Monoamine oxidases (MAO) with 2 isoforms, A and B, located at the outer mitochondrial membrane are flavoenzyme membranes with a major role in the metabolism of monoaminergic neurotransmitters and biogenic amines in the central nervous system and peripheral tissues, respectively. In the process of oxidative deamination, aldehydes, hydrogen peroxide, and ammonia are constantly generated as potential deleterious by-products. While being systematically studied for decades as sources of reactive oxygen species in brain diseases, compelling evidence nowadays supports the role of MAO-related oxidative stress in cardiovascular and metabolic pathologies. Indeed, oxidative stress and chronic inflammation are the most common pathomechanisms of the main noncommunicable diseases of our century. MAO inhibition with the new generation of reversible and selective drugs has recently emerged as a pharmacological strategy aimed at mitigating both processes. The aim of this minireview is to summarize available information regarding the contribution of MAO to the vascular oxidative stress and endothelial dysfunction in hypertension, metabolic disorders, and chronic kidney disease, all conditions associated with increased inflammatory burden.

Apigenin (4′,5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release. Caspase 3 activity was inversely proportional to the Api tested doses, namely 30 μM and 60 μM. Phenomena of early apoptosis, late apoptosis and necrosis following incubation with Api were detected by Annexin V-PI double staining. The flavone interfered with the mitochondrial respiration by modulating both glycolytic and mitochondrial pathways for ATP production. The metabolic activity of human dendritic cells (DCs) under LPS-activation was clearly attenuated by stimulation with high concentrations of Api. Il-6 and IL-10 secretion was almost completely blocked while TNF alpha secretion was reduced by about 60%. Api elicited antiangiogenic properties in a dose-dependent manner. Both concentrations of Api influenced tumour cell growth and migration, inducing a limited tumour area inside the application ring, associated with a low number of capillaries.

Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 μM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.

Phytocompounds and medicinal herbs were used in traditional ancient medicine and are nowadays increasingly screened in both experimental and clinical settings due to their beneficial effects in several major pathologies. Similar to the drug industry, phytotherapy is interested in using nanobased delivery systems to view the identification and characterization of the cellular and molecular therapeutic targets of plant components. Eugenol, the major phenolic constituent of clove essential oil, is a particularly versatile phytochemical with a vast range of therapeutic properties, among which the anti‐inflammatory, antioxidant, and anticarcinogenic effects have been systematically addressed. In the past decade, with the emerging understanding of the role of mitochondria as critical organelles in the pathophysiology of noncommunicable diseases, research regarding the role of phytochemicals as modulators of bioenergetics and metabolism is on a rise. Here, we present a brief overview of the major pharmacological properties of eugenol, with special emphasis on its applications in dental medicine, and provide preliminary data regarding its effects, alone, and included in polyurethane nanostructures, on mitochondrial bioenergetics, and glycolysis in human HaCaT keratinocytes.

Background/Objectives: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are prevalent neurological complications following cardiac surgery, significantly affecting patient recovery and long-term outcomes, including increased risk of persistent cognitive impairment, functional decline, and mortality. Understanding the underlying mechanisms and risk factors for POD/POCD is crucial for improving perioperative management. This study aimed to investigate the relationship between postoperative systemic inflammation, assessed through inflammatory markers, and the occurrence of POD and POCD in patients undergoing cardiac surgery. Methods: We prospectively enrolled 88 patients aged 18–79 years undergoing open-heart surgery. Patients with preoperative cognitive impairment or high surgical risk (based on EuroSCORE and SOFA scores) were excluded to focus on the impact of inflammation in a relatively unselected cohort. Postoperative inflammatory responses (CRP, NLR, IL-6, IL-17A, SII, and SIRI) were measured, and patients were assessed for POD (CAM-ICU) and POCD (neuropsychological testing) during hospitalization and at 3 months follow-up. Statistical comparisons were performed between patients who developed POD/POCD and those who did not. Results: Postoperative inflammation was confirmed across the cohort, with significant increases in CRP, NLR, IL-6, SII, and SIRI. While correlational analyses between changes in individual inflammatory markers and POD/POCD were not statistically significant in the entire cohort, patients who developed POD/POCD exhibited significantly higher levels of IL-6 and NLR at 48 h postoperatively (p < 0.05). Established clinical risk factors significantly associated with POD/POCD included older age, prolonged cardiopulmonary bypass (CPB) duration, extended mechanical ventilation, vasopressor support duration, blood transfusion, renal dysfunction, and elevated postoperative creatine kinase (CK) and lactate dehydrogenase (LDH) (p < 0.05). Ejection fraction (EF) < 45% and atrial fibrillation (AF) were also more prevalent in the POD/POCD group. Conclusions: Our findings emphasize the significant role of the postoperative inflammatory response, particularly IL-6 and NLR, in conjunction with established clinical risk factors, in the development of POD and POCD after cardiac surgery. Postoperative IL-6 and NLR levels, readily measurable and cost-effective markers, may contribute to identifying patients at higher risk. Comprehensive perioperative management strategies targeting inflammation, modifiable clinical risk factors, and organ function are crucial for mitigating POD and POCD and improving cognitive outcomes in this vulnerable population.

The current minireview aims to assess the implications of epicardial fat secretory function in the development of coronary artery disease. The epicardial adipose tissue (EAT) is a visceral fat depot that has been described as a cardiovascular risk factor. In addition to its mechanical protection role and physiological secretory function, it seems that various secretion products of the epicardial fat are responsible for metabolic disturbances at the level of the cardiac muscle when in association with pre-existing pathological conditions, such as metabolic syndrome. There is a pathological reduction in sarcomere shortening, abnormal cytosolic Ca²⁺ fluxes, reduced expression of sarcoplasmic endoplasmic reticulum ATPase 2a and decreased insulin-mediated Akt-Ser473-phosphorylation in association with abnormal levels of epicardial fat tissue. Activin A, angiopoietin-2, and CD14-positive monocytes selectively accumulate in the diseased myocardium, resulting in reduced cardiomyocyte contractile function. At the same time, it is believed that these alterations in secretory products directly decrease the myocyte function via molecular changes, thus contributing to the development of coronary disease when certain comorbidities are associated.