Ischemic stroke is a leading cause of disability worldwide, often triggered by atherothrombotic or embolic events. A growing body of evidence highlights the role of neuroinflammation as a central mechanism in post-stroke damage, influenced by modifiable systemic risk factors. Emerging evidence suggests that oxidative stress mediates the impact of several modifiable risk factors by activating redox-sensitive pathways (such as NF-κB), impairing nitric oxide bioavailability, and promoting matrix metalloproteinase activity that disrupts vascular integrity and contributes to ischemic injury. In this context, our meta-analysis examined major modifiable risk factors for ischemic stroke, with a particular focus on their shared ability to promote oxidative stress and neuroinflammatory cascades. By emphasizing these redox-dependent mechanisms, our work supports the biological plausibility of exploring antioxidant strategies as complementary approaches to mitigate stroke risk. Hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, and transient ischemic attacks all contribute to oxidative damage through mechanisms such as endothelial dysfunction, vascular inflammation, and excessive free radical exposure. We searched PubMed, PubMed Central, Web of Science, and Scopus for observational studies published within the last five years, identifying 23 studies (691,524 participants) meeting eligibility criteria. Using a random-effects model, we found significant associations between stroke risk and hypertension (OR = 1.58, 95% CI: 1.28–1.94), smoking (OR = 1.61, 95% CI: 1.13–2.28), type 2 diabetes (OR = 1.53, 95% CI: 1.29–1.81), atrial fibrillation (OR = 1.88, 95% CI: 1.28–2.75), and prior transient ischemic attack (OR = 1.62, 95% CI: 1.24–2.11). These risk factors are known to contribute to systemic inflammation, potentially exacerbating neuroinflammatory cascades post-stroke. Despite limitations such as heterogeneity and low certainty of evidence, our findings reinforce the relevance of targeting inflammation-driven risk factors in stroke prevention strategies and future research.

Cardio-kidney-metabolic (CKM) syndrome represents an integrated clinical and molecular continuum encompassing metabolic dysfunction, cardiovascular disease and chronic kidney disease. This multidimensional disorder arises from interdependent biological pathways that extend beyond conventional risk factors. Emerging evidence highlights a group of adipokines and vascular modulators—including retinol-binding protein 4 (RBP4), lipocalin 2 (LCN2), apolipoprotein M (ApoM), Klotho and matrix Gla protein (MGP)—emerging molecular modulators with potential involvement in CKM pathophysiology. Pro-inflammatory adipokines such as RBP4 and LCN2 contribute to insulin resistance, oxidative stress and endothelial dysfunction. In contrast, protective molecules including ApoM and Klotho preserve nitric oxide bioavailability, lipid metabolism and antioxidant defense. MGP modulates vascular calcification and adipose remodeling, with its inactive form (dp-ucMGP) linked to vascular stiffness and renal decline. The combined dysregulation of these molecules sustains cycles of inflammation, oxidative stress and tissue remodeling that drive CKM progression. Collectively, current data support their dual role as biomarkers and therapeutic targets. Nonetheless, clinical translation remains limited, emphasizing the need for standardized assays, longitudinal validation, and integrative multimarker approaches within precision medicine frameworks for CKM syndrome.

Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of exogenous compounds capable of interfering with hormonal homeostasis and endocrine-regulated physiological processes. Their widespread occurrence in food, water, air, consumer products and industrial materials has raised increasing concern regarding their contribution to chronic disease burden. This review synthesizes current evidence on the exposure characteristics, molecular mechanisms, health effects, and prevention strategies related to major EDC classes, including bisphenol A and phthalates, dioxins and polychlorinated biphenyls, per- and polyfluoroalkyl substances, pesticides, and brominated flame retardants. Evidence indicates that EDCs may act through receptor-mediated signaling, altered hormone synthesis and metabolism, oxidative stress, mitochondrial dysfunction, immune modulation, and epigenetic mechanisms, with effects that may vary according to dose, timing, sex, age, and developmental susceptibility. Reported health outcomes include metabolic and cardiovascular disorders, reproductive dysfunction, hormone-dependent cancers, thyroid disruption, immune dysregulation, and adverse developmental effects. Although complete avoidance is unrealistic, exposure reduction and risk mitigation can be achieved through coordinated individual, clinical, environmental, and regulatory interventions. A life-course approach is essential to limit the health burden associated with endocrine disruption.

Inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolic events (VTEs) and a moderate risk of arterial cardiovascular events. This varies with inflammatory activity and acute-care exposure, with pathophysiological data supporting a thromboinflammatory phenotype in which intestinal inflammation influences systemic vascular homeostasis through innate immune activation, coagulation–platelet crosstalk, endothelial dysfunction, impaired fibrinolysis, and immunothrombosis. Clinically, prevention and management should be integrated into routine care and anchored in sustained, steroid-sparing disease control, combined with guideline-based in-hospital thromboprophylaxis and standard cardiovascular prevention. Decisions regarding anticoagulant therapy after VTEs should follow established principles while recognizing that recurrence prevention depends not only on anticoagulant choice but also on minimizing repeated inflammatory and treatment-related risk exposures. Cardiovascular risk assessment and optimization of modifiable factors should be considered before therapy escalation or treatment switching. Future advances will likely come from more personalized risk assessment across dynamic high-risk windows and from adjunctive, mechanism-informed strategies targeting key nodes of the gut–vascular interface and immunothrombosis.

Colorectal cancer (CRC) is a major global health burden characterized by progressive genetic and metabolic alterations, with iron metabolism being increasingly recognized as a key contributor to tumorigenesis. This review provides an integrated synthesis of current evidence on iron metabolism across the continuum of colorectal cancer development, from preneoplastic lesions to advanced disease. We analyzed data from epidemiological, experimental, and mechanistic studies addressing systemic and cellular iron homeostasis, including the hepcidin–ferroportin axis, as well as iron handling within tumor cells and the tumor microenvironment. Available data indicate that colorectal epithelial cells progressively develop an iron-retentive phenotype, characterized by increased iron uptake and reduced export, leading to expansion of the intracellular labile iron pool. This imbalance contributes to oxidative stress, DNA damage, metabolic adaptation, and activation of oncogenic signaling pathways while also influencing immune responses. However, epidemiological findings on dietary iron and CRC risk remain inconsistent, highlighting the context-dependent nature of iron-related effects. In conclusion, iron metabolism represents a dynamic regulator of CRC progression and a mechanistic framework for understanding stage-specific tumor evolution, although further studies are needed to clarify how iron-dependent pathways differ across colorectal tumor subtypes and microenvironmental contexts.

Bisphenols and phthalates are ubiquitous endocrine-disrupting chemicals with potential effects on reproductive neuroendocrine regulation, particularly during sensitive developmental windows. This review summarizes current evidence on their exposure profile, mechanisms of reproductive disruption, and female- and male-specific reproductive adversities. A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including experimental, epidemiological, biomonitoring, systematic review, and meta-analytic studies addressing bisphenols, phthalates, fertility, hormonal regulation, gametogenesis, pregnancy outcomes, and reproductive toxicity mechanisms. Bisphenols and phthalates interfere with estrogenic and androgenic signaling, hypothalamic–pituitary–gonadal axis regulation, steroidogenesis, oxidative stress, inflammation, apoptosis, mitochondrial function, and epigenetic regulation. Reported outcomes include impaired ovarian function, altered oocyte development, hormonal imbalance, reduced semen quality, defective spermatogenesis, sperm DNA damage, infertility, and adverse developmental or pregnancy-related effects. However, human evidence remains heterogeneous and limited by observational designs, exposure misclassification, residual confounding, and insufficient mixture assessment. Current evidence supports biological plausibility for bisphenol- and phthalate-related reproductive toxicity, but causal inference remains limited. Prospective studies with repeated biomonitoring, standardized reproductive endpoints, sex- and age-specific analyses, and improved mixture modeling are needed. A precautionary reduction in avoidable exposure appears reasonable, particularly during sensitive reproductive and developmental periods.