Osteoarthritis (OA) is a common chronic joint disease, and cadmium (Cd) exposure may contribute to its progression. This study integrated network toxicology, transcriptomic datasets from the Gene Expression Omnibus (GEO), weighted gene co-expression network analysis (WGCNA), and machine-learning methods to identify molecular signatures potentially associated with Cd exposure-related OA. A total of 740 overlapping targets between Cd-associated genes and OA-related genes were identified. These targets were primarily enriched in oxidative stress, inflammation, apoptosis, extracellular matrix degradation, and the phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), nuclear factor kappa B (NF-κB), interleukin 17 (IL-17), and hypoxia-inducible factor 1 (HIF-1) signaling pathways. Integrated transcriptomic analysis identified 174 differentially expressed genes (DEGs), and WGCNA identified the yellow module as the module most strongly associated with OA. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest analyses identified BCL6 and FOSL2 as robust diagnostic feature genes. Both genes were consistently down-regulated in OA samples and demonstrated strong diagnostic performance across the analyzed cohorts. These findings suggest that BCL6 and FOSL2 may be potential diagnostic biomarkers of Cd-associated OA.
Arsenic is a ubiquitous environmental pollutant that accumulates in the liver upon chronic exposure, driving hepatic injury and carcinogenesis. Hepatic fibrosis is a critical juncture in the progression from chronic damage to cirrhosis and cancer, yet therapeutic strategies targeting the fibrotic stage of arsenic-induced liver disease remain limited. Here, we investigated whether butyrophilin subfamily 2 member A2 (BTN2A2) serves as a protective regulator in arsenic‑induced liver fibrosis and explored its underlying mechanisms. Mice were randomly divided into four groups (n = 6 per group): untreated control, 40 ppm sodium arsenite (NaAsO2), 80 ppm NaAsO2, and an intervention group receiving continuous 80 ppm NaAsO2 in drinking water for 36 weeks with BTN2A2 administration during weeks 32‑36. After 36 weeks, arsenic burdens in urine and hepatic tissue confirmed substantial accumulation, accompanied by a dose‑dependent decline in hepatic BTN2A2 protein expression. Remarkably, BTN2A2 administration alleviated liver fibrosis but did not reduce arsenic accumulation. At the molecular level, BTN2A2 suppressed the hepatic expression of pro‑inflammatory mediators, including interleukin-17 (IL-17), and pyroptotic effectors, concomitantly decreasing NLR family pyrin domain containing 3 (NLRP3), Caspase‑1, and Gasdermin D N-terminal domain (GSDMD‑N) protein levels. Flow cytometry further revealed that BTN2A2 restored the intrahepatic immune landscape by reducing T helper 17 cells and increasing regulatory T cells (Tregs). Mechanistically, BTN2A2 suppressed arsenite-triggered NLRP3/Caspase-1/GSDMD-N pyroptotic signaling in hepatocytes and reduced IL-17 secretion, thereby limiting hepatic stellate cell-mediated extracellular matrix deposition. Conversely, siRNA‑mediated knockdown of BTN2A2 in hepatocytes significantly unleashed the pyroptotic cascade, reinforcing BTN2A2 as a genuine negative regulator of hepatocyte pyroptosis. Collectively, these findings demonstrate that BTN2A2 attenuates arsenic‑induced hepatic fibrosis by suppressing IL‑17‑driven inflammation and pyroptosis, supporting its potential as a therapeutic target for environmental arsenic‑associated fibrotic liver disease.
Arsenic trioxide (ATO) is a potent therapeutic agent against acute promyelocytic leukemia; nevertheless, its clinical utility is severely restricted by dose-limiting nephrotoxicity. This study investigated the protective potential of a radiation-synthesized gallotannin hydrogel (GTH) against ATO-induced kidney injury in rats. Forty male Wistar rats were randomized into four experimental groups: Control, ATO (4 mg/kg, i.p., for 4 weeks), GTH (2 mg/kg, i.p.), and ATO + GTH. GTH treatment was initiated during the third week of ATO administration, with GTH being administrated one hour prior to ATO injection. Following the experimental period, animals were sacrificed, tissue histology was examined, and renal function was assessed by serum urea and creatinine levels. Oxidative stress was evaluated via MDA, SOD, GSH, and GPx markers. Additionally, miR-223 and TXNIP expression levels were quantified using qRT-PCR. Inflammatory mediators (NF-κB, NLRP3, Caspase-1, IL-1β, and IL-18), endoplasmic reticulum (ER) stress markers (PERK, eIF2α, and CHOP), and the apoptotic marker caspase-3 were analyzed by ELISA. Our results revealed that GTH noticeably ameliorated kidney dysfunction, as evidenced by reduced serum urea and creatinine levels. Furthermore, GTH attenuated oxidative stress by decreasing MDA levels and restoring antioxidant enzyme activities (SOD, GSH, and GPx). Histological analysis confirmed that GTH mitigated structural renal damage. Molecularly, GTH administration suppressed the ATO-induced upregulation of miR-223 and TXNIP. This downregulation correlated with a reduction in inflammatory mediators, attenuation of ER stress markers, and decreased apoptosis. These findings demonstrate that radiation-synthesized gallotannin hydrogel (GTH) exerts nephroprotective effects against ATO-induced nephrotoxicity. These benefits are driven by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms mediated via modulation of the miR-223/TXNIP axis.
Lithium is a pharmacological agent with a well-established role in psychopharmacology. Interest in its “trace” doses as a potential nutrient has increased in the context of geochemical variability of lithium concentrations in drinking water and reports suggesting its possible influence on cognitive status. Within the current regulatory framework, lithium is not recognized as an essential element for humans; no diagnosable “deficiency syndrome” exists, nor are there validated biomarkers of lithium status under background exposure. A key methodological premise of this review is to distinguish between two “dose domains”: therapeutic concentrations (mmol/L) and background intake (µg/day, µg/L). This targeted narrative review critically summarizes evidence on human lithium exposure, candidate status markers, and reported deficiency-related hypotheses in the context of the current absence of a clinically defined lithium-deficiency syndrome, validated biomarkers, and binding nutritional reference standards. A targeted narrative search was conducted in PubMed/MEDLINE, Scopus, Web of Science Core Collection, and eLIBRARY.RU. Regulatory and programmatic documents were retrieved from WHO IRIS, EFSA Publications, the U.S. Environmental Protection Agency (EPA; including the Fifth Unregulated Contaminant Monitoring Rule [UCMR-5] and related materials), the U.S. Geological Survey (USGS), and national regulatory agencies. Selected grey literature was used only to contextualize monitoring practices, exposure assessment, and water-treatment technologies. Because the evidence base is heterogeneous, sources were internally stratified into green, yellow, and red evidence zones. This stratification was used as a transparency tool in a narrative review and was not intended to represent a formal systematic-review risk-of-bias assessment or meta-analytic grading scheme. The combination of “green” evidence (lack of recognized essentiality and reference norms, regulatory monitoring without standards, and engineering challenges of lithium removal) and “yellow” signals (ecological and cohort associations, preclinical data) does not form a clinically reproducible syndrome of “lithium deficiency” in humans. Overall, lithium may be regarded as a candidate “beneficial trace element,” for which validated biomarkers and prospective studies are required.
Lead (Pb) is a prevalent environmental toxicant that induces multisystem toxicity, primarily through oxidative stress and apoptosis. Trigonella foenum-graecum L. (fenugreek) seed oil is enriched with bioactive phytoconstituents possessing potent antioxidant and anti-inflammatory properties. Therefore, this study was designed to investigate the protective effect of fenugreek oil against lead acetate trihydrate (PbAc)-induced hepatic, renal, and testicular histopathological damage in Wistar rats, with emphasis on the anti-apoptotic marker (Bcl-2). A total of 40 rats were randomly divided into four experimental groups (10 in each): a control group (CG), a Pb-intoxicated group (PbG) given 50 mg/kg of PbAc daily, a fenugreek oil-protected group (Pb + FOG) co-administered the same PbAc dose plus 250 mg/kg of fenugreek, and fenugreek oil-only group (FOG) receiving 250 mg/kg of fenugreek oil alone. All treatments were administered via oral gavage over a period of four weeks. Histopathological examination of the PbG revealed marked structural alterations in the hepatic tissue (necrosis, cytoplasmic vacuolation, and inflammatory cell infiltration), renal tissue (glomerular shrinkage and tubular degeneration), and testicular tissue (degeneration of the germinal epithelium and Leydig cells) compared to the CG. In contrast, co-administration of fenugreek seed oil in the Pb + FOG partially restored histological architecture of hepatic, renal and testicular tissues compared to the PbG. However, co-administration of fenugreek seed oil in the Pb + FOG significantly upregulated Bcl-2 mRNA expression compared to PbG (0.65 vs. 0.40; P < 0.01). Sequencing analysis of liver samples showed 97.81–100
Lead (Pb) exposure is a global health threat characterized by oxidative stress. While Nrf2 and NF-κB pathways are known mediators of systemic toxicity, the epigenetic modulation of these defences via microRNAs (miRNAs) in human cohorts remains to be fully elucidated. This study investigates the association between blood lead levels (BLL) and a potential molecular signalling involving miRNA-31, miRNA-192, Nrf2, and NF-κB. In this cross-sectional study, 80 occupationally lead-exposed healthy workers and 80 age-gender matched healthy controls were enrolled. BLL was estimated using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). Relative expressions of miRNA-31, Nrf2, and NF-κB were quantified via RT-PCR, while serum protein levels were measured using commercially available sandwich ELISA kits. The exposed group exhibited significantly higher median BLL compared to controls (p < 0.001). A significant downregulation was observed in Nrf2 mRNA expression (fold change 0.53) and serum protein levels (p < 0.001) in occupationally exposed group. Additionally, the inflammatory transcription factor, NF-κB also showed an increasing trend and a slight positive correlation with BLL. Among miRNAs, miRNA-31 was significantly upregulated (fold change 3.95). In multivariable linear regression, miRNA-31 showed a significant inverse association with Nrf2 expression in the unadjusted model ( β =-0.0471 , p=0.0008 ). However, after adjusting for blood lead levels, the effect of miRNA-31 was substantially reduced, while BLL remained significantly and inversely associated with Nrf2 expression ( β =-0.0422 , p=0.0101 ) Occupational lead exposure is accompanied by systemic miRNA-31 induction and reduced Nrf2 expression. These observational results suggest that blood lead levels exert a primary influence on Nrf2 suppression, offering hypothesis-generating insights into early epigenetic and redox responses during lead toxicity.
Dandelion (Taraxacum officinale) and hibiscus (Hibiscus sabdariffa) are notable unconventional edible flowers (UEFs) that have traditionally been used as food and in herbal preparations. This study examined the in vitro bioaccessibility content of six elements (Cr, Cu, Fe, Mn, Ni, and Zn) in edible flower capsules sold in Brazil. Acid digestion in a closed system and microwave-induced plasma optical emission spectrometry (MIP OES) were employed, as well as simulated gastrointestinal digestion according to the INFOGEST 2.0 in vitro protocol. Additionally, we examined the contribution of the in vitro bioaccessible fraction (FBio) in relation to the recommended daily intake (RDI). The concentrations (in µg g⁻1) of the target elements were as follows: Cr (< 0.46–2.82), Cu (< 0.48–11.45), Fe (159.44–1880.90), Mn (48.94–441.34), Ni (< 0.44–3.21), and Zn (< 0.55–30.98). The FBio of the evaluated elements ranged from 0.13
The giant panda (Ailuropoda melanoleuca) is an obligate bamboo specialist and exhibits pronounced seasonal shifts in diet composition. To investigate how wild pandas respond to seasonal variations in dietary trace minerals, we quantified four essential elements—iron (Fe), manganese (Mn), zinc (Zn), and copper (Cu)—in the dominant bamboo species (Bashania fargesii and Fargesia qinlingensis) and in panda feces over a full annual cycle in Foping National Nature Reserve, China. Using nutritional geometry (Geometric Framework, GF) and the Right-Angled Mixture Triangle (RMT) model, we assessed seasonal intake priorities, key elemental ratios (Cu/Mn, Cu/Zn), and relative mineral utilization. Trace mineral prioritization was strongly time-dependent: during the breeding, leaf-feeding, and overwintering periods, the prioritization pattern was Cu > Zn > Mn, whereas during the shoot-feeding stages of both bamboo species, it shifted to Cu > Mn > Zn. Copper consistently emerged as the highest ingestion priority mineral across all seasons, while iron consistently showed the lowest ingestion priority. The Cu/Mn and Cu/Zn ratios varied dynamically with dietary shifts: Cu/Mn was significantly higher in shoots than in leaves, and Cu/Zn peaked in April (Bashania shoots) and August (Fargesia leaves). Compared with wild individuals, captive pandas in Sichuan exhibited substantially higher Fe intake relative to Cu (77–623 mg Fe per 1 mg Cu vs. 13–29 mg Fe per 1 mg Cu in wild pandas), indicating a potential risk of iron overload. We conclude that wild giant pandas maintain trace mineral balance by synchronizing seasonal migration and dietary switching with fluctuations in bamboo mineral profiles. Our results emphasize the conservation importance of maintaining bamboo diversity in situ and highlight the need to refine captive feeding protocols to mimic wild seasonal nutritional patterns, particularly with respect to Fe regulation.
Trace element pollution in industrial urban environments poses a significant threat to wildlife and human health, yet the spatial resolution of these contaminants is often poorly defined. This study investigated the distance-dependent accumulation of toxic trace elements—lead (Pb), cadmium (Cd), chromium (Cr), nickel (Ni), and mercury (Hg)—in the feathers of the house sparrow (Passer domesticus) across urban and rural gradients in Gachsaran County, Iran, a major center for oil extraction. A stratified spatial design was employed, establishing concentric buffer zones at 500, 1000, and 1500 m from primary pollution sources (industrial nodes and high-traffic roads). Feather samples were analyzed using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The results revealed that all studied trace elements (Pb, Cd, Cr, Ni, and Hg) showed significant differences between urban and rural areas (p < 0.05), with consistently higher concentrations observed in urban settings. Conversely, no significant differences were found for any of the trace elements between the distances of 500, 1000, and 1500 m from the pollution sources. These findings suggest that the urban footprint of anthropogenic contaminants in industrial cities, such as Gachsaran County, is characterized by a pervasive and uniform distribution throughout the urban landscape rather than being confined to immediate point-source proximity. The study concludes that the house sparrow is an effective bioindicator for broad-scale urban environmental stressors and recommends that environmental monitoring programs account for the widespread nature of trace element signatures across urban zones to accurately identify associated ecological risks.
This study explored the relationship between serum cadmium (Cd), smoking exposure, and migraine in the ELSA-Brasil cohort (2008–2010). The analysis included 2,750 participants whose serum Cd levels were measured using inductively coupled plasma mass spectrometry. Smoking exposure was assessed using self-report data of active smoking and second-hand smoke. Migraine, including definite and probable migraine, was diagnosed according to the International Classification of Headache Disorders, 3rd edition (ICHD-3). Logistic regression was used to estimate the odds of migraine across serum Cd quintiles, using the third quintile as the reference category, while linear regression examined the relationship between smoking exposure and Cd levels. Polynomial contrasts tested linear trends. Participants had a mean (SD) age of 53.2 (9.0) years and 53.1
Keshan disease (KD) is an endemic cardiomyopathy associated with selenium deficiency and distributed mainly along China’s low-selenium belt. Sporadic cases continue to occur in some historically endemic areas despite elimination efforts. The national-scale ecological spatial association between KD prevalence and serum selenium levels remains unclear. This study examined their spatial association in China to support targeted prevention and long-term surveillance. Using 2020 national surveillance data, we applied ordinary Kriging interpolation with an exponential model to map selenium distribution. Global and local bivariate spatial autocorrelation analyses were conducted in GeoDa to assess spatial associations between serum selenium and KD prevalence. Kriging identified a northeast-to-southwest belt of selenium deficiency overlapping KD-endemic areas. Global bivariate autocorrelation showed weak but statistically significant negative spatial associations between serum selenium and overall KD prevalence (Moran’s I = -0.047, P = 0.013) and latent Keshan disease (LKD) (Moran’s I = -0.063, P = 0.002), but not chronic Keshan disease (CKD). Given the small Moran’s I values, these results should be interpreted cautiously, as national-scale analysis may obscure local heterogeneity. Local analysis identified 67, 67, and 69 low–high clusters for KD, CKD, and LKD, respectively (203 in total across the three analyses). Serum selenium levels were weakly but significantly associated with KD prevalence spatial distribution in China. These findings indicate statistically detectable ecological spatial dependence, while no inference can be made regarding individual-level causality. The identified high–low clusters may be considered priority areas for targeted KD prevention and selenium monitoring.
Accurate safety evaluation of medicinal and edible plants requires a deep understanding of heavy metal(loid) behavior during growth. To address this, we characterized the accumulation dynamics, chemical fractionation, and health risks of Pb, Cd, As, Hg, and Cu in Angelica dahurica across a complete growth cycle. Samples of roots, stems, and leaves were collected monthly from April to August and analyzed using Tessier sequential extraction. The results revealed distinct temporal and tissue-specific accumulation patterns; specifically, Pb, Cd, As, and Cu generally exhibited a decreasing trend during plant growth, with the highest concentrations predominantly found in the leaves. Pb, Hg, and Cu existed primarily in the exchangeable (F1) and carbonate-bound (F2) fractions, which were considered the absorbable fraction and represented the most bioavailable chemical forms. Health risk assessments indicated that consuming Angelica dahurica roots poses non-carcinogenic risks to children and adults in April (with children exhibiting nearly four-fold greater susceptibility), while Cd-dominated carcinogenic risks also exceed the safety thresholds. Furthermore, both non-carcinogenic and carcinogenic risks exhibit a declining trend over the growth period, with risk values based on the absorbable fraction consistently being approximately half of those based on the total content. Incorporating chemical fractionation offers a more realistic safety evaluation than traditional total concentration methods. These findings provide a scientific basis for agricultural management and the establishment of precise safety standards, thereby supporting the sustainable utilization of Angelica dahurica.
Exposure to toxic metals has become a major environmental and public health concern due to its adverse effects on reproductive health. Recent evidence indicates that, beyond their direct toxicity, toxic metals can disrupt the homeostasis of essential trace elements that are critical for maintaining normal reproductive function. This review aims to examine the role of toxic metal-induced trace element imbalance in reproductive dysfunction and to elucidate the underlying mechanisms linking metal exposure to impaired fertility. Methods: Relevant experimental, epidemiological, and clinical studies investigating the effects of lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and chromium (Cr) on reproductive health were comprehensively evaluated. We conducted a structured narrative literature search of PubMed, Scopus, Web of Science, and Google Scholar for relevant publications published between 2000 and March 2025. The study included original research articles, systematic reviews and meta-analyses investigating toxic metal induced reproductive dysfunction and trace elements dysregulation in the body. Results: Current evidence demonstrates that toxic metals interfere with the absorption, transport, distribution, and biological functions of essential trace elements by competing for transporters, binding proteins, and intracellular targets. Cd, Pb, Hg, As, and Cr are considered as the most frequently studied environmental toxic metals in association with reproductive impairment. Combinedly these metals disturb the homeostasis of important trace elements and interfere with reproductive functions by several convergent pathways such as induction of oxidative stress and dysfunction of mitochondrial, endocrine impairment, inflammation, induction of apoptosis and DNA damage, epigenetic modulation, and etc.In males, toxic metal exposure is associated with impaired testicular development, altered steroidogenesis, reduced sperm quality, decreased sperm motility, and compromised fertility. In females, it contributes to ovarian dysfunction, menstrual irregularities, implantation failure, pregnancy complications, and adverse fetal outcomes. Among the affected trace elements, zinc and selenium play particularly important protective roles through their involvement in antioxidant defense, genomic stability, mitochondrial function, and endocrine regulation. Conclusions: Trace element Dyshomeostasis represents a central mechanism linking toxic metal exposure to reproductive impairment. Present evidence indicates the similarity of mechanism of reproductive physiology modulation by cadmium, lead, mercury, arsenic and chromium involving oxidative stress, interfering hormonal axis, impairing mitochondria functions, inflammation, apoptosis and changing trace element metabolism. Detailed knowledge about this common process needs to enable efficient prevention strategies and effective treatments.
Thyroid nodules and goiter remain common conditions affecting healthy child development, attributable to diagnostic advances and environmental-genetic interactions. However, pediatric etiology research remains limited. A total of 997 children aged 8 to 10 years were recruited from iodine-adequate areas across 13 districts in Tianjin, China. Venous blood was collected for genotyping three single nucleotide polymorphisms (thyroid stimulating hormone receptor (TSHR) rs2268458, thyroid transcription factor 1 (TTF1) rs2076735 and phosphodiesterase 8B (PDE8B) rs4704397) using Sequenom MassARRAY. Data on up to 30 potential external factors were also collected. The detection rates of thyroid nodules and goiter were 23.57
Lead (Pb) is a neurotoxic heavy metal that crosses the placental barrier and may affect fetal development. However, the effects of chronic developmental Pb exposure on oxidative stress, stress-related endocrine responses, and depression-like behavior, particularly regarding sex differences, remain unclear. This study evaluated the effects of chronic Pb exposure from gestation to adulthood on redox balance, corticosterone responses, and depression-like behavior in male and female mice. Pregnant C57BL/6J mice received 250 ppm lead acetate in drinking water from gestational day 0 until offspring reached adulthood. Depression-like behavior was assessed using the forced swimming and tail suspension tests. Reactive oxygen species and lipid peroxidation were measured in the prefrontal cortex and hippocampus, and plasma corticosterone was quantified following behavioral stress. Chronic Pb exposure increased immobility in both behavioral tests and increased oxidative stress markers in the prefrontal cortex and hippocampus, with sex- and region-dependent differences. Pb exposure also altered corticosterone dynamics in both sexes: males showed a delayed corticosterone peak, whereas females exhibited a prolonged response that remained elevated 24 h after stress. Overall, chronic developmental Pb exposure was associated with depression-like behavior, oxidative imbalance, and altered corticosterone responses in a sex-dependent manner. These findings highlight biological sex as an important factor influencing the neurobehavioral, redox, and stress-related endocrine consequences of chronic developmental Pb exposure.
Nalidixic acid (Nal) is a quinolone antibiotic with activity against Gram-negative bacteria and is used to treat urinary tract infections caused by microorganisms belonging to the genera Escherichia, Proteus, Shigella, Enterobacter, and Klebsiella. The complexation of this molecule with zinc and auxiliary ligands such as phenanthroline (Phen) and 2,2’-bipyridine (Bipy) could modify its pharmacological and pharmacokinetic properties. This work presents the synthesis and characterization of the ZnNal complex ([Zn(Nal)₂(H₂O)₂]·2MeOH). Its molecular structure in the solid state was determined by X-ray diffraction. The complex crystallizes in the monoclinic space group P2₁/n with Z = 2 molecules per unit cell. In the solid state, the nalidixic acid (Nal) molecule appears as its anionic form (Nal⁻), deprotonated in the carboxyl group. The complex is centrosymmetric, with the Zn(II) ion at the center of a slightly elongated octahedral geometry, equatorially coordinated to a bidentate nalidixate anion and axially to a water molecule. The study includes the evaluation of antimicrobial activity of the binary complex and its derivatives with phenanthroline (ZnNalPhen) and bipyridine (ZnNalBipy) against both ATCC strains and clinical isolates. Additionally, compound safety was assessed using the Artemia salina model. ZnNal preserves the antimicrobial potency of the free ligand while exhibiting attenuated toxicity in this model, suggesting a more favorable biocompatibility profile for potential therapeutic applications. Notably, ZnNalPhen was the only complex active against Candida strains, highlighting that coordination with 1,10-phenanthroline expanded the antimicrobial spectrum of the parent ligand Nal to include antifungal activity. Furthermore, both ternary complexes showed an improved safety profile compared to Nal alone. Besides, zinc(II) complexes can be efficiently transported by albumin, which is a key factor in their potential therapeutic application.
In recent decades, selenium nanoparticles have attracted increasing attention as therapeutic agents for the treatment of various types of cancer. However, at certain physicochemical parameters and dosages, they can have a toxic effect or exacerbate pathological processes caused by the toxin. The aim of this study was to investigate the effect of low doses of spherical selenium nanoparticles of two sizes (50 and 100 nm), produced by laser ablation, on the mitigation of pathological processes caused by long-term injections of thioacetamide. The practical significance of this study is to understand the therapeutic value of taking dietary supplements based on selenium nanoparticles for the prevention of various liver pathologies, particularly hepatocellular carcinoma. To this end, we selected the well-known toxin thioacetamide as an HCC inducer. We administered it intraperitoneally to animals, followed by injections of 50–100 nm selenium nanoparticles. In this study, we used ultra-low concentrations of selenium nanoparticles (1 ng/g per day) with the aim of using these nanoparticles for the prevention of fibrosis, cirrhosis, and liver cancer. The results obtained in this study demonstrate a size-dependent divergence in the biological behavior of the nanoparticles: 50 nm nanoparticles failed to inhibit tumor growth and, on the contrary, exacerbated pathological processes in the liver, kidneys, and lungs across several parameters, while 100 nm selenium nanoparticles, conversely, demonstrated a powerful therapeutic effect. This paradox is confirmed at all levels: organ, tissue, and cellular. The molecular mechanisms regulating these processes using 50 and 100 nm selenium nanoparticles are also presented.
Arsenic (As) is an environmental neurotoxicant that induces oxidative stress and cognitive impairment. There are limited therapeutic options to treat As-induced neurotoxicity. This study investigated the potential for repurposing metformin (Met) and memantine (Mem) use alone, and in combination to mitigate As-induced neurotoxicity in male Wistar rats. Fifty rats were randomly divided into five groups of ten each: Group I (control) received normal feed and water, group II- Sodium arsenite (20 mg/kg), group III- Sodium arsenite (20 mg/kg) + Met (75 mg/kg), group IV- Sodium arsenite (20 mg/kg) + Mem (10 mg/kg), and group V- Sodium arsenite (20 mg/kg) + Met (75 mg/kg) + Mem 10 mg/kg), all administered p.o. for 28 days. At the end of drugs treatment, several behavioral, biochemical, and histological evaluations were performed. Results showed that all drug-treated groups demonstrated enhanced spatial and recognition memory as evidenced by increased spontaneous alternation in the Y-maze task and decreased escape latencies in the Morris Water Maze test. In both behaviors, the combination group showed the best results, followed closely by the Mem alone group. All treatment groups, especially the combination, showed the best results by restoring the activity of glutathione peroxidase, catalase, and superoxide dismutase in the cortex and hippocampus. Histological examination to study cellular preservation demonstrated that Mem alone treated group showed better results. Network pharmacology identified 66 intersecting targets; molecular docking indicated that Mem and Met had the strongest affinity for MMP9 and BDNF, respectively. All hub genes showed better binding affinities with Mem as compared to Met. In conclusion, our study demonstrated that Met and Mem improved learning and memory, reduced oxidative stress, and restored cellular density. Further validation to repurpose Met and Mem for their use against As-induced neurotoxicity can be done so that they can be used in human beings in the future.
Uranium is a naturally occurring trace element with established radiological and chemical toxicity, yet its blood burden in patients with cancer remains poorly characterized. This exploratory cross-sectional study used radon−222 as a tracer to derive model-based uranium estimates in patients with gastrointestinal (GI) cancer and healthy controls from southern Iraq, a region with documented elevated environmental radioactivity. Blood samples were collected from 78 patients with histologically confirmed GI cancer (39 females and 39 males) and 58 healthy controls (29 females and 29 males) at the National Oncology and Hematology Hospital, Najaf. CR-39 poly(allyl diglycol carbonate) solid-state nuclear track detectors were sealed with blood samples for 90 days. Track densities were quantified using TASLIMAGE automated analysis, and radon concentrations were calculated using an experimentally established calibration factor (0.048 tracks cm−2 Bq−1 m3 d). Model-based uranium estimates were derived assuming secular equilibrium between uranium-238 and radon−222. Daily alpha-particle flux, annual effective dose, and excess lifetime cancer risk were calculated according to ICRP Publications 103 and 119. Group differences were evaluated using Levene-corrected independent-samples t-tests, and effect sizes were quantified using Cohen’s d. Mean estimated blood uranium concentrations were higher in male patients than male controls (15.48 ± 5.16 vs. 10.17 ± 3.39 parts per billion (ppb)) and in female patients than female controls. Correspondingly, mean blood radon concentrations were higher in patients (males: 3.99 ± 1.50 vs. 2.62 ± 0.80 Bq m−3; females: 3.21 ± 1.07 vs. 2.31 ± 0.77 Bq m−3). Excess lifetime cancer risk remained well below the ICRP reference level in all groups (1.10 × 10–7 for male patients and 8.82 × 10–8 for female patients). Although between-group differences were not statistically significant (males: p = 0.275; females: p = 0.187), the observed effect sizes were large (Cohen’s d = 1.10 for male radon), suggesting that the study may have been underpowered to detect statistically significant differences. These findings indicate consistently higher model-based uranium estimates in patients with GI cancer than in healthy controls. However, because uranium concentrations were estimated indirectly using a model-based approach and the study employed a cross-sectional design, no causal relationship between uranium exposure and GI cancer can be inferred. Further studies with larger cohorts and direct uranium measurements using ICP-MS are warranted.
The trace element boron is a bioactive and potentially essential element for humans with a broad range of physiological effects. While dietary sources of boron are well known, significant knowledge gaps remain regarding boron intake in special dietary patterns. We estimated dietary boron intake and quantified urinary boron excretion in long-term lacto-ovo-vegetarians, vegans and omnivores in Germany. Dietary intake was estimated using weighed food diaries linked to existing databases. Boron excretion was measured using 24-hour urine samples. Differences between diet groups were compared using non-parametric tests (Kruskal–Wallis H test). The sample included 89 participants, including 28 lacto-ovo-vegetarians and 29 vegans. Vegans had the highest median boron intake (1913.38 (interquartile range: 1467.11-2615.14) µg/d), followed by lacto-ovo-vegetarians (1654.36 (1249.75-2366.01) µg/d) and omnivores (1515.35 (944.33-2067.52) µg/d). Interindividual boron intake varied largely, and ranged from 657.09 to 5835.74 µg/d. No participant exceeded the European Food Safety Authority tolerable upper intake level for boron (10 mg/day). Creatinine-corrected urinary boron excretion was highest in vegans (1559.20 (1150.62-2057.23) µg/g creatinine), followed by lacto-ovo-vegetarians (1235.40 (877.96-1814.61) µg/g creatinine) and omnivores (919.34 (639.18-1380.97) µg/g creatinine). Strong correlations between boron intakes and 24-hour urinary excretion were found in vegans (r = 0.79) and omnivores (r = 0.74) with p-values < 0.001 for both. The correlation in lacto-ovo-vegetarians was less pronounced (r = 0.43). A higher urinary boron excretion was associated with a higher excretion of potassium in all dietary patterns and specifically phosphorus in vegans (r = 0.57, p < 0.001). Our data suggest that boron intake varies across different dietary patterns. We provide first insights in boron status in German lacto-ovo-vegetarians and vegans.
