Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

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.

Background: Gallstone disease (GSD) is more commonly presented in aged people. Purpose: The purpose of the study was to explore the insights of metabolic performance of bacterial species from gut microbiota as well as the clinical background in middle-aged and elderly patients with GSD. Patients and Methods: This is an observational study concerning 120 research participants. Of those, 90 patients with symptomatic GSD addressed for cholecystectomy, average age 59.83 ± 15.32 years: 45 with cholesterol rich gallstones (CGSs), 45 with pigment gallstones (PGSs) and 30 healthy controls joined this observational study. Clinical examination, lab work-ups, upper and lower digestive video-endoscopies, abdominal ultrasound/CT and gallbladder motility assessment by Dodd’s method were performed. Overall stool dysbiosis (DB) was assessed as 1 = minor, 2 = mild, 3 = severe, species being identified by matrix-assisted laser desorption ionization method. Stool samples from dysbiotic patients were analyzed by a next generation sequencing method with operational taxonomic unit identification. Results: Patients with GSD presented with a significant high range of overall gut DB (p < 0.0001) when compared with controls. Those with CGSs compared with those having PGSs displayed significant clinical differences related to elderly age, lifestyle and diet particularities, obesity, dyslipidemia, nonalcoholic fatty liver disease, hypertension, type 2 diabetes mellitus or impaired glucose tolerance, as well as motility disturbances of gallbladder with a decrease of the ejection fraction. Significant increase of overall DB range and alterations of several functional bacterial species with a decrease of butyrate, lactate, acetate/propionate and methane producers, mucin degrading bacteria, biodiversity index of microbiota, as well as an increase of lipopolysaccharide positive bacteria were significantly present in patients with CGSs. Conclusion: Middle-aged and elderly patients with GSD and a clinical background characterized by particular lifestyle, metabolic and gallbladder motility issues displayed significant modifications of biodiversity, overall gut DB and alterations of several functional bacterial species, with a decrease of their metabolic performance. Graphical Abstract:

Purpose: This study aimed to explore inflammatory biomarkers, stool’s functional bacterial groups and their possible link to portal vein thrombosis (PVT) in patients with liver cirrhosis (LC). Materials and Methods: An observational study of 300 participants: 200 inhospital cirrhotic patients, who met inclusion criteria, equally assigned into two groups, based on the presence or absence of PVT and 100 healthy controls was carried out. Results: The PVT group displayed significant differences related to older age, cigarettes smoking history, emergency admission, higher Child-Pugh score, metabolic related disorders and nonalcoholic fatty liver disease, as well as non-obstructive aspects, with chronic thrombi. The PVT group exhibited significant differences related to biomarkers such as tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), D-dimers (D-D), as well as gut overall dysbiosis (DB) and alteration of different functional bacterial groups of the gut microbiota. Strong positive correlations were observed between PVT severity, and TNF-alpha, CRP, D-D as well as lipopolysaccharide (LPS) positive bacteria. Esophageal varices, age and abdominal pain were independent predictors for PVT severity as well as CRP, TNF-alpha and D-D. Conclusion: Patients with LC and PVT displayed elevation of TNF-alpha, CRP, D-D alterations of the functional gut microbiota, as well as several morphological and clinical particularities. Although the LPS positive gut microbiota was linked to inflammatory biomarkers and PVT severity, it was not proven to be an independent predictor of the PVT severity like CRP, TNF-alpha and D-D. Graphical Abstract:

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Cutaneous melanoma (CM) represents a severe skin cancer with a rising incidence at present and limited treatment options. 5-Fluorouracil (5-FU) is widely used, including for CM; however, the innate resistance of this cancer to conventional therapy remains problematic. Quercetin (QUE) is a flavonoid that can sensitize cancer cells to antitumor agents such as 5-FU. However, the potential sensitization capability of CM cells to 5-FU has scarcely been determined, and is investigated herein. Therefore, A375 CM cells were tested in terms of their cell viability, cell confluence, and morphological changes. Their nuclear and cytoskeletal aspects, clonogenic potential, and in ovo properties were also followed. The results showed that the 50% inhibitory concentrations (IC50s) of 5-FU and QUE determined by a cell proliferation assay were 11.56 and 11.08 µM, respectively. The addition of QUE (10 µM) to 5-FU (5–50 µM) increased the cytotoxic potential. A significant decline in cell viability (up to 43.51%), the loss of cell confluence, chromatin condensation and nuclear dysmorphology, tubulin and F-actin constriction, and a suppressed clonogenic ability were noted. The QUE + 5-FU association was non-irritating to the chorioallantoic membrane and showed an antiangiogenic effect in ovo. Thus, our results highlight that combining QUE with 5-FU can enhance the cytotoxic effect of 5-FU in A375 melanoma cells and present a safe profile in ovo.