Biological Trace Element Research最新文献

Diabetic foot ulcer (DFU) remains a formidable clinical challenge characterized by a persistent failure of the regenerative process. Affecting approximately 15-25% of diabetic individuals over their lifetime, DFU is associated with a disproportionate risk of lower-limb amputation and mortality. Although zinc is a fundamental requirement for cutaneous repair, conventional supplementation strategies often yield inconsistent therapeutic outcomes. This review addresses this clinical gap by introducing the Zinc Misallocation Hypothesis, which posits that compartment-specific collapse of ionic partitioning represents a mechanistically distinct contributor to DFU chronicity, independent of total zinc deficiency. Under conditions of chronic hyperglycemia and oxidative stress, a pathological spatiotemporal decoupling occurs, leading to functional intracellular Zn²⁺ scarcity alongside a destructive accumulation of labile Zn²⁺ in the extracellular matrix. This ionic misallocation establishes a dual-track inhibitory mechanism that may contribute to sustained repair impairment. Intracellularly, functional Zn²⁺ depletion disrupts the structural integrity of zinc-finger regulatory proteins such as A20 and CYLD, leading to the sustained disinhibition of the NF-κB signaling axis. This biochemical locking prevents the transition of macrophages from a pro-inflammatory M1 state to a pro-reparative M2 phenotype. Simultaneously, the pathological saturation of Zn²⁺ in the extracellular environment facilitates the hyperactivation of matrix metalloproteinases, specifically MMP-9, while concurrently inactivating endogenous inhibitors such as TIMP-1. The markedly elevated proteolytic activity triggers extensive degradation of the basement membrane and induces a state of multi-lineage cellular arrest, where the migratory and proliferative capacity of keratinocytes, fibroblasts, and endothelial cells is substantially attenuated. To resolve this biochemical stalemate, we propose a reciprocal regulatory paradigm utilizing advanced responsive delivery systems, such as ROS-sensitive nanocarriers and metal-organic frameworks. These precision platforms facilitate a dual-action operation designed to sequester pathogenic extracellular zinc while selectively replenishing functional intracellular pools. Ultimately, the restoration of compartment-specific zinc homeostasis represents a rational therapeutic objective for attenuating the self-reinforcing pathological state of the chronic diabetic wound.

Background: Serum micronutrients are highly intercorrelated in general populations and may affect longevity via biological aging-related pathways. Nevertheless, it remains unclear whether biological aging mediates the associations of serum micronutrient mixtures with all-cause mortality.

Methods: This prospective cohort analysis included adults from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2017-2018, with mortality follow-up until December 31, 2019. Six serum micronutrients were assessed: vitamin C, 25-hydroxyvitamin D (25(OH)D), α-tocopherol, β-carotene, lycopene, and folate. Biological aging was estimated based on nine clinical biomarkers: albumin, creatinine, glucose, C-reactive protein, lymphocyte percentage, mean cell volume, red cell distribution width, alkaline phosphatase, and white blood cell count. PhenoAgeAccel was defined as phenotypic age minus chronological age. Cox proportional hazards regression and restricted cubic splines (RCS) were applied to assess the associations of individual serum micronutrients with all-cause mortality. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) were used to explore the joint effects of micronutrient mixtures on mortality. Mediation analysis was further conducted to quantify the mediating role of PhenoAgeAccel.

Results: A total of 6,387 participants were included, with a median follow-up of 14.08 years and 932 all-cause deaths recorded. In fully adjusted Cox models, higher levels of β-carotene, lycopene, vitamin C, and 25(OH)D were significantly associated with reduced mortality risk. Compared with the lowest tertile (tertile 1), the HRs (95% CIs) for all-cause mortality were 0.80 (95% CI: 0.64-1.00, P = 0.048) for tertile 2 and 0.74 (95% CI: 0.60-0.90, P = 0.003) for tertile 3 of β-carotene. Both QGC and BKMR analyses revealed a protective joint effect of the micronutrients mixture on all-cause mortality (HR = 0.723, 95% CI: 0.646-0.809), with lycopene contributing the largest negative weight (0.455). PhenoAgeAccel significantly mediated the associations of β-carotene, lycopene, vitamin C, and 25(OH)D with all-cause mortality, with mediating proportions of 35.65%, 15.66%, 27.30%, and 6.87%, respectively.

Conclusion: Higher serum micronutrient concentrations were inversely associated with all-cause mortality, and these associations were partially mediated by decelerated biological aging. Within the micronutrient mixture, lycopene exhibited the greatest relative contribution to the overall protective effect.

This study explores how chronic cadmium exposure induces H3K18 acetylation in hepatocytes, regulating the Nrf2-Keap1/NF-κB signaling pathway and promoting liver fibrosis. A CdCl₂-induced mouse model of liver fibrosis and hepatocyte injury was established. The H3K18 acetylation inhibitor DCH36_06 was applied in combination with this model. Various assays were used to assess hepatocyte apoptosis and the expression of H3K18ac, Bax, Nrf2, Keap1, and NF-κB both in vivo and in vitro. Mice were provided with drinking water containing CdCl₂ at a final concentration of 1 g/L. Histological analysis of liver tissues using H&E and Masson staining showed mild fibrosis (G1S1) after 4 weeks and marked cirrhosis (G3S3-4) after 24 weeks. Immunohistochemistry and fluorescence analysis revealed elevated H3K18ac and Bax expression in hepatocytes following cadmium exposure. In vitro, cadmium increased intracellular and ROS accumulation, upregulated endoplasmic reticulum stress-related genes (Perk and Manf), and accelerated apoptosis. Western blotting confirmed increased expression of apoptosis-related proteins Caspase3, Bax, Bcl-2, and HO-1. Under low-dose cadmium exposure, sustained H3K18ac expression in hepatocytes activated the oxidative stress-related Nrf2-Keap1/NF-κB pathway, leading to high levels of Nrf2, Keap1, and NF-κB proteins. Treatment with DCH36_06 reduced ROS accumulation and apoptosis, and downregulated Perk and Manf expression. In the CdCl₂ + DCH36_06 mouse model, fibrosis progression was noticeably slower, indicating that inhibition of H3K18 acetylation mitigates liver damage. Low-dose cadmium exposure promotes H3K18 acetylation in hepatocytes, leading to ROS accumulation and modulation of the Nrf2-Keap1/NF-κB signaling pathways. This cascade triggers oxidative stress and apoptosis, driving the development and progression of liver fibrosis.

Light rare earth oxides (LREEs), such as cerium, lanthanum, neodymium, and praseodymium oxides, have unique redox and catalytic properties that may contribute to various therapeutic effects. Researchers in this study looked at LREEs' in vitro antioxidant, anti-diabetic, anti-Alzheimer's, anti-arthritic, and cytotoxic effects. The antioxidant potential was evaluated using Diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO), hydroxyl (OH), and hydrogen peroxide (H₂O₂) radical scavenging assays, showing a moderate inhibitory effect compared to ascorbic acid. Enzyme inhibition assays indicated weak AChE inhibition, suggesting limited anti-Alzheimer's disease potential. Moderate anti-arthritic effects were observed through inhibition of protein denaturation and proteinase activity. In anti-diabetic assays, LREEs dose-dependently inhibited α-amylase and α-glucosidase, although less potent than acarbose. Cytotoxicity testing on HepG2 cancer cells showed an IC₅₀ of 281.80 µg/mL, significantly higher than doxorubicin (34.07 µg/mL), indicating weak anticancer potential. Elevated Caspase-3 levels and diminished Bcl-2 levels indicate the initiation of apoptosis. These results indicate that LREEs oxide exhibits adequate biological activity, warranting further exploration of its mechanisms and potential biomedical applications. The investigated material was evaluated as a mixed light rare earth oxide system to obtain an integrated biological response profile rather than to determine the contribution of individual oxide components. Therefore, the present findings represent system-level biological behaviour and serve as a foundation for more detailed component-specific investigations. The investigated material was evaluated as a mixed light rare earth oxide system to obtain an integrated biological response profile rather than to determine the contribution of individual oxide components. Therefore, the present findings represent system-level biological behaviour and serve as a foundation for more detailed component-specific investigations.

Lead (Pb) and cadmium (Cd) are pervasive toxicants that bioaccumulate and cause multisystem injury. Two controlled experiments were conducted in quails, subdivided into co‑exposure (ascorbic acid (AA) given concurrently with Pb or Cd for four weeks) and post‑exposure (AA administered for three weeks after one week of metal exposure). Birds received Pb acetate or Cd chloride (500 ppm) with AA (1000 ppm). In the Pb experiment, co‑exposure with AA significantly reduced tissue burdens compared with Pb alone: liver (16.7 ± 0.8 vs. 29.0 ± 1.3 ppb), thigh (3.2 ± 0.6 vs. 10.6 ± 1.3 ppb), brisket (2.4 ± 0.4 vs. 13.7 ± 0.5 ppb), brain (21.7 ± 3.3 vs. 36.0 ± 3.9 ppb), bone (567.2 ± 81.6 vs. 1411.2 ± 9.8 ppb), and blood (15.1 ± 1.4 vs. 36.9 ± 3.7 ppb; all p < 0.001). Post‑exposure AA also lowered concentrations: liver (3.9 ± 1.4 vs. 12.3 ± 0.3 ppb), thigh (1.9 ± 0.3 vs. 11.3 ± 1.0 ppb), brisket (1.2 ± 0.1 vs. 6.4 ± 0.5 ppb), brain (5.7 ± 0.2 vs. 25.4 ± 1.4 ppb), bone (109.9 ± 23.6 vs. 384.5 ± 35.7 ppb), and blood (9.2 ± 0.9 vs. 19.9 ± 1.7 ppb; all p < 0.001). In the Cd experiment, co‑exposure with AA reduced tissue levels: liver (4381.5 ± 281.2 vs. 9291.1 ± 278.3 ppb), thigh (47.2 ± 1.0 vs. 116.6 ± 1.7 ppb), brisket (50.6 ± 3.6 vs. 82.8 ± 2.3 ppb), brain (31.4 ± 1.1 vs. 66.1 ± 2.7 ppb), bone (416.7 ± 11.0 vs. 562.3 ± 10.9 ppb), and blood (174.1 ± 7.9 vs. 298.5 ± 6.6 ppb; all p < 0.001). Post‑exposure AA likewise lowered burdens: liver (1109.5 ± 156.8 vs. 3200.6 ± 324.4 ppb), thigh (5.3 ± 0.5 vs. 32.6 ± 4.1 ppb), brisket (3.8 ± 0.7 vs. 30.4 ± 2.3 ppb), brain (6.5 ± 0.9 vs. 44.5 ± 5.8 ppb), bone (43.5 ± 3.1 vs. 187.6 ± 14.6 ppb), and blood (63.3 ± 1.1 vs. 143.5 ± 15.4 ppb; all p < 0.001). Across both paradigms, co‑exposure with AA generally produced larger relative reductions in tissue burdens compared with post‑exposure treatment, although both approaches were effective. Given its safety, availability, and low cost, AA may be incorporated into strategies for populations at risk of heavy metal exposure.

We aim to investigate the relationship between iron metabolism and prediabetes using data from the National Health and Nutrition Examination Survey (NHANES) and the China Health and Nutrition Survey (CHNS) databases, and to identify prediabetes subgroups with distinct distinct iron-related biomarker profiles through cluster analysis, while examining both universal patterns and population-specific differences across U.S. and Chinese populations. Data from NHANES 2003-2010 and 2015-2020 were used for primary analysis; these cycles were selected based on the availability of complete iron metabolism biomarker data. Participants were classified into prediabetes group and normoglycemic group. Linear regression analysis was conducted to evaluate the association between clinical indicators and iron metabolism markers. K-means cluster analysis was performed in the NHANES prediabetes subsample to identify phenotypically distinct subgroups. The identified cluster structure was subsequently validated by independently applying the same algorithm to the CHNS 2009 prediabetes subsample. Between-group comparisons were performed using the t-test or Mann-Whitney U test for continuous variables and the χ² test for categorical variables, as appropriate. A two-sided P-value of < 0.05 was considered statistically significant. Among 7110 participants from NHANES, 1528 were classified into the prediabetes group. Compared with the normoglycemic group, the prediabetes group exhibited significantly higher ferritin [82.0 (IQR 40.1-158.0) vs. 47.00 (IQR 26.1-89.3) µg/L, P < 0.001] and lower serum iron (14.9 ± 6.3 vs. 16.0 ± 7.2 µmol/L, P = 0.031), reflecting a pattern of sub-clinical iron redistribution rather than clinically defined iron overload. Three distinct prediabetes phenotypes were identified: Cluster 1 (obesity-related insulin resistant-younger phenotype, N = 424), cluster 2 (mild insulin secretion impairment-younger phenotype, N = 456), and cluster 3 (high iron store-older phenotype, N = 648). Cluster 3 demonstrated older phenotype with higher ferritin concentrations within the normal reference range and showed the highest ferritin and serum iron concentrations among the identified clusters, while Cluster 1 has intermediate ferritin levels and Cluster 2 has the lowest levels (P < 0.001). A comparable three-cluster structure was replicated in the CHNS 2009 cohort, with Cluster 3 representing a higher proportion (48.89% vs. 42.41%) and retaining the highest ferritin levels [92.6 (IQR 52.0-155.3) µg/L, P < 0.001]. Variation in iron-related markers is present in the prediabetes stage, with distinct patterns across subgroups. We identified three distinct prediabetes phenotypes characterized by different ferritin profiles within the normal reference range, providing novel insights for individualized clinical practice and risk stratification.

Boron has emerged as a nutritionally important element due to significant role in biological system, including mineral lipid and energy metabolism, immune and endocrine system and brain function. The primary objective of present investigation was to evaluate the effect of graded levels of boron supplementation (0, 12, 24 and 48 ppm) on performance and mineral metabolism of broilers. 200 day-old broiler chicks, which were randomly allotted into four dietary treatment groups, viz., BA-0: No boron supplementation, BA-12: Received boric acid 12 mg Kg^- 1 dry feed, BA-24: Received boric acid 24 mg Kg^- 1 dry feed and BA-48: Received boric acid 48 mg Kg^- 1 dry feed, with five replicates of ten birds each under a completely randomized design for 42 days experimental period. Boric acid was used as a boron source. The body weight, feed conversion ratio, energy and protein efficiency ratio improved significantly (p < 0.05) with increasing levels of boric acid supplementation, while feed intake remained non-significant (p > 0.05) across all treatment groups throughout the experimental period. The serum biochemical profile revealed that serum glucose and cholesterol levels decreased significantly (p < 0.05) with increasing levels of boric acid supplementation. The tibial bone and intestinal characteristics revealed significant improvement (p < 0.05) in the higher supplemented groups, particularly in BA-24 and BA-48, compared to the control group. Profitability and overall economic efficiency increased significantly (p < 0.05) with increasing levels of boric acid supplementation, with the highest economic returns recorded in the BA-48 group, followed by BA-24. These findings suggest that dietary supplementation of boric acid @ 48 ppm improved the growth performance and mineral metabolism in broiler chickens. Further research is warranted to explore the potential of boron in poultry nutrition.

Objective: To detect the levels of whole blood minerals and trace elements (calcium, iron, zinc, copper, magnesium) in overweight and obese patients, and explore their associations with body weight, body mass index (BMI) and other body composition indicators.

Methods: A retrospective cross-sectional analysis was conducted among 1220 enrolled patients. Participants were categorized into overweight and obese groups based on body mass index (BMI). We compared whole blood minerals and trace elements, body composition and weight-related indicators between the two groups, and explored correlations and independent associations of these elements with BMI, body fat percentage, visceral fat content and muscle mass. Statistical analyses included the Mann-Whitney U test, Spearman correlation analysis and multiple linear regression analysis.

Results: Concentrations of iron, zinc and magnesium were significantly elevated in the obese group (P < 0.001), while calcium concentrations were markedly lower (P < 0.001). No significant intergroup difference was observed for copper (P = 0.408). Correlation analysis revealed that iron, zinc and magnesium were positively correlated with BMI, visceral fat content and muscle mass (P < 0.001), and negatively correlated with body fat percentage (P < 0.001). Copper was positively correlated with body fat percentage (P < 0.001) and negatively correlated with muscle mass (P < 0.001). In multiple linear regression analysis adjusted for gender and age, copper (B = 0.157, P = 0.002) showed a significant independent positive association with body fat percentage. Zinc had a borderline positive association with BMI (B = 0.003, P = 0.069), indicating no statistical significance. None of the elements were significantly and independently associated with visceral fat content.

Conclusion: Iron, zinc, magnesium and copper are closely correlated with obesity-related indices. Copper shows a specific association with body fat percentage rather than visceral adipose tissue. As an observational study, we confirmed associations between these minerals and trace elements and obesity as well as body composition, yet causal relationships cannot be established.

Mg²⁺ deficiency has been linked to oxidative stress, inflammation, and hypertension. We have previously shown that Losartan increases plasma Mg²⁺ levels in Dahl salt-sensitive (Dahl) rats, suggesting that defective Mg²⁺ metabolism in this strain contributes to hypertension. Here, we investigated the effects of dietary Mg²⁺ supplementation (0.3% MgO) and/or Losartan (10 mg/kg/day, in drinking water) in male Dahl rats fed a high-NaCl (8%) or standard Na⁺ diet for six weeks. Six-week-old rats were randomly assigned to eight experimental groups. NO metabolites (nitrites and nitrates) were measured in plasma and kidney homogenates. Oxidative stress was assessed by lipid peroxidation in plasma and red blood cell ghosts (RBCG), and by erythrocyte osmotic fragility (OS₅₀). Both Losartan and Mg²⁺ supplementation protected against hypertension and high-salt-induced systemic and local oxidative stress, with differential regulation of Na⁺/K⁺-ATPase and Na⁺-ATPase activity. A consistent "high Na⁺ effect" was observed across NaCl-fed groups, characterized by Renin-Angiotensin-Aldosterone System (RAAS) activation, increased Reactive Oxygen Species (ROS) production, lipid peroxidation, osmotic fragility, and elevated Na⁺/K⁺-ATPase activity. Losartan normalized blood pressure (BP) by attenuating renal RAAS activity and reducing oxidative stress, whereas Mg²⁺ supplementation increased (Nitrites + Nitrates) NO_X levels, improved red blood cell (RBC) membrane stability, and stimulated Na⁺-ATPase activity. These findings highlight distinct but complementary mechanisms through which AT₁R blockade and Mg²⁺ supplementation attenuate salt-induced oxidative stress and reduce BP. Future studies incorporating immunohistochemistry and qPCR are warranted to further characterize ROS-mediated renal tissue damage across treatment groups.