Cadmium (Cd) poses a threat to fish and human health. Carp is the most widely farmed fish, and it is necessary to study the mechanism of Cd toxicity and effective mitigation methods for Cd poisoning in carps. We previously found that Cd up-regulated miR-375 in common carp spleens, and that IRS1, a factor involved in glucose (GLU) uptake, was a potential target gene of miR-375. However, whether Cd can decrease GLU uptake ability in fish remains unknown. Oxidative stress (OS) and actin cytoskeleton dysfunction (ACD) can take part in the mechanisms of GLU uptake ability reduction. Lycopene (Lyc) is a natural plant antioxidant, and epithelioma papulosum cyprini (EPC) cells are a model cell to study carps. Therefore, we conducted experiments with Cd or/and Lyc treatments to investigate the mechanisms of Lyc alleviating Cd-cytotoxicity on EPC cells from the perspectives of miR-375, OS, ACD, and GLU uptake ability. We found that Lyc mitigated Cd-caused miR-375 increase, OS, ACD, and GLU uptake ability reduction. Moreover, miR-375 overexpression/knockdown experiments demonstrated that miR-375 mediated OS, ACD, and GLU uptake ability reduction and targeted regulated IRS1-PI3K-AKT. Furthermore, NAC intervention experiment demonstrated that ROS mediated ACD and the reduction of GLU uptake via ROS/IRS1-PI3K-AKT. Taken together, Lyc alleviated Cd-decreased GLU uptake ability via miR-375-ROS/IRS1-PI3K-AKT and miR-375/IRS1-PI3K-AKT pathways in EPC cells. Our findings highlighted significant role of miR-375 in Cd-induced toxicity and elucidated the mechanism by which Lyc alleviated Cd-induced toxicity. Our study can provide new information and new targets for resisting environmental pollutant stress in animals.

The association of plasma metals on the risk of cardiovascular diseases (CVD) in adults with prediabetes remains poorly investigated. To assess the association between plasma metal exposure and the risk of CVD in prediabetic adults in the United States using five plasma metals.

Five cycles of data (2011-2012, 2013-2014, 2015-2016, and 2017-2018) from the NHANES were adopted in this study. The plasma metals were measured in 1088 participants with prediabetes. We utilized multivariate logistic regression, WQS, and BKMR models to evaluate the associations between the five plasma metals and the risk of CVD.

The risk of CVD in participants with prediabetes were found to link to the 2nd quartile, 3rd and 4th quartiles of cadmium on the basis of multivariate logistic model (OR = 3.03, 95%CI: 1.17-7.82, P<0.01). Moreover, the joint effect of the five metals on the risk of CVD participants with prediabetes were unveiled using WQS and BKMR models (OR = 1.79, 95%CI: 1.15-2.77, P<0.01). In addition, when the concentrations of the other four metals were controlled at the 25th, 50th, and 75th percentile, correspondingly, cadmium had a statistically significant positive association with the risk of CVD.

The exposure of metals documented by the five metals links to the risk of CVD in participants with prediabetes in the United States. Among all the five metals, cadmium has the strongest association with the risk of CVD in participants with prediabetes.

Although the association between heavy metals in human and the development of metabolic syndrome (MetS) have been extensively studied, the pathogenic mechanism of MetS affected by metals is not clear to date. In this study, a predictive model was developed with machine learning base on the large-scale dataset. These proposed models were evaluated via comparatively analysis of their accuracy and robustness. With the optimal model, two metals significantly correlated with MetS were screened and were employed to infer the pathogenicity mechanism of MetS via molecular docking. Significant associations between heavy metals and MetS were found. Molecular docking provided insights into the interactions between metal ions and key protein receptors involved in metabolic regulation, suggesting a mechanism by which heavy metals interfere with metabolic functions. Specifically, Ba and Cd affect the development of MetS thru their interactions with insulin and estrogen receptors. This study attempted to explore heavy metals' potential roles in MetS at the molecular level. These findings emphasize the importance of addressing environmental exposures in the prevention and treatment of MetS.

The literature has reported heavy metals might alter the physiological and biochemical functions of body organs and cause several health problems. So, the present systematic review and meta-analysis aimed to investigate the association of blood levels of essential or non-essential metals with metabolic syndrome (MetS).

In this systematic review, some international databases including PubMed, Embase, Scopus, and Web of Science were searched up to February 2024. All observational studies which assessed the association of three heavy metals (cadmium, mercury, lead) and bio-elements (chromium, iron, manganese, and magnesium, copper) with the risk of MetS were included. There was no limitation in the time of publication and language. A random-effects meta-analysis was performed to estimate the pooled effect sizes. Possible sources of heterogeneity were explored by meta-regression analysis.

Totally, 29 studies were eligible for meta-analysis. Our results showed that increased level of cadmium (pooled OR: 1.24, 95% CI: 1.05, 1.46) and mercury (pooled OR: 1.22, 95% CI: 1.08, 1.38) significantly increased the risk of MetS. In contrast, increased level of chromium significantly reduced the risk of developing MetS (pooled OR: 0.68, 95% CI: 0.56, 0.83). Moreover, association between lead, iron, copper, magnesium, and manganese with MetS was not statistically significant (P > 0.05). However, elevated lead levels in men increased the odds of MetS.

Our results show a significant association between blood levels of some heavy metals, including cadmium, mercury, and lead, with increased odds of MetS. On the other hand, chromium as a biometal decreased the odds of MetS.

The online version contains supplementary material available at 10.1007/s40200-024-01500-9.

Cardiovascular diseases (CVD), primarily ischemic heart disease and stroke, remain leading global health burdens. Environmental risk factors have a major role in the development of CVD, particularly exposure to heavy metals. The Triglyceride Glucose Index (TyG), a measure of insulin resistance and CVD risk, is the primary focus of this study, which summarizes the most recent findings on the effects of lead (Pb), arsenic (As), and cadmium (Cd) on CVD risk. A higher risk of CVD is correlated with an elevated TyG index, which has been linked to insulin resistance. Exposure to Cd is associated with disturbance of lipid metabolism and oxidative stress, which increases the risk of CVD and TyG. Exposure reduces insulin secretion and signaling, which raises the TyG index and causes dyslipidemia. Pb exposure increases the risk of CVD and TyG index via causing oxidative stress and pancreatic β-cell destruction. These results highlight the need of reducing heavy metal exposure by lifestyle and environmental modifications in order to lower the risk of CVD. To comprehend the mechanisms and create practical management plans for health hazards associated with heavy metals, more study is required.

The pathophysiological effects of chronic heavy metal exposures on human health remains uncertain. In this study, we developed a novel chronic, low-dose exposure of Cadmium (CLEC) model using the hepatocellular cell lines, HepG2 and HUH7. We modulated cell culture conditions to mimic human normoglycemic (5.6 mM) and hyperglycemic (15 mM) states with concomitant cadmium (Cd) exposures for 24 weeks. CLEC cells undergo non-trivial alterations in glucose signaling and metabolic characteristics within our model. We observe elevated baseline reactive oxygen species (ROS) production and decreased 2-NBDG uptake indicative of glucose metabolic dysfunction. Additionally, induction of metallothionein (MT) expression, increased activation of Akt signaling (via phosphorylation) and reduced IRS-2 protein expression are observed in CLEC cells. Cell line specific changes are observed with HepG2 showing a much higher MT gene induction compared to HUH7 cell line which impacts glucose metabolic dysfunction. Hyperglycemic culture conditions (representing type II diabetes) significantly modulate CLEC effects on cells. In conclusion, pathophysiologically relevant models of chronic heavy metal exposures are urgently needed to gain an in-depth, mechanistic understanding of the long-term impacts of toxic metals (e.g., Cd) on human metabolic health.

Contamination from increased anthropogenic activities poses a threat to human health as well as the ecosystem. To develop a nanotechnological approach to improve aqua fisheries, we synthesized magnetic hematite nanoparticle-based gel and evaluated its efficacy in a cadmium-polluted closed system to decontaminate water and improve tilapia fish health.

Green iron oxide nanoparticles were biosynthesized by the metabolite of bacillus subtilis and incorporated into polyvinyl alcohol to construct a hydrogel by cryogelation.

The cryogel had interconnected macropores with diameters widely ranging between 20 and 200 μm and could be free-floating in water. When applied in cadmium-polluted tilapia culture, this nanogel reduced turbidity and ammonia in the aquarium, adsorbed cadmium from the water with a larger quantity on the gel's outer surface than in its center., and reduced cadmium concentration in tilapia's liver, gills, and muscles. Application of this nano-based cryogel reduced the toxic effects of cadmium on tilapia fish. It maintained hepatic and renal cell nuclear integrity as determined by comet assay. This nano-treatment also reversed the cadmium-induced elevations of plasma lipids, glucose, stress marker cortisol, the hepatic enzymes AST and ALT, and the kidney function marker urea, and improved the lymphocytopenia and other hematological functions in tilapia fish intoxicated by cadmium.

Although cadmium exposure had been demonstrated to be toxic to the nervous system, little was known about the link between cadmium exposure and axonal injury. Therefore, the present study aimed to reveal whether there was any correlation between blood cadmium and serum neurofilament light chain (NfL) levels in the general population.

This study included 1040 participants with a median (IQR) age of 47 (35-60) years from the 2013-2014 National Health and Nutrition Examination Survey. Serum NfL levels were measured through immunoassay, and whole blood cadmium concentrations were detected by means of inductively coupled plasma mass spectrometry. Linear regression and restricted cubic spline model was applied to analyze the significance of relationship between blood cadmium and serum NfL levels.

In the full adjusted model, blood cadmium levels were found to be positively associated with serum NfL levels (Q4 vs Q1, β = 3.35, 95 %CI: 0.41, 6.30, p for trend = 0.014). A potential linear positive dose-effect relationship was discovered between blood cadmium and serum NfL levels (p for non-linearity = 0.15). According to the result of stratified analysis, the significant positive relationship between blood cadmium and serum NfL levels was present only in the population of middle-aged and older adults.

The present study suggested a positive association between blood cadmium and serum NfL levels in the general US population.

Cadmium, a common metal pollutant, has been demonstrated to induce type 2 diabetes by disrupting pancreatic β cells function. In this study, transcriptome microarray was utilized to identify differential gene expression in oxidative damage to pancreatic β cells following cadmium exposure. The results indicated that a series of mRNAs, LncRNAs, and miRNAs were altered. Of the differentially expressed miRNAs, miR-29a-3p exhibited the most pronounced alteration, with an 11.62-fold increase relative to the control group. Following this, the target gene of miR-29a-3p was identified as Col3a1 through three databases (miRDB, miRTarbase and Tarbase), which demonstrated a decrease across the transcriptome microarray. The upstream target gene of miR-29a-3p was identified as NONMMUT036805, with decreased expression observed in the microarray. Finally, the expression trend of NONMMUT036805/miR-29a-3p/Col3a1 was reversed following NAC pretreatment. This was accompanied by a reduction in oxidative damage indicators, MDA/ROS/GSH-Px appeared to be negatively affected to varying degrees. In conclusion, this study has demonstrated that multiple RNAs are altered during cadmium exposure-induced oxidative damage in pancreatic β cells. The NONMMUT036805/miR-29a-3p/Col3a1 axis has been shown to be involved in this process, which provides a foundation for the identification of potential targets for cadmium toxicity intervention.

Whilst single chemical exposures are suspected to be obesogenic, the combined role of chemical mixtures in paediatric obesity is not well understood.

We aimed to evaluate the potential associations between chemical mixtures and obesity in a population-based sample of Canadian children.

We ascertained biomonitoring and health data for children aged 3-11 from the cross-sectional Canadian Health Measures Survey from 2007 to 2019. Several chemicals of interest were measured in blood or urine and paediatric obesity was defined based on measured anthropometrics. Using quantile-based G computational analysis, we quantified the effects of three chemical mixtures selected a priori. Models were adjusted for sociodemographic and environmental factors identified through a directed acyclic graph. Results are presented through adjusted relative risks (RR) with 95% confidence intervals (95% CI).

We included 9147 children. Of these, 24.1% were overweight or obese. Exposure to the mixture of bisphenol A, acrylamide, glycidamide, metals, parabens and arsenic increased the risk of childhood overweight or obesity by 45% (95% CI 1.09, 1.93), obesity by 109% (95% CI 1.27, 3.42) and central obesity by 82% (95% CI 1.30, 2.56).

Our findings support the role of early childhood chemical exposures in paediatric obesity and the potential combined effects of chemicals.

Individuals exposed to heavy metals are known to experience physiological and biochemical changes, which raise questions regarding possible health effects. In our earlier research, significant concentrations of vanadium (V), mercury (Hg), cadmium (Cd), and arsenic (As) were found in food and medical packaging materials. This study aimed to evaluate the cognitive, physiological, and biomarker effects of select heavy metal exposure in Wistar rats.

Over a 13-week period, five groups of rats (six rats per group, with both males and females) were assessed to study the effects of oral exposure to V, Hg, Cd, and As. The study focused on evaluating physiological, cognitive, and biochemical markers, with the results compared to those of a control group.

Comparing all groups of rats treated with heavy metals, the study revealed significant deficits in learning and spatial orientation (water maze test); rats treated with V, Cd, and Hg showed signs of depression. Rats treated with As also showed signs of hyperactivity, which may indicate a connection to attention-deficit hyperactivity disorder (rat tail suspension test). The groups exposed to different heavy metals varied in their physiological (water and food intake, urine and feces output) and biochemical responses (enzyme-linked immunosorbent assay, prostate-specific antigen, T3, T4, thyroid-stimulating hormone, carcinoembryonic antigen, and blood glucose analysis), with Hg exhibiting the strongest impacts. Rats given Hg showed signs of hypothyroidism, such as increased food intake and weight gain.

This study clarifies the complex relationships between exposure to heavy metals and various biological systems, shedding light on their potential health impacts. The findings provide insight into the effects of heavy metals on neural and thyroid tissues, as well as their propensity to cause cellular dedifferentiation. However, the study has certain limitations, such as the relatively short duration of exposure and the use of only a few selected biomarkers. Future research should focus on long-term exposure studies, incorporate a broader range of biomarkers, and explore the underlying mechanisms at a molecular level to better understand the full spectrum of health risks associated with heavy metal exposure.

Occupational exposure to toxic elements can adversely affect health. The current study evaluated blood concentrations of potentially toxic elements (PTE) including As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, and Zn in formal and informal workers. Additionally, the study investigated the associations between blood PTE concentrations and reported health outcomes in the study population. The exposed group included women engaged in informal jewelry welding within their homes in Limeira, São Paulo state, Brazil (n = 36) and men who worked at a steel company in Volta Redonda, Rio de Janeiro state, Brazil (n = 22). The control group comprised residents of the same neighborhoods as the workers but without occupational exposure to chemicals (n = 28 in Limeira; n = 27 in Volta Redonda). Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry (TQ ICP-MS) was used to determine PTE concentrations in blood samples. Glycemia, insulin, and lipid profile tests were performed. All participants completed questionnaires on household risk and reported morbidity. The blood concentrations of Cd, As, and Pb, as well as glycemia, were higher in informal workers than in control subjects. No significant differences were observed between formal workers and control subjects. A robust Poisson regression model, adjusted for variables suggested by a Directed Acyclic Graph, disclosed associations of blood lead and arsenic concentrations with the prevalence of neurological manifestations in Limeira. Blood lead levels > 2.6 μg dL-1 were associated with 2.3 times the prevalence of self-reported neurological manifestations (95 % CI: 1.17-4.58; p = 0.02) than lower blood lead concentrations. Furthermore, a positive association between blood cadmium concentrations and glycemia was observed. Informal occupational exposure to these elements may indicate an increased risk of developing diseases. Monitoring exposure and implementing interventions to reduce PTE exposure in the work environment represent significant steps toward prevention.

The quantification of arsenic, mercury, cadmium and lead in the human bloodstream is routinely used today to assess exposure to these toxic metal(loid)s, but the interpretation of the obtained data in terms of their cumulative health relevance remains problematic. Seemingly unrelated to this, epidemiological studies strongly suggest that the simultaneous chronic exposure to these environmental pollutants is associated with the etiology of autism, type 2 diabetes, irritable bowel disease and other diseases. This from a public health point of view undesirable situation urgently requires research initiatives to establish functional connections between human exposure to multiple toxic metal(loid) species and adverse health effects. One way to establish causal exposure-response relationships is a molecular toxicology approach, which requires one to unravel the biomolecular mechanisms that unfold after individual toxic metal(loid)s enter the bloodstream/organ nexus as these interactions ultimately determine which metabolites impinge on target organs and thus provide mechanistic links to diseases of unknown etiology. In an attempt to underscore the importance of the toxicological chemistry of metal(loid)s in the bloodstream, this review summarizes recent progress into relevant bioinorganic processes that are implicated in the etiology of adverse organ-based health effects and possibly diseases. A better understanding of these bioinorganic processes will not only help to improve the regulatory framework to better protect humans from the adverse effects of toxic metal(loid) species, but also represents an important starting point for the development of treatments to ameliorate pollution-induced adverse health effects on human populations, including pregnant women, the fetus and children.

The rising prevalence of diabetes underscores the need for identifying effective prevention strategies. Recent research suggests environmental factors, particularly heavy metals like copper, significantly influence health outcomes, including diabetes, through mechanisms involving inflammation and oxidative stress. This study aims to explore how serum copper levels affect blood glucose, employing NHANES data from 2011 to 2016, to provide insights into environmental health's role in diabetes prevention and management.

The study analyzed data from 2,318 NHANES participants across three cycles (2011-2016), focusing on those with available data on serum copper, inflammatory markers, and blood glucose levels. We utilized principal component analysis for selecting inflammatory markers, mediation analysis to examine direct and indirect effects, multiple linear regression for assessing relationships between markers and glucose levels, and weighted quantile sum regression for evaluating individual and collective marker effects, adjusting for demographic variables and serum copper.

Participants averaged 42.70 years of age, with a near-even split between genders. Average serum copper was 119.50 μg/dL, white blood cell count 6.82 × 109/L, and fasting blood glucose 107.10 mg/dL. Analyses identified significant mediation by inflammatory markers (especially white blood cells: 39.78%) in the copper-blood glucose relationship. Regression analyses highlighted a positive correlation between white blood cells (estimate: 1.077, 95% CI: 0.432 to 2.490, p = 0.013) and copper levels and a negative correlation for monocyte percentage (estimate: -1.573, 95% CI: 0.520 to -3.025, p = 0.003). Neutrophil percentage was notably influential in glucose levels. Sensitive analyses confirmed the study's findings.

Serum copper levels significantly impact blood glucose through inflammatory marker mediation, highlighting the importance of considering environmental factors in diabetes management and prevention. These findings advocate for public health interventions and policies targeting environmental monitoring and heavy metal exposure reduction, emphasizing the potential of environmental health measures in combating diabetes incidence.

Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and air. Most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, and Ca). Cd preferentially accumulates in the proximal tubular epithelium of the kidney, and is excreted in urine when these cells die. Thus, excretion of Cd reflects renal accumulation (body burden) and the current toxicity of Cd. The kidney is the only organ other than liver that produces and releases glucose into the circulation. Also, the kidney is responsible for filtration and the re-absorption of glucose. Cd is the least recognized diabetogenic substance although research performed in the 1980s demonstrated the diabetogenic effects of chronic oral Cd administration in neonatal rats. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and lifestyle factors that could induce excessive weight gain. However, whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of adiposity. This review highlights Cd exposure sources and levels associated with diabetes type 2 and the mechanisms by which Cd disrupts glucose metabolism. Special emphasis is on roles of the liver and kidney, and cellular stress responses and defenses, involving heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide, and a precursor substrate for producing a potent antioxidant, bilirubin. HO-2 appears to have also anti-diabetic and anti-obese actions. In old age, HO-2 deficient mice display a symptomatic spectrum of human diabetes, including hyperglycemia, insulin resistance, increased fat deposition, and hypertension.

Cadmium is a heavy metal that increasingly contaminates food and drink products. Once ingested, cadmium exerts toxic effects that pose a significant threat to human health. The nervous system is particularly vulnerable to prolonged, low-dose cadmium exposure. This review article provides an overview of cadmium's primary mechanisms of neurotoxicity. Cadmium gains entry into the nervous system via zinc and calcium transporters, altering the homeostasis for these metal ions. Once within the nervous system, cadmium disrupts mitochondrial respiration by decreasing ATP synthesis and increasing the production of reactive oxygen species. Cadmium also impairs normal neurotransmission by increasing neurotransmitter release asynchronicity and disrupting neurotransmitter signaling proteins. Cadmium furthermore impairs the blood-brain barrier and alters the regulation of glycogen metabolism. Together, these mechanisms represent multiple sites of biochemical perturbation that result in cumulative nervous system damage which can increase the risk for neurological and neurodegenerative disorders. Understanding the way by which cadmium exerts its effects is critical for developing effective treatment and prevention strategies against cadmium-induced neurotoxic insult.

Variations in dietary intake and environmental exposure patterns of essential and non-essential trace metals influence many aspects of human health throughout the life span.

To examine the relationship between urine profiles of essential and non-essential metals in mother-offspring pairs and their association with early dysglycemia.

Herein, we report findings from an ancillary study to the international Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study (HAPO-FUS) that examined urinary essential and non-essential metal profiles from mothers and offspring ages 10-14 years (1012 mothers, 1013 offspring, 968 matched pairs) from 10 international sites.

Our analysis demonstrated a diverse exposure pattern across participating sites. In multiple regression modelling, a positive association between markers of early dysglycemia and urinary zinc was found in both mothers and offspring after adjustment for common risk factors for diabetes. The analysis showed weaker, positive, and negative associations of the 2-h glucose value with urinary selenium and arsenic respectively. A positive association between 2-h glucose values and cadmium was found only in mothers in the fully adjusted model when participants with established diabetes were excluded. There was a high degree of concordance between mother and offspring urinary metal profiles. Mother-to-offspring urinary metal ratios were unique for each metal, providing insights into changes in their homeostasis across the lifespan.

Urinary levels of essential and non-essential metals are closely correlated between mothers and their offspring in an international cohort. Urinary levels of zinc, selenium, arsenic, and cadmium showed varying degrees of association with early dysglycemia in a comparatively healthy cohort with a low rate of preexisting diabetes.

Our data provides novel evidence for a strong correlation between mother and offspring urinary metal patterns with a unique mother-to-offspring ratio for each metal. The study also provides new evidence for a strong positive association between early dysglycemia and urinary zinc, both in mothers and offspring. Weaker positive associations with urinary selenium and cadmium and negative associations with arsenic were also found. The low rate of preexisting diabetes in this population provides the unique advantage of minimizing the confounding effect of preexisting, diabetes related renal changes that would alter the relationship between dysglycemia and renal metal excretion.

Metabolic syndrome (MetS) is an important public health issue that affects millions of people around the world and is growing to pandemic-like proportions. This syndrome is defined by the World Health Organization (WHO) as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Moreover, the etiology of MetS is multifactorial, involving many environmental factors, including toxicant exposures. Several studies have associated MetS with heavy metals exposure, which is the focus of this review. Environmental and/or occupational exposure to heavy metals are a major risk, contributing to the development of chronic diseases. Of particular note, toxic metals such as mercury, lead, and cadmium may contribute to the development of MetS by altering oxidative stress, IL-6 signaling, apoptosis, altered lipoprotein metabolism, fluid shear stress and atherosclerosis, and other mechanisms. In this review, we discuss the known and potential roles of heavy metals in MetS etiology as well as potential targeted pathways that are associated with MetS. Furthermore, we describe how new approaches involving proteomic and transcriptome analysis, as well as bioinformatic tools, may help bring about an understanding of the involvement of heavy metals and metalloids in MetS.

The link between mixed heavy metals (mercury, lead, and cadmium), prediabetes, and type 2 diabetes mellitus (T2DM), especially molecular mechanisms, is poorly understood. Thus, we aimed to identify the association between mixed heavy metals and T2DM and its components using a data set from the Korean National Health and Nutrition Examination Survey. We further analyzed the main molecular mechanisms implicated in T2DM development induced by mixed heavy metals using in-silico analysis. Our findings observed that serum mercury was associated with prediabetes, elevated glucose, and ln2-transformed glucose when using different statistical methods. "AGE-RAGE signaling pathway in diabetic complications", "non-alcoholic fatty liver disease", "metabolic Syndrome X", and three miRNAs (hsa-miR-98-5p, hsa-let-7a-5p, and hsa-miR-34a-5p) were listed as the most important molecular mechanisms related to T2DM development caused by mixed heavy metals. These miRNA sponge structures were created and examined, and they may be beneficial in the treatment of T2DM. The predicted cutoff values for three heavy metal levels linked to T2DM and its components were specifically identified. Our results imply that chronic exposure to heavy metals, particularly mercury, may contribute to the development of T2DM. To understand the changes in the pathophysiology of T2DM brought on by a combination of heavy metals, more research is required.

To meet the increased need for food and energy because of the economic shift brought about by the Industrial Revolution in the 19th century, there has been an increase in persistent organic pollutants (POPs), atmospheric emissions and metals in the environment. Several studies have reported a relationship between these pollutants and obesity, and diabetes (type 1, type 2 and gestational). All of the major pollutants are considered to be endocrine disruptors because of their interactions with various transcription factors, receptors and tissues that result in alterations of metabolic function. POPs impact adipogenesis, thereby increasing the prevalence of obesity in exposed individuals. Metals impact glucose regulation by disrupting pancreatic β-cells, causing hyperglycemia and impaired insulin signaling. Additionally, a positive association has been observed between the concentration of endocrine disrupting chemicals (EDCs) in the 12 weeks prior to conception and fasting glucose levels. Here, we evaluate what is currently known regarding the link between environmental pollutants and metabolic disorders. In addition, we indicate where further research is required to improve our understanding of the specific effects of pollutants on these metabolic disorders which would enable implementation of changes to enable their prevention.

Cadmium is a hazardous metal with multiple organ toxicity that causes great harm to human health. Cadmium enters the human body through occupational exposure, diet, drinking water, breathing, and smoking. Cadmium accumulation in the human body is associated with increased risk of developing obesity, cardiovascular disease, diabetes, and metabolic syndrome (MetS). Cadmium uptake is enhanced during pregnancy and can cross the placenta affecting placental development and function. Subsequently, cadmium can pass to fetus, gathering in multiple organs such as the liver and pancreas. Early-life cadmium exposure can induce hepatic oxidative stress and pancreatic β-cell dysfunction, resulting in insulin resistance and glucose metabolic dyshomeostasis in the offspring. Prenatal exposure to cadmium is also associated with increasing epigenetic effects on the offspring's multi-organ functions. However, whether and how maternal exposure to low-dose cadmium impacts the risks of developing type 2 diabetes (T2D) in the young and/or adult offspring remains unclear. This review collected available data to address the current evidence for the potential role of cadmium exposure, leading to insulin resistance and the development of T2D in offspring. However, this review reveals that underlying mechanisms linking prenatal cadmium exposure during pregnancy with T2D in offspring remain to be adequately investigated.

Non-alcoholic fatty liver disease (NAFLD), which starts with liver steatosis, is a growing worldwide epidemic responsible for chronic liver diseases. Among its risk factors, exposure to environmental contaminants, such as endocrine disrupting compounds (EDC), has been recently emphasized. Given this important public health concern, regulation agencies need novel simple and fast biological tests to evaluate chemical risks. In this context, we developed a new in vivo bioassay called StAZ (Steatogenic Assay on Zebrafish) using an alternative model to animal experimentation, the zebrafish larva, to screen EDCs for their steatogenic properties. Taking advantage of the transparency of zebrafish larvae, we established a method based on fluorescent staining with Nile red to estimate liver lipid content. Following testing of known steatogenic molecules, 10 EDCs suspected to induce metabolic disorders were screened and DDE, the main metabolite of the insecticide DDT, was identified as a potent inducer of steatosis. To confirm this and optimize the assay, we used it in a transgenic zebrafish line expressing a blue fluorescent liver protein reporter. To obtain insight into DDE's effect, the expression of several genes related to steatosis was analyzed; an up-regulation of scd1 expression, probably relying on PXR activation, was found, partly responsible for both membrane remodeling and steatosis.

In much of the world, currently employed upper limits of tolerable intake and acceptable excretion of cadmium (Cd) (ECd/Ecr) are 0.83 µg/kg body weight/day and 5.24 µg/g creatinine, respectively. These figures were derived from a risk assessment model that interpreted β2-microglobulin (β2MG) excretion > 300 μg/g creatinine as a "critical" endpoint. However, current evidence suggests that Cd accumulation reduces glomerular filtration rate at values of ECd/Ecr much lower than 5.24 µg/g creatinine. Low ECd/Ecr has also been associated with increased risks of kidney disease, type 2 diabetes, osteoporosis, cancer, and other disorders. These associations have cast considerable doubt on conventional guidelines. The goals of this paper are to evaluate whether these guidelines are low enough to minimize associated health risks reliably, and indeed whether permissible intake of a cumulative toxin like Cd is a valid concept. We highlight sources and levels of Cd in the human diet and review absorption, distribution, kidney accumulation, and excretion of the metal. We present evidence for the following propositions: excreted Cd emanates from injured tubular epithelial cells of the kidney; Cd excretion is a manifestation of current tissue injury; reduction of present and future exposure to environmental Cd cannot mitigate injury in progress; and Cd excretion is optimally expressed as a function of creatinine clearance rather than creatinine excretion. We comprehensively review the adverse health effects of Cd and urine and blood Cd levels at which adverse effects have been observed. The cumulative nature of Cd toxicity and the susceptibility of multiple organs to toxicity at low body burdens raise serious doubt that guidelines concerning permissible intake of Cd can be meaningful.

Previous findings have reported the role of different types of heavy metals in cardiometabolic diseases. In the present research, we aim to evaluate the association between blood cadmium levels and Metabolic Syndrome (MetS) based on the large-sample NHANES data. Public availably data from NHANES 2017-2020 cycle was obtained. Participants were divided into MetS and non-MetS groups according to waist circumference (WC), triglyceride (TG), high-density lipoprotein (HDL), blood pressure (BP) and fasting plasma glucose (FPG) levels based on the National Cholesterol Education Program (NCEP) criteria. Student's t test, Mann-Whitney U test, and Chi-square test were performed for univariate analysis. Multivariate logistic analysis was performed to explore the relationship between blood cadmium and MetS and research findings were presented in forest plot. We also investigated the association of blood cadmium and MetS in subgroups stratified by age, gender and race. Population with MetS had significantly higher levels of blood [0.30 (0.18-0.54) vs. 0.24 (0.15-0.46) ug/L, p < 0.001] and urinary cadmium levels [0.29 (0.17-0.52) vs. 0.20 (0.09-0.42) ug/L, p < 0.001] compared with those without MetS. Higher blood cadmium concentrations were also observed in participants with elevated WC (0.28 vs. 023 ug/L, p < 0.001], TG (0.28 vs. 0.26 ug/L, p = 0.029), BP (0.33 vs. 0.23 ug/L, p < 0.001) and FPG (0.29 vs. 0.24 ug/L, p < 0.001) compared with those with normal metabolic parameters. Multivariate logistic regression showed that one-unit increasement of blood cadmium was associated with 1.25 times higher prevalence ratios for MetS after adjusting potential confounders (95% CI: 1.06-1.48, p = 0.0083). The associations between serum cadmium concentrations and MetS components were then evaluated, and the results showed higher blood cadmium levels were associated with higher risk for elevated TG, low HDL and elevated BP when treated as continuous variable. When treated as categorical variable, only BP was found positively associated with blood cadmium. Stratified multiple logistic regression analysis indicated that the positive association between blood cadmium and MetS remained significant in subjects less than 60 years old and female subgroup. In conclusion, the cross-sectional survey suggested the positive association between blood cadmium levels and risk for MetS, prospective research need to be conducted for further evaluation of the causal relationship between blood cadmium and MetS.

Environmentally relevant toxic substances may affect human health, provoking numerous harmful effects on central nervous, respiratory, cardiovascular, endocrine and reproductive system, and even cause various types of carcinoma. These substances, to which general population is constantly and simultaneously exposed, enter human body via food and water, but also by inhalation and dermal contact, while accumulating evidence suggests that probiotic cultures are able to efficiently adsorb and/or degrade them. Cell wall of probiotic bacteria/fungi, which contains structures such as exopolysaccharide, teichoic acid, protein and peptidoglycan components, is considered the main place of toxic substances adsorption. Moreover, probiotics are able to induce metabolism and degradation of various toxic substances, making them less toxic and more suitable for elimination. Other probable in vivo protective effects have also been suggested, including decreased intestinal absorption and increased excretion of toxic substances, prevented gut microbial dysbiosis, increase in the intestinal mucus secretion, decreased production of reactive oxygen species, reduction of inflammation, etc. Having all of this in mind, this review aims to summarize the state-of-the-art knowledge regarding the potential protective effects of different probiotic strains against environmentally relevant toxic substances (mycotoxins, polycyclic aromatic hydrocarbons, pesticides, perfluoroalkyl and polyfluoroalkyl substances, phthalates, bisphenol A and toxic metals).

The workers exposed to metal fumes had an increased risk of metabolic syndrome, which was correlated with decreased serum adiponectin. Thus, we aimed to explore whether heavy metal exposure affects the adiponectin level. There were 96 male workers recruited from a shipyard at baseline. Apart from 82 participants completed the follow-up assessments, new participants were recruited in next year. Finally, there were 100 welding workers in the exposure group and 31 office workers in the control group. Inferential statistics on repeated measures were performed using generalized estimating equations. A weighted quantile sum (WQS) regression model was conducted to examine the joint effect of the multimetal exposure with serum adiponectin. Significantly negative associations of metals with adiponectin were detected in the welding workers, including Cr (β = -0.088; 95% CI: -0.148, -0.027), Mn (β = -0.174; 95% CI: -0.267, -0.081), Co (β = -0.094; 95% CI: -0.158, -0.029), Ni (β = -0.108; 95% CI: -0.208, -0.008), Cd (β = -0.067; 95% CI: -0.115, -0.018), and Pb (β = -0.089; 95% CI: -0.163, -0.015). The WQS regression suggested that Pb was the greatest contributor. In conclusion, our findings highlighted that welding workers exposed to heavy metals would reduce serum adiponectin.

Cadmium (Cd) is a toxic metal, present in all matrices of the environment and a common food contaminant. Human exposure to it may elicit many diverse health impairments. The aim of this study was to assess the dietary exposure to Cd for the adult population and preschool children in Serbia using probabilistic methodology. We measured Cd in 11,227 food samples belonging to 50 food items on the Serbian market. Cd was detected in 90% of the tested food items, and in 30.8% of the overall tested samples. The food item that contributed the most to total dietary Cd intake was potatoes (median Cd concentration of 7 ng/g) in adults, and fruit and vegetable juices in children (median Cd concentration of 19 ng/g). Weekly Cd intake shown as 50th and 95th percentiles were 2.54 and 4.74 µg/kg bw in the adult population, and 3.29 and 4.93 µg/kg bw in children. The results of this study are rather preliminary and should be considered as an indication of the need for further, more refined research, which would contribute to a more realistic risk assessment as a high-priority approach, especially in the case of vulnerable subpopulations such as children. Abbreviations: AT SDR: Agency for Toxic Substances and Disease Registry; EEA: European Environment Agency; EFSA: European Food Safety Authority; FAO/WHO: Food and Agriculture Organization/World Health Organization; HI: hazard index; IARC: International Agency for Research on Cancer; JECFA: Joint FAO/WHO Expert Committee on Food Additives; LOD: limit of detection; Cd: cadmium; TWI: tolerable weekly intake; UNEP: United Nations Environment Program; WI: weekly intake.

The major goal of this study was to estimate the correlations and dose-response pattern between the measured blood toxic metals (cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni))/metalloid (arsenic (As)) and serum insulin level by conducting Benchmark dose (BMD) analysis of human data. The study involved 435 non-occupationally exposed individuals (217 men and 218 women). The samples were collected at health care institutions in Belgrade, Serbia, from January 2019 to May 2021. Blood sample preparation was conducted by microwave digestion. Cd was measured by graphite furnace atomic absorption spectrophotometry (GF-AAS), while inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure Hg, Ni, Cr and As. BMD analysis of insulin levels represented as quantal data was done using the PROAST software version 70.1 (model averaging methodology, BMD response: 10%). In the male population, there was no correlation between toxic metal/metalloid concentrations and insulin level. However, in the female population/whole population, a high positive correlation for As and Hg, and a strong negative correlation for Ni and measured serum insulin level was established. BMD modelling revealed quantitative associations between blood toxic metal/metalloid concentrations and serum insulin levels. All the estimated BMD intervals were wide except the one for As, reflecting a high degree of confidence in the estimations and possible role of As as a metabolic disruptor. These results indicate that, in the case of As blood concentrations, even values higher than BMD (BMDL): 3.27 (1.26) (male population), 2.79 (0.771) (female population), or 1.18 (2.96) μg/L (whole population) might contribute to a 10% higher risk of insulin level alterations, meaning 10% higher risk of blood insulin increasing from within reference range to above reference range. The obtained results contribute to the current body of knowledge on the use of BMD modelling for analysing human data.

Gestational diabetes mellitus (GDM) has become a global concern for its severe adverse effects on both mother and fetus. Recent epidemiological studies reported inconsistent results of the association between cadmium (Cd) exposure and GDM. Therefore, a systematic review and meta- analysis were performed. PubMed, Web of Science, Scopus, Embase, and SpringerLink were searched up to July 2021. Observational studies containing the adjusted relative risks between Cd exposure and GDM were included in the quantitative synthesis. The retrieval comprised 218 articles out of which 11 met our criteria and 9 were included in the meta-analysis, representing a total of 32,392 subjects (2881 GDM). In total, Cd exposure might increase the risk of GDM in some extent (OR = 1.21, 95% CI [0.89, 1.64]), even without statistical significance in high heterogeneity (Q = 28.45, p < 0.05, I² = 71.9%). Filtering two outliers indicated by Galbraith plot yielded a similar risk (OR = 1.19, 95% CI [1.02, 1.39]) with statistical significance. However, the heterogeneity among studies was obviously reduced (Q = 11.75, p = 0.068, I² = 48.9%). Additionally, biological specimen, study design, and diagnostic criteria contributed to the high heterogeneity according to the subgroup analysis. Since some important results do not deny that Cd exposure increases the risk of GDM, high-quality multi-centered large cohort studies are required in the future.

While metal exposures are generally high among informal electronic waste (e-waste) recyclers, the joint effect of metals and dietary macronutrients on their metabolic health is unknown. Therefore, we investigated the relationship between metal exposures, dietary macronutrients intake, and blood glucose levels of e-waste recyclers at Agbogbloshie using dietary information (48-h recall survey), blood metals (Pb & Cd), and HbA1C levels of 151 participants (100 e-waste recyclers and 51 controls from the Accra, Ghana) in March 2017. A linear regression model was used to estimate the joint relationship between metal exposures, dietary macronutrient intake, and blood glucose levels. Except for dietary proteins, both groups had macronutrient deficiencies. Diabetes prevalence was significantly higher among controls. Saturated fat, OMEGA-3, and cholesterol intake were associated with significant increases in blood glucose levels of recyclers. In a joint model, while 1 mg of cholesterol consumed was associated with a 0.7% increase in blood glucose, 1 g/L of Pb was found to significantly increase blood glucose levels by 0.9% among recyclers. Although the dietary consumption of cholesterol and fat was not high, it is still possible that exposure to Pb and Cd may still increase the risk of diabetes among both e-waste recyclers and the general population.

Metals play an important role in diabetes mellitus. This cross-sectional study aimed to evaluate the overall, individual and interactive effects of multi-metal exposure on the prevalence of diabetes mellitus, impaired fasting glucose (IFG) rate and fasting blood glucose (FBG) levels.

The FBG levels of a study population from a cadmium (Cd)-polluted area (n = 250) and an unpolluted area (n = 204), and the metal levels, including magnesium, calcium (Ca), iron (Fe), zinc (Zn), arsenic (As), Cd, copper and lead (Pb) in blood and urine were detected. The study population was divided into a normal fasting glucose group, an IFG group and a diabetes mellitus group on the basis of FBG levels.

The IFG rate and diabetes mellitus prevalence were negatively associated with blood Cd and urine Zn levels (IFG rate: odds ratio [OR] 0.780, 95% confidence interval [CI] 0.655-0.928; OR 0.622, 95% CI 0.465-0.831. Diabetes mellitus prevalence: OR 0.506, 95% CI 0.288-0.888; OR 0.609, 95% CI 0.395-0.939), the IFG rate was positively associated with urine Fe levels (OR 1.876, 95% CI 1.290-2.778), and diabetes mellitus prevalence was positively associated with urine Pb and blood Fe levels (OR 1.185, 95% CI 1.022-1.376; OR 1.008, 95% CI 1.001-1.014). A linear negative correlation was observed between FBG levels and blood Cd, and non-linear inverted U-shaped associations were found between FBG levels and Zn, Pb and copper in urine.

This research suggests that multi-metal exposure, especially Cd, Fe, Zn, copper and Pb, is linked to diabetes mellitus, and the interactive effects of multiple metals require further exploration.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.

Cadmium (Cd) exposure is a worldwide environmental threat to the public health and participates in the pathogenesis of multiple diseases. Epidemiologic research have established a direct relation between Cd exposure and diabetes development in humans. Although pancreatic β-cell dysfunction has been considered as the major culprit in the pathogenesis of diabetes, there is a paucity of studies to elucidate the molecular mechanism of Cd toxicity on β-cells.

To unveil the toxic effect and its underlying mechanism of Cd exposure on β-cells, we used an in vitro MIN6 cell model of environment-relevant Cd exposure to elucidate the crucial role of mtROS-mediated mitochondrial dysfunction and inflammatory response in suppression of pancreatic β-cell insulin secretion.

We uncovered that Cd treatment suppresses cell viability and induces insulin secretion dysfunction in a dose-dependent manner. Moreover, Cd exposure elicits the inflammatory response, as indicated by increased IL-1β, IL-6 and TNF-α expressions. Significant elevations of intracellular ROS and mitochondrial ROS levels were detected as early as 3 h after Cd treatment. In mitochondrial function analysis, we demonstrated that Cd treatment induced mitochondrial dysfunction and disorder of mitochondrial fission indicated by the significant decline in ATP production, the marked depolarization of mitochondrial membrane potential, the decrease in mtDNA copy numbers, the suppressions of mitochondrial transcription factor A (Tfam) and mitochondrial fission-related gene Drp1 expressions. Pretreatment with TEMPO, a specific mitochondrial ROS (mtROS) scavenger, efficiently antagonizes Cd cytotoxicity, which is indicated by attenuating Cd-induced mitochondrial dysfunction, suppressing IL-1β, IL-6 and TNF-α expressions, ameliorating insulin production dysfunction and preserving cell viability in MIN6 cells.

Our study demonstrates that Cd exposure induces an inflammatory response through mtROS-mediated mitochondrial dysfunction. Antagonism of mtROS production might be an effective strategy to prevent pancreatic toxicity from environment-relevant Cd exposure.

Many metals exhibit genotoxic and/or carcinogenic effects. These toxic metals can be found ubiquitously - in drinking water, food, air, general use products, in everyday and occupational settings. Exposure to such carcinogenic metals can result in serious health disorders, including cancer. Arsenic, cadmium, chromium, nickel, and their compounds have already been recognized as carcinogens by the International Agency for Research on Cancer. This review summarizes a wide range of epigenetic mechanisms contributing to carcinogenesis induced by these metals, primarily including, but not limited to, DNA methylation, miRNA regulation, and histone posttranslational modifications. The mechanisms are described and discussed both from a metal-centric and a mechanism-centric standpoint. The review takes a broad perspective, putting the mechanisms in the context of real-life exposure, and aims to assist in guiding future research, particularly with respect to the assessment and control of exposure to carcinogenic metals and novel therapy development.

Cd exposure has been demonstrated to induce a variety of metabolic disorders accompanied with imbalance of glucose and lipid homeostasis. The metabolic toxicity of Cd exposure at metabolome-wide level remains elusive. In our study, we demonstrated that Cd exposure via drinking water increased blood glucose levels, decreased serum insulin levels, led to glucose intolerance and suppressed insulin expression in the pancreas of C57/6J mice. Cd exposure significantly inhibited cell viability and suppressed insulin secretion in MIN6 cells in vitro. Since pancreatic β-cells are the only source of insulin production in the body and play a pivotal role in modulating glucose and lipid metabolisms, we further delineated the metabolomic signatures of Cd exposure in insulin-secreting MIN6 cells by using non-target metabolomics. PCA and OPLS-DA analysis clearly suggested that Cd exposure led to a marked metabolic alteration in MIN6 cells. 76 perturbed metabolites were identified after Cd exposure. Classification of metabolites suggested that Cd perturbed metabolites belong to nucleosides, nucleotides and analogues, organic acids and derivatives, and lipids and lipid-like molecules. 28 perturbed metabolites existed in mitochondrion, suggesting mitochondrion as the major target organelle in metabolic toxicity of Cd exposure. KEGG pathway analysis revealed that 20 metabolic pathways were disturbed by Cd exposure. Mitochondrial TCA cycle and glycerophospholipid metabolism were remarkably disturbed. The mRNA expressions of genes in mitochondrial TCA cycle and fatty acid oxidation in pancreas and MIN6 cells were significantly dysregulated by Cd exposure. Disturbances in mitochondrial TCA cycle and glycerophospholipid metabolism result in producing perturbed metabolites in pancreatic β-cells. Moreover, 14 perturbed metabolites identified in MIN6 cells co-existed in the urine of Cd exposed workers. 11 biomarkers of diabetes mellitus were also found to be significantly altered in the urine of Cd exposed workers. In conclusion, findings of this study greatly extend our understanding of metabolic toxicity of Cd exposure in pancreatic β-cells at metabolome-wide level and offer some new clues for linking Cd exposure to development of diabetes mellitus. Results of this study also support the notion that Cd induced metabolic toxicity could be monitored by examining perturbed urinary metabolites in humans and highlight the significance of reducing Cd exposure via drinking water at population level.

The study investigated the potential relationships between air pollution, socio-economy, and proven pathologies (e.g., respiratory, cardiovascular) within an industrial area in Southern France (Etang de Berre), gathering steel industries, oil refineries, shipping, road traffic and experiencing a Mediterranean climate. A total of 178 variables were simultaneously integrated within a Bayesian model at intra-urban scale. Various unsupervised and supervised algorithms (maximum spanning tree, tree-augmented naive classifier) as well as sensitivity analyses were used to better understand the links between all variables, and highlighted correlations between population exposure to air pollutants and some pathologies. Adverse health effects (bronchus and lung cancers for 15-65 years old people) were observed for hydrofluoric acid at low background concentration (<0.003 μg m^-3) while exposure to particulate cadmium (0.210-0.250 μg m^-3) disrupts insulin metabolism for people over 65 years-old leading to diabetes. Bronchus and lung cancers for people over 65 years-old occurred at low background SO₂ concentration (6 μg m^-3) below European limit values. When benzo[k]fluoranthene exceeded 0.672 μg m^-3, we observed a high number of hospital admissions for respiratory diseases for 15-65 years-old people. The study also revealed the important influence of socio-economy (e.g., single-parent family, people with no qualification at 15 years-old) on pathologies (e.g., cardiovascular diseases). Finally, a diffuse polychlorinated biphenyl (PCB) pollution was observed in the study area and can potentially cause lung cancers.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal and aggressive malignancies with a 5-year survival rate less than 9%. Early detection is particularly difficult due to the lack of symptoms even in advanced stages. microRNAs (miRs/miRNAs) are small (~ 18-24 nucleotides), endogenous, non-coding RNAs, which are involved in the pathogenesis of several malignancies including PDAC. Alterations of miR expressions can lead to apoptosis, angiogenesis, and metastasis. The role of environmental pollutants such as cadmium (Cd) in PDAC has been suggested but not fully understood. This study underlines the role of miRs (miR-221, miR-155, miR-126) in response to cadmium chloride (CdCl2) in vitro. Lethal concentration (LC50) values for CdCl2 resulted in a toxicity series of AsPC-1 > HPNE > BxPC-3 > Panc-1 = Panc-10.5. Following the treatment with CdCl2, miR-221 and miR-155 were significantly overexpressed, whereas miR-126 was downregulated. An increase in epithelial-mesenchymal transition (EMT) via the dysregulation of mesenchymal markers such as Wnt-11, E-cadherin, Snail, and Zeb1 was also observed. Hence, this study has provided evidence to suggest that the environmental pollutant Cd can have a significant role in the development of PDAC, suggesting a significant correlation between miRs and Cd exposure during PDAC progression. Further studies are needed to investigate the precise role of miRs in PDAC progression as well as the role of Cd and other environmental pollutants.

Growing evidence suggests that metal exposure contributes to metabolic syndrome (MetS), but little is known about the effects of combined exposure to metal mixtures. This cross-sectional study included 3748 adults who were recruited from the Medical Physical Examination Center of Tongji Hospital, Wuhan, China. The levels of 21 metal(loid)s in urine were measured by inductively coupled plasma mass spectrometry. MetS was diagnosed according to National Cholesterol Education Program's Adult Treatment Panel III recommendations. Multivariate logistic regression model was uesd to explore the effects of single-metal and multi-metal exposures. The elastic net (ENET) regularization with an environmental risk score (ERS) was performed to estimate the joint effects of exposure to metal mixtures. A total of 636 participants (17%) were diagnosed with MetS. In single metal models, MetS was positively associated with zinc (Zn) and negatively associated with nickel (Ni). In multiple metal models, the associations remained significant after adjusting for the other metals. In the joint association analysis, the ENET models selected Zn as the strongest predictor of MetS. Compared to the lowest quartile, the highest quartile of ERS was associated with an elevated risk of MetS (OR = 3.72; 95% CI: 2.77, 5.91; P-trend < 0.001). Overall, we identified that the combined effect of multiple metals was related to an increased MetS risk, with Zn being the major contributor. These findings need further validation in prospective studies.

Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association.

To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association.

After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes.

We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only.

Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model.

In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine.

This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.