Copper, one of the most prolific transition metals in the body, is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations. Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins, including copper transporters (CTR1 and CTR2), the two copper ion transporters the Cu -transporting ATPase 1 (ATP7A) and Cu-transporting beta (ATP7B), and the three copper chaperones ATOX1, CCS, and COX17. Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue. Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins, including ceruloplasmin and metallothionein, is involved in the pathogenesis of neurodegenerative disorders. However, the exact mechanisms underlying these processes are not known. Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress. Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction. Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation, with elevated levels activating several critical inflammatory pathways. Additionally, copper can bind aberrantly to several neuronal proteins, including alpha-synuclein, tau, superoxide dismutase 1, and huntingtin, thereby inducing neurotoxicity and ultimately cell death. This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases, with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis. By synthesizing the current findings on the functions of copper in oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding, we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders, such as Wilson's disease, Menkes' disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Potential clinically significant therapeutic targets, including superoxide dismutase 1, D-penicillamine, and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline, along with their associated therapeutic agents, are further discussed. Ultimately, we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

Maternal exposure to toxic and essential elements can be transferred to the fetus. Deciduous tooth dentine, formed prenatally, serves as a potential biomarker for fetal exposure.

To investigate the relationship between maternal blood Pb, Mn, Cu, Mo and Zn element concentrations and the corresponding child tooth dentine levels in mid pregnancy. A secondary objective explores the predictive value of maternal blood element concentrations for child dentine element levels for the same metals.

Early-life element concentrations were measured in maternal whole blood from the 2nd trimester and in child tooth dentine from 94 child-mother dyads enrolled in the Norwegian Mother, Father and Child Cohort Study (MoBa), The Norwegian Environmental Biobank (NEB) and the MoBaTooth biobank. The relationship between lead (Pb), manganese (Mn), copper (Cu), molybdenum (Mo) and zinc (Zn) in maternal blood and child dentine was examined using correlations and Receiver Operating Characteristic (ROC) curves.

Maternal blood Pb concentration and child dentine Pb in 2nd trimester-average correlated strongly for both girls and boys (r = 0.58, p < 0.001 and r = 0.51, p < 0.001) and was able to predict child dentine Pb. Cu correlated negatively between mothers and boys (r = -0.35, p < 0.001), and with borderline significance for girls (r = -0.17, p = 0.058). For Mn, Mo and Zn the associations between maternal blood and child dentine were less clear and differed by child sex.

Our analysis confirmed a strong association between maternal blood Pb concentration and child tooth dentine Pb. These findings offer a promising biomarker of early life exposure and may help to identify consequences of maternal exposure during pregnancy.

Manganese (Mn) has been characterized as an environmental pollutant. Excessive releases of Mn due to human activities have increased Mn levels in the environment over the years, posing a threat to human health and the environment. Long-term exposure to high concentrations of Mn can induce neurotoxicity. Therefore, toxicological studies on Mn are of paramount importance. Mn induces oxidative stress through affecting the level of reactive oxygen species (ROS), and the overabundance of ROS further triggers ferroptosis. Additionally, Mn2+ was found to be a novel activator of the cyclic guanosine-adenosine synthase (cGAS)-stimulator of interferon genes (STING) pathway in the innate immune system. Thus, we speculate that Mn exposure may promote ROS production by activating the cGAS-STING pathway, which further induces oxidative stress and ferroptosis, and ultimately triggers Mn neurotoxicity. This review discusses the mechanism between Mn-induced oxidative stress and ferroptosis via activation of the cGAS-STING pathway, which may offer a prospective direction for future in-depth studies on the mechanism of Mn neurotoxicity.

Evidence on the relationship between dietary zinc intake and stroke in American populations is limited. This study aimed to investigate the association between dietary zinc consumption and stroke prevalence among US adults. This cross-sectional study analyzed data from adults (≥ 18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2020. Dietary zinc intake, stroke history, and other relevant factors were examined. Logistic regression models were used to assess the association between dietary zinc consumption and stroke risk, while restricted cubic splines (RCS) were applied to explore potential non-linear relationships. A total of 2642 adults from four NHANES cycles (2013-2020) were included in the analysis. In multivariate logistic regression, individuals in the second quartile of dietary zinc intake (Q2: 6.09-8.83 mg/day) had a significantly lower odds ratio (OR) for stroke (OR = 0.64, 95% confidence interval (CI) 0.41-0.99, p = 0.044) compared with those in the lowest quartile (Q1: ≤6.08 mg/day). RCS analysis indicated an L-shaped relationship between dietary zinc intake and stroke odds (p = 0.041). Threshold analysis revealed that for individuals consuming less than 8.82 mg of zinc daily, the OR for stroke was 0.858 (95% CI 0.74-0.99, p = 0.037). Our findings suggest an L-shaped association between dietary zinc intake and stroke prevalence in American adults, with higher zinc intake associated with lower odds of stroke within a specific intake range.

Enhancers play critical roles in gene expression, but a full understanding of their complex functions has yet to be defined. The cellular response to excess zinc levels in Caenorhabditis elegans requires the HIZR-1 transcription factor, which binds the high-zinc activation (HZA) enhancer in the promoters of multiple target genes. Cadmium hijacks the excess zinc response by binding and activating HIZR-1. By analyzing the genome-wide transcriptional response to excess zinc and cadmium, we identified two positions in the genome where head-to-head oriented genes are both induced by metals. In both examples, a single predicted HZA enhancer is positioned between the two translational start sites. We hypothesized that a single enhancer can control both head-to-head genes, an arrangement that has not been extensively characterized. To test this hypothesis, we used CRISPR genome editing to precisely delete the HZAmT enhancer positioned between mtl-2 and T08G5.1; in this mutant, both head-to-head genes display severely reduced zinc-activated transcription, whereas zinc-activated transcription of more distant genes was not strongly affected. Deleting the HZAcF enhancer positioned between cdr-1 and F35E8.10 caused both head-to-head genes to display reduced cadmium-activated transcription, whereas cadmium-activated transcription of more distant genes was not strongly affected. These studies rigorously document that a single HZA enhancer can control two head-to-head genes, advancing our understanding of the diverse functions of enhancers.

The growing global population and the environmental impact of traditional livestock farming have made the need for sustainable and nutritious protein sources more urgent than ever. Pumpkin seed cake (or meal), a major by-product of oil extraction from pumpkin seeds, is rich in high-quality protein. Despite its nutritional value, this resource remains largely underutilized in industrial food formulations. This literature review explores the nutritional composition and health benefits of pumpkin seed proteins (PSPs), alongside their extraction methods, potential applications, and modification strategies, highlighting their potential as sustainable protein sources for innovative food products. Specifically, it examines the use of PSPs as nanocarriers for bioactives, emulsifiers, edible inks for 3D food printing, and biomaterials for biodegradable packaging. This approach not only addresses the growing demand for protein but also promotes resource efficiency and environmental sustainability.

Compare the burden of heavy metals in plasma from people with frontotemporal degeneration (FTD) and healthy controls.

A cross-sectional study of 14 FTD cases and 28 healthy controls recruited from the University of Cincinnati. Plasma samples were sent to the Trace Element Analysis Core at Dartmouth College for assessment of 24 metals or metalloids via inductively coupled plasma mass spectrometry (ICP-MS). Unconditional logistic regression models were performed with adjustments for age (centered at the median) and sex.

After adjusting for age and sex, there was a significant positive association of FTD with the highest tertile of Manganese (ORadjusted = 11.1, 95% CI: 1.57-132) and Chromium (ORadjusted = 9.86, 95% CI: 1.24-218). There was significant inverse associations observed between FTD and the highest tertile of Barium (ORadjusted = 0.06, 95% CI: <0.01-0.47) and Mercury (ORadjusted = 0.13, 95% CI: 0.01-0.74), with a significant inverse trend (ptrend = 0.03).

Significant associations between plasma concentration of several trace metals and FTD. The significantly elevated levels of Manganese and Chromium may suggest a role of environmental exposure in the pathogenesis of FTD. However, larger, well-designed prospective studies, along with complementary experimental work, are needed to better elucidate this relationship.

This review aimed to consolidate and compare reference values (RVs) for various elements and metals in biological samples from healthy populations worldwide.

A Web of Science/PubMed/Scopus review was conducted. Original articles in the English language, from January 2012 to February 2022, with at least 120 participants and 3 evaluated elements, and biological samples of whole blood, serum, plasma, umbilical cord, and hair included in this review.

Ninety-nine studies were screened and assessed, and eventually, 29 eligible studies from 15 countries and a total recruitment of 26,676 healthy subjects, ages ranging from zero to 80 years were included in this review. The results of evaluating 36 trace/micro/meso/macro/ toxic metals and elements in biological fluids and hair were extracted from eligible studies. Several indicators include reference range (lower, upper), arithmetic and geometric mean, median, percentile (lower, upper), and confidence interval (CI) 95 % of evaluated elements were reported. Due to geographical conditions, different demographic factors, and different analytical methodologies, the results of the analysis were various in different countries.

This review points out the necessity for localized RVs and standardized methodologies for accurate clinical evaluations and bio-monitoring. The findings call for extensive studies across diverse populations to develop comprehensive RVs for elements and metals, ensuring effective health assessments and environmental exposure controls.

Chelation therapy is a promising approach to mitigating health risks associated with toxic metal exposure, which contributes to cardiovascular disease, neurotoxicity, and other chronic conditions. disodium ethylene diamine tetraacetic acid (EDTA) is widely used, but its optimal dosing strategy remains unclear. This study evaluates the dose-dependent efficacy of EDTA in mobilizing toxic metals, including lead (Pb), cadmium (Cd), and gadolinium (Gd), while minimizing the loss of essential metals like copper (Cu) and manganese (Mn) to optimize therapeutic safety and efficacy. Ten volunteers (≥50 years) received 3 infusions at doses of 0.5, 1, and 3 g of EDTA over 30 min, 1 h, and 3 h, respectively. Urine and blood samples were analyzed pre- and post-infusion to assess pharmacokinetics of metal chelation. Urinary Pb excretion increased by 2200% at 0.5 g, with only a marginal gain at higher doses (3300%), supporting low-dose EDTA efficacy. Urinary Cd clearance required 3 g EDTA due to its strong tissue binding. Notably, Gd excretion increased by up to 78 000% even at 0.5 g EDTA, highlighting EDTA's potential to reduce long-term Gd burden post-MRI. Urinary excretion of essential metals varied, with Mn and Zn loss increasing at higher EDTA doses, underscoring the need for dose optimization while Cu and Ca only showed a clear increase urinary excretion at 3 g EDTA. Overall, a 0.5 g EDTA dose effectively mobilized Pb and Gd while minimizing essential metal depletion, reducing infusion time to 30 min, and improving patient compliance. These findings align with TACT and TACT 2 studies, reinforcing EDTA's long-term benefits in Pb reduction and supporting low-dose EDTA as a safe, efficient, and well-tolerated detoxification strategy.

Bisphenol S (BPS), as an environmental pollutant, is known to reduce brain lipid levels and induce neurotoxicity. However, whether brain lipid imbalance can induce neurotoxicity has not yet been clarified. Here, wild-type zebrafish and apoEb mutant zebrafish were used to investigate the effect of BPS on the macrophages proliferation and microglia mobilization caused by the decrease of cerebral lipids and its potential neurotoxic effects. The zebrafish exposed to BPS (1, 10, or 100 μg/L) from 2 hours after fertilization (hpf) to 3 days after fertilization (dpf) displayed microglial aggregation, as well as a decrease in brain lipid content. Lipidomic analyses of the brains and plasma of 50 dpf zebrafish exposed to BPS were used to identify key lipids, including lysophosphatidylcholine and phosphatidylcholine in brain and phosphatidylcholine in plasma. The apoEb mutant zebrafish as a hyperlipidemia model was used to further demonstrate that BPS-induced lipid reduction increased the number of microglia in the brain. Our data provide new insight into the mechanism by which pollutants cause neurotoxicity.

In the past few years, the double PHD fingers 3 (DPF3) protein isoforms (DPF3b and DPF3a) have been identified as new amyloidogenic intrinsically disordered proteins (IDPs). Although such discovery is coherent and promising in light of their involvement in proteinopathies, their amyloidogenic pathway remains largely unexplored. As environmental variations in pH and ionic strength are relevant to DPF3 pathophysiological landscape, we therefore enquired the effect of these physicochemical parameters on the protein structural and prone-to-aggregation properties, by focusing on the more disordered DPF3a isoform. In the present study, we exploited in vitro and in silico strategies by combining spectroscopy, microscopy, and all-atom molecular dynamics methods. Very good consistency and complementary information were found between the experiments and the simulations. Acidification unequivocally abrogated DPF3a fibrillation upon maintaining the protein in highly hydrated and expanded conformers due to extensive repulsion between positively charged regions. In contrast, alkaline pH delayed the aggregation process due to loss in intramolecular contacts and chain decompaction, the extent of which was partly reduced thanks to the compensation of negative charge by arginine side chains. Through screening attractive electrostatic interactions, high ionic strength conditions (300 and 500 mM NaCl) shifted the conformational ensemble towards more swollen, heterogeneous, and less H-bonded structures, which were responsible for slowing down the conversion into β-sheeted species and restricting the fibril elongation. For defining the self-assembly pathway of DPF3a, we unveiled that the protein amyloidogenicity intimately communicates with its conformational landscape, which is particularly sensitive to modification of its physicochemical environment. As such, understanding how to modulate DPF3a conformational ensemble will help designing novel protein-specific strategies for targeting neurodegeneration.

Iron plays a pivotal role in numerous fundamental biological processes in the brain. Among the various cell types in the central nervous system, microglia are recognized as the most proficient cells in accumulating and storing iron. Nonetheless, iron overload can induce inflammatory phenotype of microglia, leading to the production of proinflammatory cytokines and contributing to neurodegeneration. A growing body of evidence shows that disturbances in iron homeostasis in microglia is associated with a range of neurodegenerative disorders. Recent research has revealed that microglia are highly sensitive to ferroptosis, a form of iron-dependent cell death. How iron overload influences microglial function? Whether disbiosis in iron metabolism and ferroptosis in microglia are involved in neurodegenerative disorders and the underlying mechanisms remain to be elucidated. In this review we focus on the recent advances in research on microglial iron metabolism as well as ferroptosis in microglia. Meanwhile, we provide a comprehensive overview of the involvement of microglial ferroptosis in neurodegenerative disorders from the perspective of crosstalk between microglia and neuron, with a focus on Alzheimer's disease and Parkinson's disease.

Spinal cord injury (SCI) severely affects the central nervous system. Copper homeostasis is closely related to mitochondrial regulation, and cuproptosis is a novel form of cell death associated with mitochondrial metabolism. This study aimed to explore the relationship between SCI and cuproptosis and construct prediction models.

Gene expression data of SCI patient samples from the GSE151371 dataset were analyzed. The differential expression and correlation of 13 cuproptosis-related genes (CRGs) between SCI and non-SCI samples were identified, and the ssGSEA algorithm was used for immunological infiltration analysis. Unsupervised clustering was performed based on differentially expressed CRGs, followed by weighted gene co-expression network analysis (WGCNA) and enrichment analysis. Three machine learning models (RF, LASSO, and SVM) were constructed to screen candidate genes, and a Nomogram model was used for verification. Animal experiments were carried out on an SCI rat model, including behavioral scoring, histological staining, electron microscopic observation, and qRT-PCR.

Seven CRGs showed differential expression between SCI and non-SCI samples, and there were significant differences in immune cell infiltration levels. Unsupervised clustering divided 38 SCI samples into two clusters (Cluster C1 and Cluster C2). WGCNA identified key modules related to the clusters, and enrichment analysis showed involvement in pathways such as the Ribosome and HIF-1 signaling pathway. Four candidate genes (SLC31A1, DBT, DLST, LIAS) were obtained from the machine learning models, with SLC31A1 performing best (AUC = 0.958). Animal experiments confirmed a significant decrease in the behavioral scores of rats in the SCI group, pathological changes in tissue sections, and differential expression of candidate genes in the SCI rat model.

This study revealed a close association between SCI and cuproptosis. Abnormal expression of the four candidate genes affects mitochondrial function, energy metabolism, oxidative stress, and the immune response, which is detrimental to the recovery of neurological function in SCI. However, this study has some limitations, such as unidentified SRGs, a small sample size. Future research requires more in vitro and in vivo experiments to deeply explore regulatory mechanisms and develop intervention methods.

Overexposure to manganese (Mn) or iron (Fe) may lead to neurological damage. The aim of this study was to investigate the effects of subchronic Mn and Fe exposure, alone or in combination, on the distribution of other elements and the relationship between Mn and Fe levels in whole blood and brain. Forty male Sprague-Dawley (SD) rats were divided into control, Mn-exposed, Fe-exposed, and combined Mn-Fe-exposed groups, with 10 rats assigned randomly to each group. The control, Mn-exposed, Fe-exposed group and the combined Mn-Fe-exposed groups were injected intraperitoneally with equal amounts of saline, 5 mg/kg MnCl2, 20 mg/kg FeSO4 or 5 mg/kg MnCl2+20 mg/kg FeSO4 once a day, 5 days a week for 8 weeks. The levels of Mn, Fe and other metallic elements [including barium (Ba), beryllium (Be), strontium (Sr), antimony (Sb), lead (Pb), vanadium (V) and copper (Cu)] in whole blood and brain tissue (including the globus pallidus, hippocampus, striatum and substantia nigra) were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The results of this study show that, in whole blood, Mn levels were increased (p < 0.05) in the Mn-exposed group, Fe levels were decreased in both the Fe-exposed (p < 0.05) and Mn-exposed groups (p < 0.01), and Sb levels were increased in both the Mn-exposed and combined Mn-Fe-exposed groups (p < 0.05). In the substantia nigra, the levels of Be (p < 0.01), Sr (p < 0.05), and Cu (p < 0.001) were increased in the Fe-exposed group; the levels of Cu were also significantly increased in the Mn-exposed group (p < 0.01) and the combined Mn-Fe-exposed group (p < 0.0001); the levels of V were decreased (p < 0.05) in the combined Mn-Fe-exposed group; and the levels of V were decreased in the Fe-exposed group (p < 0.01 ), Mn-exposed group (p < 0.05) and combined Mn-Fe-exposed group (p < 0.001) had decreased Ba levels. In the pallidum, Fe levels were increased in the Mn-Fe co-exposed group (p < 0.0001); Ba (p < 0.01) and Pb (p < 0.05) levels were decreased in the Fe-exposed group; Ba (p < 0.05) levels were decreased in the Mn-exposed group; and Ba levels were increased in the Mn-Fe co-exposed group (p < 0.05). In the hippocampus, Mn (p < 0.01), Cu (p < 0.05), Sb (p < 0.01), and V (p < 0.05) levels were increased in the Fe-exposed group; Mn levels were increased in the Mn-exposed group (p < 0.01) and the combined Mn-Fe-exposed group (p < 0.0001). In the striatum, Be levels were decreased in the Mn-Fe combined exposure group (p < 0.05). Mn and Fe levels in whole blood and brain tissue can reflect the accumulation of Mn and Fe. These measurements can serve as valuable predictive biomarkers for subchronic Mn or Fe exposure and combined Mn-Fe exposure. The interactions between Mn and Fe and the distribution and abnormalities of the essential metal elements in the central nervous system and other organs need to be further investigated.

Betalain, a natural pigment found in red dragon fruit, has been proposed as a natural reagent for metal detection. In the present study, this pigment was extracted and used as a colorimetric reagent for Cu and Fe on a paper-based analytical device (PAD) and then applied to water samples. The extract was stable at 5 ± 3 °C for 16 weeks. In a solution with a pH of 4-5, the betalain extract changed color from pink to light orange (Cu) and yellow (Fe) and was selective against Na, K, Ca, Ba, Al, Mg, Zn, Hg, Ni, and Pb. The color change was caused by a metal-betalain complex with an estimated ratio of 1:2 (Cu-betalain) and 1:9 (Fe-betalain). Betalain PAD was produced under optimal conditions using Whatman CF1 paper containing 20 µL of 100 mg/mL betalain extract at pH 4-5. This process resulted in a limit of quantification of 3.133 mg/L (Cu) and 4.736 mg/L (Fe) and a limit of detection of 1.034 mg/L (Cu) and 1.563 mg/L (Fe). Based on these findings, betalain PAD made from red dragon fruit could be a viable alternative for the on-site detection of Cu and Fe in water. Ultimately, betalain PAD is a toxic waste-free, portable, fast, and prospective on-site tool for metal detection.

Parkinson's disease is a complex neurological ailment manifested by dopaminergic neurodegeneration in the substantia nigra of the brain. This study investigates the molecular tripartite interaction between Lewy bodies, amyloid beta, and tau protein in the pathogenesis of Parkinson's disease. Lewy bodies which have been found as the important pathological hallmark in the degenerative neurons of Parkinson's patients, are mainly composed of α-synuclein. The accumulation of α-synuclein has been directly and indirectly linked to the severity and degree of progression of the disease. In addition, approximately 50% of Parkinson's disease cases are also described by hyperphosphorylation of tau protein indicating its significant involvement in the disease. The study further explains how α-synuclein, tau and amyloid beta can spread via cross-seeding mechanisms and accelerate each other's aggregation leading to neuronal death. Both GSK-3β and CDK5 are involved in phosphorylation which among other effects contributes to the misfolding of both α-synuclein and tau proteins that lead to neurodegeneration in Alzheimer's disease. Several mediators, that contribute to mitochondrial damage through elevated oxidative stress pathology are clearly described. Because of the increase in the incidence of Parkinson's disease, as predicted to be 17 million when the study was being conducted, studying these pathological mechanisms is very important in trying to establish treatments. This work contributes a path to finding a multi-target treatment regimen to alleviate the burden of this devastating disease.

A Schiff base fluorescent probe, HTT, based on a sulfonylhydrazone structure was designed and synthesized for the sensitive and selective detection of Cu2+. The probe HTT exhibits good anti-interference performance toward Cu2+ in the presence of a variety of metal ions. After the addition of Cu2+, it can quickly respond within 40 seconds, and the fluorescence detection limit is 1.10 nM. The coordination ratio of probe HTT and Cu2+ is 2 : 1, and the coordination reaction between CN, SO and Cu2+ limits the formation of hydrogen bonds between the hydroxyl group and CN, disrupting the spatial coplanar effect of the probe molecule and thereby inducing fluorescence quenching. The probes can be recovered and reused using EDTA for the detection of Cu2+. The probe was also applied to the successful monitoring of Cu2+ in living cells and real water samples.

Heavy metals, including lead, mercury, cadmium, and arsenic, along with emerging contaminants, pose significant threats to cardiovascular health. These metals are linked to oxidative stress, endothelial dysfunction, inflammation, and epigenetic alterations, contributing to various cardiovascular diseases.

This review synthesizes current research on the pathways by which heavy metal exposure affects cardiovascular health, highlighting epidemiological trends, vulnerable populations, and potential preventive strategies.

A comprehensive review of molecular mechanisms, epidemiological studies, and public health data was conducted to elucidate the links between heavy metal exposure and cardiovascular health.

Mechanisms of Toxicity: Heavy metals induce oxidative stress and inflammation, impair endothelial function, and disrupt calcium signaling. These effects culminate in hypertension, atherosclerosis, myocardial dysfunction, and other cardiovascular pathologies. Epidemiological Trends: Evidence links even low-level exposures to increased Cardio Vascular Disease risk. Regional trends show elevated risks in areas with significant industrial activity or contaminated water supplies. Vulnerable Populations: Children, the elderly, and individuals in low-income or industrially polluted regions exhibit heightened susceptibility. Preventive Strategies: Regulatory actions, improved water safety, dietary interventions, and community awareness are critical in mitigating exposure and its health impacts.

Environmental exposure to heavy metals significantly elevates cardiovascular disease risk, particularly among vulnerable groups. Urgent public health measures and further research are needed to address the cumulative and synergistic effects of these toxicants.

Manganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to as manganism, which shares some similarities with Parkinson's disease. Mn levels seem regulated by many transporters responsible for its uptake and efflux. These transporters play an established role in many inherited disorders of Mn metabolism and neurotoxicity. Some inherited Mn metabolism disorders, caused by mutations of SLC30A10 and SLC39A14, assume crucial importance since earlier treatment results in a better prognosis. Physicians should be familiar with the clinical presentation of these disorders as the underlying cause of dystonia/parkinsonism and look for other accompanying features, such as liver disease and polycythemia, which are typically associated with SLC30A10 mutations. This review aims to highlight the currently known Mn transporters, Mn-related neurotoxicity, and its consequences, and it provides an overview of inherited and acquired disorders of Mn metabolism. Currently available treatments are also discussed, focusing on the most frequently encountered presentations.

Antioxidants found naturally in foods have a significant effect on preventing several human diseases. However, the use of synthetic antioxidants in studies has raised concerns about their potential link to liver disease and cancer. The findings show that postbiotics have the potential to act as a suitable alternative to chemical antioxidants in the food and pharmaceutical sectors. Postbiotics are bioactive compounds generated by probiotic bacteria as they ferment prebiotic fibers in the gut. These compounds can also be produced from a variety of substrates, including non-prebiotic carbohydrates such as starches and sugars, as well as proteins and organic acids, all of which probiotics utilize during the fermentation process. These are known for their antioxidant, antibacterial, anti-inflammatory, and anti-cancer properties that help improve human health. Various methodologies have been suggested to assess the antioxidant characteristics of postbiotics. While there are several techniques to evaluate the antioxidant properties of foods and their bioactive compounds, the absence of a convenient and uncomplicated method is remarkable. However, cell-based assays have become increasingly important as an intermediate method that bridges the gap between chemical experiments and in vivo research due to the limitations of in vitro and in vivo assays. This review highlights the necessity of transitioning towards more biologically relevant cell-based assays to effectively evaluate the antioxidant activity of postbiotics. These experiments are crucial for assessing the biological efficacy of dietary antioxidants. This review focuses on the latest applications of the Caco-2 cell line in the assessment of cellular antioxidant activity (CAA) and bioavailability. Understanding the impact of processing processes on the biological properties of postbiotic antioxidants can facilitate the development of new food and pharmaceutical products.

Aging is a major risk factor for neurodegenerative diseases. With aging of the global population, the prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), has increased worldwide. Unfortunately, the available therapeutic options for these neurodegenerative diseases are limited, most of which only provide symptomatic relief and have potentially serious side effects. Epidemiological studies have shown that green tea consumption is associated with a lower prevalence of cognitive decline and decreased risk of AD and PD, providing an attractive preventive and therapeutic option. Polyphenols are major bioactive components in green tea, which contribute to the beneficial effects of green tea. Accumulating data suggest that green tea polyphenols (GTPs) have neuroprotective properties that inhibit the pathological development of neurodegenerative diseases; however, the underlying mechanisms are not yet completely understood. This paper reviews both in vitro and in vivo evidence that demonstrates the neuroprotective effects of GTPs against neurodegenerative diseases, with the main focus on AD and PD, and summarizes the possible molecular mechanisms by which GTPs impede the progression of neurodegeneration. In particular, this review highlights the modulation of GTPs on the common mechanisms involved in pathogenesis of neurodegenerative diseases, including oxidative stress-mediated neuronal toxicity, impaired proteostasis, and metal ion dyshomeostasis. The potential of using GTPs in the intervention of neurodegenerative diseases is also discussed, hopefully, providing useful insights into novel preventive and therapeutic strategies for these diseases.

Maternal depression during and after pregnancy is a worldwide public concern. Low omega-3 FAs levels and intake in women during pregnancy were associated with a high rate of maternal depression and poor pregnancy outcomes. The study examines the association between FAs intake and levels and prenatal depressive and anxiety symptoms among pregnant Arabic-speaking women in Oman.

In 302 pregnant Omani women, level of depression and anxiety is assessed at the 8-12 and 24-28 weeks of pregnancy using the Arabic version of (EPDS). Seafood and the omega-3 FAs intakes of pregnant women has been quantified by using a validated (FFQ). FAs analysis of erythrocytes was carried out using the method of Folch et al. RESULTS: Maternal depression and anxiety symptoms (30.5 % and 26.1 %) were associated with low fish consumption and omega-3 FAs intake with depressive and anxiety symptoms (p = 0.01), Women with antenatal depression or anxiety symptoms had a lower erythrocyte concentration of arachidonic acid (20:4 n-6), (p = 0.01), total omega 6 FAs, (p = 0.03), docosahexaenoic acid (22:6 n-3) (p = 0.03), docosapentaenoic acid (22:5 n-3) (p = 0.04), eicosapentaenoic acid (20:5 n-3) (p = 0.005), total omega 3 FAs (p = 0.005), omega-3 index (p = 0.01), compared to healthy pregnant women. These findings did not change after adjusting for potential confounders.

Maternal omega-3 FAs exert a favourable effect on vital perinatal health outcomes. Fish and seafood intake or omega-3 FAs supplementation are highly recommended for women during pregnancy to ensure the well-being of both the mother and fetus.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by oxidative stress, neuroinflammation, mitochondrial dysfunction, neurotransmitter imbalance, tau hyperphosphorylation, and amyloid beta (Aβ) accumulation in brain regions. The gut microbiota (GM) has a major impact on brain function due to its bidirectional interaction with the gut through the gut-brain axis. The gut dysbiosis has been associated with neurological disorders, emphasizing the importance of gut homeostasis in maintaining appropriate brain function. The changes in the composition of microbiomes influence neuroinflammation and Aβ accumulation by releasing pro-inflammatory cytokines, decreasing gut and blood-brain barrier (BBB) integrity, and microglial activation in the brain. Postbiotics, are bioactive compounds produced after fermentation, have been shown to provide several health benefits, particularly in terms of neuroinflammation and cognitive alterations associated with AD. Several research studies on animal models and human have successfully proven the effects of postbiotics on enhancing cognition and memory in experimental animals. This article explores the protective effects of postbiotics on cellular mechanisms responsible for AD pathogenesis and studies highlighting the influence of postbiotics as a total combination and specific compounds, including short-chain fatty acids (SCFAs). In addition, postbiotics act as a promising option for future research to deal with AD's progressive nature and improve an individual's life quality using microbiota modulation.

Enhancers play critical roles in gene expression, but a full understanding of their complex functions has yet to be defined. The cellular response to excess zinc levels in C. elegans requires the HIZR-1 transcription factor, which binds the high-zinc activation (HZA) enhancer in the promoters of multiple target genes. Cadmium hijacks the excess zinc response by binding and activating HIZR-1. By analyzing the genome-wide transcriptional response to excess zinc and cadmium, we identified two positions in the genome where head-to-head oriented genes are both induced by metals. In both examples, a single predicted HZA enhancer is positioned between the two translational start sites. We hypothesized that a single enhancer can control both head-to-head genes, an arrangement that has not been extensively characterized. To test this hypothesis, we used CRISPR genome editing to precisely delete the HZAmT enhancer positioned between mtl-2 and T08G5.1; in this mutant, both head-to-head genes display severely reduced zinc-activated transcription, whereas zinc-activated transcription of more distant genes was not strongly affected. Deleting the HZAcF enhancer positioned between cdr-1 and F35E8.10 caused both head-to-head genes to display reduced cadmium-activated transcription, whereas cadmium-activated transcription of more distant genes was not strongly affected. These studies rigorously document that a single HZA enhancer can control two head-to-head genes, advancing our understanding of the diverse functions of enhancers.

Legumes enhance food security in developing countries, necessitating an understanding of their properties. This study examined the nutritional, functional, and microbial qualities of legume-based flour blends from Small and Medium Enterprises (SMEs) in Malawi and Zambia. SMEs were chosen for their key role in local food production, distribution, and complementary food supply.

A total of 36 legume-based flour blend samples were collected using snowball sampling, consisting of 21 samples (7 sets of 3 similar samples) from SMEs in Zambia and 15 samples (5 sets of 3 similar samples) from SMEs in Malawi. Samples were analyzed for proximate composition, energy, iron, and zinc content. The nutritional contributions to the Recommended Dietary Allowances (RDA) for children aged 1-3 years were assessed. Additionally, functional properties such as water-holding and oil-holding capacities were measured. Microbial analysis was performed, and the data were statistically analyzed to determine significance (p ≤ 0.05).

Our findings revealed substantial variability in the nutritional content of these flour blends. Protein content ranged from 9.4% to 41.5%, carbohydrates from 8.1% to 71.3%, crude fat from 2.3% to 26.8%, and crude fiber from 6.2% to 35.2%. Iron and zinc levels also varied significantly, from 2.9 to 21.9 mg/100 g and 2.2 to 5.2 mg/100 g, respectively. These inconsistencies highlight a lack of standardization in nutrient content for blends intended for infant feeding. When prepared as 96 g porridge servings for children aged 1-3 years, the blends provided notable contributions to the Recommended Dietary Allowance (RDA). However, their nutrient levels were generally lower compared to the standard Corn-Soy Blend Plus (CSB +). The flour blends also showed variations in physico-functional properties, and some had microbial loads exceeding 250 cfu/g, reflecting inadequate hygiene practices during processing.

To enhance their products, SMEs should ensure that their flour blends meet both nutritional and safety standards while striving to match or surpass the nutrient content of CSB + to remain competitive in the market.

Parkinson's disease is a progressive neurodegenerative disorder that predominantly affects motor function due to the loss of dopaminergic neurons in the substantia nigra. It presents significant challenges, impacting millions worldwide with symptoms such as tremors, rigidity, bradykinesia, and postural instability, leading to decreased quality of life and increased morbidity. The pathogenesis of Parkinson's disease is multifaceted, involving complex interactions between genetic susceptibility, environmental factors, and aging, with oxidative stress playing a central role in neuronal degeneration. Glutathione S-Transferase enzymes are critical in the cellular defense mechanism against oxidative stress, catalysing the conjugation of the antioxidant glutathione to various toxic compounds, thereby facilitating their detoxification. Recent research underscores the importance of Glutathione S-Transferase in the pathophysiology of Parkinson's disease, revealing that genetic polymorphisms in Glutathione S-Transferase genes influence the risk and progression of the disease. These genetic variations can affect the enzymatic activity of Glutathione S-Transferase, thereby modulating an individual's capacity to detoxify reactive oxygen species and xenobiotics, which are implicated in Parkinson's disease neuropathological processes. Moreover, biochemical studies have elucidated the role of Glutathione S-Transferase in not only maintaining cellular redox balance but also in modulating various cellular signalling pathways, highlighting its neuroprotective potential. From a therapeutic perspective, targeting Glutathione S-Transferase pathways offers promising avenues for the development of novel treatments aimed at enhancing neuroprotection and mitigating disease progression. This review explores the evident and hypothesized roles of Glutathione S-Transferase in Parkinson's disease, providing a comprehensive overview of its importance and potential as a target for therapeutic intervention.

Alzheimer's disease (AD) is multifactorial, which makes the design of multi-target-directed ligands an attractive strategy for the development of anti-AD drugs. In order to enhance the anti-AD effects and reduce the toxicity, two usnic acid (UA) derivatives (1-2) were designed, synthesized and fully characterized by introducing dimethylamine Schiff base moiety into the toxic "triketone" portion. Ellman's method and molecular docking were used to test the cholinesterase inhibitory activities. Antioxidant activities were studied with Fenton reaction, cyclic voltammetry and C. elegans. The results showed that compared with UA, 1-2 had stronger anti-cholinesterase activities and similar antioxidant activities. Notably, solvent evaporation of 2 and ZnCl2 formed a single crystal, which was revealed to be a Zn(II) complex with UA and tertiary amine as mixed ligands by X-ray diffraction. The hydrolysis of 2 was thus furtherly studied by HPLC. Furthermore, the crystal structure supported the replacement of toxic "triketone" moiety in the chelation process, playing a detoxifying role and at the same time regulating metal homeostasis. In silico prediction also showed low hepatotoxicity and acceptable drug-likeness of 1-2. Overall, this work provided useful insights into multi-target anti-AD candidates with the natural product UA as the lead compound.

Research has demonstrated a link between metal exposure and inflammation. However, little is known about this relationship among adolescents, especially in prospective cohort studies. The aim of this study was to investigate the relationship between serum metal exposure and inflammatory status in Chinese early adolescents.

In this study, 12 serum metals were detected at baseline in 1551 participants from the Chinese Early Adolescents Cohort. The participants' inflammatory status was assessed via three systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) at both baseline and follow-up. Generalized linear mixed models and restricted cubic splines regression were used to examine the linear and nonlinear relationships between single metal concentrations and systemic inflammation indices. Multiple mixture models were implemented to assess the relationships of mixed metals with systemic inflammation indices. Additionally, sex subgroup analyses were conducted to explore the sex-specific associations between serum metals and inflammatory status.

Single-exposure analysis revealed that exposure to multiple serum metals, such as chromium, cobalt, copper and lead, was positively associated with the NLR and SII, whereas iron was negatively correlated with the three systemic inflammation indices (PFDR<0.05). Additionally, inverted U-shaped associations were observed between vanadium, manganese and systemic inflammation indices. According to the mixture models, high levels of the serum metal mixture were positively correlated with the NLR and the SII. Cobalt had the highest positive weight in the mixed samples, whereas iron had the greatest negative weight in the serum-metal mixtures. Subgroup analyses revealed that serum exposure to the metal mixture had a more significant effect on systemic inflammation markers in females than in males.

This study reveals the impact of real-world mixed metal exposure on adolescents' inflammatory levels, which is of primary significance for protecting the healthy development of early adolescents.

Heavy metals, omnipresent in the environment, though imperative in trace quantities for human physiology, become a serious health hazard due to their toxicity. Copper, arsenic, lead, iron, and mercury are some examples of the heavy metals responsible for oxidative stress, which is one of the primary factors behind neurodegenerative diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Neurodegeneration is caused by toxicity due to environmental exposure to these toxic substances or genetic variation. Conventional therapies, relying on chelation and antioxidants, suffer from the broader perspective of metal removal in a non-selective manner and poor targeting of the brain. In this respect, treatments based on nanotechnology that employ nanoparticles such as dendrimers, micelles, and liposomes constitute a promising interest in enhancing drug delivery with minimal neurotoxicity. The present review outlines the heavy metals responsible for neurodegenerative diseases, their pathophysiology, management strategies available at present, and the scope of nanotechnology intervention in overcoming shortcomings of conventional therapies. The genetic influence of heavy metals on neurological health is also part of this article.

In Wilson's disease (WD) improper copper metabolism results in copper accumulation in various organs, mainly brain and liver. The sense of smell is today one of the focuses of interest in aging and neurodegenerative diseases research. However, in WD olfactory function (OF) is still poorly investigated. Our aim was to perform a systematic review of the studies evaluating OF in WD. We searched PubMed for original papers evaluating olfactory function in WD and retrieved five articles. Additionally, one article was identified while viewing the references lists of the included studies. Finally, we included 6 studies. The number of patients ranged from 12 to 68 (altogether 222 WD patients) and their clinical characteristics were variable. Differences in methodology (mainly various tests used for OF evaluation) made it impossible to meta-analyze the data. OF was worse in WD than in controls in all studies. In 3 studies OF was impaired significantly in neurologic phenotype vs hepatic, which was not confirmed in 2 other studies. Correlation between OF and presence of brain lesions in magnetic resonance imaging was inconsistent across two studies. Only one study assessed brain regions involved in the olfactory tract by evaluating olfactory bulb volume. There was no effect of WD treatment, including its type and duration on OF (4 studies). One study additionally assessed taste which was preserved in WD. Although OF was found to be abnormal in WD, this area remains insufficiently explored. Further studies conducted on larger cohorts, with a focus on olfactory tract damage, is essential.

Metal homeostasis in the nervous system is subtly regulated and changes in metal distribution or content, either increases or decreases, are associated with neurodegeneration or cognitive impairment. Determining the localization and quantification of metals in different types of neurons is important information for understanding their role in neurobiology. Synchrotron X-ray fluorescence imaging is a powerful technique that provides very high sensitivity and high spatial resolution for imaging metals in cells. However, additional biological information is often required to correlate the subcellular localization of metals with specific proteins or organelles. The purpose of this article is to review the studies in neuroscience that correlate metal imaging by synchrotron X-ray fluorescence with protein localization by other techniques. This article highlights the diversity of correlative modalities that have been used, from fluorescence to super-resolution and infrared microscopy, and the wealth of information that has been extracted, but also discusses some current limitations. Future developments are needed, particularly for direct imaging of metals and proteins with a single instrument.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective disease-modifying treatments. The blood-brain barrier hinders drug delivery to the brain, limiting therapeutic efficacy. Nanoparticle-based systems have emerged as promising tools to overcome these challenges. This review highlights recent advances in nanoparticle technologies for AD treatment, including liposomes, polymeric, inorganic, and biomimetic nanoparticles. These nanoparticles improve drug delivery across the blood-brain barrier, improve stability and bioavailability, and enable targeted delivery to affected brain regions. Functionalization strategies further enhance their therapeutic potential. Multifunctional nanoparticles combining therapeutic and diagnostic properties offer theranostic approaches. While progress has been made, challenges related to safety, targeting precision, and clinical translation remain. Future perspectives emphasize the need for collaborative efforts to optimize nanoparticle design, conduct rigorous studies, and accelerate the development of effective nanotherapeutics. With continued innovation, nanoparticle-based delivery systems hold great promise for revolutionizing AD treatment.

The soil environment has been considered capable of storing toxic substances without serious consequences for the inhabitants since plants are able to bioaccumulate pollutants without compromising their survival. The application of chemicals to increase soil productivity and the dumping of waste have worsened soil quality. Recently, following a greater awareness of the importance of monitoring the damage deriving from the consumption of contaminated crops for humans and of the protection of biodiversity, studies aimed at identifying the effects of soil contamination on terrestrial animals have increased considerably. Studies using field lizards as model organisms fit into this scenario; this research has shed light on the uptake, accumulation, and toxicity of soil pollutants on reptiles. This review summarizes data collected on lizards of the Podarcis genus, a group of resilient wild species capable of living in both pristine and anthropized areas; the data reveal that many of the effects recorded in lizard tissues at the molecular, biochemical, and histological levels are independent of the chemical composition of the contaminants and are mostly linked to the type of cellular response. Overall, these studies confirm Podarcis lizards as a good model system in ecotoxicological and cytotoxicological research, providing an accurate description of the effects of pollutants, clarifying the defense mechanisms activated in relation to different exposure routes and, finally, providing predictive information on the risks faced by other animals. Since the effects recorded in lizards have often also been observed in mammals, it can be concluded that the results obtained from studies on these animals can be translated to other terrestrial vertebrates, including mammals.

Extracellular vesicles (EVs) have the ability to regulate physiological and pathological processes across species and have been shown to be present in plants. Tomatoes are one of the most widespread vegetables on the market and exhibit a broad range of health-promoting effects, including antioxidant and anti-inflammatory properties. However, little is known about the bioactivity of tomato-derived EVs. Here, we isolated EVs from tomatoes and explored their gene regulatory potential using array-based transcriptomics. Interestingly, using a differentiated Caco-2 monolayer model, tomato-derived EVs were shown to upregulate the transportation of zinc, which may involve the down-regulation of metallothionein proteins (MTs). Differentiated Caco-2 cells internalized tomato-derived EVs. Post-EV treatment the relative expression levels of MT-related mRNAs within the cells decreased by approximately threefold, accompanied by an approximately twofold reduction in intracellular zinc concentration. Additionally, the amount of secreted zinc in the basolateral medium increased by approximately threefold. Moreover, tomato-derived EV regulation of MT gene expression occurred only in differentiated epithelial cells. This effect was observed in differentiated Caco-2 and HIEC-6 cells, whereas no impact was seen on the MT gene in undifferentiated cells. This mechanistic study uniquely demonstrates the bioactivity of tomato-derived EVs, and for the first time, reveals the ability of plant-derived EVs to modify zinc regulation across the intestinal epithelia. This further suggests the potential of plant-derived EVs as functional food supplements in the future.

Parkinson's disease (PD) is a progressive age-related neurodegenerative disease whose annual incidence is increasing as populations continue to age. Although its pathogenesis has not been fully elucidated, oxidative stress has been shown to play an important role in promoting the occurrence and development of the disease. Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length, are also involved in the pathogenesis of PD at the transcriptional level via epigenetic regulation, or at the post-transcriptional level by participating in physiological processes, including aggregation of the α-synuclein, mitochondrial dysfunction, oxidative stress, calcium stabilization, and neuroinflammation. LncRNAs and oxidative stress are correlated during neurodegenerative processes: oxidative stress affects the expression of multiple lncRNAs, while lncRNAs regulate many genes involved in oxidative stress responses. Oxidative stress and lncRNAs also affect other processes associated with neurodegeneration, including mitochondrial dysfunction and increased neuroinflammation that lead to neuronal death. Therefore, modulating the levels of specific lncRNAs may alleviate pathological oxidative damage and have neuroprotective effects. This review discusses the general mechanisms of oxidative stress, pathological mechanism underlying the role of oxidative stress in the pathogenesis of PD, and teases out the mechanisms through which lncRNAs regulate oxidative stress during PD pathogenesis, as well as identifies the possible neuroprotective mechanisms of lncRNAs. Reviewing published studies will help us further understand the mechanisms underlying the role of lncRNAs in the oxidative stress process in PD and to identify potential therapeutic strategies for PD.

Copper (Cu) is a global environmental pollutant that poses a serious threat to humans and ecosystems. Copper induces developmental neurotoxicity, but the underlying molecular mechanisms are unknown. Neurons are nonrenewable, and they are unable to mitigate the excessive accumulation of pathological proteins and organelles in cells, which can be ameliorated by autophagic degradation. In this study, we established an in vitro model of Cu2+-exposed (0, 15, 30, 60 and 120 μM) SH-SY5Y cells to explore the role of autophagy in copper-induced developmental neurotoxicity. The results showed that copper resulted in the reduction and shortening of neural synapses in differentiated cultured SH-SY5Y cells, a downregulated Wnt signaling pathway, and nuclear translocation of β-catenin. Exposure to Cu2+ increased autophagosome accumulation and autophagic flux blockage in terms of increased sequestosome 1 (p62/SQSTM1) and microtubule-associated protein 1 light chain 3B (LC3B) II/LC3BI expressions and inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. Furthermore, copper induced apoptosis, characterized by increased expressions of Bcl2 X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and decreased expression of B-cell lymphoma 2 (Bcl2). Compared with the 120 μM Cu2+ exposure group alone, autophagy activator rapamycin pretreatment increased expression of Wnt and β-catenin nuclear translocation, decreased expression of LC3BII/LC3BI and p62, as well as upregulated expression of Bcl2 and downregulated expressions of caspase 3 and PARP. In contrast, after autophagy inhibitor chloroquine pretreatment, expressions of Wnt and β-catenin nuclear translocation were decreased, expression levels of LC3BII/LC3BI and p62 were upregulated, expression of Bcl2 was decreased, while expression levels of caspase 3, Bax, and PARP were increased. In conclusion, the study demonstrated that autophagosome accumulation and autophagic flux blockage were associated with copper-induced developmental neurotoxicity via the Wnt signaling pathway, which might deepen the understanding of the developmental neurotoxicity mechanism of environmental copper exposure.

The Gut-Brain Axis (GBA) is a crucial link between the gut microbiota and the central nervous system. Xenobiotics, originating from diverse sources, play a significant role in shaping this interaction. This review examines how these compounds influence neurotransmitter dynamics within the GBA. Environmental pollutants can disrupt microbial populations, impacting neurotransmitter synthesis-especially serotonin, gamma-aminobutyric acid (GABA), and dopamine pathways. Such disruptions affect mood regulation, cognition, and overall neurological function. Xenobiotics also contribute to the pathophysiology of neurological disorders, with changes in serotonin levels linked to mood disorders and imbalances in GABA and dopamine associated with anxiety, stress, and reward pathway disorders. These alterations extend beyond the GBA, leading to complications in neurological health, including increased risk of neurodegenerative diseases due to neuroinflammation triggered by neurotransmitter imbalances. This review provides a comprehensive overview of how xenobiotics influence the GBA and their implications for neurological well-being.

Heavy metals such as lead, cadmium, mercury, and arsenic are prevalent in the environment due to both natural and anthropogenic sources, leading to significant public health concerns. These heavy metals are known to cause damage to the nervous system, potentially leading to a range of neurological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and attention-deficit hyperactivity disorder (ADHD). The present study examines the complex relationship between heavy metal exposure and AD, focusing on the underlying mechanisms of toxicity and potential therapeutic approaches. This review article highlights how these metals can impair brain function through mechanisms such as oxidative stress, inflammation, and neurotransmitter disruption, ultimately contributing to neurodegenerative diseases like AD. It also addresses the challenges in diagnosing heavy metal-induced cognitive impairments and emphasizes the need for further research to explore effective treatment strategies and preventive measures against heavy metal exposure.

The discovery of food-derived biopeptides is becoming increasingly prevalent in the scientific community. Some peptides possess multiple biological functions that can confer health benefits through various mechanisms following ingestion. The present review targets food-derived antioxidant and mineral-binding peptides (AMBPs) including their production procedure i.e., enzymolysis, separation, and purification (through membrane separation, gel filtration, ion exchange chromatography, and high-performance liquid chromatography), followed by mass spectrometry for identification. The most effective AMBPs exhibit radical scavenging activity, detoxification of excess metals, and reduction of lipid peroxidation to facilitate mineral bioavailability. The metal complexation of AMBPs necessitates an optimal metal-to-peptide ratio, specific ligands, precursors, and complexation reactions. The bioavailability and absorbability mechanisms of AMBPs are also elucidated, encompassing gastrointestinal stability, binding mode, and cell absorption machinery. Ultimately, further considerations regarding additional research on AMBPs are provided, which will assist researchers in conducting more comprehensive studies to promote the effective and safe use of AMBPs.

In the past decade, evidence for the numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries of Cu involvement in cell signaling, autophagy, cell motility, differentiation, and regulated cell death (cuproptosis) have markedly extended the list of already known functions of Cu, such as a cofactor of essential metabolic enzymes, a protein structural component, and a regulator of protein trafficking. Novel and unexpected functions of Cu transporting proteins and enzymes have been identified, and new disorders of Cu homeostasis have been described. Significant progress has been made in the mechanistic studies of two classic disorders of Cu metabolism, Menkes disease and Wilson's disease, which paved the way for novel approaches to their treatment. The discovery of cuproptosis and the role of Cu in cell metastatic growth have markedly increased interest in targeting Cu homeostatic pathways to treat cancer. In this review, we summarize the established concepts in the field of mammalian Cu physiology and discuss how new discoveries of the past decade expand and modify these concepts. The roles of Cu in brain metabolism and in cell functional speciation and a recently discovered regulated cell death have attracted significant attention and are highlighted in this review.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder emerging during early childhood. However, the mechanism underlying the pathogenesis of ASD remains unclear. This study investigated the alterations of elements in serum and prefrontal cortex of BTBR T + tf/J (BTBR) mice and potential mechanisms. The male BTBR mice were used for experimental group and C57BL/6 J (C57) mice were used for control group (n = 15). After behavioral tests were monitored, serum and prefrontal cortex of mice were analyzed by ICP-MS. The results demonstrated that the level of copper (Cu) was increased, and the levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co), iron (Fe) and zinc (Zn) were decreased in BTBR mice compared to C57 mice (p < 0.01). The levels of above differential elements in serum demonstrated positive correlations with those in prefrontal cortex. Meanwhile, differential elements in prefrontal cortex had correlations with the total distance traveled (open field test) and the number of marbles buried (marble burying test) in BTBR mice (p < 0.05 or p < 0.01). The abnormally changed elements in serum might cross blood-brain-barrier into the brain and lead to oxidative stress, causing inflammation. Furtherly, the levels of inflammation-related indicators including tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were increased in prefrontal cortex of BTBR mice (p < 0.01), which were consistent with the aforementioned results. Our study suggested that the abnormal elements in the serum of BTBR mice may cause oxidative stress and inflammation in prefrontal cortex, which might contribute to increase the understanding of ASD pathogenesis.

Endosomes are crucial sites for intracellular material sorting and transportation. Endosomal transport is a critical process involved in the selective uptake, processing, and intracellular transport of substances. The equilibrium between endocytosis and circulation mediated by the endosome-centered transport pathway plays a significant role in cell homeostasis, signal transduction, and immune response. In recent years, there have been hints linking endosomal transport abnormalities to neurodegenerative diseases, including Alzheimer's disease. Nonetheless, the related mechanisms remain unclear. Here, we provide an overview of endosomal-centered transport pathways and highlight potential physiological processes regulated by these pathways, with a particular focus on the correlation of endosomal trafficking disorders with common pathological features of neurodegenerative diseases. Additionally, we summarize potential therapeutic agents targeting endosomal trafficking for the treatment of neurodegenerative diseases.

Metal ions, either essential or therapeutic, play critical roles in life processes or in the treatment of diseases. Proteins and enzymes are involved in metal homeostasis and the action of metallodrugs. Imaging and identifying these metal-binding proteins will facilitate the elucidation of metal-mediated life processes. The emerging research field of metallomics and metalloproteomics has significantly advanced our understanding of metal homeostasis and the roles that metals play in biology and medicine. Fluorescence-based metalloproteomics offers the possibility of not only visualization but also identification of metal-binding proteins in living cells and tissues. Herein, we summarize different strategies of labeling and tracking of metal-binding proteins with the aid of fluorescent probes. We highlight several examples as showcases of how this fluorescence-based metalloproteomics approach could be utilized in metallobiology and chemical biology. In conclusion, we also discuss the advantages and limitations of fluorescence-based metalloproteomics approaches and point out future directions of metalloproteomics including development of more sensitive and selective fluorescence probes, integration with other omics approaches, as well as application of emerging advanced super-resolution imaging techniques that utilize fluorescent molecules or proteins. We aim to attract more scientists to engage in this exciting field.

A limited number of studies have investigated the role of environmental chemicals in the etiology of mild cognitive impairment (MCI). We performed a cross-sectional study of the association between exposure to selected trace elements and the biomarkers of cognitive decline.

During 2019-2021, we recruited 128 newly diagnosed patients with MCI from two Neurology Clinics in Northern Italy, i.e., Modena and Reggio Emilia. At baseline, we measured serum and cerebrospinal fluid (CSF) concentrations of cadmium, copper, iron, manganese, and zinc using inductively coupled plasma mass spectrometry. With immuno-enzymatic assays, we estimated concentrations of β-amyloid 1-40, β-amyloid 1-42, Total Tau and phosphorylated Tau181 proteins, neurofilament light chain (NfL), and the mini-mental state examination (MMSE) to assess cognitive status. We used spline regression to explore the shape of the association between exposure and each endpoint, adjusted for age at diagnosis, educational attainment, MMSE, and sex.

In analyses between the serum and CSF concentrations of trace metals, we found monotonic positive correlations between copper and zinc, while an inverse association was observed for cadmium. Serum cadmium concentrations were inversely associated with amyloid ratio and positively associated with Tau proteins. Serum iron concentrations showed the opposite trend, while copper, manganese, and zinc displayed heterogeneous non-linear associations with amyloid ratio and Tau biomarkers. Regarding CSF exposure biomarkers, only cadmium consistently showed an inverse association with amyloid ratio, while iron was positively associated with Tau. Cadmium concentrations in CSF were not appreciably associated with serum NfL levels, while we observed an inverted U-shaped association with CSF NfL, similar to that observed for copper. In CSF, zinc was the only trace element positively associated with NfL at high concentrations.

In this cross-sectional study, high serum cadmium concentrations were associated with selected biomarkers of cognitive impairment. Findings for the other trace elements were difficult to interpret, showing complex and inconsistent associations with the neurodegenerative endpoints examined.