Search Results (107)

Background: Hexavalent chromium (Cr(VI)) is a widespread environmental toxic heavy metal with strong oxidative properties; however, its immunotoxicity and metabolic mechanisms in rabbit spleen remain largely unclear. Methods: In this study, New Zealand rabbits were exposed to 0, 12.5, 25, and 50 mg/L Cr(VI) (as potassium dichromate, K₂Cr₂O₇) via drinking water for four weeks to investigate splenic damage and the underlying molecular pathways. Spleen pathological injury was evaluated by hematoxylin and eosin (H&E) staining, and the distribution of T cells, B cells, and macrophages was assessed by immunohistochemistry. Antioxidant enzyme activities and antioxidant substance levels were determined using ELISA, and the relative mRNA expression of immune factor genes, antioxidant-related genes, and ferroptosis-related genes was quantified by quantitative real-time PCR (qRT-PCR). In addition, the distribution of iron in splenic tissue was detected by enhanced Prussian blue staining. Results: Our results demonstrate that high-dose Cr(VI) significantly inhibited body weight gain, induced lymphocyte atrophy, vacuolization, and widening of intercellular spaces in the splenic white pulp. Furthermore, Cr(VI) reduced T and B lymphocyte populations, promoted macrophage infiltration and inflammatory cytokine gene expression in a concentration-dependent manner, impaired total antioxidant capacity, and led to a decrease in glutathione (GSH) levels in the spleen. Additionally, Cr(VI) exposure increased iron accumulation, activated the ACSL4–NOX lipid peroxidation cascade, and downregulated GPX4 expression, ultimately triggering ferroptosis. Conclusions: These findings reveal that Cr(VI) causes splenic immune injury by disrupting oxidative homeostasis and inducing ferroptosis, providing novel insights for evaluating immunotoxicity and identifying metabolic targets under Cr(VI) pollution. Full article

Objectives: To evaluate serum zonulin and CHI3L1 as indicators of intestinal permeability and disease activity in pediatric celiac disease and to explore their associations with histopathological findings and nutritional status. Methods: This prospective cross-sectional study included 131 pediatric patients with CD (aged 2–18 years) and 42 healthy controls. Patients were classified as newly diagnosed, gluten-free diet (GFD)-adherent, or GFD-nonadherent. Body mass index was calculated, and serum levels of micronutrients, zonulin, and CHI3L1 were measured using a sandwich enzyme-linked immunosorbent assay. Associations with histopathological findings, serological markers, and nutritional parameters were analyzed. Results: Age and sex distributions were similar across groups (mean age: 10.9 ± 4.27 years). Serum zonulin and CHI3L1 levels were moderately positively correlated (r = 0.525, p < 0.001). Both biomarkers showed significant positive correlations with Marsh scores and tissue transglutaminase IgA levels. Zonulin was inversely correlated with hemoglobin, serum iron, and ferritin, whereas CHI3L1 showed negative correlations with hemoglobin and folate. Parathyroid hormone levels were positively correlated with both biomarkers. Receiver operating characteristic analysis demonstrated acceptable discriminatory performance for distinguishing CD from controls (AUC: 0.713 for zonulin and 0.709 for CHI3L1). Conclusions: Serum zonulin and CHI3L1 levels are associated with disease activity and mucosal injury in pediatric CD but do not directly reflect micronutrient status. These biomarkers may complement conventional monitoring parameters by providing additional information on intestinal permeability and inflammatory activity during follow-up. Full article

Metal accumulation in cacao (Theobroma cacao L.) cultivation represents an important agronomic and food-safety concern, particularly in acidic tropical soils where cadmium (Cd) and other trace metals can become bioavailable and translocate to plant tissues. Green magnetic nanomaterials offer a potential strategy for reducing metal mobility in agricultural substrates, but their performance depends on surface chemistry, dose, and plant genotype. In this study, we synthesized and evaluated MCRES, defined here as a maghemite–Citrus reticulata extract system, a biofunctionalized γ-Fe₂O₃-based nanosystem prepared by coupling iron oxide nanoparticles (NPs) with a 3% (w/v) Citrus reticulata peel extract. The objective was to determine whether citrus-mediated biofunctionalization could produce a scalable magnetic nanoamendment capable of modifying Cd and naturally occurring Ni partitioning in cacao seedlings. MCRES was recovered magnetically and dried, yielding 8.44 g of product from 10 g of precursor. Rietveld analysis performed in X ray diffractograms confirmed phase-pure cubic γ-Fe₂O₃ with a lattice parameter of 0.8332 nm, a crystallite size of 11.3(1) nm, and satisfactory refinement quality (χ² ≈ 1.34). Transmission electron microscope images showed quasi-spherical NPs with a log-normal size distribution centered at 7.5 nm. Magnetic measurements showed superparamagnetic-like behavior at 300 K, high saturation magnetization values of 62 emu g⁻¹ at 300 K and 71 emu g⁻¹ at 5 K, and elevated effective anisotropy values obtained from the Law of Approach to Saturation fitting. MCRES was applied at 0, 1, 2, 4, and 6 g pot⁻¹ to cacao seedlings containing Cd-amended Ultisol with naturally occurring Ni. Plant responses were genotype and dose dependent: TSH-1188 genotype showed limited dose sensitivity for most biometric variables, whereas ICS-95 genotype showed significant dose effects, with maximum growth at the 2 g pot⁻¹ treatment. Metal-partitioning results indicated that Cd remained comparatively mobile toward shoots, whereas Ni was preferentially retained in roots. In TSH-1188 genotype, the Ni translocation factor decreased from 3.07 in the control to 0.85–1.00 at higher MCRES doses. Compared with previous work on non-biofunctionalized nanomaghemite, these results suggest that citrus-mediated biofunctionalization produces a distinct Cd/Ni partitioning response. Overall, MCRES is recommended as a promising nursery-scale green nanoamendment for reducing metal mobility in cacao cultivation, but its agronomic use should be optimized according to genotype and dose. Future work should include side-by-side comparisons with unfunctionalized γ-Fe₂O₃, Citrus reticulata extract alone, and non-contaminated controls under field conditions to validate its long-term effectiveness and environmental safety. Full article

Frataxin is a conserved mitochondrial protein essential for cellular iron–sulfur (Fe–S) cluster biogenesis and oxidative balance, with its deficiency causing Friedreich’s ataxia in humans. The hypomagnetic field (HMF), an environmental stressor known to influence oxidative stress and neurodevelopment, may interact with such inherent metabolic vulnerabilities. This study investigated whether HMF exposure exacerbates Fe–S homeostasis and oxidative disruption in a Drosophila melanogaster model of frataxin deficiency. Using synchrotron radiation-based X-ray fluorescence (SR-XRF) spectroscopy for in situ elemental analysis in live tissues, we found that HMF significantly altered iron distribution and content in a tissue-specific manner. In frataxin-silenced brains, HMF decreased iron distribution but increased total iron content, whereas in eyes it reduced iron content. Sulfur content decreased in frataxin-deficient eyes but increased in brains under HMF, though its spatial distribution was unchanged. Critically, HMF elevated reactive oxygen species (ROS) in frataxin-deficient brains. Transcriptomic analysis identified 202 differentially expressed genes under HMF in frataxin-silenced flies, including key regulators of iron metabolism and oxidative stress pathways. These findings demonstrate that HMF disrupts tissue-specific iron and sulfur homeostasis and intensifies oxidative stress in a frataxin-deficient insect system, underscoring its role as an environmental factor capable of aggravating metabolic fragility. Full article

Ensuring efficient nutrient delivery and waste removal within the interior of three-dimensional (3D) cultures remains a major challenge in tissue engineering. Here, we demonstrate a proof-of-concept methodology that creates internally distributed driving sources to enhance diffusion and perfusion within 3D constructs. Iron microparticles or iron-containing microtubes were incorporated into collagen gels used for the 3D culture of dermal or cardiac fibroblasts, and cyclic dynamic magnetic fields were applied to the constructs. Oscillatory motion of the iron particles enhanced diffusion within the gels, as evidenced by increases in the fast diffusion coefficient of more than threefold and the slow diffusion coefficient of more than tenfold under conditions suitable for cell culture. In cardiac fibroblast cultures, this enhancement significantly increased proliferation by approximately twofold and reduced cytotoxicity by half compared with controls. In contrast, no significant effects were observed in dermal fibroblast cultures. Cyclic compression of microtubes within the collagen gels induced by dynamic magnetic fields primarily resulted in cellular morphological changes, including a reduction in cell area to approximately 0.8-fold of the control values, increased cell polarization with the cellular aspect ratio rising from 1.4 to 1.9, and preferred cell orientations either parallel or perpendicular to the microtube axis. Together, these results suggest that this methodology has the potential to be developed as an effective strategy for improving diffusivity in 3D metabolic environments and for promoting angiogenesis in hydrogel-based cultures. Full article

Background/Objectives: Assessing trace-element status is fundamental for maintaining health across species. However, serum primarily reflects acute physiological variability rather than chronic exposure. Thus, we investigate the cornea as a possible stable, practical alternative for assessing chronic copper and iron accumulation in rabbit’s cornea. Methods: A group of laboratory rabbits was housed under standardized husbandry conditions with comparable environmental and dietary backgrounds for trace-element intake. After completion of the experimental phase, corneal tissues were collected and subjected to quantitative elemental analysis using validated spectrometric procedures. In parallel, the structural integrity of the cornea was evaluated with standard histological techniques to determine whether elevated trace-element levels were associated with detectable morphological alterations. Results: Copper and iron concentrations showed approximately normal distributions, with mean values of 0.93 ± 0.46 μg/g and 0.78 ± 0.32 μg/g. All elemental concentrations were calculated relative to the original (native) wet tissue weight. Several samples exhibited elevated levels of both elements. Importantly, even in the samples with the highest copper and iron concentrations, no histological abnormalities were observed. Epithelial layers were intact, stromal collagen was well organized, and no inflammation or edema was observed. Conclusions: Overall, the cornea contained measurable copper and iron levels, and higher concentrations were not associated with morphological disruption under the trace-element conditions studied. Because ocular tissues are not used in food processing and can be collected in a standardized way during slaughter, the cornea offers a practical matrix for post-mortem monitoring of trace-element load in commercial animal production. Full article

Obesity is recognized as a causal risk factor for the development of multiple cancers, with risk magnitude varying by tumor site, sex, life stage, and adipose tissue distribution. This narrative review synthesizes recent epidemiological evidence linking excess body fatness with cancer incidence and mortality and integrates the biological mechanisms that explain this association. Chronic low-grade inflammation, insulin resistance with compensatory hyperinsulinemia, dysregulation of adipose-derived hormones and sex steroids, impairment of anti-tumor immune responses, alterations in the gut microbiota, and remodeling of the tumor microenvironment collectively create conditions that favor tumor initiation and progression. Bariatric surgery is the most effective clinical intervention for achieving substantial and sustained weight loss in individuals with severe obesity, and growing evidence indicates that it is associated with a reduction in overall cancer risk and cancer-related mortality, particularly for malignancies strongly linked to obesity. However, the extent of this benefit differs by surgical technique and remains less consistent for colorectal cancer. Beyond metabolic improvements, bariatric surgery produces long-term changes in nutritional physiology that may also influence oncologic outcomes. Persistent deficiencies of micronutrients such as iron, folate, vitamin B12, vitamin D, and calcium can affect DNA synthesis, methylation, oxidative balance, and cellular repair. Altered protein and energy intake may contribute to loss of lean mass and reduced metabolic resilience, while changes in alcohol absorption and metabolism can increase systemic exposure to ethanol and its carcinogenic metabolites. In addition, bariatric surgery induces sustained remodeling of the gut microbiome and bile acid metabolism, which may further modulate tumorigenic signaling. Overall, the oncological impact of bariatric surgery reflects a balance between metabolic improvement and long-term nutritional management, underscoring the need for structured follow-up and targeted nutritional strategies to optimize cancer risk reduction. Full article

Intracerebral hemorrhage (ICH) is a type of stroke with high mortality and disability rates. The hemoglobin and iron ions released by ruptured red blood cells after ICH can induce programmed cell death characterized by lipid peroxide accumulation—a defining feature of ferroptosis—which is one of the key mechanisms for the occurrence and progression of secondary brain injury after ICH. Betaine (BET), a natural amino acid derivative, is known to be an antioxidant, but its protective effect and molecular mechanisms in ICH-induced ferroptosis have not been studied yet. In this study, we investigated the effect of BET intervention on ICH-induced ferroptosis and possible mechanisms in vitro and in vivo, and we evaluated the expression of ferroptosis and oxidative stress molecules through in vivo and in vitro experiments. We analyzed the distribution of nuclear factor E2-related factor 2 (Nrf2) and assessed neurobehavioral function, hematoma volume, and iron content in the brain tissue of mice with ICH. BET upregulates nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling, reducing long-chain acyl-CoA synthetase 4 (ACSL4), reactive oxygen species (ROS), and malondialdehyde (MDA) while increasing glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels. It also decreases brain iron accumulation, aids hematoma clearance, and protects against ferroptosis and oxidative damage post ICH. Inhibition of Nrf2 with ML385 diminishes BET’s neuroprotective effects, highlighting the pathway’s importance in BET’s mechanism of action. BET boosts antioxidant capacity via the Nrf2/HO-1 pathway; inhibits ferroptosis; reduces oxidative stress, brain edema, and iron accumulation post ICH; and aids hematoma clearance, offering neuroprotection. Full article

Red blood cells (RBCs) are essential for transporting oxygen from lungs to peripheral tissues. However, the impact of transmissible gastroenteritis virus (TGEV) infection on RBCs and its potential pathophysiological significance during disease progression remain largely unexplored. In this study, hematological analysis of TGEV-infected piglets revealed significant reduction in both RBC distribution width–coefficient of variation and RBC distribution width–standard deviation, alongside elevated pCO₂ levels. Viral detection confirmed the presence of TGEV within RBCs from infected piglets. Further investigation demonstrated that TGEV could bind to, but not replicate in, RBCs. TGEV-bound RBCs exhibited crenated and impaired deformability, which were associated with reduced oxygen-carrying capacity. Additionally, TGEV infection promoted macrophage-mediated phagocytosis of RBCs and led to decreased serum iron levels, factors that might enhance TGEV infection. Collectively, these results demonstrated the involvement of RBCs in the progression of TGEV infection, providing new insights for the development of diagnostic and therapeutic strategies. Full article

Background/Objectives: Hepcidin is a cysteine-rich antimicrobial peptide that links iron homeostasis and innate immunity in vertebrates, but its functions in amphibians remain poorly understood. The Chinese spiny frog (Quasipaa spinosa) is an economically important species that suffers serious losses from bacterial diseases. This study aimed to identify and functionally characterize a hepcidin homolog (QsHep) from Q. spinosa, focusing on its antibacterial activity, immunomodulatory effects on primary macrophages, and protective efficacy against Elizabethkingia miricola infection. Methods: The QsHep gene was cloned and analyzed, its tissue distribution and inducible expression were examined by qRT-PCR, and the synthetic peptide was tested for antimicrobial, membrane-disruptive, and immunomodulatory activities in vitro, as well as for in vivo protection in an E. miricola infection model. Results: QsHep encodes a typical preprohepcidin with a signal peptide, prodomain, and a conserved mature peptide containing eight cysteine residues. QsHep was widely expressed, with the highest levels in liver, and was significantly upregulated in liver and spleen following bacterial challenge. Synthetic QsHep displayed broad-spectrum antibacterial activity, including strong inhibition of E. miricola, and induced dose-dependent membrane damage in E. miricola. QsHep showed no obvious cytotoxicity but significantly enhanced chemotaxis, phagocytic activity, and respiratory burst in primary macrophages. In vivo, QsHep treatment markedly improved the survival of E. miricola-infected frogs in a dose-dependent manner. Conclusions: QsHep is an amphibian hepcidin that combines membrane-disruptive antibacterial activity with the activation of macrophage effector functions and confers significant protection against bacterial infection in vivo. These findings expand our understanding of hepcidin-mediated innate immunity in amphibians and highlight QsHep as a promising peptide candidate for controlling bacterial diseases in frog aquaculture. Full article

The present study investigated the effects of hierarchical molecular weights and iron chelation on the in vivo absorption and the inflammatory bioactivity of chondroitin sulfate (CS). Firstly, CS, chondroitin sulfate-iron complex (CS-Fe), and low-molecular-weight chondroitin sulfate-iron complex (LCS-Fe) were fluorescently labeled and characterized. Then, the plasma concentration–time profiles and fluorescence imaging results demonstrated that LCS-Fe was more efficiently absorbed into the bloodstream and showed a higher Cmax (415.16 ± 109.50 μg/mL) than CS-Fe (376.60 ± 214.10 μg/mL) and CS (135.27 ± 236.82 μg/mL), and it clearly accumulated in the liver. Furthermore, the anti-inflammatory effect of CS-Fe and LCS-Fe was assayed in LPS-induced macrophages, and LCS-Fe and CS-Fe both showed a better inhibitory effect on NO production, COX-2 and IL-1β gene expression levels compared to CS. Additionally, targeted metabolic analysis of macrophages using LC-MS/MS revealed that CS, CS-Fe, and LCS-Fe could reverse approximately one quarter of the LPS-induced differential metabolites, and the biosynthesis of valine, leucine, and isoleucine was the most significantly involved metabolic pathway. Notably, the molecular weight reduction and iron chelation could both enhance the bioavailability and anti-inflammatory efficacy of CS. Full article

Phytoremediation is widely acknowledged as a viable method for soil remediation; however, its efficacy remains limited in soils co-polluted with petroleum hydrocarbons and heavy metals. To overcome this constraint, the present study explored an innovative approach utilizing ferrate-modified biochar (FeBC) to augment phytoremediation efficiency. Experimental findings revealed that ferrate treatment markedly modified the physicochemical characteristics of biochar, yielding thinner, smoother-surfaced structures with pronounced iron enrichment. At a 5% application rate alongside ryegrass cultivation, FeBC exhibited superior remediation performance, achieving 52.0% degradation of petroleum hydrocarbons (notably within the meso-aggregate fraction) and a 19.2% decline in zinc bioavailability via immobilization, thereby reducing zinc uptake in ryegrass tissues. Furthermore, FeBC amendment induced significant shifts in rhizosphere soil biochemistry and microbial ecology, characterized by diminished catalase activity but elevated urease and alkaline phosphatase activities. Phospholipid fatty acid profiling indicated a substantial rise in bacterial biomass (encompassing both Gram-positive and Gram-negative groups), particularly in meso- and micro-aggregates, whereas soil bacterial α-diversity declined markedly, accompanied by distinct compositional changes across aggregate size fractions. These results offer mechanistic insights into the synergistic interaction between FeBC and ryegrass in co-contaminated soil rehabilitation, the aggregate-dependent distribution of remediation effects, and microbial community adaptations to FeBC treatment. Collectively, this study advances the understanding of ferrate-modified biochar’s role in phytoremediation enhancement and clarifies its operational mechanisms in petroleum-zinc co-contaminated soil systems. Full article

Cilantro (Coriandrum sativum L.) is a popular annual culinary herb grown for its leaves or seeds. With the increase in hydroponic herb production in controlled environments, a need exists for leaf tissue nutrient standards specific to this production system. The objective of this study was to develop comprehensive foliar mineral nutrient interpretation ranges for greenhouse-grown cilantro. Cilantro plants were grown in a hydroponic sand culture system to induce and document nutritional disorders. Plants were supplied with a modified Hoagland’s solution, which was adjusted to individually add or omit one nutrient per treatment while holding all others constant. Deficiency and toxicity symptoms were photographed, after which the plant tissue was collected to determine plant dry weight and critical tissue nutrient concentrations. Nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), sulfur (S), boron (B), iron (Fe), and zinc (Zn) deficiencies, as well as B toxicity, were induced. Deficiencies of copper (Cu), manganese (Mn), and molybdenum (Mo) were not observed during the experiment. Additional foliar tissue analysis data (n = 463) were compiled to create nutrient interpretation ranges for 12 essential elements based on a hybrid meta-analysis Sufficiency Range Approach (SRA). This approach defines ranges for deficient, low, sufficient, high, and excessive values. For each element, the optimal distribution was selected according to the lowest Bayesian Information Criterion (BIC) value. A Normal distribution best represented K and S. A Gamma distribution best represented P, Ca, Mn, and Mo, whereas a Weibull distribution best represented N, Mg, B, Cu, Fe, and Zn. These interpretation ranges, along with descriptions of typical symptomology and critical tissue nutrient concentrations, provide useful tools for both diagnosing nutritional disorders and interpreting foliar nutrient analysis results of greenhouse-grown cilantro. Full article

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic inflammation, endothelial dysfunction, and placental insufficiency. While inadequate trophoblast invasion and impaired spiral artery remodeling have long been recognized as central to its pathogenesis, emerging evidence underscores the critical roles of dysregulated iron metabolism and its crosstalk with immune responses, particularly macrophage-mediated inflammation, in driving PE development. This review systematically explores the dynamic changes in iron metabolism during pregnancy, including increased maternal iron demand, placental iron transport mechanisms, and the molecular regulation of placental iron homeostasis. We further explore the contribution of ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, to trophoblast dysfunction and pregnancy-related diseases, including PE. Macrophages, pivotal immune regulators at the maternal–fetal interface, exhibit distinct polarization states that shape tissue remodeling and immune tolerance. We outline their origin, distribution, and polarization in pregnancy, and emphasize their aberrant phenotype and function in PE. The bidirectional crosstalk between iron and macrophages is also dissected: iron shapes macrophage polarization and function, while macrophages reciprocally modulate iron homeostasis. Notably, excessive reactive oxygen species (ROS) and pro-inflammatory cytokines secreted by M1-polarized macrophages may exacerbate trophoblast ferroptosis, amplifying placental injury. Within the context of PE, we delineate how iron overload and macrophage dysfunction synergize to potentiate placental inflammation and oxidative stress. Key iron-responsive immune pathways, such as the HO-1/hepcidin axis and IL-6/TNF-α signaling, are discussed in relation to disease severity. Finally, we highlight promising therapeutic strategies targeting the iron–immune axis, encompassing three key modalities—iron chelation therapy, precision immunomodulation, and metabolic reprogramming interventions—which may offer novel avenues for PE prevention and treatment. Full article

Tracking T cells in vivo using MRI is a major challenge due to the difficulty of labeling these non-phagocytic cells with a sufficient contrast agent to generate a detectable signal change. In this study, we explored CD4-Superparamagnetic iron oxide nanoparticles (SPION), which is commonly used in magnetic cell sorting, as a potential receptor-mediated, specific CD4⁺ T cell MRI labeling agent. We optimized the labeling protocol for maximal CD4⁺ cell labeling and viability. Cell health was confirmed with trypan blue assay, and labeling efficacy was confirmed with Prussian blue staining, transmission electron microscopy, and MRI of labeled cell pellets. Key cell functionality was assessed by flow cytometry. Next, CD4-SPION-labeled T cells or unlabeled T cells were delivered via intravenous injection in naïve mice. Liver MRIs pre-, 24 h, and 72 h post-T cell injection were performed to determine in vivo tracking ability. Our results show that CD4-SPION induces significant attenuation of T2 signals in a concentration-dependent manner, confirming their potential as an effective MRI contrast agent. In vitro, analyses showed that CD4⁺ T cells were able to uptake CD4-SPION without affecting cellular activity and key functions, as evidenced by Prussian blue staining and flow cytometric analysis of IL-2 receptor and the IL-7 receptor α-chains, CD69 upregulation, and IFN-γ secretion. In vivo, systemically distributed CD4-SPION-labeled T cells could be tracked in the liver at 24 and 72 h after injection, contrary to controls. Histological staining of tissue sections validated the findings. Our results showed that SPION CD4⁺ T cell sorting coupled with longitudinal MR imaging is a valid method to track CD4⁺ T cells in vivo. This safe, specific, and sensitive approach will facilitate the use of SPION as an MRI contrast agent in clinical practice, allowing for non-invasive tracking of adoptive cell therapies in multiple disease conditions. Full article