Cholangiopathies include a group of chronic progressive disorders, affecting the cholangiocytes, the epithelial cells that line the biliary tree, leading to liver parenchymal fibrosis and eventually end-stage liver disease necessitating transplantation. Experimental modeling of these multifactorial cholestatic diseases faces challenges due to the lack of adequate experimental in vitro and in vivo models. A novel approach employs three-dimensional organoid systems that offer several advantages for modeling disease and testing drug response in vitro. Organoids mimic intercellular communication, replicate the architecture of organs, and maintain the cell’s original phenotype. Cholangiocyte organoids provide an in vitro model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies and show great promise for regenerative therapies. In particular, patient-derived organoids allow personalized medicine approaches and the study of individual disease characteristics. This review highlights the significance of cholangiocyte organoid models in advancing our understanding of cholangiopathies and driving advancements in regenerative medicine strategies.

Environmental exposure to persistent and non-persistent endocrine-disrupting chemicals (EDCs), including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), dioxins, phthalates, and bisphenols, has been increasingly associated with elevated cardiovascular disease (CVD) risk. Emerging evidence suggests the importance of gene–environment interactions in modulating individual susceptibility to EDC-related cardiovascular effects. This review summarizes current knowledge by synthesizing the main classes of EDCs, evaluating the evidence linking them to cardiovascular outcomes, and highlighting how genetic variability may modulate EDC-induced cardiovascular risk. Across the studies analyzed, the most extensively investigated genetic polymorphisms involve pathways related to oxidative stress regulation, xenobiotic metabolism and detoxification, hormone signaling, and lipid homeostasis. Variants in antioxidant defense genes, such as CAT, eNOS, and PON1, have been associated with increased hypertension risk and vascular dysfunction following exposure to bisphenols and PAHs. Polymorphisms in GSTP1, CYP2C19, CYP1A2, CYP2E1, ABCB1, and MTHFR may influence susceptibility to cardiometabolic alterations and congenital heart defects, whereas variants in ESR2, FTO, LEPR, and INSIG2 have been linked to obesity, dyslipidemia, and hypertension associated with PFAS, PBDEs, and bisphenols. A deeper understanding of gene–environment interactions is essential to advance preventive cardiology and mitigate the cardiovascular impact of environmental pollutants.

Background: New-onset postoperative atrial fibrillation (NOAF) is the most prevalent arrythmia after cardiac surgery with a significant clinical and economic impact. Therefore, simple and practical biomarkers for NOAF prediction remain a clinical priority. Increasing evidence indicates that malnutrition is linked to postoperative complications, including the onset of atrial fibrillation. The Prognostic Nutritional Index (PNI), which reflects the immunonutritional and inflammatory status through serum albumin concentration and lymphocyte count, has emerged as a reliable prognostic indicator in cardiovascular disease. The present study aimed to investigate the association between PNI and the development of NOAF in patients undergoing surgical aortic valve replacement (SAVR). Methods: A total of 241 consecutive patients who underwent AVR for severe aortic stenosis or regurgitation were enrolled in this study. The population was stratified into two groups according to the development of NOAF (NOAF group) or the lack thereof (no NOAF group). Results: In both univariate and multivariate logistic regression analyses adjusted for several established NOAF determinants, age and PNI, both as continuous variables, were independently associated with NOAF in both univariate (OR = 1.03; CI 95% = 1.01–1.06, p = 0.009, and OR = 0.9; CI 95% = 0.8–0.9, p = 0.01, respectively) and multivariate models (OR = 1.02; CI 95% = 1.01–1.06, p = 0.05, and OR = 0.9; CI 95% = 0.8–0.9, p = 0.03, respectively). When PNI was analyzed by tertiles, patients in the lowest tertile (PNI < 41.5) showed a significantly higher risk of developing NOAF at both univariate (OR = 1.9; CI 95% = 1.2–2.8, p = 0.004) and multivariate analysis (OR = 1.6; CI 95% = 1–2.6, p = 0.03), whereas age lost statistical significance (OR = 1.0; 95% CI = 0.9–1.05; p = 0.06). Furthermore, when the study population was divided into two groups based on the median age (70 years), PNI values differed significantly between NOAF and no NOAF patients only in patients under 70 years (p = 0.01). In this younger subgroup, PNI remained an independent predictor of NOAF, both when considered as a continuous variable (OR = 0.86; CI 95% = 0.74–0.98, p = 0.02), and nominal variable (PNI < 41.5, OR = 0.88; CI 95% = 0.80–0.97, p = 0.01). Conclusions: Overall, these findings identify PNI as an independent predictor of NOAF following SAVR, particularly in patients younger than 70 years. This study underlines the potential clinical value of preoperative nutritional assessment for risk stratification. Incorporating nutritional parameters such as PNI into current predictive models may enhance the accuracy of prognostic evaluation and support targeted perioperative management strategies.

Environmental exposure to persistent and non-persistent endocrine-disrupting chemicals (EDCs), including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), dioxins, phthalates, and bisphenols, has been increasingly associated with elevated cardiovascular disease (CVD) risk. Emerging evidence suggests the importance of gene–environment interactions in modulating individual susceptibility to EDC-related cardiovascular effects. This review summarizes current knowledge by synthesizing the main classes of EDCs, evaluating the evidence linking them to cardiovascular outcomes, and highlighting how genetic variability may modulate EDC-induced cardiovascular risk. Across the studies analyzed, the most extensively investigated genetic polymorphisms involve pathways related to oxidative stress regulation, xenobiotic metabolism and detoxification, hormone signaling, and lipid homeostasis. Variants in antioxidant defense genes, such as CAT, eNOS, and PON1, have been associated with increased hypertension risk and vascular dysfunction following exposure to bisphenols and PAHs. Polymorphisms in GSTP1, CYP2C19, ABCB1, and MTHFR may influence susceptibility to cardiometabolic alterations and congenital heart defects, whereas variants in ESR2, FTO, LEPR, and INSIG2 have been linked to obesity, dyslipidemia, and hypertension associated with PFAS, PBDEs, and bisphenols. A deeper understanding of gene–environment interactions is essential to advance preventive cardiology and mitigate the cardiovascular impact of environmental pollutants.

Aortic valve stenosis (AVS) is the most common valvular heart disease that was considered, for a long time, a passive degenerative disease due to physiological aging. More recently, it has been recognized as an active, modifiable disease in which many cellular processes are involved. Nevertheless, since aging remains the major risk factor for AVS, a field of research has focused on the role of early (biological) aging and its dependent pathways in the initiation and progression of AVS. Telomeres are regions at the ends of chromosomes that are critical for maintaining genome stability in eukaryotic cells. Telomeres are the hallmarks and molecular drivers of aging and age-related degenerative pathologies. Clonal hematopoiesis of indeterminate potential (CHIP), a condition caused by somatic mutations of leukemia-associated genes in individuals without hematologic abnormalities or clonal disorders, has been reported to be associated with aging. CHIP represents a new and independent risk factor in cardiovascular diseases, including AVS. Interestingly, evidence suggests a causal link between telomere biology and CHIP in several pathological disorders. In this review, we discussed the current knowledge of telomere biology and CHIP as possible mechanisms of aortic valve degeneration. We speculated on how a better understanding of the complex relationship between telomere and CHIP might provide great potential for an early diagnosis and for developing novel medical therapies to reduce the constant increasing health burden of AVS.

Atherosclerosis is a complex, multifactorial disease and the leading underlying cause of cardiovascular morbidity and mortality worldwide. Beyond traditional risk factors, growing evidence highlights the critical role of environmental exposures in modulating atherogenesis. In real-world scenarios, individuals are exposed to complex mixtures of contaminants, including particulate matter, toxic metals, pesticides, polycyclic aromatic hydrocarbons, and endocrine-disrupting chemicals. These combined exposures may exert additive, synergistic or antagonistic effects, resulting in biological responses that cannot always be predicted from single-agent exposures. At the cellular and molecular level, both chemical mixtures and environmental co-exposures converge on key pathogenic pathways, including oxidative stress, endothelial dysfunction, chronic inflammation, and lipid dysregulation. These processes may favor monocyte recruitment, foam cell formation, vascular smooth muscle cell remodeling, and plaque instability. Moreover, cumulative exposures are associated with epigenetic alterations, such as dysregulation of DNA methylation and non-coding expression patterns, which may influence long-term susceptibility to atherosclerosis. This structured narrative review synthesizes evidence from 37 studies investigating the cellular and molecular mechanisms underlying the impact of environmental mixtures and multipollutant co-exposures on atherosclerosis. By integrating evidence from epidemiological, toxicological, experimental, bioinformatics and multi-omics studies, while recognizing the predominantly associative nature of the available human evidence, we highlight emerging mechanistic insights and discuss the relevance of mixture-based approaches for improving risk assessment and informing future preventive strategies.