Biomarkers For Risk Assessment Research Articles

Effects of pesticide exposure on the expression of selected genes in normal and cancer samples: Identification of predictive biomarkers for risk assessment

Pesticides pivotal in controlling pests, can represent a threat for human health. Regulatory agencies constantly monitor their harmful effects, regulating their use. Several studies support a positive association between long-term exposure to pesticides and chronic pathologies, such as cancer. Geno-toxicological biomonitoring has proven to be valuable to assess genetic risks associated with exposure to pesticides, representing a promising tool to improve preventive measures and identify workers at higher risk. In this study, a differential gene expression analysis of 70 candidate genes deregulated upon pesticide exposure, was performed in 10 GEO human gene expression DataSets. It was found that six genes (PMAIP1, GCLM, CD36, SQSTM1, ABCC3, NR4A2) had significant AUC predictive values. Also, CD36 was upregulated in non-transformed cell samples and healthy workers, but downregulated in cancer cells. Further validation in larger groups of workers will corroborate the importance of the identified candidates as biomarkers of exposure/effect.

Increased TMEM166 Level in Patients with Postoperative Stroke after Carotid Endarterectomy

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia–reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.

Inflammasome-related gene signatures as prognostic biomarkers in osteosarcoma.

Osteosarcoma, the primary bone cancer in adolescents and young adults, is notorious for its aggressive growth and metastatic potential. Our study delved into the prognostic impact of inflammasome-related gene signatures in osteosarcoma patients, employing comprehensive genetic profiling to uncover signatures linked with patient outcomes. We identified three patient subgroups through consensus clustering, with one showing worse survival rates correlated with high FGFR3 and RARB expressions. Immune profiling revealed significant immune cell infiltration differences among these subgroups, affecting survival. Utilising advanced machine learning, including StepCox and gradient boosting machine algorithms, we developed a prognostic model with a notable c-index of 0.706, highlighting CD36 and MYD88 as key genes. Higher inflammasome risk scores from our model were associated with poorer survival, corroborated across datasets. Invitro experiments validated CD36 and MYD88's roles in promoting osteosarcoma cell proliferation, invasion and migration, emphasising their therapeutic potential. This research offers new insights into inflammasomes' role in osteosarcoma, introducing novel biomarkers for risk assessment and potential therapeutic targets. Our findings suggest a pathway towards personalised treatment strategies, potentially improving patient outcomes in osteosarcoma.

Unraveling paraquat-induced toxicity on mouse neural stem cells: Dose-response metabolomics insights and identification of sensitive biomarkers for risk assessment

Exposure to pesticide could contribute to neurodevelopmental and neurodegenerative disorders. Notably, research suggests that prenatal or early postnatal exposure to paraquat (PQ), an herbicide, might trigger neurodevelopmental toxicity in neural stem cells (NSCs) via oxidative stress. However, the molecular mechanisms of PQ-induced perturbations in NSCs, particularly at the metabolite level, are not fully understood. Using a dose-response metabolomics approach, we examined metabolic changes in murine NSCs exposed to different PQ doses (0, 10, 20, 40 μM) for 24h. At 20 μM, PQ treatment led to significant metabolic alterations, highlighting unique toxic mechanisms. Metabolic perturbations, mainly affecting amino acid metabolism pathways (e.g., phenylalanine, tyrosine, arginine, tryptophan, and pyrimidine metabolism), were associated with oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. Dose-response models were used to identify potential biomarkers (e.g., Putrescine, L-arginine, ornithine, L-histidine, N-acetyl-L-phenylalanine, thymidine) reflecting early damage from low-dose PQ exposure. These biomarkers could be used as points of departure (PoD) for characterizing PQ exposure hazard in risk assessment. Our study offers insights into mechanisms and risk assessment related to PQ-induced neurotoxicity in NSCs.

Exposure and Early Effect Biomarkers for Risk Assessment of Occupational Exposure to Formaldehyde: A Systematic Review

The aim of the present review was to identify all the biomarkers used for assessing the internal dose and the related early effects determined by the occupational exposure to formaldehyde. For this purpose, a systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered in PROSPERO (ID: CRD42023416960). An electronic search of Pubmed, Scopus, and Web of Science was performed to collect all the papers concerning the focus of the review and published from the inception of each database until 18 September 2023. Articles were considered eligible if they reported data from observational studies, semi-experimental, and experimental studies on adult workers who were occupationally exposed to formaldehyde, regardless of gender or age. The quality assessment was performed using the adapted Newcastle–Ottawa Quality Assessment Scale. From 1524 articles, 52 were included. Few studies assessed the exposure to formaldehyde in occupational settings through biomarkers, especially by measuring formic acid in urine. The most common approach for evaluating the effects derived from occupational exposure to formaldehyde was the use of the cytogenetic biomarker micronucleus assay in peripheral blood lymphocytes and/or epithelial buccal cells.

Flow patterns in ascending aortic aneurysms: Determining the role of hypertension using phase contrast magnetic resonance and computational fluid dynamics

Thoracic aortic aneurysm (TAA) is a local dilation of the thoracic aorta. Although universally used, aneurysm diameter alone is a poor predictor of major complications such as rupture. There is a need for better biomarkers for risk assessment that also reflect the aberrant flow patterns found in TAAs. Furthermore, hypertension is often present in TAA patients and may play a role in progression of aneurysm. The exact relation between TAAs and hypertension is poorly understood. This study aims to create a numerical model of hypertension in the aorta by using computational fluid dynamics. First, a normotensive state was simulated in which flow and resistance were kept unaltered. Second, a hypertensive state was modeled in which blood inflow was increased by 30%. Third, a hypertensive state was modeled in which the proximal and peripheral resistances and capacitance parameters from the three-element Windkessel boundary condition were adjusted to mimic an increase in resistance of the rest of the cardiovascular system. One patient with degenerative TAA and one healthy control were successfully simulated at hypertensive states and were extensively analyzed. Furthermore, three additional TAA patients and controls were simulated to validate our method. Hemodynamic variables such as wall shear stress, oscillatory shear index, endothelial cell activation potential (ECAP), vorticity and helicity were studied to gain more insight on the effects of hypertension on flow patterns in TAAs. By comparing a TAA patient and a control at normotensive state at peak-systole, helicity and vorticity were found to be lower in the TAA patient throughout the entire domain. No major changes in flow and flow derived quantities were observed for the TAA patient and control when resistance was increased. When flow rate was increased, regions with high ECAP values were found to reduce in TAA patients in the aneurysm region which could reduce the risk of thrombogenesis. Thus, it may be important to assess cardiac output in patients with TAA.

Understanding the Impact of COVID-19 on Roma Vulnerable Communities in Western Romania: Insights and Predictive Factors from a Retrospective Study.

The COVID-19 pandemic disproportionately affected vulnerable populations like Roma patients in Western Romania due to marginalization and limited healthcare access. A retrospective study analyzed COVID-19 cases between March 2020 and August 2022 using data from the Directorate of Public Health in Timis county. Demographic, epidemiological, clinical, and laboratory data were assessed, along with risk factors and biomarkers for ICU admission and mortality prediction. The following biomarkers were assessed: C-reactive protein (CRP), ferritin (FER), IL-6, D-dimers, lactate dehydrogenase (LDH), high density lipoprotein cholesterol (HDL), and 25-OH vitamin D (25-OHD). In comparison with the general population (GP), Roma patients were more overweight (p = 0.0292), came from rural areas (p = 0.0001), could not recall transmission source (p = 0.0215), were admitted to the intensive care unit (ICU, p = 0.0399) more frequently, had worse symptomatology (p = 0.0490), showed more elevated levels of CRP (p = 0.0245) and IL-6 (p < 0.0001) and lower levels of HDL (p = 0.0008) and 25-OHD (p = 0.0299). A stronger, significant correlation was observed between CRP and severity (rho = 0.791 vs. 0.433 in GP), and an inverse stronger significant one was observed between HDL and severity (rho = -0.850 vs. -0.734 in GP) in the Roma patients. The male sex continues to be an important risk factor for ICU admission (OR = 2.379) and death (OR = 1.975), while heavy smoking was more important in relation to ICU admission (OR = 1.768). Although the Roma ethnicity was 1.454 times more at risk of ICU admission than the GP, this did not prove statistically significant (p = 0.0751). CRP was the most important predictive factor in regards to admission to the ICU for both Roma (OR = 1.381) and the GP (OR = 1.110) and in regards to death (OR = 1.154 for Roma, OR = 1.104 for GP). A protective effect of normal values of HDL and 25-OHD was observed in the GP for both ICU admission (OR = 0.947, 0.853, respectively) and death (OR = 0.920, 0.921, respectively), while for the Roma group, normal 25-OHD values were only considered protective in regards to death (OR = 0.703). Cutoff values for ICU admission were 28.98 mg/L for Roma and 29.03 mg/L for GP patients, with high specificity for both groups (over 95). Higher rates of ICU admissions, severe symptomatology, and distinct laboratory biomarker profiles among Roma patients emphasize the critical importance of personalized care strategies and targeted interventions to mitigate the disproportionate burden of COVID-19 on vulnerable communities. CRP values at admission have had a clear impact as a risk assessment biomarker for Roma patients, while the significance of IL-6, HDL, and 25-OHD should also not be overlooked in these patients.

Automated determination of 8-OHdG in cells and tissue via immunofluorescence using a specially created antibody

Despite powerful DNA repair systems, oxidative damage/modification to DNA is an inevitable side effect of metabolism, ionizing radiation, lifestyle habits, inflammatory pathologies such as type-2 diabetes or metabolic syndrome, cancer and natural aging.One of the most common oxidative DNA modifications is 8-OHdG (8‑hydroxy-2′-deoxyguanosine), which is the most widely used marker in research and clinical diagnostics. 8-OHdG is easily and specifically detectable in various samples such as urine, plasma, cells and tissues via a large variety of methods like ELISA, HPLC, chromatographic methods, and immunochemistry.Formed by oxidation of guanine and being representative for the degree of DNA damage, 8-OHdG can be also used as biomarker for risk assessment of various cancers as well as degenerative diseases.Here, we present a highly specific, self-developed 8-OHdG antibody in successful comparison to a commercially one, tested in cells (FF95, HCT116, and HT22) and intestinal tissue, focusing on automatized evaluation via fluorescence/confocal microscopy.

The impact of age and number of mutations on the size of clonal hematopoiesis

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Microglia Autophagy Mediated by TMEM166 Promotes Ischemic Stroke Secondary to Carotid Artery Stenosis.

Ischemic stroke can be a serious complication of selective carotid endarterectomy (CEA) in patients with carotid artery stenosis (CAS). The underlying risk factors and mechanisms of these postoperative strokes are not completely understood. Our previous study showed that TMEM166-induced neuronal autophagy is involved in the development of secondary brain injury following cerebral ischemia-reperfusion injury in rats. This current study aimed to investigate the role of TMEM166 in ischemic stroke following CEA. In the clinical part of this study, the quantitative analysis demonstrated circulating TMEM166, interleukin 6 (IL-6), and C-reactive protein (CRP) levels were significantly elevated in patients who suffered an ischemic stroke after CEA compared to those who did not. Furthermore, non-survivors exhibited higher levels of these proteins than survivors. In the preclinical part of this study, a middle cerebral artery occlusion (MCAO) model was implemented following CAS simulation in TMEM166-/- mice. We found TMEM166 expression was positively correlated with the degree of ischemic brain injury. Ad5-TMEM166 transfection aggravated ischemic brain injury by inducing microglial autophagy activation and release of inflammatory cytokines. Accordingly, TMEM166 deficiency reduced brain inflammation and inhibited excessive microglial autophagy through the mammalian target of rapamycin (mTOR) pathway. These findings suggest that TMEM166 may play a key role in the development of ischemic injury after CEA and may serve as a biomarker for risk assessment of postoperative ischemic stroke.

Eosinophil-to-Leukocyte Ratio as an Inflammatory Marker in Patients With Coronary Artery Disease—A Retrospective Cohort Study

BACKGROUND: Cardiovascular disease remains one of the leading causes of death and major causes of disability and loss of productivity in adults worldwide. Inflammation is a key feature of atherosclerosis and its clinical manifestations. Because inflammation plays a key role in atherosclerosis and its end results, discovering new biomarkers of inflammation becomes important to help diagnostic accuracy and provide prognostic information about coronary artery disease (CAD). The eosinophil count and eosinophil-to-leukocyte ratio (ELR), in particular, have become novel biomarkers for risk assessment in patients with CAD. The current study aimed to evaluate the association of ELR with presence of CAD. OBJECTIVES: The aim of this study was to investigate the prognostic value and predictive performance of ELR in patients with suspected CAD. Furthermore, if proven of value, this study aims to use ELR as a biomarker for screening patients at risk for CAD for early prevention and intervention. METHODS: This is a retrospective cohort study involving a chart review of CAD suspects 40 years or older who underwent elective coronary angiogram from January 2019 to December 2019. Eosinophil-to-leukocyte ratio was calculated by dividing the number of eosinophils by the number of leukocytes RESULTS: A total of 436 patients were included in this study. With an optimal cutoff value of 0.5 (area under the curve, 0.9911; sensitivity, 96.63%; specificity, 95.27%), ELR demonstrated efficiency in detecting CAD. CONCLUSION: Patients with CAD has a higher ELR than those without CAD in the control group. Furthermore, this study supports the positive association of ELR in predicting CAD. KEYWORDS: eosinophil-to-leukocyte ratio, coronary artery disease

Endogenous and microbial biomarkers for periodontitis and type 2 diabetes mellitus.

It has been well documented that there is a two-way relationship between diabetes mellitus and periodontitis. Diabetes mellitus represents an established risk factor for chronic periodontitis. Conversely, chronic periodontitis adversely modulates serum glucose levels in diabetic patients. Activated immune and inflammatory responses are noted during diabetes and periodontitis, under the modulation of similar biological mediators. These activated responses result in increased activity of certain immune-inflammatory mediators including adipokines and microRNAs in diabetic patients with periodontal disease. Notably, certain microbes in the oral cavity were identified to be involved in the occurrence of diabetes and periodontitis. In other words, these immune-inflammatory mediators and microbes may potentially serve as biomarkers for risk assessment and therapy selection in diabetes and periodontitis. In this review, we briefly provide an updated overview on different potential biomarkers, providing novel diagnostic and therapeutic insights on periodontal complications and diabetes mellitus.

Validating the NIH LDL-C equation for provincial implementation in Alberta

BackgroundLDL-C, a cardiovascular disease risk assessment biomarker, is commonly calculated using the Friedewald equation. The NIH equation overcomes several limitations of the Friedewald equation. Consistent with the Canadian Society of Clinical Chemists (CSCC) lipid reporting recommendations, we assessed the NIH LDL-C equation in Alberta prior to its provincial implementation. Methods1-year (01/01/2021–12/31/2021) of lipid results (n = 1,486,584 after data cleaning) were obtained from five analytical instrument groups used across Alberta. Analyses were performed on all data and after separating by age, analytical instrument group, and fasting status. The correlation between Friedewald- and NIH-calculated LDL-C and between Friedewald- and NIH-calculated LDL-C difference and each lipid parameter, was determined. The frequency of unreportable/inaccurate LDL-C results was compared between the two equations. The concordance between the two equations and with non-HDL-C was determined at LDL-C thresholds. Lastly, LDL-C calculated by Friedewald, NIH, and Martin-Hopkins equations was compared to density-gradient ultracentrifugation. ResultsFriedewald- and NIH-calculated LDL-C exhibit the strongest correlation when triglycerides ≤ 4.52 mmol/L. The difference between Friedewald- and NIH-calculated LDL-C increases with decreasing LDL-C concentration. The NIH equation yields fewer inaccurate results (0.35 % vs. 22.0 %). The percent agreement between equations was > 96 % at all LDL-C thresholds, suggesting most patients will not require treatment changes. NIH-calculated LDL-C exhibited better agreement with non-HDL-C when triglycerides ≤ 9.04 mmol/L and better correlated with LDL-C measured by ultracentrifugation (r2 = 0.926 vs. 0.775 (Friedewald) and 0.863 (Martin-Hopkins)). Results were consistent across age, analytical instrument group, and fasting status. ConclusionsOur findings demonstrate the benefits of implementing the NIH equation across Alberta.

MiR-20a-5p targeting mfn2-mediated mitochondria-lipid droplet contacts regulated differential changes in hepatic lipid metabolism induced by two Mn sources in yellow catfish

Understanding the hazards of different forms of metal elements provided innovative insights into their toxicity and environmental risk assessment. To date, few studies had been conducted to investigate the differential effects and mechanisms of MnO2 NPs and MnSO4, two widely distributed environmental pollutants, on hepatic toxicity and lipid metabolism since lipid metabolism-relevant parameters were broadly used as biomarkers for risk assessment of hazardous contaminants. Thus, using yellow catfish Pelteobagrus fulvidraco, an ecologically and economically important freshwater fish as the model, the present study investigated the differential effects and mechanisms of MnO2 NPs and MnSO4 influencing hepatic lipid metabolism. Compared to MnSO4, MnO2 NPs increased hepatic Mn content, induced lipotoxicity, up-regulated the mRNA expression of lipogenic genes, increased peridroplet mitochondrial (PDM) contents, intensified the contact between mitochondria and lipid droplets (LDs), and downregulated miR-20a-5p abundance. Importantly, miR-20a-5p targeted mfn2, which mediated the contact between mitochondria and LDs and influenced changes in lipid metabolism induced by MnO2 NPs. Mechanistically, the direct Mfn2-Plin2 binding and Mfn2 GTPase activity promoted the MnO2 NPs-induced interactions between mitochondria and LDs, which in turn influenced MnO2 NPs-induced changes in hepatic lipid metabolism. For the first time, our findings indicated the significant differences between the changes in body metabolism induced by nanoparticles and inorganic elements, which helped to illuminate different mechanisms governing the responses of aquatic vertebrates to hazardous metal pollutants (MnO2 NPs and MnSO4).

Precision Medicine Approaches to Diabetic Kidney Disease: Personalized Interventions on the Horizon.

Diabetic kidney disease (DKD) is a significant complication of diabetes that requires innovative interventions to address its increasing impact. Precision medicine is a rapidly emerging paradigm that shows excellent promise in tailoring therapeutic strategies to the unique profiles of individual patients. This abstract examines the potential of precision medicine in managing DKD. It explores the genetic and molecular foundations, identifies biomarkers for risk assessment, provides insights into pharmacogenomics, and discusses targeted therapies. Integrating omics data and data analytics provides a comprehensive landscape for making informed decisions. The abstract highlights the difficulties encountered during the clinical implementation process, the ethical factors to be considered, and the importance of involving patients. In addition, it showcases case studies that demonstrate the effectiveness of precision-based interventions. As the field progresses, the abstract anticipates a future characterized by the integration of artificial intelligence in diagnostics and treatment. It highlights the significant impact that precision medicine can have in revolutionizing the provision of care for DKD.

Mitochondrial dysfunction in the pathogenesis of endothelial dysfunction.

Cardiovascular diseases (CVDs) are a matter of concern worldwide, and mitochondrial dysfunction is one of the major contributing factors. Vascular endothelial dysfunction has a major role in the development of atherosclerosis because of the abnormal chemokine secretion, inflammatory mediators, enhancement of LDL oxidation, cytokine elevation, and smooth muscle cell proliferation. Endothelial cells transfer oxygen from the pulmonary circulatory system to the tissue surrounding the blood vessels, and a majority of oxygen is transferred to the myocardium by endothelial cells, which utilise a small amount of oxygen to generate ATP. Free radicals of oxide are produced by mitochondria, which are responsible for cellular oxygen uptake. Increased mitochondrial ROS generation and reduction in agonist-stimulated eNOS activation and nitric oxide bioavailability were directly linked to the observed change in mitochondrial dynamics, resulting in various CVDs and endothelial dysfunction. Presently, the manuscript mainly focuses on endothelial dysfunction, providing a deep understanding of the various features of mitochondrial mechanisms that are used to modulate endothelial dysfunction. We talk about recent findings and approaches that may make it possible to detect mitochondrial dysfunction as a potential biomarker for risk assessment and diagnosis of endothelial dysfunction. In the end, we cover several targets that may reduce mitochondrial dysfunction through both direct and indirect processes and assess the impact of several different classes of drugs in the context of endothelial dysfunction.

Metabolomics of head and neck cancer in biofluids: an integrative systematic review.

Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC. To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine. A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine). Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented. The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.

Stroke risk management in carotid atherosclerotic disease: A Clinical Consensus Statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making.

MnO2 nanoparticles and MnSO4 differentially affected hepatic lipid metabolism through miR-92a/acsl3-dependent de novo lipogenesis in yellow catfish Pelteobagrusfulvidraco

With the increasing production and use of MnO2 NPs and MnSO4 in various fields, their discharge into the aquatic environment is inevitable, which poses potential threats to aquatic organisms and humans. However, to date, few studies have been conducted to investigate the potential mechanism of the toxicity of MnO2 NPs, and a comprehensive understanding of the differences between this mechanism and the toxicity mechanism of inorganic Mn (MnSO4) is still lacking. Since lipid metabolism-relevant parameters have been widely recognized as novel biomarkers for risk assessment of environmental contaminants, the present study investigated the differential mechanisms of how MnO2 NPs and MnSO4 affect hepatic lipid metabolism in a freshwater fish yellow catfish. Compared to MnSO4, dietary MnO2 NPs caused liver injury, increased hepatic lipid accumulation and induced lipotoxicity, and up-regulated mRNA expression of de novo lipogenic genes. Moreover, MnO2 NPs downregulated the expression of miR-92a and miR-92b-3p, microRNAs involved in regulation of lipid metabolism, in the liver. Mechanistically, we found that acls3, an acetyl-coenzyme A synthetase, is target gene of miR-92a, and miR-92a-acsl3-dependent de novo lipogenesis contributes to lipid accumulation and lipotoxicity induced by MnO2 NPs. Collectively, these findings provided novel insights into mechanism whereby miRNAs mediate nanoparticles- and inorganic Mn-induced hepatic lipotoxicity and changes of lipid metabolism in vertebrates. Our findings also shed new perspective for ecotoxicity and ecological risk of MnO2 NPs and MnSO4 in aquatic environment.

PIG-A gene mutation as a mutagenicity biomarker among coke oven workers.

PIG-A gene mutations can be detected in humans, and PIG-A assays can potentially predict the risk of exposure to carcinogens. However, extensive, population-based studies to validate this are lacking. We studied a cohort of occupational coke oven workers with chronic high exposure to carcinogenic polycyclic aromatic hydrocarbons, which are well-studied genotoxins classified by the IARC as carcinogenic to humans. Peripheral blood erythrocytes of workers were assessed for gene mutations using a PIG-A assay, and chromosome damage using the cytokinesis-block micronucleus test with lymphocytes. Two sample populations from a non-industrialized city and new employees in industrial plants were selected as controls. We observed a significantly elevated PIG-A mutation frequency (MF) and increased frequencies of micronuclei (MN) and nuclear buds (NBUDs) in coke oven workers, compared with levels in the control groups. We found that the coke oven workers with different lengths of service had a relatively high mutation frequency. Overall, the study findings showed that occupational exposure of coke oven workers increases the genetic damage and the PIG-A MF could be a potential biomarker for risk assessment of carcinogen exposure.