Mitochondria are central regulators of cardiac homeostasis, integrating energy production, redox balance, calcium handling, and innate immune signaling. In cardiovascular disease (CVD), mitochondrial dysfunction acts as a unifying mechanism connecting oxidative stress, metabolic inflexibility, inflammation, and structural remodeling. Disturbances in mitochondrial quality control—encompassing fusion–fission dynamics, PINK1/Parkin- and receptor-mediated mitophagy, biogenesis, and proteostasis—compromise mitochondrial integrity and amplify cardiomyocyte injury. Excess reactive oxygen species, mitochondrial DNA release, and calcium overload further activate cGAS–STING, NLRP3 inflammasomes, and mPTP-driven cell death pathways, perpetuating maladaptive remodeling. Therapeutic strategies targeting mitochondrial dysfunction have rapidly expanded, ranging from mitochondria-targeted antioxidants (such as MitoQ and SS-31), nutraceuticals, metabolic modulators (SGLT2 inhibitors, metformin), and mitophagy or biogenesis activators to innovative approaches including mtDNA editing, nanocarrier-based delivery, and mitochondrial transplantation. These interventions aim to restore organelle structure, improve bioenergetics, and reestablish balanced quality control networks. This review integrates recent mechanistic insights with emerging translational evidence, outlining how mitochondria function as bioenergetic and inflammatory hubs in CVD. By synthesizing established and next-generation therapeutic strategies, it highlights the potential of precision mitochondrial medicine to reshape the future management of cardiovascular disease.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline and neuropathological hallmarks such as amyloid-β plaques and neurofibrillary tangles. In recent years, chronic neuroinflammation has emerged as a central mechanism linking genetic, metabolic, and immune dysfunctions in AD. Activated microglia and astrocytes release pro-inflammatory cytokines and reactive oxygen species that exacerbate synaptic and neuronal injury, while impaired clearance mechanisms and blood–brain barrier disruption further sustain inflammation. A growing body of research highlights the role of immunometabolism—the bidirectional interaction between immune activation and cellular metabolism—in shaping glial phenotypes and disease progression. Dysregulation of glucose, lipid, and amino acid metabolism, together with alterations in key metabolites such as lactate, NAD⁺, and reactive oxygen species, promotes a maladaptive inflammatory state. Genetic factors including APOE4 and TREM2 variants affect microglial lipid handling pathways, while systemic metabolic disorders and gut microbiota alterations amplify neuroinflammatory cascades. Natural bioactive compounds, particularly polyphenols, have gained attention for their ability to modulate immunometabolic pathways. By activating AMPK and SIRT1 and inhibiting mTOR and NLRP3 inflammasome signaling, polyphenols may tune mitochondrial function, redox homeostasis, and autophagy, promoting adaptation to chronic metabolic stress. Therefore, metabolic-immune interactions represent pleiotropic therapeutic avenues for AD. Understanding how immunometabolites and nutrient-sensing pathways regulate compartmentalized inflammation in the CNS may pave the way for novel interventions that combine metabolic precision with neuroprotective efficacy.

Anaphylaxis is a severe systemic hypersensitivity reaction characterized by rapid onset, unpredictable clinical course, and potentially fatal outcomes. Although its diagnosis remains primarily clinical, the identification of biomarkers capable of improving risk stratification and understanding disease mechanisms remains an important unmet need. Among the mediators implicated in anaphylaxis, platelet-activating factor (PAF) has emerged as a key effector molecule involved in vascular permeability, bronchoconstriction, platelet activation, and cardiovascular dysfunction. The biological activity of PAF is tightly regulated by platelet-activating factor acetylhydrolase (PAF-AH), the enzyme responsible for its degradation, making the PAF–PAF-AH axis a potentially important determinant of reaction severity. OBJECTIVES: The present review summarizes current knowledge regarding the biology of PAF and PAF-AH and examines their role in the pathophysiology of anaphylaxis, with particular emphasis on Hymenoptera venom allergy (HVA). The therapeutic potential of targeting the PAF pathway is also discussed. Experimental and clinical evidence consistently suggests an association between increased PAF activity, reduced PAF-AH activity, and more severe anaphylactic reactions. However, methodological limitations, biological variability, and conflicting findings across studies currently limit the clinical applicability of these molecules as standalone biomarkers. Overall, the PAF–PAF-AH axis represents a biologically plausible link between molecular mechanisms and clinical severity in anaphylaxis. Further studies are required to standardize measurements, validate clinical utility, and define the role of this pathway as both a biomarker and therapeutic target; hence gaining insight into PAF’s role in various biological processes is critical.

Background: Conservation agriculture has emerged as a sustainable strategy to improve soil quality while maintaining crop productivity and grain nutritional value. However, limited information is available on how agronomic practices influence the biological activity of durum wheat grain. This study, conducted within the framework of the PFRLab project, investigated the effects of no-tillage (NT) and conventional tillage (CT) under two nitrogen fertilization levels (0 and 180 kg ha⁻¹ N) on durum wheat grain quality and the biological responses of Caco-2 intestinal epithelial cells. Methods: Grain quality was evaluated by determining protein, lutein, and mineral contents. The biological activity of grain extracts was assessed by measuring Caco-2 cell viability using the MTT assay and intracellular oxidative activity using H₂DCFDA-derived fluorescence after 3, 24, and 48 h of incubation. Results: Grain protein and lutein contents tended to be higher under nitrogen fertilization, whereas differences between tillage systems were less consistent for the measured compositional traits. In contrast, distinct responses emerged in the cellular assays. NT-derived extracts generally maintained higher Caco-2 cell viability than CT-derived extracts, particularly after 24 and 48 h, while CT-derived extracts generally elicited higher H₂DCFDA-derived intracellular fluorescence. Nitrogen fertilization influenced both cellular endpoints, with effects varying according to incubation time and tillage system. Correlation analysis revealed negative but non-significant associations between intracellular fluorescence and cell viability at individual incubation times (r = −0.649 at 3 h, −0.353 at 24 h, and −0.198 at 48 h). Conclusions: The findings of this pilot exploratory study suggest that long-term no-tillage can maintain the measured durum wheat grain-quality traits at levels comparable to conventional tillage under Mediterranean conditions, while agronomic management is also associated with differences in the biological activity of grain extracts. The cellular findings provide complementary information rather than evidence of direct health effects or specific chemical mechanisms. Future studies integrating targeted phytochemical characterization of grain extracts, soil microbial analyses, and complementary cellular approaches may help clarify the relationships between agronomic management, grain composition, and biological activity.