Selenomethionine (SeMet) is an organic selenium form with high bioavailability. Its regulation of intestinal barrier dysfunction and immune-inflammatory dysregulation through the microbial–immune axis remains incompletely understood. Forty-eight 7-day-old male Sprague-Dawley rats were randomized into four groups: Control, LPS, SeMet, and SeMet‑LPS four groups. Pups received daily oral SeMet (0.2mg/kg) from postnatal day 7 to 21, and LPS (10mg/kg) was intraperitoneally injected after weaning. SeMet pretreatment significantly alleviated LPS-induced growth suppression. It reduced serum and intestinal levels of IL‑6 and TNF‑α and restored antioxidant enzyme activities. Moreover, SeMet upregulated the expression of tight junction proteins ZO‑1 and Claudin‑1. 16S rRNA sequencing revealed that SeMet enriched the beneficial genera Akkermansia and Parasutterella while decreasing pathogenic taxa. Transcriptomic analysis showed that SeMet suppressed activation of the NF‑κB, TNF, and IL‑17 pathways. Microbial–gene association analysis further linked key bacterial genera with host immune and barrier genes, including Traf1, S100a8, Arf4, and Arf6. Collectively, SeMet attenuates LPS-induced intestinal injury by modulating inflammation, oxidative stress, and the microbial–immune axis.
PURPOSE:This systematic scoping review critically assessed whether silver nanoparticles (AgNPs) can sensitize breast cancer to cytotoxic drugs and distinguished between experimentally supported mechanisms and hypothesis-level claims of subtype-specific responses. METHODS:Searches were conducted in PubMed/MEDLINE, Scopus, and Web of Science Core Collection from January 2010 to January 2026 and complemented by backward citation searching and searches by DOI with the same eligibility criteria. Selected studies were quantitatively extracted and appraised using an adapted version of the Toxicological Data Reliability Assessment Tool (ToxRTool). RESULTS:The evidence base is largely composed of in vitro studies, and there are few studies on breast cancer in animals and no clinical trials on this topic. Combination studies have assessed doxorubicin, cisplatin, paclitaxel, capecitabine, and 5-fluorouracil; however, studies that simultaneously measure drug response and dosimetry of Ag(I) in cells are rare. CONCLUSION:Despite preclinical chemosensitizing activity, preclinical findings for AgNPs have been somewhat inconsistent, and therapeutic windows for specific subtypes have yet to be defined owing to the lack of consistency with silver speciation and drug response. Standardized dose metrics, orthogonal Ag(0)/Ag(I) speciation, formal combination analysis, subtype-matched models, and tumor-to-liver and tumor-to-spleen dosimetry should be used for studies to enable translation, and baseline silver and selenium statuses should be evaluated as exploratory covariates.
Oily, cream, and powder cosmetics (OCPCs) are widely used worldwide, especially in Arab nations, highlighting the need for ongoing heavy metal (HM) monitoring. This systematic review examined 16 HM concentrations in 14 OCPC product categories across 11 of the 22 Arab countries, selected countries based on predefined inclusion and exclusion criteria, and evaluated their associated health risks for only 9 of the 14 OCPCs for which sufficient data were available. The analysis included 24 papers published between June 1, 2007, and January 30, 2026, selected according to prescribed inclusion and exclusion criteria. International authorities like the WHO and the EU set acceptable limits (ALs) for HM levels. According to EPA criteria, all detected HMs underwent a health risk assessment (HRA). Saudi Arabia and Jordan had the highest HM detection rates in OCPCs among the 11 Arab countries analyzed, underscoring the need for stronger regulation. Moisturizing creams, toners, cosmetic masks, and oils were mostly contaminated with non-toxic HMs, whereas facial foundation and face cream samples were contaminated with toxic HMs. Despite exceedances of WHO and EU ALs for several elements, the EPA-based dermal risk indices remained below acceptable thresholds, reflecting the distinction between concentration-based regulatory limits and exposure-based health risk assessment. Arab regulatory agencies should establish monitoring systems to limit HMs in OCPCs, in line with WHO and EU guidelines on HM ALs in cosmetics, before market access.
INTRODUCTION AND OBJECTIVES:Data on molecular sub-typing of bladder cancer (BC) associated with heavy metals (HMTE) are lacking. Clinical significance of luminal (GATA3) and basal (cytokeratin 5/6) markers in BC is controversial. Therefore, objective is to use these markers to characterize BC associated with HMTE into luminal and basal, and to investigate their clinical significance. METHODS:Study included 143 patients undergoing radical cystectomy (RC) for urothelial carcinoma. Two fresh samples were obtained from cancerous and non-cancerous RC specimens to measure [aluminum-Al, cadmium-Cd, cobalt-Co, chromium-Cr, copper-Cu, iron-Fe, nickel-Ni, lead-Pb, zinc-Zn] concentration and GATA3,CK5,CK6, by ICP-OES and RT-PCR, respectively. Also, histopathology and immunohistochemistry for GATA3/CK5/6 were performed. RESULTS:Stage was pT1/pT2/pT3/pT4 in 36/17/75/15 and grade was G1/G2/G3 in 26/32/85 patients, respectively. High Cd, Co, Cr, Ni, and/or Pb concentration in BC tissue was associated with high CK5/6 and lower GATA3 expression. High GATA3 was associated with low stages, low grade and negative lymph nodes (LN), while high CK5/6 expression was associated with the reverse. Cu had antagonistic effects to (Cd, Co, Cr, Ni, Pb) regarding both markers. No significant association was found between Fe or Zn and GATA3or CK5/6 expression. CONCLUSIONS:High BC tissue concentration of Cd, Co, Cr, Ni, and/or Pb has been proved to be associated with high expression of the basal Cytokeratin 5/6 and lower expression of luminal marker GATA3. High GATA3 and CK5/6 expression are associated with favorable (low stages, low grade, negative LN) and aggressive BC, respectively. However, data on cancer specific survival are awaited.
New mixed ligand compounds FeSUPT and CoSUPT were successfully prepared using sulfasalazine (SU) and phenanthroline (PT). The compounds were recovered as solid, non-electrolyte substances with good thermal stability (above 300°C) and low molar conductivities (11.85 and 10.63 Ω-1cm2mol-1). Elemental and spectroscopic analyses confirmed the proposed formulations and a 1:1:1 metal-to-ligand ratio. FT-IR data indicated coordination through phenolic oxygen, and carboxylate oxygen from SU, and nitrogen atoms from PT. Electronic spectra and magnetic moments (1.85 and 1.80 B.M.) supported octahedral geometries. TGA results confirmed coordinated water molecules and high structural stability. DFT calculations revealed reduced energy gaps for FeSUPT (2.27 eV)and CoSUPT (2.11 eV), indicating higher reactivity compared to SU (3.37 eV) and PT (4.65 eV). The complexes also showed higher softness (0.44-0.47) and electrophilicity (up to 8.98 eV). Biological evaluation showed a strong enhancement after complexation. Antibacterial activity reached 24-27 mm for the complexes, compared to 5-8 mm for ligands. Activity indices approached 96%, close to amoxicillin. Antifungal activity displayed inhibition zones up to 18 mm, with activity indications reaching 90%. MIC values decreased significantly to 40-50 μM for the complexes, compared to 90-100 μM for ligands. Molecular docking studies against DNA gyrase B (PDB ID: 1KZN) revealed favorable binding affinities, particularly for CoSUPT (-8.40 kcal/mol). These results provide preliminary computational support for the observed antibacterial activity, although they do not constitute direct evidence of enzyme inhibition.
BACKGROUND:Previous studies have explored the effects of metal exposure on sleep indifferent age groups, but few have examined the effects in postmenopausal women. The study was aimed to investigate the single and mixed effects of exposure to 22 metals on sleep quality in postmenopausal women. METHODS:The baseline data of 1914 postmenopausal women were extracted from the Prospective Cohort of Chronic Diseases in Guangxi Ethnic Minority Natural Population in China. Concentrations of 22 metals in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality in postmenopausal women. The binary logistic regression model was used to analyze the effect of single metals exposure on the risk of poor sleep quality and quantile g-computation regression model was applied to assess the mixed effects of multiple metals exposure. RESULTS:Among the 1914 participants,736(38.5%) had poor sleep quality. In single-metal analyses, only manganese showed a positive association with poor sleep quality before multiple comparison correction (continuous variable, adjusted OR=1.21,95%CI:1.03-1.41), but this did not remain significant after false discovery rate (FDR) correction. Similarly, quartile-based analyses showed nominally positive associations for Mn (Q2:OR=1.51,95%CI:1.16-1.98,Q4:OR=1.41, 95%CI:1.07-1.85), Zn (Q2:OR=1.40, 95%CI:1.07-1.83), Ca (Q3:OR=1.36,95%CI:1.04-1.77), and Mo (Q3:OR=1.30, 95%CI:1.00-1.70), but none remained significant after FDR correction. However, the qgcomp mixture analysis revealed that exposure to the essential metal mixture was significantly associated with poor sleep quality (OR=1.23, 95%CI:1.05-1.44), with Mn, Zn, Ca, and Mo as the main positive contributors. CONCLUSION:No single metal remained significantly associated with poor sleep quality after FDR correction, whereas the essential metal mixture showed a significant positive association, with Mn identified as the primary contributor. Associations for Ca, Zn, and Mo were observed only in specific quartiles with non-monotonic patterns and should therefore be considered exploratory. These findings highlight the importance of mixture-based approaches in environmental health research. Further longitudinal studies, animal experiments, and cell-based investigations are warranted to validate these findings.
BACKGROUND:Optimal intake of iodine is fundamental to maintain an adequate thyroid function during pregnancy. Selenium and iron are also involved in thyroid homeostasis and could modify the effect of iodine in thyroid hormones synthesis, but the interaction between these minerals has been scarcely studied. We aimed to evaluate the association between urinary iodine concentration (UIC) and the levels of thyroid stimulating hormone (TSH), triiodothyronine, and thyroxine during the first half of pregnancy, as well as the interaction with selenium and iron intake. METHODS:We conducted a cross-sectional analysis of data from 370 pregnant Mexican women with gestational age ≤ 18 weeks. TSH, triiodothyronine and thyroxine were measured by ELISA and UIC by ammonium persulfate digestion method. The association between UIC and each hormone adjusting for potential confounders was assessed via multiple linear regression models. RESULTS:The median of UIC was 180.3 µg/L, within the adequate category as stated by the WHO for pregnant women (150-249 µg/L). The majority (58.3%) of the participants had UIC into this range while 28.7% were below 150 and 13% above 249 µg/L, respectively. After adjusting by the confounders, participants with concentrations ≥ 250 μg/L showed free thyroxine levels significantly lower than women with adequate UIC (β = -0.07, 95% CI = -0.13, -0.01). Selenium and iron intake did not modify this association. CONCLUSION:These results suggest that UIC above requirements could disrupt thyroid function during pregnancy.
Trace elements are integral regulators of mitochondrial bioenergetics, antioxidant defense, immune signaling, and regulated cell death. However, disruption of trace element homeostasis may convert physiologically essential micronutrients into active contributors to oxidative injury, mitochondrial dysfunction, inflammation, ferroptosis, and toxicity. This PRISMA-ScR-informed critical review maps and critically evaluates experimental, observational, and interventional evidence linking selenium, zinc, iron, copper, and manganese dysregulation with mitochondrial redox dysfunction and disease progression. Particular emphasis is placed on quantitative evidence, methodological strength, hierarchical appraisal of study designs, and explicit distinction between associative, mechanistically supported, and interventional evidence. Mechanistic evidence is synthesized across glutathione peroxidase 4-dependent ferroptosis, iron-driven lipid peroxidation, cuproptosis, mitochondrial quality control, AMPK/SIRT1/PGC-1α signaling, cGAS-STING activation, macrophage polarization, and interconnected regulated cell-death networks. Current evidence supports a bidirectional and context-dependent trace element-mitochondrial redox-ferroptosis axis rather than a simple relationship between isolated micronutrient deficiency and oxidative stress. Experimental studies provide comparatively strong mechanistic evidence, whereas much of the human literature remains observational and is limited by reverse causality, residual confounding, inconsistent biomarker assessment, and insufficient characterization of dose-response relationships. Both trace element deficiency and excess may be harmful, emphasizing the importance of quantitatively defining dose-response relationships, bioavailability, toxicity thresholds, and disease-specific therapeutic windows rather than pursuing indiscriminate supplementation. Future translation requires standardized analytical approaches, longitudinal and mechanistically informed interventional studies, quantitative characterization of exposure and toxicity, multi-element profiling, validated biomarkers of metal-dependent regulated cell death, and integration of multi-omics and artificial intelligence-assisted biomarker analysis. Precision modulation of trace element-redox networks may ultimately provide greater therapeutic potential than non-selective antioxidant strategies.
BACKGROUND:Meeting the increased iodine needs in pregnancy is vital, as deficiency, especially early on, can cause irreversible cognitive impairment of the infant. The American Thyroid Association advises that women who are planning a pregnancy should begin taking a daily iodine supplement containing 150 µg of iodine at least three months before conception to meet iodine needs in early pregnancy. Recently, it was reported that just 36% of women in a Québec pregnancy cohort initiated iodine supplementation before conception. OBJECTIVES:Using thyroglobulin (Tg) as a sensitive, functional marker, this study compared the effect of pre- vs. postconception iodine supplement initiation on long-term iodine (thyroid) status in this Québec cohort. METHODS:Serum Tg, thyroid stimulating hormone (TSH), and free thyroxine (FT4) were measured in pregnant women at 10.1-14.9 (T1) and 19.7-24.9 (T2) weeks gestation, with pre- vs. postconception iodine groups compared using Generalized Linear Mixed Models. RESULTS:Of the 474 participants analysed, 64% began iodine-inclusive multivitamin/mineral supplementation after conception. Iodine dose (median 220 µg/day) and daily usage rates (90.5-95.3%) were similar between preconception and postconception groups (p > 0.05). Tg estimated marginal means declined in both groups from T1 to T2 (p < 0.0001), with the postconception group showing a significantly greater reduction (interaction p = 0.049; median change: -1.22 µg/L vs. -2.14 µg/L, p = 0.008). At T1, median Tg levels (10.2 µg/L preconception vs. 12.5 µg/L postconception) failed to meet a recommended iodine sufficiency requirement (median Tg <10 µg/L and <3% of values ≥44 µg/L). Differences between groups were not observed in TSH and FT4 and prevalence of subclinical (0.7-2.6%) or primary (0-0.3%) hypothyroidism was low. CONCLUSIONS:In this observational cohort, the greater T1-to-T2 decline in Tg in women who began iodine supplementation postconception suggests that supplementation may have helped normalize thyroid stimulation caused by prior iodine deficiency.
PURPOSE:Rare earth element (REE) occurrence and fractionation in modern human dental enamel remain poorly characterized, limiting the use of enamel as a biomineral archive and for archaeological comparisons. This study characterized REE abundance, lanthanide fractionation, anomaly behavior and Y/Ho variability in modern enamel. METHODS:REEs from La to Lu together with Y were measured by inductively coupled plasma mass spectrometry in modern human enamel samples from Beijing, China. Data were evaluated using total REE abundance, patterns normalized to Post-Archean Australian Shale (PAAS), Ce, Eu and Gd anomalies, and molar Y/Ho ratios. RESULTS:REEs were quantifiable at ng/g levels, with total REE abundance (ΣREE) ranging from 4.47 to 159 ng/g. Variation was primarily interindividual. Age at extraction and sex were treated descriptively and were not interpreted as independent controls. Light REEs dominated the total REE budget, neighboring lanthanides were generally correlated, and normalized patterns documented fractionation across the series. Ce remained broadly coupled with adjacent light REEs. Eu anomalies were predominantly positive, whereas positive Gd anomalies occurred in a smaller subset of samples. These departures require cautious interpretation in view of the low concentrations, analytical constraints and possible components retained on enamel surfaces. Molar Y/Ho ratios varied among samples, supporting Y and Ho fractionation rather than a simple provenance interpretation. CONCLUSION:Modern human enamel contains a low but internally structured REE inventory. These results provide a modern reference for REE concentrations, fractionation, anomaly behavior and Y/Ho variability, supporting comparisons with other biomineral tissues and diagenetically modified ancient enamel.
BACKGROUND:Ischemic stroke is a major cause of mortality and disability, largely driven by excessive reactive oxygen species (ROS) during ischemia-reperfusion injury. Current reperfusion therapies restore blood flow but fail to effectively prevent oxidative damage or promote neuronal survival. OBJECTIVE:This review summarizes the therapeutic potential of metal-based nanoparticles (MNPs) for ischemic stroke, focusing on their catalytic antioxidant mechanisms, regulation of cellular signaling, and strategies for targeted delivery and clinical translation. METHODS:A systematic literature search was performed following PRISMA guidelines in PubMed, Web of Science, Scopus, and Google Scholar (January 2000-March 2026). Studies investigating metal-based nanoparticles in ROS regulation, neuroprotection, and drug delivery were included, while non-metal nanomaterials, irrelevant studies, and duplicates were excluded. RESULTS:Cerium-, manganese-, copper-, and iron-based nanoparticles exhibit enzyme-mimetic antioxidant activity by scavenging ROS and regulating oxidative stress pathways. Nanozymes and drug-loaded nanoparticles enhance neuronal survival, reduce infarction, and modulate inflammation. BBB penetration can be improved through surface functionalization, receptor-mediated transcytosis, magnetic guidance, and biomimetic coatings. MNPs also show potential as imaging agents and biomarker detectors. However, biosafety, targeting efficiency, and clinical translation remain challenges. CONCLUSIONS:Metal-based nanoparticles are promising multifunctional platforms for ischemic stroke therapy through ROS scavenging, antioxidant pathway activation, and targeted drug delivery. Future studies should optimize nanoparticle design and validate safety and efficacy in clinical trials.
Calcium fructoborate (CaFB) is one of the most promising organic complexes in boron chemistry due to its chemical stability and biological activity. The toxicological safety, high bioavailability, and multiple mechanisms of action of organic boron compounds render CaFB not only a nutritional supplement but also a metabolic regulatory agent. Although boron is a necessary micronutrient for plant metabolism, its biochemical role in human physiology has remained controversial for many years. Current research, however, clearly demonstrates that boron is not merely a trace element but also a bioactive compound effective in regulating metabolic processes. Beyond its antioxidant and anti-inflammatory properties, its effects on cellular energy metabolism, mineral balance, and hormone regulation are also becoming increasingly well understood. In this study, the synthesis of CaFB was reproduced based on patented methods described in the literature, and fructoborate esters with different metal ions (Na, Mg, Ca) were synthesized. The structural characterization of the synthesized compounds, obtained by crystallization or precipitation from aqueous solutions in the solid state, was carried out using elemental analysis, melting point determination, infrared spectroscopy (FT-IR), thermal analysis (TGA/DTA), and mass spectrometry (GC-MS). Furthermore, the cytotoxic activities of these compounds were evaluated in MCF-7 (breast cancer) and MCF-12A (normal breast epithelial) cell lines using the MTT assay. Among the tested compounds, CaBF-mono and CaBF-di exhibited the highest cytotoxic activity against MCF-7 cells, with IC₅₀ values of 8.488 and 8.614 µg/mL, respectively, whereas NaBF-di showed moderate activity (IC₅₀ = 31.500 µg/mL), and MgBF-mono exhibited no significant cytotoxic activity (IC₅₀ > 100 µg/mL). In contrast, the synthesized compounds exhibited relatively low cytotoxicity against normal MCF-12A cells, demonstrating a selective activity profile against cancer cells. These preliminary findings indicate that fructose-boron ester compounds represent a promising group of candidates warranting further investigation in terms of their cytotoxic and selective activity profiles.
Cuproptosis is a recently identified form of regulated cell death driven by the direct binding of Cu⁺ to the lipoyl moiety of mitochondrial tricarboxylic acid (TCA) cycle enzymes, leading to dihydrolipoamide S-acetyltransferase (DLAT) oligomerisation, iron-sulfur cluster (Fe-S) protein depletion, and proteotoxic stress, and is uniquely dependent on mitochondrial respiration. This review critically synthesises current evidence on the role of cuproptosis in type 2 diabetes mellitus (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and obesity. In T2DM, three causally validated pathways of copper transporter dysregulation converge on ferredoxin 1 (FDX1)-dependent DLAT oligomerisation, with substantial FDX1 reduction in diabetic skeletal muscle providing quantitative evidence of cuproptotic commitment; however, β-cell-specific knockout studies remain critically absent. In MASLD, indirect reactive oxygen species (ROS)-mediated insulin resistance is favoured over direct copper-receptor interactions. We propose the metabolic threshold hypothesis, positing that cuproptosis represents failed adaptation to chronic lipid overload, triggered when copper influx exceeds the combined buffering capacity of ATPase copper transporting beta (ATP7B)-mediated efflux, metallothionein sequestration, and glutathione (GSH) chelation. The serum Cu/Zn ratio cannot distinguish cuproptosis from ferroptosis; precise identification requires combined detection of FDX1, DLAT, lipoic acid synthase (LIAS), and lipoyltransferase 1 (LIPT1) with mitochondrial copper content, with immunohistochemistry (IHC) for DLAT oligomerisation as the most clinically accessible surrogate marker. Copper chelators including tetrathiomolybdate and merestinib are primary agents for metabolic tissue preservation, whereas ionophores such as elesclomol are restricted to oncology, with lipid nanoparticle-based delivery platforms essential to overcome the blood-brain barrier challenge, as underscored by the neurological worsening documented in D-penicillamine-treated Wilson disease patients. The interplay between cuproptosis and ferroptosis, sharing GSH depletion but diverging at lipoylated protein aggregation versus glutathione peroxidase 4 (GPX4)-dependent lipid peroxidation, suggests dual-pathway inhibition may be necessary. Future priorities include validation of the metabolic threshold hypothesis, β-cell-specific knockout studies, standardised DLAT oligomerisation diagnostics, tissue-targeted copper modulator delivery, and integration of cuproptosis biomarkers with multi-omics and artificial intelligence for clinically stratified precision medicine.
Ceruloplasmin (Cp) is a multifunctional multicopper oxidase principally produced in the liver and, to a lesser extent, in the central nervous system. It regulates iron homeostasis and oxidative balance, Cp oxidizes ferrous iron (Fe²⁺) to ferric iron (Fe³⁺), thereby enabling its safe integration into transferrin and averting reactive oxygen species formation. Beyond its ferroxidase activity, Cp also serves as a major copper carrier in plasma and contributes to antioxidant defense mechanisms. Although, the imbalance of ceruloplasmin has been gradually recognized as a key marker in the pathogenesis of neurodegenerative disorders. It is associated with neurofibrillary tangles, amyloid plaques, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. In the past, Cp and neuropathology were first established when a decreased level of serum ceruloplasmin was reported as a diagnostic biomarker of Wilson's disease, a disorder characterized by copper build-up triggered by mutations in the ATP7B gene. Furthermore, some studies suggest the absence of Cp was known in aceruloplasminemia, a different neurodegenerative condition characterized by extensive deposition of iron in the brain and progressive neuronal loss. However, several studies have reported that Cp's function and expression undergo important modifications in Alzheimer's, Parkinson's, Wilson's disease, and other neurological conditions. These alterations in Cp are directly linked to disrupted metal homeostasis, alleviating oxidative stress and neuroinflammation. Thus, besides understanding the structural, metabolic, and biological roles of Cp, this review aims at explaining its possible effects on common neurological disorders. The review also focusses on the therapeutic opportunities targeting Cp-mediated pathways, primarily, focusing on how Cp dysfunction interrelates with copper metabolism, iron dysregulation, and neuroinflammatory signalling, as reported in various clinical and experimental studies. Understanding Cp mechanism may highlight novel strategies for overcoming these neurodegenerative diseases.
BACKGROUND:Cisplatin is a prevalent anti-tumor agent despite its association with DNA damage, oxidative stress, myelosuppression, and hepatotoxicity, which may limit its use. The current study aims to assess the mitigating effect of selenium on cisplatin-induced hepatotoxicity. METHODS:Thirty-two adult albino rats were evenly divided into four groups: the control group received normal saline, the CIS group was IP injected with a single dose of cisplatin (7.5 mg/kg BW) on the 22nd day, the SE group received selenium (1 mg/kg BW, orally) for 21 days, and the SE + CIS group received selenium daily followed by a single IP dose of cisplatin. Samples were collected for hemogram, liver function tests, hepatic redox status, expression of pro- and anti-inflammatory cytokines, and evaluation of pro-apoptotic proteins. RESULTS:In the CIS group, hepatobiliary enzymes, bilirubin, cholesterol, triglycerides, blood glucose, hepatic MDA, and TNF-α mRNA expression increased significantly (P ≤ 0.001) and correlated positively (r = 0.99-0.80) with hepatocyte necrosis, pro-apoptotic Bax, and Caspase-3 markers immunoreactivity. Total protein, albumin, globulin, SOD, CAT, GSH, and IL-10 expression significantly decreased (P ≤ 0.001) and correlated negatively (r = -0.99 to -0.80) with hepatopathies and pro-apoptotic marker expression. Indeed, hepatic damage scores and immunoreactivity for the pro-apoptotic markers Bax and caspase-3 were significantly ameliorated in the SE + CIS group. These mitigations showed strong correlations with improved liver function panel results, antioxidant capacity, and hepatocyte expression of IL-10 and TNF-α. CONCLUSIONS:Pretreatment with selenium mitigates cisplatin-induced hepatocellular toxicity by promoting IL-10 expression, quenching free radicals, and activating downstream Bax/Caspase-3 apoptotic signaling cascades.
Selenium nanoparticles (SeNPs) have emerged as physicochemically tunable nanoplatforms at the intersection of redox biology and post-transcriptional gene regulation. This review provides a systems-level synthesis of current evidence linking SeNPs to microRNA (miRNA) modulation across cancer, inflammatory, metabolic, and degenerative disorders. A hybrid bibliometric-narrative strategy integrating Scopus, Web of Science, and PubMed initially identified 53 records, of which five met all inclusion criteria and were retained for mechanistic analysis of SeNP-mediated miRNA modulation. Recent studies predominantly employ green and biologically mediated synthesis routes, yielding biocompatible SeNPs with tunable physicochemical properties that determine cellular uptake, redox activity, and gene-regulatory engagement. Mechanistically, current evidence supports the working hypothesis that SeNPs influence redox-sensitive pathways-including Keap1-Nrf2, NF-κB, and p53/SIRT1-to potentially reshape miRNA networks central to oxidative stress, apoptosis, inflammation, and metabolic homeostasis. Key miRNA nodes modulated by SeNPs include miR-16, miR-20b, miR-21, miR-155, and members of the miR-200 family. Functionally, SeNP platforms upregulate tumor-suppressive miRNAs while attenuating oncogenic or pro-inflammatory counterparts, resulting in apoptosis induction, anti-metastatic signaling, mitochondrial restoration, immune modulation, and tissue-regenerative effects in preclinical models. Surface functionalization with polymers, peptides, or aptamers enhances targeting precision and supports integration with biosensing technologies such as surface-enhanced Raman spectroscopy and electrochemical platforms for miRNA detection. Despite promising preclinical evidence, translation remains constrained by synthesis variability, selenium's narrow therapeutic index, incomplete pharmacokinetic-pharmacodynamic mapping, and regulatory ambiguity. Advancing SeNP-miRNA therapeutics will require standardized green manufacturing, quality-by-design frameworks, and multi-omics-guided biomarker integration. Collectively, SeNP-mediated miRNA modulation represents a mechanistically grounded and adaptable platform for precision nanomedicine with emerging theranostic potential.
BACKGROUND:This study evaluated temporal changes in fluoride concentrations in distinct salivary compartments, supernatant and sediment, up to 12 h after application of fluoridated products with different concentrations and delivery modes. METHODS:This short-term, parallel, randomized clinical trial included 40 participants allocated into four groups: dentifrice containing 1450 ppm F, dentifrice containing 5000 ppm F, acidulated phosphate fluoride (APF) gel, and fluoride varnish. Unstimulated saliva was collected at baseline and at 5, 30, and 60 min, and 4, 8, and 12 h after product application. TISAB-extractable fluoride concentrations were determined in salivary supernatant and sediment and compared using ANOVA, paired t-tests, and ANOVA followed by Dunnett's post hoc test. RESULTS:For APF gel and fluoride varnish, no significant differences in measured fluoride concentrations were observed between salivary compartments. In contrast, for the 1450 and 5000 ppm F dentifrices, fluoride concentrations were consistently higher in the sediment at all time points. In the supernatant, treatments differed significantly at 5 and 30 min (p < 0.05), and from 1 to 8 h both dentifrices showed lower fluoride concentrations than APF gel and varnish. In the sediment, fluoride varnish resulted in higher fluoride concentrations than the other treatments (p < 0.05), except at 5 min. CONCLUSIONS:fluoride concentrations in saliva varied according to salivary compartment, time after application, and product formulation. The sediment fraction retained higher fluoride concentrations under several experimental conditions, suggesting a role for the particulate phase in salivary fluoride retention. These findings provide new insights into fluoride kinetics and compartmental distribution in saliva, contributing to the understanding of fluoride behavior as a trace element in biological fluids.
BACKGROUND:Although selenium has been implicated in cardiometabolic diseases, its specific role in the pediatric population is not yet clearly established. The aim of this study was to analyze the linear and non-linear association between serum selenium levels and cardiometabolic markers in Mexican schoolchildren. METHODS:A cross-sectional study was conducted in 194 schoolchildren (6-10 years old) from primary schools. Anthropometric indicators, blood pressure, and cardiometabolic markers [Fasting Blood Glucose (FBG), insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), Triglyceride-Glucose Index (TyG)] were evaluated. Serum selenium levels were determined by inductively coupled plasma mass spectrometry (ICP-MS). Quantile regression models and nonlinear relationships adjusted for nutritional status were used to assess associations between selenium levels and cardiometabolic markers. RESULTS:The results showed that 39.6% of the participants had serum selenium levels below 6.0 µg/dL and 5.2% had levels above 12.9 µg/dL. Severe selenium deficiency was positively associated with higher insulin (β = 1.9; 95% CI: 0.7-3.1), HOMA-IR (β = 0.4; 95% CI: 0.1-0.7), TG (β = 17.0 mg/dL; 95% CI: 1.2-32.8), and TyG (β = 0.2; 95% CI: 0.1-0.4). A U-shaped relationship was found between HOMA-IR and serum selenium concentrations (p = 0.016). CONCLUSION:Selenium deficiency was associated with adverse cardiometabolic markers in schoolchildren, regardless of nutritional status. Additionally, the observed U-shaped relationship suggests that both low and high selenium levels may influence insulin resistance in this population.
BACKGROUND:With the wide use of ZnONPs in industry and biomedicine, their reproductive toxicity has raised great concern. Soybean isoflavone (SI), a natural antioxidant phytoestrogen, was used to alleviate ZnONPs-induced ovarian damage in mice. METHOD:Five groups of mice were used: control, 50 mg/kg ZnONPs, 100 mg/kg ZnONPs, 50 mg/kg ZnONPs + 50 mg/kg SI, and 100 mg/kg ZnONPs + 50 mg/kg SI. All mice were administered daily by gavage for 45 days. Ovaries were then collected for analysis of zinc content, histopathology, apoptosis, and related protein expression. RESULT:ZnONPs exposure caused severe ovarian histopathological damage and significantly elevated zinc levels in blood and ovarian tissue (P < 0.01). Body weight, ovarian index, and follicle number decreased dose-dependently, while apoptosis increased. RNA-seq revealed that ZnONPs induced oxidative stress, apoptosis, hormonal disturbance, and impaired follicular development. SI effectively reversed these alterations by enhancing antioxidant capacity, inhibiting oxidative stress-related apoptosis, and normalizing the expression of Ddx4, Er, H2ab1, and Ar, thus preserving ovarian structure and function. CONCLUSION:SI alleviates ZnONPs-induced reproductive toxicity by reducing oxidative stress, inhibiting apoptosis, and regulating hormone pathways. SI protects ovaries via the Ddx4/Er/Ar/H2ab1 network and provides a new natural intervention for nanoparticle damage.
