Background: Lipid vesicles, especially those utilizing biocompatible materials like chitosan (CHIT), hold significant promise for enhancing the stability and release characteristics of drugs such as indomethacin (IND), effectively overcoming the drawbacks associated with conventional drug formulations. Objectives: This study seeks to develop and characterize novel lipid vesicles composed of phosphatidylcholine and CHIT that encapsulate indomethacin (IND-ves), as well as to evaluate their in vitro hemocompatibility. Methods: The systems encapsulating IND were prepared using a molecular droplet self-assembly technique, involving the dissolution of lipids, cholesterol, and indomethacin in ethanol, followed by sonication and the gradual incorporation of a CHIT solution to form stable vesicular structures. The vesicles were characterized in terms of size, morphology, Zeta potential, and encapsulation efficiency and the profile release of drug was assessd. In vitro hemocompatibility was evaluated by measuring erythrocyte lysis and quantifying hemolysis rates. Results: The IND-ves exhibited an entrapment efficiency of 85%, with vesicles averaging 317.6 nm in size, and a Zeta potential of 24 mV, indicating good stability in suspension. In vitro release kinetics demonstrated an extended release profile of IND from the vesicles over 8 h, contrasting with the immediate release observed from plain drug solutions. The hemocompatibility assessment revealed that IND-ves exhibited minimal hemolysis, comparable to control groups, indicating good compatibility with erythrocytes. Conclusions: IND-ves provide a promising approach for modified indomethacin delivery, enhancing stability and hemocompatibility. These findings suggest their potential for effective NSAID delivery, with further in vivo studies required to explore clinical applications.

Background: Gallbladder carcinoma (GBC) represents one of the most aggressive malignancies of the hepatobiliary system, evolving along a continuum from chronic inflammation to preneoplastic lesions and invasive cancer. This progression is frequently associated with gallstones and chronic cholecystitis and shares common pathogenic mechanisms with systemic inflammatory and metabolic disorders. Despite its relatively low incidence, GBC is characterized by poor prognosis, largely due to late-stage diagnosis and limited understanding of its molecular underpinnings. Methods: We conducted an observational study including 60 adult patients with radiologically suspected gallbladder cancer (GBC). Patients with disseminated disease, ongoing oncologic treatment, or synchronous malignancies were excluded. Fasting venous blood samples were collected to evaluate tumor markers and biochemical parameters, including carcinoembryonic antigen (CEA) and carbohydrate antigen CA 19-9. Surgical specimens were analyzed histopathologically and staged according to the European Society for Medical Oncology TNM classification system. Statistical analysis was performed using SPSS software (version 26.0), with appropriate parametric or non-parametric tests applied based on data distribution, and a p-value < 0.05 considered statistically significant. Results: Based on histological findings, patients were stratified into benign gallbladder disease (GBD) and GBC groups. CA 19-9 demonstrated higher mean serum levels with lower variability compared to CEA, suggesting superior sensitivity and diagnostic stability for gallbladder adenocarcinoma. In contrast, CEA levels exhibited greater fluctuation, limiting its reliability as a standalone biomarker. Importantly, the combined use of CA 19-9 and CEA improved diagnostic accuracy, supporting a multimarker approach for better clinical stratification. Our findings highlight the diagnostic value of CA 19-9 as a robust biomarker in GBC and support the integration of combined biomarker panels. Beyond tumor markers, the study identified a strong interplay between systemic inflammation and metabolic comorbidities, with obesity and hypertension significantly associated with chronic gallbladder pathology, and diabetes mellitus contributing to increased risk of acute inflammatory episodes. Elevated inflammatory markers, leukocytosis, and cholestatic enzyme alterations further supported the presence of a systemic inflammatory milieu. Multivariate analysis revealed that C-reactive protein (CRP), as a marker of systemic inflammation, was significantly influenced by a combination of clinical and biochemical variables, including age, hemoglobin, hypertension, amylase, CA 19-9, and CEA, explaining over 50% of its variability and up to 85% in advanced fibrotic changes. Additionally, platelet counts were significantly reduced in adenocarcinoma and correlated specifically with CA 19-9 levels, suggesting a potential link between tumor burden, inflammation, and platelet dynamics. Conclusions: Therefore, the observed associations between chronic inflammation, metabolic dysregulation, and tumor marker expression suggest a potential link between gallbladder carcinogenesis and systemic cardiometabolic pathways, opening new perspectives for early detection and targeted therapeutic strategies.

Compelling evidence indicates that nitric oxide (NO) exerts a significant influence on the central nervous system, participates in the modulation of neurotransmitter release, contributes to the regulation of cognitive functions, and plays a crucial role in modulating various aspects of neural activity. We aimed to explore the influence of two NO donors, molsidomine (MSD) and V-pyrro/NO, on the innate spontaneous psychomotor abilities and short-term memory in rats. Using an actimeter test, the locomotor activity, stress-sensitive behavior, and anxiety level were investigated. The influence on the animal`s cognitive functions was evaluated usingthe Y-maze test to assess the spontaneous alternation percentage, number of arms visited, number of alternations, and the preference index. Four distinct groups of five white male Wistar rats were exposed to the intraperitoneal treatments as follows: Control batch—0.3 mL/100 g of body weight saline solution, Mg batch—200 mg/kbwof magnesium chloride, MSD batch—1 mg/kbw of molsidomine, and V-pyrro/NO batch—5 mg/kbwof V-pyrro/NO. The intraperitoneal administration of MSD resulted in a significant reduction in spontaneous behavior and exploratory skills but was less pronounced than the positive control drug, magnesium chloride. Conversely, treatment with V-pyrro/NO led to only a slight decrease in horizontal movements during the actimeter test. MSD administration, but not V-pyrro/NO, notably increased the rate of spontaneous alternation in the Y-maze test. Additionally, the use of MSD resulted in an increase in the blood level of brain-derived neurotrophic factor and the intensification of the antioxidant enzymes, superoxide dismutase, and glutathione peroxidase activity. In our experimental setup, we demonstrated that MSD exposure led to a decrease in spontaneous behavior, showed anxiolytic effects and antioxidant activity, and improved spatial memory acquisition in rats.

Myocardial ischemia–reperfusion injury (MIRI) represents a major contributor to morbidity and mortality in patients undergoing reperfusion therapy after acute myocardial infarction. Although timely restoration of coronary blood flow is essential for myocardial salvage, reperfusion paradoxically initiates a complex cascade of molecular and cellular events that may aggravate myocardial injury. Oxidative stress is considered one of the central mechanisms underlying MIRI, primarily through excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to mitochondrial dysfunction, calcium overload, endothelial injury, inflammatory activation, and cardiomyocyte death. This review summarizes the current understanding of the pathophysiological mechanisms involved in oxidative stress-mediated reperfusion injury, with emphasis on mitochondrial permeability transition pore opening, inflammasome activation, cytokine release, neutrophil extracellular trap formation, macrophage polarization, and interconnected cell death pathways including PANoptosis. Emerging evidence regarding immunometabolic regulation and epigenetic modulation in MIRI is also discussed. In addition, current pharmacological and non-pharmacological cardioprotective strategies targeting oxidative stress, mitochondrial dysfunction, and inflammatory signaling are reviewed, highlighting both promising experimental findings and the persistent challenges in clinical translation. A deeper understanding of the molecular interplay between oxidative stress and inflammatory pathways may facilitate the development of integrated therapeutic approaches aimed at improving myocardial recovery and long-term cardiovascular outcomes following reperfusion therapy.

Both diabetes mellitus (DM) and stroke are major global health challenges with high morbidity and mortality. DM is a major risk factor for stroke, contributing to both increased incidence and worse clinical outcomes. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), as well as dual agonists like tirzepatide, have demonstrated significant cardiovascular benefits, raising interest in their potential cerebrovascular effects. This narrative review examines the pathophysiological links between DM and stroke and summarizes recent clinical evidence on the efficacy of GLP-1 RAs and dual GLP-1/GIP receptor agonists (GLP-1/GIP RAs) in stroke prevention and management. Current evidence from large cardiovascular outcome trials supports the role of GLP-1 RAs in reducing major adverse cardiovascular events, including stroke, primarily in the context of primary and secondary prevention. Findings suggest that semaglutide and liraglutide may reduce non-fatal stroke incidence, decrease hospitalizations, and improve neurological outcomes in patients with prior stroke. Comparative analyses of major trials suggest that, although stroke reduction may be a class effect of GLP-1 RAs, meaningful differences exist between individual agents, likely due to variations in pharmacokinetics, receptor affinity, and study populations. Additionally, much of the evidence in acute stroke derives from early-phase or ongoing trials, warranting cautious interpretation. Novel therapies, including orforglipron and retatrutide, as well as combinations like Maridebart cafraglutide and CagriSema, may expand future therapeutic options for individuals at high cerebrovascular risk. GLP-1-based therapies show promising neurovascular effects, but large-scale, long-term studies are needed to define their role in post-stroke management and cerebrovascular risk reduction. Overall, GLP-1 RAs should currently be regarded primarily as agents for long-term vascular risk reduction rather than established therapies for acute stroke. While potential neuroprotective effects are emerging, these require confirmation in adequately powered randomized trials. Future studies should aim to identify the patient subgroups most likely to benefit and to determine whether specific agents confer advantages in acute cerebrovascular contexts. A better understanding of the mechanisms underlying potential neuroprotection will be essential to determine whether these therapies can be effectively integrated into stroke management strategies.

Subacute inflammation represents a transitional stage between acute and chronic inflammatory processes, characterized by fibroblast proliferation and granulomatous tissue development. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac and ketoprofen are widely used to control these processes. Some antibiotics, including cefuroxime and levofloxacin, have also been reported to exhibit secondary anti-inflammatory or immunomodulatory effects. This study investigated the anti-inflammatory efficacy of these agents, administered individually or in combination, using the cotton pellet-induced granuloma model in rats. Materials and methods: Adult Wistar rats were divided into experimental groups receiving intraperitoneal doses of NSAIDs and antibiotics alone or in combination. Granulomatous tissue formation was assessed after subcutaneous implantation of sterile cotton pellets, and the degree of inflammation was evaluated by measuring granuloma development and comparing it across treatment groups. Results: Both NSAIDs produced clear reductions in granuloma formation compared with the untreated control group, confirming their significant anti-inflammatory potential. Levofloxacin showed a moderate inhibitory effect, consistent with its reported cytokine-suppressive and immunomodulatory properties, whereas cefuroxime exhibited minimal influence on inflammatory tissue growth. When combined, NSAIDs and antibiotics produced a greater reduction in granuloma formation than either agent alone, with diclofenac-based combinations showing the strongest overall activity. Conclusions: The findings indicate that diclofenac and ketoprofen effectively suppress subacute inflammatory responses, and that levofloxacin may contribute complementary immunomodulatory effects. Combined administration enhances the anti-inflammatory outcome, suggesting a potential pharmacological synergy between NSAIDs and certain antibiotics in conditions involving both infection and inflammation.