Biological Trace Element Research最新文献

Boron is a biologically active trace element essential to plants and is increasingly recognized as a potentially important modulator of human physiology. This critical narrative review evaluates evidence concerning mineral metabolism, endocrine-related pathways, redox balance, immune signaling, neurological function, cardiometabolic health, osteoarticular disorders, host-microbiome interactions, and boron-containing pharmaceuticals. Boron's Lewis acid properties and its ability to form reversible complexes with cis-diol-containing biomolecules provide a plausible basis for its broad biological effects, including interactions with NAD⁺- and S-adenosylmethionine-related pathways, membrane-associated glycoconjugates, and inflammatory signaling networks. Experimental and limited clinical studies suggest that boron intake at the doses evaluated may influence bone mineralization, vitamin D metabolism, selected endocrine-related biomarkers, antioxidant defense, and inflammatory homeostasis. In parallel, boron-containing compounds have emerged as valuable pharmacological scaffolds, as illustrated by boron-based agents used in oncology, dermatology, infectious disease, and boron neutron capture therapy. However, despite promising mechanistic and translational findings, evidence for boron's strict essentiality in humans remains limited, and no indispensable boron-dependent human pathway has yet been established. Recent concepts, such as conditional essentiality, suggest that boron may become biologically relevant in specific nutritional, metabolic, inflammatory, skeletal, or microbiome-related contexts. Nevertheless, small sample sizes, short intervention periods, heterogeneous formulations, and reliance on surrogate endpoints continue to constrain clinical interpretation. Future studies require speciation-resolved dosing, pharmacokinetic monitoring, adequately powered randomized designs, long-term safety assessment, and clinically meaningful outcomes. Overall, boron represents a promising but incompletely defined trace element at the intersection of nutrition, immunometabolism, host-microbiome biology, and therapeutic drug design.

Colorectal cancer (CRC) is a leading cause of cancer mortality, and the mechanisms linking lead exposure to CRC remain unclear. In this study, we integrated population-level association (NHANES), transcriptomic analyses (bulk and single-cell RNA-seq), and genetic evidence to prioritize candidate genes potentially connecting lead exposure and CRC. In NHANES, higher blood lead levels were associated with increased odds of self-reported CRC in the crude and partially adjusted models, but this association was attenuated and no longer statistically significant after full adjustment. Database-driven prioritization combining network toxicology and machine-learning highlighted several candidate genes (HMOX1, IL1B, NLRP3, BCL2, MAPK3, and ALAD). Single-cell RNA-seq and CellChat analyses indicated that HMOX1 is enriched in monocytes/macrophages and may be involved in immune- and oxidative-stress-related signaling within the CRC microenvironment. Exploratory two-sample MR using whole-blood eQTL as an exposure proxy provided genetic evidence consistent with an association between genetically predicted HMOX1 expression and CRC risk. Molecular docking suggested a plausible binding pose of plumbagin within the HMOX1 pocket. Collectively, these results suggest that the crude epidemiologic association between blood lead and CRC prevalence is sensitive to covariate adjustment and generate testable hypotheses implicating HMOX1 for future experimental validation.

Antimony (Sb) is a metalloid widely used in industry, especially in the manufacture of polyethylene terephthalate (PET), commonly used to make water bottles, food packaging, and other consumer products. Recently, Sb has been identified as a novel nerve toxin, which elicits neuronal death and associated neurodegeneration. Montelukast, a cysteinyl leukotriene receptor antagonist, has demonstrated neuroprotective effects in various experimental models of neurodegenerative disorders. This study was designed to explore the neuroprotective effect of montelukast against Sb-induced neurotoxicity. Thirty Swiss albino mice were randomly allocated into five different groups: control, montelukast (M) per se, Sb-10 mg/kg, Sb + M1 (Sb 10 mg/kg + montelukast 5 mg/kg), and Sb + M2 (Sb 10 mg/kg + montelukast 10 mg/kg) groups. Spatial memory, oxidative stress (lipid peroxides, reduced glutathione), cholinergic function (acetylcholinesterase), neuroinflammatory parameters (myeloperoxidase, tumour necrosis factor-α, interleukins-6 and 10), mitochondrial enzyme activities (I, II, IV), neurotrophin (BDNF and CREB), and histopathological alterations were assessed. Sb exposure significantly impaired cognitive performance, which was associated with increased oxidative stress (↑ lipid peroxides and ↓ glutathione), cholinergic dysfunction (↓ acetylcholinesterase), neuroinflammation (↑ myeloperoxidase, ↑ IL-6, and ↑ TNF-α and ↓ IL-10), disturbed mitochondrial enzyme functions (↓ complex I, II, and IV), reduced neurotrophin levels (↓ BDNF and ↓ CREB), and neuronal damage. Montelukast significantly (p ≤ 0.05) attenuated these alterations and improved behavioural function compared with the Sb-treated group. The findings suggest that montelukast can reduce Sb-induced neurotoxic alterations in mice, likely through regulating oxidative stress, neuroinflammatory responses, and mitochondrial enzyme dysfunction. However, these findings are derived from a preclinical mouse model. Further mechanistic studies and clinical trials are required to validate these findings and evaluate their translational implications.

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.

Blood lead levels were associated with increased mortality in cancer patients, with mediation analyses suggesting a partial role of oxidative stress and inflammation, and heterogeneity across cancer types linked to Hallmark pathway activity. We analyzed 2,689 cancer patients from NHANES (1999-2016) using Cox regression, restricted cubic spline, and mediation analyses. Over 22,151.5 person-years, 983 deaths occurred. Compared with the lowest quartile, the highest blood lead quartile was associated with increased all-cause mortality (HR = 2.44; 95% CI: 1.79-3.34) and cancer mortality (HR = 2.34; 95% CI: 1.20-4.46). Lipid-adjusted inflammation indicators-including uric acid-to-high-density lipoprotein ratio (UHR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index (SIRI)-mediated 4.51-5.72% of the association, supporting partial mediation through oxidative stress and inflammation. The effect varied by cancer type and correlated with TCGA Hallmark pathway activities, including KRAS signaling (ρ = -0.95) and xenobiotic metabolism (ρ = 0.79), suggesting that molecular context modulates lead toxicity.

The deficiency of trace element selenium is a global nutritional issue. Selenium exerts its biological functions in the human body through selenoproteins, which play crucial roles in bone and cartilage development. Selenoprotein S (SelS), a key selenoprotein involved in the regulation of oxidative stress and inflammation, has not been fully elucidated in cartilage development. The purpose of this study was to investigate the effects of SelS deficiency on cartilage matrix degradation. Chondrocytes with SelS gene knockdown (sh-Sels) and mice with SelS gene knockout were constructed. The mRNA and protein levels of type II collagen (COL II), matrix metalloproteinases (MMP3, MMP10 and MMP13) were measured by RT-qPCR and western blotting, respectively. Changes in cartilage morphology and matrix composition were evaluated using histological staining techniques, including toluidine blue (TB), safranin O-fast green, and sirius red staining. The expression levels of MMP3, MMP13, MMP19 and COL II in the knee joints of mice were detected by immunohistochemical (IHC) staining. A TGF-β pathway inhibitor (GW788388) was administered to SelS knockdown chondrocytes to verify whether the TGF-β signaling pathway was involved in the matrix degradation induced by SelS deficiency. Compared with the negative vector control (sh-NC) group, the mRNA and protein levels of COL II were decreased in the sh-Sels group. The expression levels of Mmp3, Mmp10 and Mmp13 were also increased significantly, while the metallopeptidase inhibitor Timp2 was downregulated in the sh-Sels group. SelS gene knockout in mice did not affect body length or weight but resulted in reduced proteoglycan and collagen content in articular cartilage. Compared with wild-type mice, the expression of COL II was decreased, while the expressions of MMP3, MMP13, and MMP19 were increased in the articular cartilage of SelS knockout mice. Furthermore, treatment with the TGF-β pathway inhibitor (GW788388) partially rescued the reduction in Col2a1 expression induced by SelS deficiency. SelS plays a crucial role in maintaining cartilage homeostasis, and its deficiency results in cartilage matrix degradation. The TGF-β signaling pathway is involved in the degradation of cartilage matrix caused by SelS silencing. This study provides novel insights into the treatment of fibrotic and degenerative cartilage diseases by focusing on selenoproteins.

Propolis, a natural resinous substance collected by honeybees from plant exudates, has gained considerable attention as a promising complementary therapeutic agent owing to its broad-spectrum pharmacological activities. Oxaliplatin (OXA), a platinum analogue, is one of the most effective chemotherapeutic agents commonly used in chemotherapy for colorectal malignancies. Previous investigations have confirmed that OXA has a severe hazardous effect on pregnant mothers and their progeny. Propolis extract has been suggested to confer potent antioxidant and free radical-scavenging abilities in several diseased conditions. This experimental study aimed to investigate propolis as a protective natural antioxidant that ameliorates OXA-induced genetic changes in pregnant females and their neonates. A total of 35 adult female albino rats were randomly assigned to seven equal groups (n = 5). The pre-pregnancy experimental groups (groups 2, 3, and 4) were exposed to either OXA or a combination of OXA and PRO for 21 days prior to conception. During pregnancy, experimental groups 5, 6, and 7 received identical treatment protocols and equivalent doses during gestation for the same duration (21 days). OXA was injected intravenously at 3 mg/kg body weight three times per week, whereas the propolis-treated groups were orally administered 200 mg/kg body weight/day. At the end of the supplementation period, following parturition, both mothers and their neonates in each group were euthanized, the kidneys were immediately excised, and DNA was extracted from maternal kidney tissues. The mitochondrial 16 S rRNA gene was used to clarify the differences between different treatment groups. In addition, the immunohistochemical activity in the hepatorenal and splenic tissues was evaluated for caspase-3 protein expression. The results confirmed a marked reduction in genetic variation in the mitochondrial 16 S rRNA sequences in pregnant rats with concomitant administration of propolis and OXA. Moreover, the potential ameliorating effect of propolis evidently suppressed caspase-3 protein immune reactivity compared to the OXA-treated group. Based on previous findings, it can be concluded that propolis extract has a mitigating effect on OXA-induced genetic alterations in pregnant females and their neonates.

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.