Biological Trace Element Research最新文献

{"title":"Boric Acid Combined with Venetoclax Induces Apoptosis in CLL Cell Lines via Caspase Activation and Oxidative Stress Modulation: In Vitro and In Silico Study.","authors":"Dilek Nur Bestil, Hamdi Uysal","doi":"10.1007/s12011-026-05248-6","DOIUrl":"10.1007/s12011-026-05248-6","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation of mature B lymphocytes in the blood, bone marrow, and lymph nodes. The development of chemotherapy resistance has increased the need for novel and less toxic therapeutic approaches. Owing to its unique biological properties, the anticancer potential of boric acid (BA) has attracted increasing attention. This study investigated the effects of BA on cell viability, apoptosis, and oxidative stress in HG-3 and MEC-1 CLL cell lines and evaluated its synergistic potential in combination with Venetoclax. Cell viability was assessed after 24 and 48 h of treatment, and the IC₅₀ values of BA were determined as 75 µg/mL for HG-3 cells and 80 µg/mL for MEC-1 cells. Apoptosis was evaluated by measuring caspase-3 and caspase-8 activities, which were significantly increased in the combination groups compared with the control group (p < 0.05). Oxidative stress was assessed using total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, molecular docking, molecular dynamics, reduced density gradient (RDG), and molecular electrostatic potential (MEP) analyses were performed to investigate the molecular interactions of BA. Taken together, these findings provide preliminary evidence supporting the biological activity of the BA-Venetoclax combination and justify further mechanistic and in vivo studies to evaluate its potential relevance in chronic lymphocytic leukemia.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"8130-8142"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oridonin Protects Mice Against Cadmium-induced Kidney Injury by Inhibiting Ferroptosis via SIRT1 Regulation.","authors":"Sixuan Li, Siqi Liu, Huafeng Geng, Yang Li, Cong Ye, Chunxi Wang, Yue Zhang","doi":"10.1007/s12011-026-05228-w","DOIUrl":"10.1007/s12011-026-05228-w","url":null,"abstract":"<p><p>Kidney injury is a clinical condition characterized by a rapid decline in renal function, associated with high morbidity and mortality. This study aimed to investigate the protective effects and mechanism of oridonin against cadmium-induced kidney injury in mice. A mouse model of cadmium-induced kidney injury was established by cadmium administration. Inflammatory cytokines were tested by ELISA. Protein expression was measured by western blot analysis. Oridonin treatment reduced cadmium-induced serum creatinine and blood urea nitrogen (BUN), kidney myeloperoxidase (MPO) activity, and TNF-α and IL-1β production. Oridonin also alleviated pathological changes in the kidney caused by cadmium. Furthermore, cadmium-induced hypoxia-inducible factor-1α (HIF-1α), NLRP3 inflammasome and NF-κB activation were inhibited by oridonin. Oridonin also suppressed cadmium-induced ferroptosis. In addition, oridonin upregulated SIRT1 expression and the protective effects of oridonin on cadmium-induced inflammation and ferroptosis were abolished by SIRT1 inhibitor. In conclusion, oridonin attenuates cadmium-induced kidney injury by activating SIRT1, which in turn suppresses inflammation and ferroptosis.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7870-7883"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between Salivary and Urinary Iodine Indicators in Lactating Women: A Cross-Sectional Study.","authors":"Ziyun Pan, Xiaorui Li, Teng Zhao, Xiru Wang, Ying Zhang, Jingyi Wang, Haozhuo Xie, Yuyang Cai, Changjiang Li, Wenhui Zhang, Ziyan Zeng, Lijun Duan, Zhongna Sang","doi":"10.1007/s12011-026-05239-7","DOIUrl":"10.1007/s12011-026-05239-7","url":null,"abstract":"<p><p>Iodine is essential for infant growth and neurodevelopment. To assess iodine nutritional status in populations or individuals a 24-hour urinary iodine concentration (24 h-UIC) is a reliable biomarker but relatively time-consuming and inconvenient method, therefore, more simple alternatives are required. This study examined the correlation between salivary iodine concentration (SIC) and commonly used iodine-related indicators, that is, 24 h-UIC and breast milk iodine concentration (BMIC), and explored the potential of SIC as a biomarker in lactating women. This study recruited 29 healthy lactating women in Luoyang City, Henan Province, China. Over five consecutive days, 24-hour urine samples were collected daily, while saliva and breast milk samples were collected once a day. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine iodine concentrations in urine, saliva and breast milk. Statistical analyses included Spearman correlation analysis to assess associations between SIC and urinary iodine-related measurements. The median 24 h-UIC was 114.8 µg/L, indicating adequate iodine nutrition in this study population (median UIC < 100 µg/L). SIC showed significant positive correlations with 24 h-UIC and 24-hour urinary iodine excretion (24 h-UIE) (r = 0.689 and 0.460, respectively; P < 0.001), whereas no significant correlation was observed between SIC and BMIC (r = 0.047, P > 0.05). When participants were grouped according to 24 h-UIC (< 100 µg/L vs. ≥100 µg/L), higher SIC levels were observed in the group with higher 24 h-UIC (SIC: 163.4 vs. 109.2 µg/L). The intraindividual variability of SIC was lower than inter-individual variability (18.5 vs. 35.2%), suggesting relatively stable within-subject measurements over repeated sampling. The positive correlation between SIC and 24 h-UIC or 24 h-UIE suggests that SIC may serve as a convenient non-invasive indicator associated with urinary iodine-related measurements in lactating women. However, the observed relationships are exploratory, and further validation in larger and more diverse populations is needed.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"8001-8009"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the Impact of Acidification and Toxic Metal Stress on Tea Soil Bacteriome: Integrating 16S rRNA Sequencing with Multivariate Approaches.","authors":"Riddhi Basu, Sonali Banerjee, Saibal Ghosh, Gourav Mondal, Sumit Kumar, Pradip Bhattacharyya","doi":"10.1007/s12011-026-05211-5","DOIUrl":"10.1007/s12011-026-05211-5","url":null,"abstract":"<p><p>Acidification coupled with TMs pollution in tea soil pose a significant threat to the ecosystem by adversely affecting soil health. This research links 16 S rRNA sequencing analysis with advanced statistical tools to evaluate synergistic effect of acidity and TMs pollution on bacteriome of two tea-cultivating zones of India. Results indicated bioavailable TMs level was substantially greater in zone 1 (WS_Cr: 2.98 mg/kg, Ex_Cr: 6.98 mg/kg, WS_Ni: 1.39 mg/kg, Ex_Ni: 4.54 mg/kg) than in zone 2. Elevated acidity levels in zone 1 fostered substantial accumulation of TMs in soil. In contrast, zone 2 exhibited improved microbial activity due to reduced TMs and acidity stress.16 S rRNA sequencing reflected higher prevalence of Cyanobacteria across zones (zone 1: 2.81%, zone 2: 8.715%). GIS and SOM maps illustrated impact of bioavailable TMs and acidity on soil microbial activity. Random Forest analysis highlighted significant influence of BA_Cr and Ex_Al on Acidobacteria. Strikingly, both zones exhibited diverse bacteriome. Increased TOC content may have compensated for adverse impacts of soil stressors, thereby facilitating the survival of diverse bacteriome in both zones. This research provides valuable insights into dual effect of soil acidity and TMs on tea soil bacteriome, aiding scientists and policymakers in promoting sustainable tea cultivation worldwide.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7625-7641"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compartment-specific Zinc Misallocation in Diabetic Foot Ulcers: Mechanistic Coupling Between Macrophage M1 Locking and MMP-9 Hyperactivation.","authors":"Aiden Yi-Fei Wang, Atiqah Aziz, Han-Ling Tan, Xiu-Wen Ling, Terry Hao-Yu Qin","doi":"10.1007/s12011-026-05225-z","DOIUrl":"10.1007/s12011-026-05225-z","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7817-7832"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological Aging Mediates the Associations Between Multiple Serum Micronutrients and All-Cause Mortality Among U.S. Adults.","authors":"Chaoyi Bian, Wanting Wang, Zhengyang Wu, Hongling Zhang, Chuanting Wen, Kangkang Zhong, Rui Yang, Qi Zhong","doi":"10.1007/s12011-026-05214-2","DOIUrl":"10.1007/s12011-026-05214-2","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7677-7687"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of H3K18 Acetylation in Cadmium-Associated Modulation of the Nrf2-Keap1/NF-κB Axis and Liver Fibrosis Progression.","authors":"Yilin Liu, Yanling Zhou, Xiaole Liang, Jiaohua Chen, Xiufang Li, Sibiao Su","doi":"10.1007/s12011-026-05202-6","DOIUrl":"10.1007/s12011-026-05202-6","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7490-7500"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional in Vitro Biological Activities of Mixed Light Rare Earth Oxides: Antioxidant, Enzyme Inhibitory and Cytotoxic Potential.","authors":"Mona M Khalifa, Hesham A M Ibrahim, Mohammed E Gad, Ibrahim A I Hassan, Soad A Elshanawany, Soma A El Mogy, A I L Abd El Fatah","doi":"10.1007/s12011-026-05199-y","DOIUrl":"10.1007/s12011-026-05199-y","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7441-7453"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascorbic Acid as a Dual Therapeutic and Preventive Agent against Lead and Cadmium Toxicity: Evidence from Controlled Quail Experiments.","authors":"Shadi Mousa, Ahed H Zyoud, Ramzi Shawahna","doi":"10.1007/s12011-026-05195-2","DOIUrl":"10.1007/s12011-026-05195-2","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7387-7401"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediabetes Subtypes with Divergent Iron Metabolism Profiles: A Cluster Analysis from Two Cohorts in the United States and China.","authors":"Mei Huang, Wencan Jiang, Yanyan Wu, Yao Qin, Liuyan Dai, Xinyi Qu, Suyu Wang, Mei Zhang","doi":"10.1007/s12011-026-05215-1","DOIUrl":"10.1007/s12011-026-05215-1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":" ","pages":"7688-7701"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}