustainable source of bioactive polyphenols, particularly punicalagin, which has been associated with antioxidant and photoprotective potential. This study aimed to develop microemulsions (MEs) containing pomegranate peel extract for dermal delivery of punicalagin using biocompatible surfactant systems. Three MEs differing in surfactant–cosurfactant composition (ME-A, ME-P, and ME-E) were prepared. Each formulation solubilized 1% (w/w) of pomegranate peel extract and was evaluated regarding in vitro release behavior, skin permeation/retention, antioxidant activity, and in vitro sun protection factor (SPF). All investigated MEs provided sustained release of punicalagin (≈10–17% of the applied dose in 8 h). ME-A, based on an alkyl polyglucoside surfactant, showed a significantly higher cumulative release of punicalagin (60.4 µg/cm2) compared with ME-E and ME-P. In skin penetration/permeation studies, ME-A also exhibited the highest numerical total delivery of punicalagin (≈48.2 µg/cm2 after 24 h), although differences among formulations were not statistically significant. All formulations demonstrated high antioxidant activity in the DPPH assay and measurable in vitro photoprotective potential, with SPF values ranging from approximately 11 to 14. Overall, pomegranate peel extract-loaded MEs showed potential as dermal delivery systems capable of improving solubilization and modulating skin delivery of punicalagin. The combination of agro-waste-derived bioactives with biocompatible surfactants highlights the potential of these systems as sustainable approaches for skincare formulations.

The mechanisms linking chronic hyperglycemia to intestinal inflammation and epithelial dysfunction remain incompletely understood, highlighting an important gap in our understanding of diabetes-associated gastrointestinal pathology. In this study, we investigated the effects of sustained hyperglycemia on intestinal inflammation, endoplasmic reticulum (ER) stress, and autophagy in a translational porcine model of diabetes. Diabetes was induced in Yucatan mini pigs using a high-fat, high-carbohydrate/fructose diet (HFHFD) followed by streptozotocin administration. Intestinal tissues from the terminal ileum and sigmoid colon were analyzed using histological evaluation, quantitative real-time PCR, and immunohistochemistry. Histological analysis revealed structural alterations in diabetic animals, including villous degeneration, crypt depletion, goblet-cell loss, and increased inflammatory-cell infiltration. Gene expression analysis revealed significant upregulation of inflammatory mediators (NF-κB, TNF-α, IL-6, IL-1β), inflammasome components (NLRP3), and macrophage markers (CD68, CD86, CD163). In parallel, ER stress-related genes (ORMDL3, ATF6) and autophagy-associated genes (NOD2, ULK1, ATG4a) were significantly elevated in diabetic pigs. At the protein level, increased expression of ER stress markers was confirmed in both intestinal regions, while autophagy-related proteins showed less consistent changes and did not fully reflect the observed transcriptional patterns, suggesting a potential disconnect between transcriptional activation and functional autophagic response under diabetic conditions. Chronic hyperglycemia is associated with intestinal inflammation and disruption of cellular stress pathways, including ER stress and autophagy, in a porcine model. These findings provide mechanistic insight into how chronic hyperglycemia contributes to intestinal dysfunction through coordinated alterations in inflammatory signaling, ER stress, and autophagy pathways, identifying these processes as potential targets for therapeutic intervention in diabetes-associated gastrointestinal disease.

Clinical pharmacists enhance safe and high-quality patient care through effective interprofessional collaboration. This study aimed to evaluate pharmacotherapy counseling services provided by clinical pharmacists, assess physician acceptance of recommendations, and determine their impact on patients and the healthcare system. A retrospective observational study was conducted at the University Hospital’s Pharmacotherapy Counseling Unit over a 15-month period. Pharmacotherapy plans of 61 ambulatory patients were analyzed, and therapy modifications were classified according to PCNE V9.1. After clinical pharmacist intervention, the median (IQR) number of prescribed medications significantly decreased from 7.5 (8) to 3 (9) ( p < 0.05) and drug-related problems (DRPs) from 2 (4) to 0 (4) ( p < 0.05). Among patients aged ≥65 years ( n = 22), potentially inappropriate medications were significantly reduced ( p < 0.05). Most DRPs were related to inappropriate drug selection. This study demonstrates the positive impact of clinical pharmacists in improving pharmacotherapy quality in ambulatory care in Bosnia and Herzegovina.

Background Recent 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. Objective To evaluate the metabolic effects of probiotic supplementation and its combination with UDCA in metformin-treated T2D patients. Methods In 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. Results After 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. Conclusion Co-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.

Oxidative stress is a critical pathophysiological factor in sepsis. Ursodeoxycholic acid (UDCA), a bile acid with anti-inflammatory, antioxidant, and anti-apoptotic properties, may protect against lipopolysaccharide (LPS)-induced myocardial injury. In an experimental study, 32 male Wistar rats were randomly assigned to four groups: control, LPS, UDCA, and UDCA + LPS. UDCA was administered orally for 10 days prior to LPS-induced endotoxemia. Serum levels of high-sensitive troponin I (hsTnI), homocysteine, and oxidative stress markers were measured, and immunohistochemistry and immunofluorescence were used to assess inflammation (nuclear factor kappa B, NF-κB), apoptosis (caspase 3), and signaling pathways related to protein kinase B (Akt)/NF-κB and silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1). UDCA pretreatment significantly reduced myocardial pathological changes, serum hsTnI, homocysteine, and total oxidative stress compared with LPS alone. It enhanced catalase (CAT) activity and glutathione (GSH) levels while lowering thiobarbituric acid reactive substances (TBARS) and nitrite concentrations in cardiac tissue. UDCA modulated cellular signaling by decreasing Akt phosphorylation and activating the SIRT1/Nrf2/HO-1 pathway. These results indicate that UDCA protects the heart from LPS-induced damage by reducing oxidative stress, inflammation, and apoptosis. UDCA modulates cellular signaling by decreasing pro-inflammatory pathways and activating anti-inflammatory pathways associated with SIRT1/Nrf2/HO-1 signaling, emphasizing its key role in myocardial protection during sepsis.