The CX₃CL1/CX₃CR1 chemokine axis regulates synaptic pruning, plasticity, and stress-related behaviors, influencing resilience or vulnerability to psychiatric disorders. Adolescence, a critical period for neuroimmune development, increases susceptibility to stressors. This study investigated how adolescent restraint stress and alcohol exposure affect stress-coping behavior, neuroimmune signaling, and systemic inflammation in adult wild-type (WT) and CX₃CR1 knock-out (KO) mice. Eighty-one male and female WT and KO mice were assigned to control (non-stressed, saline-treated), stress (stressed, saline-treated), alcohol (non-stressed, alcohol-treated), and stress + alcohol (stressed, alcohol-treated) groups. Behavioral responses were evaluated using the tail suspension test. Hypothalamic gene expression of CX₃CL1/CX₃CR1, corticotropin-releasing hormone (CRH), and neuropeptide Y (NPY) systems was analyzed alongside plasma corticosterone, adrenocorticotropic hormone (ACTH), CX₃CL1, and inflammatory mediators. Adolescent stress-but not alcohol-increased plasma CX₃CL1 levels, which inversely correlated with immobility time in WT mice. KO mice displayed higher baseline immobility than WT mice, whereas stress and/or alcohol paradoxically reduced immobility. These behavioral effects were reproduced by pharmacological inhibition of CX₃CR1. Additionally, KO mice showed disrupted hypothalamic expression of multiple genes in the CRH pathway and Npy1r, attenuated corticosterone responses to stress, and abolished ACTH-corticosterone correlation, suggesting HPA axis dysregulation. KO mice also exhibited exacerbated inflammatory responses to stress and alcohol, including elevated IL-17A/F, IL-11, and IFN-β1 levels. CX₃CR1 deficiency disrupts neuroimmune homeostasis, leading to maladaptive stress-coping behaviors and heightened inflammatory reactivity. These findings underscore the protective role of the CX₃CL1/CX₃CR1 axis in neuroinflammatory regulation and stress resilience, supporting CX₃CR1 as a potential therapeutic target in stress-related disorders.

Background/Objectives: Coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) are characterized by chronic low-grade inflammation. However, measuring cytokines typically involves invasive blood sampling, which can be problematic for CAD patients. This study aimed to assess ophthalmological parameters and tear cytokines in patients with CAD, comparing those with comorbid T2DM to those without to understand their inflammatory profiles. Methods: One hundred subjects with suspected chronic or acute CAD were initially included in this single-center cross-sectional study after clinical stabilization. Seventy-two patients with confirmed CAD were divided into two groups: 32 patients with T2DM and 40 patients without T2DM. A total of 144 eyes were examined, and tear fluid samples were collected to determine cytokine concentrations. Ophthalmological parameters and tear concentrations of cytokines were analyzed, controlling for age, sex, and other cardiovascular risk factors. Results: Patients with CAD and T2DM exhibited decreased ophthalmological parameters and increased cytokine concentrations in comparison to those without T2DM. Significant inverse correlations between ophthalmological parameters and cytokine concentrations were observed. Following adjustment, a full logistic regression model for distinguishing patients with CAD and comorbid T2DM included macular cube volume, mean macular thickness, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), CCL3, CCL4, and CCL11/eotaxin-1, demonstrating excellent discriminatory power (Area Under the Curve = 0.95, 95% Confidence Interval = 0.91–0.99; p < 0.001). Subsequently, IL-5 (Odds Ratio = 1.68, 95% CI = 1.26–2.24; p < 0.001), G-CSF (OR = 1.06, 95% CI = 1.02–1.11; p < 0.01), and CCL11/eotaxin-1 (OR = 1.56, 95% CI = 1.19–2.05; p = 0.001) emerged as the most distinguishing variables in a reduced model (AUC = 0.89, 95% CI = 0.84–0.95; p < 0.001). Conclusions: Differences in ophthalmological variables, mainly in cytokine concentrations, suggest distinct pathophysiological mechanisms in patients with CAD based on the presence of T2DM. These findings demonstrate that the inflammatory profile can be readily detected through tear sample cytokines, proving valuable for establishing more accurate prognoses and monitoring in cardiometabolic disorders.

Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.

Purpose: Aortic valve disease (AVD) is a common condition that leads to pressure and/or volume overload in the left ventricle. Aortic valve replacement is the standard treatment, as no pharmacological therapies are currently available. The incidence of AVD is increasing in developed countries, making the discovery of new biomarkers for early detection crucial. The importance of mitochondria in heart function is well established, and various cardiovascular pathologies are associated with mitochondrial dysfunction. In this cross-sectional study, we evaluated for the first time the role of mitochondria in AVD, aiming to identify new pathways involved in the disease and discover potential biomarkers. Patients and Methods: We recruited 17 patients diagnosed with AVD and scheduled for aortic valve replacement, and 22 healthy controls. Plasma levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial open reading frame of the 12S rRNA type-c peptide (MOTS-c) were measured by ELISA. Results: We observed significantly reduced levels of both proteins in patients, suggesting that substantial mitochondrial dysfunction occurs in AVD patients, independent of sex or age, but directly related to the disease. Conclusion: Mitochondria may represent a promising target for studying new pathways involved in AVD. We propose PGC1α and MOTS-c as potential plasma biomarkers for AVD detection. Further studies, including early-stage patients, are necessary to confirm the significance of our findings.

Background Continuous glucose monitoring (CGM) captures dysglycaemia and glycaemic variability after acute coronary syndrome (ACS), but patient-level trajectories from early recovery to mid-term follow-up—particularly in people without diabetes—remain insufficiently characterised. Methods In this prospective multicentre observational study (ORACLE programme), consecutive high-risk ACS patients wore a FreeStyle Libre 3/3 Plus sensor for 14–15 days near discharge and again at ~ 4 months. We quantified CGM time-in-range metrics (70–180 mg/dL and tight range 70–140 mg/dL), time above/below range, and variability/risk indices, including within-day profiles. Clinically relevant changes were categorised using pre-specified thresholds, and predictors of worsening were explored using multivariable models. Results Among 274 enrolled patients, 213 had analyzable baseline CGM recordings meeting quality criteria. Early post-ACS mean time-in-range 70–180 was 85.7 ± 21.4%, time in tight range 70–140 was 69.6 ± 27.7%, time above range > 180 was 12.8 ± 21.5%, and time below range < 70 was 1.5 ± 3.3% (mean glucose 131.4 ± 35.6 mg/dL; glucose management indicator 6.4 ± 0.8%). CGM demonstrated marked inter-individual heterogeneity and a reproducible late-morning (10:00–12:00) vulnerability window with lower range time and higher hyperglycaemic exposure, consistent across diabetes status and similar on weekdays and weekends; adverse CGM profiles were more prominent in patients with diabetes, older individuals, and women. Although CGM parameters improved modestly over the initial monitoring period, overall control deteriorated from baseline to ~ 4 months, including in patients without diabetes. Tight-range time decreased by 3.8% (95% CI − 6.67 to − 0.99; p = 0.0077) and mean glucose increased by 3.85 mg/dL (p = 0.035), accompanied by worsening variability and risk indices. Across CGM endpoints, ~ 20–40% of patients showed a worsening trajectory (20.2% by broad time-in-range thresholds); higher comorbidity burden clustered with deterioration, with hypertension and COPD independently associated with tight-range worsening. Conclusions After ACS, CGM reveals substantial inter-individual heterogeneity and a reproducible late-morning vulnerability window. From discharge to mid-term follow-up, deterioration—also affecting patients without diabetes—may be preferentially detected by tight-range and variability/risk metrics that traditional monitoring of blood glucose and static measures such as HbA1c may overlook, supporting CGM-informed phenotyping to refine post-ACS metabolic surveillance.