Lead (Pb) contamination in phosphate mining wasteland soils severely inhibits plant growth and compromises ecological safety, thereby necessitating long-term remediation strategies to restore ecosystem functions. Pot experiments were conducted to evaluate the synergistic effects of microbially induced carbonate precipitation (MICP) and magnesium polypeptide (MP) amendments on celery growth and the restructuring of rhizosphere microbial communities. Under Pb stress (200 mg/kg), Pb accumulation in celery was significantly reduced by the combined MICP-MP treatment, with concentrations decreasing to 4.49, 0.26, and 1.93 mg/kg in roots, stems, and leaves, respectively; concurrently, plant growth and development were promoted. Correlation analysis revealed that the remediation-induced enhancement of soil physicochemical properties acted as a primary environmental driver, showing a significant negative correlation with exchangeable Pb content. The transformation of Pb from high-risk, bioavailable exchangeable forms to low-risk, stable fractions, such as carbonate-bound and Fe/Mn oxide-bound forms, was successfully promoted by the treatment, concomitant with enhanced soil physicochemical properties and biological activity. Furthermore, rigorous compositional analysis demonstrated that the MICP-MP treatment significantly enriched beneficial bacterial taxa, such as Nocardiopsis and Planococcus. These shifts in community composition played a key role in enhancing the soil bacterial community's adaptation to Pb stress. In summary, Pb-induced phytotoxicity was alleviated, and rhizosphere microbial stability and assembly were modulated by the MICP-peptide combination, providing new insights into plant-microbe interactions under heavy metal stress.
{"title":"Synergistic mitigation of lead accumulation in celery by magnesium polypeptide and microbially induced calcite precipitation in phosphate mining wasteland soils.","authors":"Shuyi Yu, Ziwei Wang, Yi Xiong, Yushan Chen, Yuxin Zhang, Yun Fang, Guowei Wang, Ruan Chi, Chunqiao Xiao","doi":"10.1007/s10534-025-00782-7","DOIUrl":"https://doi.org/10.1007/s10534-025-00782-7","url":null,"abstract":"<p><p>Lead (Pb) contamination in phosphate mining wasteland soils severely inhibits plant growth and compromises ecological safety, thereby necessitating long-term remediation strategies to restore ecosystem functions. Pot experiments were conducted to evaluate the synergistic effects of microbially induced carbonate precipitation (MICP) and magnesium polypeptide (MP) amendments on celery growth and the restructuring of rhizosphere microbial communities. Under Pb stress (200 mg/kg), Pb accumulation in celery was significantly reduced by the combined MICP-MP treatment, with concentrations decreasing to 4.49, 0.26, and 1.93 mg/kg in roots, stems, and leaves, respectively; concurrently, plant growth and development were promoted. Correlation analysis revealed that the remediation-induced enhancement of soil physicochemical properties acted as a primary environmental driver, showing a significant negative correlation with exchangeable Pb content. The transformation of Pb from high-risk, bioavailable exchangeable forms to low-risk, stable fractions, such as carbonate-bound and Fe/Mn oxide-bound forms, was successfully promoted by the treatment, concomitant with enhanced soil physicochemical properties and biological activity. Furthermore, rigorous compositional analysis demonstrated that the MICP-MP treatment significantly enriched beneficial bacterial taxa, such as Nocardiopsis and Planococcus. These shifts in community composition played a key role in enhancing the soil bacterial community's adaptation to Pb stress. In summary, Pb-induced phytotoxicity was alleviated, and rhizosphere microbial stability and assembly were modulated by the MICP-peptide combination, providing new insights into plant-microbe interactions under heavy metal stress.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905343","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}
Pub Date : 2025-12-26DOI: 10.1007/s10534-025-00781-8
Meenu Singh, Yeshvandra Verma, Suresh Vir Singh Rana
Extensive growth in the production of nanoparticles (NPs) together with increased usage in a variety of consumer products has introduced potential health risks amongst organisms, humans and ecosystems. Unique physico-chemical properties of nanoparticles facilitate their entry, bioaccumulation and subsequent interaction with biounterfaces in diverse cellular systems. These nano bio-interfaces occur in different cells/organ systems and contribute to selective toxicity through a cross talk amongst couple of mechanisms viz. oxidative stress, inflammation, apoptosis, DNA damage and redox signaling pathways. Present review describes the role of these mechanisms especially in teratogenicity induced by metallic nanoparticles. Available data suggests that generation of ROS and oxidative stress are the predominant mechanisms of NP induced materno-fetal toxicity. They do trigger inflammatory responses in the fetus and lead to structural abnormalities. Exposure to NPs induces apoptosis and DNA damage that result in fetal cytotoxicity. Autophagy has been recognized as a major form of cell death encountered during pregnancy in NP treated models. It may involve oocytogenesis, implantation, placentation, embryogenesis and preterm delivery. Vascular signaling and toll like receptors are also involved in the feto-toxicity of NPs. It is concluded that mechanism based high throughput in vitro screening of NPs can predict the genesis of teratogenicity. A better understanding of teratogenicity induced by NPs is not only essential for health risk assessment but also for the design and synthesis of novel and safer nanomaterials.
{"title":"Mechanistic paradigms of teratogenicity induced by metallic nanoparticles-a mini review.","authors":"Meenu Singh, Yeshvandra Verma, Suresh Vir Singh Rana","doi":"10.1007/s10534-025-00781-8","DOIUrl":"https://doi.org/10.1007/s10534-025-00781-8","url":null,"abstract":"<p><p>Extensive growth in the production of nanoparticles (NPs) together with increased usage in a variety of consumer products has introduced potential health risks amongst organisms, humans and ecosystems. Unique physico-chemical properties of nanoparticles facilitate their entry, bioaccumulation and subsequent interaction with biounterfaces in diverse cellular systems. These nano bio-interfaces occur in different cells/organ systems and contribute to selective toxicity through a cross talk amongst couple of mechanisms viz. oxidative stress, inflammation, apoptosis, DNA damage and redox signaling pathways. Present review describes the role of these mechanisms especially in teratogenicity induced by metallic nanoparticles. Available data suggests that generation of ROS and oxidative stress are the predominant mechanisms of NP induced materno-fetal toxicity. They do trigger inflammatory responses in the fetus and lead to structural abnormalities. Exposure to NPs induces apoptosis and DNA damage that result in fetal cytotoxicity. Autophagy has been recognized as a major form of cell death encountered during pregnancy in NP treated models. It may involve oocytogenesis, implantation, placentation, embryogenesis and preterm delivery. Vascular signaling and toll like receptors are also involved in the feto-toxicity of NPs. It is concluded that mechanism based high throughput in vitro screening of NPs can predict the genesis of teratogenicity. A better understanding of teratogenicity induced by NPs is not only essential for health risk assessment but also for the design and synthesis of novel and safer nanomaterials.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145832097","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}
Pub Date : 2025-12-23DOI: 10.1007/s10534-025-00778-3
Nivedita Bisht, Shailender Kumar Verma
Bread wheat is the staple food, but the concentration of mineral micronutrient, Copper (Cu) is relatively low with limited bioavailability. This study investigates the various copper-associated proteins in bread wheat using high-throughput systematic bioinformatics approaches. The wheat proteome was investigated for putative copper-associated proteins, and 47 Copper-binding proteins (CBPs) and 24 Copper transporter proteins (CTPs) were shortlisted. Out of these proteins, 11 were reported as common proteins and predicted to perform both functions. The identified 60 putative proteins showed diverse coordination geometry when bound to Cuprous (Cu+) and Cupric (Cu2+) ions. The Cysteine, Histidine, Glutamate, and Aspartate (CHED) amino acid residues were mostly found in the binding pockets of the proteins bound to copper. Functional classification and subcellular localisation of these proteins were also performed using sequence-based and annotation-based tools. Proteins were segregated based on their family, subfamily, functional classes and gene ontology (GO) terms, and a comprehensive report was prepared. A network analysis of the shortlisted proteins was also done, and network clusters were made using annotation tools. This report highlights the diverse roles of copper-associated proteins in the proper functioning of the plant and explains their importance in the major functions performed by the plant cell, like energy production, photosynthesis, plant growth and development, and maintaining homeostasis.
{"title":"Bioinformatic study of copper-associated proteins of bread wheat.","authors":"Nivedita Bisht, Shailender Kumar Verma","doi":"10.1007/s10534-025-00778-3","DOIUrl":"https://doi.org/10.1007/s10534-025-00778-3","url":null,"abstract":"<p><p>Bread wheat is the staple food, but the concentration of mineral micronutrient, Copper (Cu) is relatively low with limited bioavailability. This study investigates the various copper-associated proteins in bread wheat using high-throughput systematic bioinformatics approaches. The wheat proteome was investigated for putative copper-associated proteins, and 47 Copper-binding proteins (CBPs) and 24 Copper transporter proteins (CTPs) were shortlisted. Out of these proteins, 11 were reported as common proteins and predicted to perform both functions. The identified 60 putative proteins showed diverse coordination geometry when bound to Cuprous (Cu<sup>+</sup>) and Cupric (Cu<sup>2+</sup>) ions. The Cysteine, Histidine, Glutamate, and Aspartate (CHED) amino acid residues were mostly found in the binding pockets of the proteins bound to copper. Functional classification and subcellular localisation of these proteins were also performed using sequence-based and annotation-based tools. Proteins were segregated based on their family, subfamily, functional classes and gene ontology (GO) terms, and a comprehensive report was prepared. A network analysis of the shortlisted proteins was also done, and network clusters were made using annotation tools. This report highlights the diverse roles of copper-associated proteins in the proper functioning of the plant and explains their importance in the major functions performed by the plant cell, like energy production, photosynthesis, plant growth and development, and maintaining homeostasis.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809231","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}
Pub Date : 2025-12-22DOI: 10.1007/s10534-025-00773-8
Gihani Vidanapathirana, Jun Yu Woon, Fentaw Tadese Berhe, Md Sajedul Islam, Neda Moetamedirad, Md Nurujjaman, Zhuo Chen, Cu Tai Lu, Sujani Kodagoda Gamage, Alfred K Lam, Vinod Gopalan
Macroelements and microelements/ trace elements are vital for human physiological processes. Alterations in these elements have been linked to various pathological conditions, including colorectal cancer (CRC), a significant cause of cancer-related mortality. This study investigated the concentrations of macroelements and microelements across different stages of CRC and compared them with non-neoplastic colon tissues. Additionally, four toxic elements (Hg, As, Cd, and Pb) were analysed in these tissues. Sixty tissue samples were prospectively collected from patients undergoing CRC resections and large bowel mucosal tissue samples without tumour (n=10) were also collected. The concentrations of 21 elements, including macro and microelements, were quantified using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Data analysis was performed using RStudio and SPSS software version 30. Significant differences in the concentrations of K, Mg, P, Si, Fe, Mn, Cu, Cr, and Co were observed across different colorectal cancer and non-neoplastic tissues. Heavy metals such as Hg, Cd, and As were undetectable in all tissues, except for one control sample containing 2.44 µg/g of Pb. The Cu/Zn ratio was significantly lower in advanced CRC (stages III-IV) compared to early stages (I-II). Fe, Mn, Cu, Zn, Si, Cr, P, and Co concentrations were significantly associated with CRC stages. Fe levels are also associated with metastasis and tumour site. Tumour size was linked to Na, K, and Mg, while disease spread (localised vs. advanced) was associated with K, Mn, Zn, Si, Cr, and P. These findings highlight dynamic alterations in element concentrations across different stages of CRC. This elemental profiling could form the basis of future research into stage-specific biomarkers or prognostic indicators in CRC.
{"title":"Profiling of macroelements and microelements in colorectal cancer patients and their clinicopathological characteristics.","authors":"Gihani Vidanapathirana, Jun Yu Woon, Fentaw Tadese Berhe, Md Sajedul Islam, Neda Moetamedirad, Md Nurujjaman, Zhuo Chen, Cu Tai Lu, Sujani Kodagoda Gamage, Alfred K Lam, Vinod Gopalan","doi":"10.1007/s10534-025-00773-8","DOIUrl":"https://doi.org/10.1007/s10534-025-00773-8","url":null,"abstract":"<p><p>Macroelements and microelements/ trace elements are vital for human physiological processes. Alterations in these elements have been linked to various pathological conditions, including colorectal cancer (CRC), a significant cause of cancer-related mortality. This study investigated the concentrations of macroelements and microelements across different stages of CRC and compared them with non-neoplastic colon tissues. Additionally, four toxic elements (Hg, As, Cd, and Pb) were analysed in these tissues. Sixty tissue samples were prospectively collected from patients undergoing CRC resections and large bowel mucosal tissue samples without tumour (n=10) were also collected. The concentrations of 21 elements, including macro and microelements, were quantified using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Data analysis was performed using RStudio and SPSS software version 30. Significant differences in the concentrations of K, Mg, P, Si, Fe, Mn, Cu, Cr, and Co were observed across different colorectal cancer and non-neoplastic tissues. Heavy metals such as Hg, Cd, and As were undetectable in all tissues, except for one control sample containing 2.44 µg/g of Pb. The Cu/Zn ratio was significantly lower in advanced CRC (stages III-IV) compared to early stages (I-II). Fe, Mn, Cu, Zn, Si, Cr, P, and Co concentrations were significantly associated with CRC stages. Fe levels are also associated with metastasis and tumour site. Tumour size was linked to Na, K, and Mg, while disease spread (localised vs. advanced) was associated with K, Mn, Zn, Si, Cr, and P. These findings highlight dynamic alterations in element concentrations across different stages of CRC. This elemental profiling could form the basis of future research into stage-specific biomarkers or prognostic indicators in CRC.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802883","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}
Pub Date : 2025-12-18DOI: 10.1007/s10534-025-00779-2
Ahmad Ali, Zaffar Malik, Muhammad Abdul Basit, Abubakar Dar, Usman Zulfiqar, Dilnoza Sotiboldiyeva, Muydinjon Muminov, Hossam S. El-Beltagi, Mashael Daghash Alqahtani
Heavy metal contamination, especially cadmium (Cd) in agricultural lands had significantly impacted sustainability and wheat production. This study tested the effectiveness of organic and inorganic amendments viz. phosphorus-modified biochar (PMBC), vermicomposting, and bentonite for their beneficial impact on plant biomass, physiological parameters, and biochemical assays, including oxidative stress markers. Results indicated that PMBC, vermicompost, and bentonite significantly improved wheat studied parameters and their effect was more pronounced at BN1% + VC2% + PMBC2% amendment combination at 5, 10 and 15 mg kg−1 Cd levels compared to control. The wheat dry biomass (51%, 41% and 44%), root surface area (35%, 37% and 33%) significantly increased, while enhancing physiological traits such as chlorophyll a and b (21%, 24% and 21% and 19%, 23% and 18%), carotenoids content (22%, 24% and 27%), and the membrane stability index (MSI) (34%, 43% and 43%) were improved at BN1% + VC2% + PMBC2% compared to control at 5, 10 and 15 mg kg−1 Cd levels, respectively. Similar treatment also significantly reduces Cd-induced oxidative stress by improving Cd stress indicators viz. malondialdehyde (MDA), proline and hydrogen peroxide (H2O2) through enhancing activities of catalase (CAT) and superoxide dismutase (SOD). Along with growth and physiological improvements, the treatment BN1% + VC2% + PMBC2% provides a significant reduction in soil Cd, its uptake and translocation in wheat plants. Hence, it can be concluded that integration of PMBC, VC and BN is a sustainable and eco-friendly technology in improving wheat growth, physiology and yield along with alleviating oxidative damage to wheat and Cd translocation in wheat through roots.
{"title":"Integrating organic and inorganic amendments to enhance wheat growth, physiology and antioxidant activity while reducing cadmium accumulation","authors":"Ahmad Ali, Zaffar Malik, Muhammad Abdul Basit, Abubakar Dar, Usman Zulfiqar, Dilnoza Sotiboldiyeva, Muydinjon Muminov, Hossam S. El-Beltagi, Mashael Daghash Alqahtani","doi":"10.1007/s10534-025-00779-2","DOIUrl":"10.1007/s10534-025-00779-2","url":null,"abstract":"<div><p>Heavy metal contamination, especially cadmium (Cd) in agricultural lands had significantly impacted sustainability and wheat production. This study tested the effectiveness of organic and inorganic amendments viz. phosphorus-modified biochar (PMBC), vermicomposting, and bentonite for their beneficial impact on plant biomass, physiological parameters, and biochemical assays, including oxidative stress markers. Results indicated that PMBC, vermicompost, and bentonite significantly improved wheat studied parameters and their effect was more pronounced at BN1% + VC2% + PMBC2% amendment combination at 5, 10 and 15 mg kg<sup>−1</sup> Cd levels compared to control. The wheat dry biomass (51%, 41% and 44%), root surface area (35%, 37% and 33%) significantly increased, while enhancing physiological traits such as chlorophyll a and b (21%, 24% and 21% and 19%, 23% and 18%), carotenoids content (22%, 24% and 27%), and the membrane stability index (MSI) (34%, 43% and 43%) were improved at BN1% + VC2% + PMBC2% compared to control at 5, 10 and 15 mg kg<sup>−1</sup> Cd levels, respectively. Similar treatment also significantly reduces Cd-induced oxidative stress by improving Cd stress indicators viz. malondialdehyde (MDA), proline and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) through enhancing activities of catalase (CAT) and superoxide dismutase (SOD). Along with growth and physiological improvements, the treatment BN1% + VC2% + PMBC2% provides a significant reduction in soil Cd, its uptake and translocation in wheat plants. Hence, it can be concluded that integration of PMBC, VC and BN is a sustainable and eco-friendly technology in improving wheat growth, physiology and yield along with alleviating oxidative damage to wheat and Cd translocation in wheat through roots.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"389 - 408"},"PeriodicalIF":3.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773114","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}
Pub Date : 2025-12-10DOI: 10.1007/s10534-025-00758-7
Paul A. Lindahl, Jay R. Walton
The individual functions of most iron-containing species in Saccharomyces cerevisiae are fairly-well understood, but less is known regarding how they function collectively as a unified system. Here, an ODE-based kinetic cell model was developed to reveal system’s-level behavior of iron metabolism. The dimensionally-accurate in silico cell was divided into 5 compartments. It contained 80 components that engaged in 169 reactions. The cell grew on nutrients IRON, CARBON and OXYGEN. All major iron-related processes were represented including the biosynthesis and metallation of iron-containing proteins, trafficking of labile iron pools, homeostatic regulation, respiration, the TCA cycle, iron-sulfur-cluster and heme biosynthesis, the synthesis of DNA, phospholipids, amino acids, and nucleotide triphosphates, and reactions involving oxygen and reactive-oxygen-species. Iron and carbon were conserved in reaction stoichiometries. The time-dependent model was solved using the Basic Pathways approach, despite limited kinetic information. Once regulated appropriately, the system could withstand perturbations in component concentrations by returning to its original steady-state. It responded to changes in nutrient iron and oxygen concentrations and to changes in rate-constants, yielding altered sets of steady-state component concentrations. The latter type of perturbation is tantamount to altering the expression level of a gene. This ability offers the potential to explain phenotypic changes of genetic mutations on the mechanistic molecular level. The model included all established iron-related cellular processes (albeit in combined forms), and a highly interrelated reaction network reflecting a mutually autocatalytic system. Steady-state iron concentrations in the cell, organelles, and components were reasonably near to those observed/estimated experimentally.
{"title":"A kinetic mathematical model of comprehensive iron metabolism in a respiring yeast cell: a basic-pathways approach to solving a large system dynamically","authors":"Paul A. Lindahl, Jay R. Walton","doi":"10.1007/s10534-025-00758-7","DOIUrl":"10.1007/s10534-025-00758-7","url":null,"abstract":"<div><p>The individual functions of most iron-containing species in <i>Saccharomyces cerevisiae</i> are fairly-well understood, but less is known regarding how they function collectively as a unified system. Here, an ODE-based kinetic cell model was developed to reveal system’s-level behavior of iron metabolism. The dimensionally-accurate in silico cell was divided into 5 compartments. It contained 80 components that engaged in 169 reactions. The cell grew on nutrients IRON, CARBON and OXYGEN. All major iron-related processes were represented including the biosynthesis and metallation of iron-containing proteins, trafficking of labile iron pools, homeostatic regulation, respiration, the TCA cycle, iron-sulfur-cluster and heme biosynthesis, the synthesis of DNA, phospholipids, amino acids, and nucleotide triphosphates, and reactions involving oxygen and reactive-oxygen-species. Iron and carbon were conserved in reaction stoichiometries. The time-dependent model was solved using the Basic Pathways approach, despite limited kinetic information. Once regulated appropriately, the system could withstand perturbations in component concentrations by returning to its original steady-state. It responded to changes in nutrient iron and oxygen concentrations and to changes in rate-constants, yielding altered sets of steady-state component concentrations. The latter type of perturbation is tantamount to altering the expression level of a gene. This ability offers the potential to explain phenotypic changes of genetic mutations on the mechanistic molecular level. The model included all established iron-related cellular processes (albeit in combined forms), and a highly interrelated reaction network reflecting a mutually autocatalytic system. Steady-state iron concentrations in the cell, organelles, and components were reasonably near to those observed/estimated experimentally.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"231 - 257"},"PeriodicalIF":3.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-025-00758-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720182","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}
Pub Date : 2025-12-10DOI: 10.1007/s10534-025-00761-y
Geir Bjørklund
Disturbances in zinc (Zn) and copper (Cu) homeostasis have emerged as reproducible biochemical features of autism spectrum disorder (ASD). This study presents an integrative reanalysis of six investigations (2014–2025) encompassing serum, whole-blood, and plasma measurements in ASD cases and controls, and one supplementation trial. Three case–control studies reporting mean ± SD values in circulating matrices were meta-analyzed. Circulating Zn levels were significantly lower in ASD (fixed-effect Hedges’ g = –0.95; 95% CI –1.22 to –0.68; Q = 1.72, p = 0.42; I2 = 0%; Egger intercept = 4.86, one-sided p = 0.044). The Zn/Cu ratio showed greater dispersion (random-effects g = –1.28; 95% CI –2.59 to 0.03; Q = 39.5, p < 0.001; I2 = 95%), driven primarily by one cohort (leave-one-out g = –0.63; 95% CI –0.99 to –0.26). In Brazilian subjects, plasma Zn and Cu fell within reference ranges, consistent with short-term plasma buffering of marginal deficits. In an Egyptian 12-week oral elemental Zn intervention in children with ASD, serum Cu fell by ~8%, circulating metallothionein (MT) protein increased, and CARS and TGMD-2 motor scores improved. MT-1A gene expression changed with Zn. Taken together, the evidence indicates that Zn insufficiency and altered Cu homeostasis are recurring features of ASD and that oral elemental Zn lowers serum Cu and increases MT.
锌(Zn)和铜(Cu)体内平衡紊乱已成为自闭症谱系障碍(ASD)可重复的生化特征。本研究对6项调查(2014-2025)进行了综合再分析,包括ASD病例和对照组的血清、全血和血浆测量,以及一项补充试验。三个报告循环基质中平均值±SD值的病例对照研究进行meta分析。ASD患者循环锌水平显著降低(固定效应Hedges’g = -0.95; 95% CI为-1.22 ~ -0.68;Q = 1.72, p = 0.42; I2 = 0%; Egger截距= 4.86,单侧p = 0.044)。Zn/Cu比显示出更大的分散性(随机效应g = -1.28; 95% CI -2.59至0.03;Q = 39.5, p = 95%),主要由一个队列驱动(留一组g = -0.63; 95% CI -0.99至-0.26)。在巴西受试者中,血浆锌和铜降在参考范围内,与血浆短期缓冲边际缺陷一致。在埃及对ASD儿童进行为期12周的口服元素锌干预后,血清铜下降了约8%,循环金属硫蛋白(MT)蛋白升高,CARS和TGMD-2运动评分得到改善。MT-1A基因表达随Zn的变化而变化。综上所述,有证据表明锌不足和铜稳态改变是ASD的反复出现的特征,口服元素锌降低血清铜并增加MT。
{"title":"Zinc deficiency and zinc/copper ratio imbalance in autism spectrum disorder: a reanalysis of six multinational studies","authors":"Geir Bjørklund","doi":"10.1007/s10534-025-00761-y","DOIUrl":"10.1007/s10534-025-00761-y","url":null,"abstract":"<div><p>Disturbances in zinc (Zn) and copper (Cu) homeostasis have emerged as reproducible biochemical features of autism spectrum disorder (ASD). This study presents an integrative reanalysis of six investigations (2014–2025) encompassing serum, whole-blood, and plasma measurements in ASD cases and controls, and one supplementation trial. Three case–control studies reporting mean ± SD values in circulating matrices were meta-analyzed. Circulating Zn levels were significantly lower in ASD (fixed-effect Hedges’ g = –0.95; 95% CI –1.22 to –0.68; Q = 1.72, p = 0.42; I<sup>2</sup> = 0%; Egger intercept = 4.86, one-sided p = 0.044). The Zn/Cu ratio showed greater dispersion (random-effects g = –1.28; 95% CI –2.59 to 0.03; Q = 39.5, p < 0.001; I<sup>2</sup> = 95%), driven primarily by one cohort (leave-one-out g = –0.63; 95% CI –0.99 to –0.26). In Brazilian subjects, plasma Zn and Cu fell within reference ranges, consistent with short-term plasma buffering of marginal deficits. In an Egyptian 12-week oral elemental Zn intervention in children with ASD, serum Cu fell by ~8%, circulating metallothionein (MT) protein increased, and CARS and TGMD-2 motor scores improved. MT-1A gene expression changed with Zn. Taken together, the evidence indicates that Zn insufficiency and altered Cu homeostasis are recurring features of ASD and that oral elemental Zn lowers serum Cu and increases MT.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"285 - 296"},"PeriodicalIF":3.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720098","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}
Pub Date : 2025-12-07DOI: 10.1007/s10534-025-00776-5
Geir Bjørklund, Yuliya Semenova
The relationship between serum electrolyte levels and nutrient intake in environmentally exposed populations has received little attention in the international literature. This study aimed to investigate serum potassium and sodium levels and nutrient intake in populations exposed to radiation from the former Semipalatinsk Nuclear Test Site compared with non-exposed populations. A cross-sectional study was conducted in four settlements of East Kazakhstan and Pavlodar provinces, with three classified as exposed and one as non-exposed. A total of 907 adults with lifelong residency were enrolled, and exposure status was verified using official residency documents and the state automated medical registry. Dietary intake was assessed using the validated EPIC-Norfolk Food Frequency Questionnaire, and fasting blood samples were collected to measure serum potassium and sodium using ion-selective electrodes. Compared with the non-exposed group, exposed individuals reported significantly lower consumption of nearly all macro- and micronutrients, except for vitamin A. Serum potassium levels did not differ significantly between groups (median 4.3 mmol/l, p = 0.337), whereas median serum sodium levels were significantly higher in the non-exposed group (141 vs. 140 mmol/l, p = 0.02). The sodium-to-potassium ratio was not significantly different between groups (32.56 in exposed vs. 32.79 in non-exposed, p = 0.156). Correlation analysis showed a moderate positive association between serum sodium levels and sodium intake (rho = 0.495, p < 0.001), and a strong positive association between sodium and potassium intake (rho = 0.642, p < 0.001). These findings underscore the need for further investigation into dietary patterns and possible physiological adaptations in environmentally exposed populations.
国际文献很少关注环境暴露人群血清电解质水平与营养摄入之间的关系。本研究旨在调查受前塞米巴拉金斯克核试验场辐射的人群与未受辐射人群的血清钾和钠水平和营养摄入量。在东哈萨克斯坦和巴甫洛达尔省的四个定居点进行了一项横断面研究,其中三个被列为受暴露,一个被列为未受暴露。共登记了907名终身居住的成年人,并使用官方居住文件和国家自动医疗登记处验证了暴露状况。采用经验证的EPIC-Norfolk食物频率问卷评估膳食摄入量,并采集空腹血样,采用离子选择电极测定血清钾和钠。与未暴露组相比,暴露个体报告的几乎所有宏量和微量营养素的摄入量都显著降低,除了维生素a。血清钾水平在组间无显著差异(中位数为4.3 mmol/l, p = 0.337),而血清钠水平中位数在未暴露组显著较高(141对140 mmol/l, p = 0.02)。钠钾比各组间无显著差异(暴露组32.56 vs.未暴露组32.79,p = 0.156)。相关分析显示血清钠水平与钠摄入量呈正相关(rho = 0.495, p
{"title":"Serum potassium and sodium levels and nutrient intake in population exposed to radiation from the Semipalatinsk nuclear test site.","authors":"Geir Bjørklund, Yuliya Semenova","doi":"10.1007/s10534-025-00776-5","DOIUrl":"https://doi.org/10.1007/s10534-025-00776-5","url":null,"abstract":"<p><p>The relationship between serum electrolyte levels and nutrient intake in environmentally exposed populations has received little attention in the international literature. This study aimed to investigate serum potassium and sodium levels and nutrient intake in populations exposed to radiation from the former Semipalatinsk Nuclear Test Site compared with non-exposed populations. A cross-sectional study was conducted in four settlements of East Kazakhstan and Pavlodar provinces, with three classified as exposed and one as non-exposed. A total of 907 adults with lifelong residency were enrolled, and exposure status was verified using official residency documents and the state automated medical registry. Dietary intake was assessed using the validated EPIC-Norfolk Food Frequency Questionnaire, and fasting blood samples were collected to measure serum potassium and sodium using ion-selective electrodes. Compared with the non-exposed group, exposed individuals reported significantly lower consumption of nearly all macro- and micronutrients, except for vitamin A. Serum potassium levels did not differ significantly between groups (median 4.3 mmol/l, p = 0.337), whereas median serum sodium levels were significantly higher in the non-exposed group (141 vs. 140 mmol/l, p = 0.02). The sodium-to-potassium ratio was not significantly different between groups (32.56 in exposed vs. 32.79 in non-exposed, p = 0.156). Correlation analysis showed a moderate positive association between serum sodium levels and sodium intake (rho = 0.495, p < 0.001), and a strong positive association between sodium and potassium intake (rho = 0.642, p < 0.001). These findings underscore the need for further investigation into dietary patterns and possible physiological adaptations in environmentally exposed populations.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695741","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}
Pub Date : 2025-12-07DOI: 10.1007/s10534-025-00775-6
Igor Andrade Santos, Josielle V Fontes, Gustavo C Rodrigues, Mariana Ortiz de Godoy, Glaucius Oliva, Rafael V C Guido, Andres Merits, Camilla Abbehausen, Mark Harris, Ana Carolina Gomes Jardim
SARS-CoV-2 still poses as a threat to health systems despite the vaccination and the use of emergency repurposed drugs. Therefore, the development of novel anti-SARS-CoV-2 compounds is still needed. Organometallic copper(I)-N-heterocyclic carbenes [Cu(NHC)] are a class of metallodrugs that hold promise for drug development due to their variety of geometries, charges, and ligand design. Here we evaluated the activity of Cu(IPr)Cl, Cu(IMes)Cl, and [Cu(IMes)2]BF4 molecules against SARS-CoV-2 infection. Through a dose-response assay using A549-AT cells and the SARS-CoV-2-Wuhan infectious clone expressing mNeonGreen (SARS-CoV-2-mNeonGreen), Cu(IPr)Cl, Cu(IMes)Cl, and [Cu(IMes)2]BF4 inhibited SARS-CoV-2 replication with a selectivity index (SI) of 11.23, 10.84, and 5.94, respectively. The complexes Cu(IMes)Cl and [Cu(IMes)2]BF4 inhibited all stages of viral replication (pretreatment: 99.9% and 87.7%, entry: 99.6% and 74%, post-entry steps: 99.6% and 87.6%, respectively), while Cu(IPr)Cl impaired only entry (48%) and post-entry steps (95%). In addition, Cu(IMes)Cl and [Cu(IMes)2]BF4 complexes decreased the titres of both Delta and Omicron variants, while Cu(IPr)Cl only inhibited Omicron. In addition, [Cu(IMes)2]BF4 was able to decrease cell to cell spread of SARS-CoV-2; and for Cu(IMes)Cl a strong interaction with PLpro was revealed. Based on this data further investigations of Cu(I) based organometallics are warranted and Cu(IPr)Cl and Cu(IMes)Cl may be considered for utilization in pre-clinical assays.
{"title":"Cu(I)-N-Heterocyclic carbenes as potent inhibitors of SARS-CoV-2 replication.","authors":"Igor Andrade Santos, Josielle V Fontes, Gustavo C Rodrigues, Mariana Ortiz de Godoy, Glaucius Oliva, Rafael V C Guido, Andres Merits, Camilla Abbehausen, Mark Harris, Ana Carolina Gomes Jardim","doi":"10.1007/s10534-025-00775-6","DOIUrl":"https://doi.org/10.1007/s10534-025-00775-6","url":null,"abstract":"<p><p>SARS-CoV-2 still poses as a threat to health systems despite the vaccination and the use of emergency repurposed drugs. Therefore, the development of novel anti-SARS-CoV-2 compounds is still needed. Organometallic copper(I)-N-heterocyclic carbenes [Cu(NHC)] are a class of metallodrugs that hold promise for drug development due to their variety of geometries, charges, and ligand design. Here we evaluated the activity of Cu(IPr)Cl, Cu(IMes)Cl, and [Cu(IMes)<sub>2</sub>]BF<sub>4</sub> molecules against SARS-CoV-2 infection. Through a dose-response assay using A549-AT cells and the SARS-CoV-2-Wuhan infectious clone expressing mNeonGreen (SARS-CoV-2-mNeonGreen), Cu(IPr)Cl, Cu(IMes)Cl, and [Cu(IMes)<sub>2</sub>]BF<sub>4</sub> inhibited SARS-CoV-2 replication with a selectivity index (SI) of 11.23, 10.84, and 5.94, respectively. The complexes Cu(IMes)Cl and [Cu(IMes)<sub>2</sub>]BF<sub>4</sub> inhibited all stages of viral replication (pretreatment: 99.9% and 87.7%, entry: 99.6% and 74%, post-entry steps: 99.6% and 87.6%, respectively), while Cu(IPr)Cl impaired only entry (48%) and post-entry steps (95%). In addition, Cu(IMes)Cl and [Cu(IMes)<sub>2</sub>]BF<sub>4</sub> complexes decreased the titres of both Delta and Omicron variants, while Cu(IPr)Cl only inhibited Omicron. In addition, [Cu(IMes)<sub>2</sub>]BF<sub>4</sub> was able to decrease cell to cell spread of SARS-CoV-2; and for Cu(IMes)Cl a strong interaction with PL<sup>pro</sup> was revealed. Based on this data further investigations of Cu(I) based organometallics are warranted and Cu(IPr)Cl and Cu(IMes)Cl may be considered for utilization in pre-clinical assays.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699442","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}
Copper (Cu) is a vital trace element essential for numerous neurological functions, such as neurotransmission and antioxidant defense mechanisms. Nevertheless, Cu dyshomeostasis has been increasingly associated with neurodegenerative diseases, particularly Alzheimer's disease (AD).This review provides an overview of the intricate mechanisms of Cu homeostasis in the brain, detailing the pathways through which Cu enters neural tissues and its subsequent metabolic roles. We also discuss the emerging concept of cuproptosis, a Cu-dependent regulated cell death mechanism, and highlight its relevance to AD pathophysiology. Furthermore, we examine the interplay between glutamate, a key excitatory neurotransmitter, and cuproptosis, illustrating how alterations in glutamate levels may exacerbate Cu toxicity and contribute to neuronal degeneration in AD. Additionally, we review several compounds with the potential to modulate Cu concentrations, emphasizing their therapeutic implications for restoring Cu balance and mitigating neurodegenerative processes.By integrating current findings on Cu metabolism, cuproptosis, and glutamate interactions, this review provides novel insights into potential therapeutic interventions that may help prevent or slow AD progression.
{"title":"The interactions of copper, glutamate, and cuproptosis: insights into brain health and Alzheimer's disease pathology.","authors":"Maryam Alsadat Mousavi, Shakiba Salarvandian, Sara Rafiee, Mahya Mohammadi, Fariba Khodagholi, Pegah Javadpour","doi":"10.1007/s10534-025-00771-w","DOIUrl":"https://doi.org/10.1007/s10534-025-00771-w","url":null,"abstract":"<p><p>Copper (Cu) is a vital trace element essential for numerous neurological functions, such as neurotransmission and antioxidant defense mechanisms. Nevertheless, Cu dyshomeostasis has been increasingly associated with neurodegenerative diseases, particularly Alzheimer's disease (AD).This review provides an overview of the intricate mechanisms of Cu homeostasis in the brain, detailing the pathways through which Cu enters neural tissues and its subsequent metabolic roles. We also discuss the emerging concept of cuproptosis, a Cu-dependent regulated cell death mechanism, and highlight its relevance to AD pathophysiology. Furthermore, we examine the interplay between glutamate, a key excitatory neurotransmitter, and cuproptosis, illustrating how alterations in glutamate levels may exacerbate Cu toxicity and contribute to neuronal degeneration in AD. Additionally, we review several compounds with the potential to modulate Cu concentrations, emphasizing their therapeutic implications for restoring Cu balance and mitigating neurodegenerative processes.By integrating current findings on Cu metabolism, cuproptosis, and glutamate interactions, this review provides novel insights into potential therapeutic interventions that may help prevent or slow AD progression.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647170","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}