Colorectal cancer is a major public health concern, with increasing incidence and mortality rates worldwide. Environmental factors, including exposure to toxic metals, such as lead, chromium, cadmium, aluminium, copper, arsenic and mercury, have been suggested to play a significant role in the development and progression of this neoplasia. In particular, the bioaccumulation of toxic metals can play a significant role in colorectal cancer by regulating biological phenomenon associated to both cancer occurrence and progression, such as cell death and proliferation. Also, frequently these metals can induce DNA mutations in well-known oncogenes. This review provides a critical analysis of the current evidence, highlighting the need for further research to fully grasp the complex interplay between toxic metal bioaccumulation and colorectal cancer. Understanding the contribution of toxic metals to colorectal cancer occurrence and progression is essential for the development of targeted preventive strategies and social interventions, with the ultimate goal of reducing the burden of this disease.

Background: this study aims to investigate the possible association among the histopathologic features of carotid plaque instability, the presence of micro- or macrocalcifications, the expression of in situ inflammatory biomarkers, and the occurrence of the major risk factors in this process in a large series of carotid plaques. Methods: a total of 687 carotid plaques from symptomatic and asymptomatic patients were collected. Histological evaluation was performed to classify the calcium deposits in micro or macrocalcifications according to their morphological features (location and size). Immunohistochemistry was performed to study the expression of the main inflammatory biomarkers. Results: results here reported demonstrated that calcifications are very frequent in carotid plaques, with a significant difference between the presence of micro- and macrocalcifications. Specifically, microcalcifications were significantly associated to high inflamed unstable plaques. Paradoxically, macrocalcifications seem to stabilize the plaque and are associated to a M2 macrophage polarization instead. Discussion: the characterization of mechanisms involved in the formation of carotid calcifications can lay the foundation for developing new strategies for the management of patients affected by carotid atherosclerosis. Data of this study could provide key elements for an exhaustive evaluation of carotid plaque calcifications allowing to establish the risk of associated clinical events.

Environmental pollution poses a significant threat to human health, particularly concerning its impact on cardiovascular diseases (CVDs). This review synthesizes epidemiological and molecular evidence to elucidate the intricate relationship between environmental pollutants and CVDs. Epidemiological studies highlight the association between exposure to air, water, and soil pollutants and increased CVD risk, including hypertension, coronary artery disease, and stroke. Furthermore, molecular investigations unravel the underlying mechanisms linking pollutant exposure to CVD pathogenesis, such as oxidative stress, inflammation, endothelial dysfunction, and autonomic imbalance. Understanding these molecular pathways is crucial for developing targeted interventions and policy strategies to mitigate the adverse effects of environmental pollution on cardiovascular health. By integrating epidemiological and molecular evidence, this review provides insights into the complex interplay between environmental factors and CVDs, emphasizing the urgent need for comprehensive preventive measures and environmental policies to safeguard public health.

We investigated the presence of aluminium (Al) in human colon cancer samples and its potential association with biological processes involved in cancer progression, such as epithelial to mesenchymal transition (EMT) and cell death. 25 consecutive colon samples were collected from patients undergoing colonic resection. Both neoplastic and normal mucosa were collected from each patient and subjected to histological, ultrastructural and immunohistochemical analyses. Moreover, colon samples from two Al-positive patients underwent multi-omic analyses, including whole genome sequencing and RNA sequencing (RNAseq). Morin staining, used to identify in situ aluminium bioaccumulation, showed the presence of Al in tumor areas of 24 % of patients. Transmission electron microscopy and energy-dispersive X-ray microanalysis confirmed the presence of Al specifically in intracytoplasmic electrondense nanodeposits adjacent to mitochondria of colon cancer cells. Immunohistochemical analyses for vimentin and nuclear β-catenin were performed to highlight the occurrence of the EMT phenomenon in association to Al bioaccumulation. Al-positive samples showed a significant increase in both the number of vimentin-positive and nuclear β-catenin-positive cancer cells compared to Al-negative samples. Moreover, Al-positive samples exhibited a significant decrease in the number of apoptotic cells, as well as the expression of the anti-apoptotic molecule BCL-2. Multi-omic analyses revealed a higher tumor mutational burden (TMB) in Al-positive colon cancers (n = 2) compared to a control cohort (n = 100). Additionally, somatic mutations in genes associated with EMT (GATA3) and apoptosis (TP53) were observed in Al-positive colon cancers. In conclusion, this study provides the first evidence of Al bioaccumulation in colon cancer and its potential role in modulating molecular pathways involved in cancer progression, such as EMT and apoptosis. Understanding the molecular mechanisms underlying Al toxicity might contribute to improve strategies for prevention, early detection, and targeted therapies for the management of colon cancer patients.

Background: Metabolic syndrome certainly favors growth of carotid plaque; however, it is uncertain if it determines plaque destabilization. Furthermore, it is likely that only some components of metabolic syndrome are associated with increased risk of plaque destabilization. Therefore, we evaluated the effect of different elements of metabolic syndrome, individually and in association, on carotid plaques destabilization. Methods: A total of 186 carotid endarterectomies from symptomatic and asymptomatic patients were histologically analysed and correlated with major cardiovascular risk factors. Results: Metabolic syndrome, regardless of the cluster of its components, is not associated with a significant increase in risk of plaque destabilization, rather with the presence of stable plaques. The incidence of unstable plaques in patients with metabolic syndrome is quite low (43.9 %), when compared with that seen in the presence of some risk factors, but significantly increases in the subgroup of female patients with hypertriglyceridemia, showing an odds ratio of 3.01 (95% CI, 0.25–36.30). Conclusions: Our data may help to identify patients with real increased risk of acute cerebrovascular diseases thus supporting the hypothesis that the control of hypertriglyceridemia should be a key point on prevention of carotid atherosclerotic plaque destabilization, especially in post-menopausal female patients.

BACKGROUND: Dyslipidemia plays a critical role in carotid plaque instability and related cerebrovascular events. Reduction of low-density lipoprotein cholesterol (LDL-C) levels decreases ischemic stroke risk; however, a residual cardiovascular risk persists. Starting from this evidence, this study evaluated the impact of dyslipidemia on carotid plaque instability while also considering age and sex. METHODS: In this observational study, a total of 354 carotid plaques from symptomatic and asymptomatic patients undergoing endarterectomy were analyzed histologically. Dyslipidemic profiles, including high LDL-C, remnant cholesterol, triglycerides, and low high-density lipoprotein cholesterol, were assessed alongside other risk factors. Logistic regression identified independent predictors of unstable plaques, and subgroup analyses evaluated the influence of age (<70, ≥70 years) and sex. RESULTS: Unstable plaques were observed in 45.2% of cases. High LDL-C emerged as the strongest independent risk factor for plaque instability. The combination of high LDL-C with elevated remnant cholesterol or triglycerides significantly increased the risk of plaque destabilization. Age and sex influenced the risk associated with dyslipidemic profiles, with women who had elevated LDL-C combined with high-remnant cholesterol or triglycerides showing a substantially higher risk of carotid plaque instability compared with men. Furthermore, individuals <70 years of age exhibited a greater risk of plaque instability compared with older patients, highlighting the critical role of these nonmodifiable factors. CONCLUSIONS: The data reported here highlight the importance of a personalized medicine approach to lipid management, addressing not only LDL-C but also remnant cholesterol and triglycerides. Tailored interventions targeting specific dyslipidemic profiles could more effectively reduce the risk of carotid plaque rupture and cerebrovascular events, particularly in women and patients aged <70 years.