Pub Date : 2025-11-28DOI: 10.1016/j.jtemb.2025.127800
Elena G. Varlamova , Sergey V. Gudkov , Vladimir V. Rogachev , Egor A. Turovsky
Objective
The objective of this work was to develop and study the therapeutic properties of a nanocomplex based on selenium nanoparticles, an important microelement, and sorafenib, a known anticancer drug, on a model of hepatocellular carcinoma in mice. This nanocomplex combines the anticancer activity of selenium and sorafenib, which significantly increases its effectiveness in the treatment of HCC
Methods
A nanocomplex of selenium and sorafenib (SeSo) was obtained by laser ablation. To test the physicochemical properties of the nanocomplex, absorption spectrometry, dynamic light scattering, fluorimetry and electron microscopy were used. In the course of the work, real-time PCR was used to screen the mRNA expression levels of more than 40 genes encoding key markers of various signaling cascades associated with HCC, separately in the liver and tumor. Western blotting was used to test the reliability of real-time PCR. To assess the tumor size and the liver size and weight of mice, morphometric and statistical analyses were used.
Results
Based on the results of a large-scale analysis of the expression of a large number of genes, the advantages of SeSo over the well-known drug sorafenib were revealed and the molecular mechanisms of its therapeutic effect were established.
Conclusions
SeSo is a multikinase inhibitor, which significantly inhibits tumor growth. SeSo differentially regulates anti-cancer processes in tumor tissue and simultaneously triggers regenerative therapeutic processes in the liver itself.
{"title":"Therapeutic effects of a new selenium-sorafenib nanocomplex in liver and tumor in a TAA-induced HCC model","authors":"Elena G. Varlamova , Sergey V. Gudkov , Vladimir V. Rogachev , Egor A. Turovsky","doi":"10.1016/j.jtemb.2025.127800","DOIUrl":"10.1016/j.jtemb.2025.127800","url":null,"abstract":"<div><h3>Objective</h3><div>The objective of this work was to develop and study the therapeutic properties of a nanocomplex based on selenium nanoparticles, an important microelement, and sorafenib, a known anticancer drug, on a model of hepatocellular carcinoma in mice. This nanocomplex combines the anticancer activity of selenium and sorafenib, which significantly increases its effectiveness in the treatment of HCC</div></div><div><h3>Methods</h3><div>A nanocomplex of selenium and sorafenib (SeSo) was obtained by laser ablation. To test the physicochemical properties of the nanocomplex, absorption spectrometry, dynamic light scattering, fluorimetry and electron microscopy were used. In the course of the work, real-time PCR was used to screen the mRNA expression levels of more than 40 genes encoding key markers of various signaling cascades associated with HCC, separately in the liver and tumor. Western blotting was used to test the reliability of real-time PCR. To assess the tumor size and the liver size and weight of mice, morphometric and statistical analyses were used.</div></div><div><h3>Results</h3><div>Based on the results of a large-scale analysis of the expression of a large number of genes, the advantages of SeSo over the well-known drug sorafenib were revealed and the molecular mechanisms of its therapeutic effect were established.</div></div><div><h3>Conclusions</h3><div>SeSo is a multikinase inhibitor, which significantly inhibits tumor growth. SeSo differentially regulates anti-cancer processes in tumor tissue and simultaneously triggers regenerative therapeutic processes in the liver itself.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"93 ","pages":"Article 127800"},"PeriodicalIF":3.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.jtemb.2025.127798
Mashooq Ali , Aqsa Akram , Farid Ahmad Jan , Aziz Ahmad , Ashiq Hussain , Fahim Ullah Khan , Muhammad Arshad
Trout is a prized fish mostly cultured under high stocking densities (SD), which relates to many physiological challenges. The present study determines the significance of nano selenium (Se-N), while rearing Rainbow trout (Oncorhynchus mykiss) under various SD. Healthy O. mykiss juvenile were randomly distributed in concrete raceways in a 4 × 5 factorial experimental design. Five experimental feeds (NS0, NS1, NS2, NS3, NS4) containing 0, 1, 2, 3, and 4 mg Se-N per Kg were tested in four SDs (SD-L=168, SD-M=300, SD-H=433, SD-V=567 g/m3). Inference revealed significant effects of both SD and Se-N on growth (NWG), antioxidant activity and molecular regulation of myogenesis, and immunity. Our results show no significant effect of SD on growth at SD-L and SD-M, however at higher SD (SD-H and SD-V) Se-N role became prominent as significantly high NWG was observed in NS3 followed by NS2, NS4, NS1 and NS0, respectively. Lower cortisol in NS3 at higher SD might be the result of higher antioxidant activity (SOD, CAT, GPx), which seems to counter the chronic stress caused by SD. High SD also induced expression of immunity related genes (Lysozyme and IL-1β) especially in absence/lower inclusion of Se-N, while upregulated hsp70 expression. Finally, the dose dependent (Se-N) high expression of MyoD and gh, and a very slight effect on igf-1 justify the higher growth in NS3 by hyperplasia and not by hypertrophy. Our study suggests supplementation of 3 mg/kg Se-N in the diet of O. mykiss, especially in culture condition of high SD.
{"title":"Alleviating stocking density stress in juvenile rainbow trout (Oncorhynchus mykiss) through dietary nano-selenium: Effects on growth, antioxidant activity, and immune response","authors":"Mashooq Ali , Aqsa Akram , Farid Ahmad Jan , Aziz Ahmad , Ashiq Hussain , Fahim Ullah Khan , Muhammad Arshad","doi":"10.1016/j.jtemb.2025.127798","DOIUrl":"10.1016/j.jtemb.2025.127798","url":null,"abstract":"<div><div>Trout is a prized fish mostly cultured under high stocking densities (SD), which relates to many physiological challenges. The present study determines the significance of nano selenium (Se-N), while rearing Rainbow trout (<em>Oncorhynchus mykiss</em>) under various SD. Healthy <em>O. mykiss</em> juvenile were randomly distributed in concrete raceways in a 4 × 5 factorial experimental design. Five experimental feeds (NS0, NS1, NS2, NS3, NS4) containing 0, 1, 2, 3, and 4 mg Se-N per Kg were tested in four SDs (SD-L=168, SD-M=300, SD-H=433, SD-V=567 g/m<sup>3</sup>). Inference revealed significant effects of both SD and Se-N on growth (NWG), antioxidant activity and molecular regulation of myogenesis, and immunity. Our results show no significant effect of SD on growth at SD-L and SD-M, however at higher SD (SD-H and SD-V) Se-N role became prominent as significantly high NWG was observed in NS3 followed by NS2, NS4, NS1 and NS0, respectively. Lower cortisol in NS3 at higher SD might be the result of higher antioxidant activity (SOD, CAT, GPx), which seems to counter the chronic stress caused by SD. High SD also induced expression of immunity related genes (<em>Lysozyme</em> and <em>IL-1β</em>) especially in absence/lower inclusion of Se-N, while upregulated <em>hsp70</em> expression. Finally, the dose dependent (Se-N) high expression of <em>MyoD</em> and <em>gh,</em> and a very slight effect on <em>igf-1</em> justify the higher growth in NS3 by hyperplasia and not by hypertrophy. Our study suggests supplementation of 3 mg/kg Se-N in the diet of <em>O. mykiss</em>, especially in culture condition of high SD.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127798"},"PeriodicalIF":3.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1016/j.jtemb.2025.127799
Ye Htut Linn , Sohail Aziz , Shiueh Lian Mok
Selenium (Se), an essential trace element, plays a pivotal role in thyroid hormone synthesis and antioxidant defence mechanisms. This narrative review comprehensively examines the current evidence on Se status and supplementation in various thyroid disorders. Numerous studies indicate that Se deficiency may contribute to the development and progression of thyroid diseases, particularly autoimmune conditions such as Graves’ disease (GD), Graves’ orbitopathy (GO), and autoimmune thyroiditis (AIT), including Hashimoto’s thyroiditis (HT). In GD and GO, Se supplementation, especially when combined with methimazole, has been shown to enhance hormone normalization and antioxidant capacity, although results vary across studies. In AIT and HT, consistent reductions in thyroid autoantibodies and inflammatory markers have been observed following Se supplementation, particularly with selenomethionine. However, the evidence remains inconsistent regarding Se’s impact on hypothyroidism, pregnancy-related thyroid dysfunction, goitre, and thyroid cancer. Supplementation of Se has been associated with improvements in quality of life in some thyroid disorders such as GD, GO and HT with subclinical hypothyroidism. While some studies suggest a potential protective or modulatory role, findings vary by geographic region, baseline Se status, and study designs. Excessive intake of Se may also carry risks of toxicity (selenosis) and should be approached with caution. In conclusion, Se supplementation offers potential therapeutic benefits, particularly in autoimmune thyroid diseases. However, further well-designed randomized-controlled trials are necessary to define the optimal form, dose, and duration of supplementation and to clarify its role across diverse thyroid conditions.
{"title":"Selenium status and supplementation in thyroid disorders: A narrative review of current evidence","authors":"Ye Htut Linn , Sohail Aziz , Shiueh Lian Mok","doi":"10.1016/j.jtemb.2025.127799","DOIUrl":"10.1016/j.jtemb.2025.127799","url":null,"abstract":"<div><div>Selenium (Se), an essential trace element, plays a pivotal role in thyroid hormone synthesis and antioxidant defence mechanisms. This narrative review comprehensively examines the current evidence on Se status and supplementation in various thyroid disorders. Numerous studies indicate that Se deficiency may contribute to the development and progression of thyroid diseases, particularly autoimmune conditions such as Graves’ disease (GD), Graves’ orbitopathy (GO), and autoimmune thyroiditis (AIT), including Hashimoto’s thyroiditis (HT). In GD and GO, Se supplementation, especially when combined with methimazole, has been shown to enhance hormone normalization and antioxidant capacity, although results vary across studies. In AIT and HT, consistent reductions in thyroid autoantibodies and inflammatory markers have been observed following Se supplementation, particularly with selenomethionine. However, the evidence remains inconsistent regarding Se’s impact on hypothyroidism, pregnancy-related thyroid dysfunction, goitre, and thyroid cancer. Supplementation of Se has been associated with improvements in quality of life in some thyroid disorders such as GD, GO and HT with subclinical hypothyroidism. While some studies suggest a potential protective or modulatory role, findings vary by geographic region, baseline Se status, and study designs. Excessive intake of Se may also carry risks of toxicity (selenosis) and should be approached with caution. In conclusion, Se supplementation offers potential therapeutic benefits, particularly in autoimmune thyroid diseases. However, further well-designed randomized-controlled trials are necessary to define the optimal form, dose, and duration of supplementation and to clarify its role across diverse thyroid conditions.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127799"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to Letter to the editor: Sex difference in the association between dietary iron intake and bone mineral density in adolescents aged 12–19: A cross-sectional study","authors":"Keyi Li, Jun Han, Jinyu Zhu, Xiang Zhu, Yanfang Zhong, Zefeng Zhu","doi":"10.1016/j.jtemb.2025.127797","DOIUrl":"10.1016/j.jtemb.2025.127797","url":null,"abstract":"","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127797"},"PeriodicalIF":3.6,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.jtemb.2025.127790
Muhammad Muddassir Ali , Furqan Awan , Muhammad Usman Jamil , Muhammad Ijaz , Asad Ullah , Wasim Shehzad
This study investigates the genotoxic effects and oxidative stress of heavy metal contaminated soil and water on human and bovine blood, as well as bovine milk samples, from industrial zones of Punjab, Pakistan. Samples were collected from Multan, Lahore, Gujranwala, Bahawalpur and Faisalabad and analyzed through Atomic Absorption Spectrophotometry (AAS) for heavy metal analysis. Heavy metals such as lead (Pb), chromium (Cr), arsenic (As), zinc (Zn), cadmium (Cd), copper (Cu), molybdenum (Mo), iron (Fe), mercury (Hg), and nickel (Ni) were identified. The highest levels were found in district Faisalabad across water, soil, bovine, and human samples whereas, Gujranwala showed the lowest concentrations except for Pb and Cr in water and Hg in human plasma samples (P < 0.05). Additionally, Principal Component Analysis (PCA) highlighted that Faisalabad had the highest burden of Ni, Cu and Zn followed by Lahore with significantly higher levels of Pb and Cr. Among all districts, human and bovine blood and bovine milk samples displayed the highest amount of DNA damage via comet assay, while lowest levels were seen in these samples belonging to Bahawalpur (P < 0.05). Human and bovine blood samples from Faisalabad showed elevated Total Oxidant Status (TOS) along with reduced Total Antioxidant Status (TAS) (P < 0.05), whereas blood samples from Bahawalpur exhibited the lowest TOS and TAS levels (P < 0.05). Moreover, human and bovine blood samples from Faisalabad exhibited a significant upregulation of caspase-3 compared to other districts (P < 0.05). The study concluded that industrialization in Punjab results in significant heavy metal contamination, causing genotoxicity and oxidative stress in livestock and humans.
{"title":"Genotoxic and oxidative stress assessment of heavy metal contaminated soil and water in human blood and bovine milk samples from the different industrial zones of Punjab, Pakistan","authors":"Muhammad Muddassir Ali , Furqan Awan , Muhammad Usman Jamil , Muhammad Ijaz , Asad Ullah , Wasim Shehzad","doi":"10.1016/j.jtemb.2025.127790","DOIUrl":"10.1016/j.jtemb.2025.127790","url":null,"abstract":"<div><div>This study investigates the genotoxic effects and oxidative stress of heavy metal contaminated soil and water on human and bovine blood, as well as bovine milk samples, from industrial zones of Punjab, Pakistan. Samples were collected from Multan, Lahore, Gujranwala, Bahawalpur and Faisalabad and analyzed through Atomic Absorption Spectrophotometry (AAS) for heavy metal analysis. Heavy metals such as lead (Pb), chromium (Cr), arsenic (As), zinc (Zn), cadmium (Cd), copper (Cu), molybdenum (Mo), iron (Fe), mercury (Hg), and nickel (Ni) were identified. The highest levels were found in district Faisalabad across water, soil, bovine, and human samples whereas, Gujranwala showed the lowest concentrations except for Pb and Cr in water and Hg in human plasma samples (P < 0.05). Additionally, Principal Component Analysis (PCA) highlighted that Faisalabad had the highest burden of Ni, Cu and Zn followed by Lahore with significantly higher levels of Pb and Cr. Among all districts, human and bovine blood and bovine milk samples displayed the highest amount of DNA damage via comet assay, while lowest levels were seen in these samples belonging to Bahawalpur (P < 0.05). Human and bovine blood samples from Faisalabad showed elevated Total Oxidant Status (TOS) along with reduced Total Antioxidant Status (TAS) (P < 0.05), whereas blood samples from Bahawalpur exhibited the lowest TOS and TAS levels (P < 0.05). Moreover, human and bovine blood samples from Faisalabad exhibited a significant upregulation of caspase-3 compared to other districts (P < 0.05). The study concluded that industrialization in Punjab results in significant heavy metal contamination, causing genotoxicity and oxidative stress in livestock and humans.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127790"},"PeriodicalIF":3.6,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.jtemb.2025.127796
Yanfang Shen , Haobiao Liu , Yuwen Shangguan , Qingsong Li , Xuefeng Yu , Huiyan Tang , Xue Lin
Background
Adolescence is a critical window for bone development, during which trace elements like copper, zinc, and selenium play essential roles. While previous studies have focused on individual elements, trace element ratios such as the copper-zinc and copper-selenium ratios may better capture biological interactions relevant to bone health.
Methods
We used data from the NHANES to examine the association between serum copper-zinc and copper-selenium ratios and whole-body bone mineral density (BMD) among U.S. adolescents. Multivariable linear regression was used to assess associations. Smooth curve fitting visualized dose-response trends. We also compared the strength of associations for ratios and individual elements, and performed mediation and subgroup analyses.
Results
Higher copper-zinc and copper-selenium ratios were significantly associated with lower BMD. Specifically, each one-unit increase in the copper-zinc ratio was associated with a 0.016 g/cm² decrease in BMD (β=-0.016, 95 % CI: −0.026 to −0.006, P = 0.002), while each one-unit increase in the copper-selenium ratio corresponded to a 0.019 g/cm² decrease (β=-0.019, 95 % CI: −0.028 to −0.010, P < 0.001). These associations were stronger than those observed for trace elements alone, especially the copper-selenium ratio. Serum albumin partially mediated the association between these ratios and BMD (mediated proportions: 26.89 % and 14.20 %). Notably, sex-stratified analyses showed significant inverse associations in males, but not in females.
Conclusions
As the first ratio-based NHANES study on adolescent bone health, our analysis shows that serum trace element ratios are inversely associated with BMD, with stronger effects in males. These findings highlight the importance of micronutrient balance in maintaining bone health.
背景：青春期是骨骼发育的关键时期，铜、锌、硒等微量元素在此期间起着至关重要的作用。虽然以前的研究集中在单个元素上，但微量元素的比例，如铜锌和铜硒的比例，可能更好地捕捉与骨骼健康相关的生物相互作用。方法：我们使用NHANES的数据来研究美国青少年血清铜锌和铜硒比例与全身骨密度（BMD）之间的关系。多变量线性回归用于评估相关性。平滑曲线拟合可视化剂量-反应趋势。我们还比较了比率和单个因素的关联强度，并进行了中介和亚组分析。结果：较高的铜锌和铜硒比例与较低的骨密度显著相关。具体来说，铜锌比每增加一个单位，骨密度降低0.016 g/cm²（β=-0.016, 95 % CI: -0.026 ~ -0.006, P = 0.002），而铜硒比每增加一个单位，骨密度降低0.019 g/cm²（β=-0.019, 95 % CI: -0.028 ~ -0.010, P ）。结论：作为第一个基于比率的NHANES青少年骨骼健康研究，我们的分析表明血清微量元素比与骨密度呈负相关，且在男性中效果更明显。这些发现强调了微量营养素平衡对维持骨骼健康的重要性。
{"title":"Serum copper-zinc and copper-selenium ratios in relation to bone health among U.S. adolescents","authors":"Yanfang Shen , Haobiao Liu , Yuwen Shangguan , Qingsong Li , Xuefeng Yu , Huiyan Tang , Xue Lin","doi":"10.1016/j.jtemb.2025.127796","DOIUrl":"10.1016/j.jtemb.2025.127796","url":null,"abstract":"<div><h3>Background</h3><div>Adolescence is a critical window for bone development, during which trace elements like copper, zinc, and selenium play essential roles. While previous studies have focused on individual elements, trace element ratios such as the copper-zinc and copper-selenium ratios may better capture biological interactions relevant to bone health.</div></div><div><h3>Methods</h3><div>We used data from the NHANES to examine the association between serum copper-zinc and copper-selenium ratios and whole-body bone mineral density (BMD) among U.S. adolescents. Multivariable linear regression was used to assess associations. Smooth curve fitting visualized dose-response trends. We also compared the strength of associations for ratios and individual elements, and performed mediation and subgroup analyses.</div></div><div><h3>Results</h3><div>Higher copper-zinc and copper-selenium ratios were significantly associated with lower BMD. Specifically, each one-unit increase in the copper-zinc ratio was associated with a 0.016 g/cm² decrease in BMD (<em>β</em>=-0.016, 95 % CI: −0.026 to −0.006, <em>P</em> = 0.002), while each one-unit increase in the copper-selenium ratio corresponded to a 0.019 g/cm² decrease (<em>β</em>=-0.019, 95 % CI: −0.028 to −0.010, <em>P</em> < 0.001). These associations were stronger than those observed for trace elements alone, especially the copper-selenium ratio. Serum albumin partially mediated the association between these ratios and BMD (mediated proportions: 26.89 % and 14.20 %). Notably, sex-stratified analyses showed significant inverse associations in males, but not in females.</div></div><div><h3>Conclusions</h3><div>As the first ratio-based NHANES study on adolescent bone health, our analysis shows that serum trace element ratios are inversely associated with BMD, with stronger effects in males. These findings highlight the importance of micronutrient balance in maintaining bone health.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127796"},"PeriodicalIF":3.6,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.jtemb.2025.127795
Shengmin Li , Wenjia Tian , Ke Han , Yi Zhang , Ying Wang , Kejian Shi
Background
Hypoxia existing inside tumor tissues stimulates proliferation, metastasis and drug resistance of lung cancer. Selenite, an inorganic form of selenium, has been widely confirmed to induce apoptosis of multiple kinds of tumors. However, its therapeutic effects on hypoxic lung cancer were still unclear.
Methods
RNA sequencing experiment was carried out to identify the differential expression patterns of transcriptomes in A549 lung cancer cells under nomorxic and hypoxic conditions. siRNA was transfected to knock down the expression of TCF19, and Western blot or qPCR was used to detect gene expression. Cell counting kit 8 was carried out to test the viability of lung cancer cells, while the flow cytometry was used to determine the ratio of apoptosis.
Results
Compared to normoxia conditions, the genes related to immune regulation, proliferation or reproduction have been identified to be expressed differentially under hypoxia. Among them, TCF19 was increased significantly and exerted a pro-survival function in A549 cells under hypoxia. Further experiment discovered that selenite dose-dependently inhibited the growth of normoxic lung cancer cells, whereas hypoxic cells exhibited partial drug resistance. However, inhibiting TCF19 expression would finally result in the enhancement of selenite-induced apoptosis of hypoxic A549 cells.
Conclusion
All of the results listed above had explored the molecular mechanisms of hypoxic tumor proliferation, which undoubtedly provided TCF19 as a promising synergistic target to treat selenite-resistant hypoxic lung tumors.
{"title":"TCF19 up-regulated in hypoxic lung cancer cells attenuates the anti-tumor effects of sodium selenite","authors":"Shengmin Li , Wenjia Tian , Ke Han , Yi Zhang , Ying Wang , Kejian Shi","doi":"10.1016/j.jtemb.2025.127795","DOIUrl":"10.1016/j.jtemb.2025.127795","url":null,"abstract":"<div><h3>Background</h3><div>Hypoxia existing inside tumor tissues stimulates proliferation, metastasis and drug resistance of lung cancer. Selenite, an inorganic form of selenium, has been widely confirmed to induce apoptosis of multiple kinds of tumors. However, its therapeutic effects on hypoxic lung cancer were still unclear.</div></div><div><h3>Methods</h3><div>RNA sequencing experiment was carried out to identify the differential expression patterns of transcriptomes in A549 lung cancer cells under nomorxic and hypoxic conditions. siRNA was transfected to knock down the expression of TCF19, and Western blot or qPCR was used to detect gene expression. Cell counting kit 8 was carried out to test the viability of lung cancer cells, while the flow cytometry was used to determine the ratio of apoptosis.</div></div><div><h3>Results</h3><div>Compared to normoxia conditions, the genes related to immune regulation, proliferation or reproduction have been identified to be expressed differentially under hypoxia. Among them, TCF19 was increased significantly and exerted a pro-survival function in A549 cells under hypoxia. Further experiment discovered that selenite dose-dependently inhibited the growth of normoxic lung cancer cells, whereas hypoxic cells exhibited partial drug resistance. However, inhibiting TCF19 expression would finally result in the enhancement of selenite-induced apoptosis of hypoxic A549 cells.</div></div><div><h3>Conclusion</h3><div>All of the results listed above had explored the molecular mechanisms of hypoxic tumor proliferation, which undoubtedly provided TCF19 as a promising synergistic target to treat selenite-resistant hypoxic lung tumors.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127795"},"PeriodicalIF":3.6,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.jtemb.2025.127783
Eman M. Emara , Hassan IH El-Sayyad , Amr M. Mowafy , Heba A. El-Ghaweet
Background
Lipopolysaccharide (LPS), a potent endotoxin, triggers oxidative stress and inflammatory cascades that contribute to retinal degeneration and disruption of the gut–retina axis. Zinc oxide nanoparticles (ZnO NPs) have emerged as promising agents owing to their strong antioxidant and anti-inflammatory activities, yet their role in retinal protection remains underexplored.
Objective
This study investigated the protective and therapeutic effects of ZnO NPs against LPS-induced retinal injury, with emphasis on their impact on oxidative stress, inflammatory responses, and gut microbiota composition in mother rats and their offspring.
Methods
Eight males and forty female albino rats were used. Pregnant rats were divided into four groups: control, LPS-exposed, ZnO NP-treated, and combined treatment. ZnO NPs were administered four times (three doses during gestation and one post-delivery), whereas LPS was injected twice during gestation. Retinal tissues were examined histologically and immunohistochemically for markers of oxidative stress, inflammation, and apoptosis (including PCNA, p53, and vimentin), while gut microbiota composition was assessed by 16S rRNA sequencing.
Results
LPS exposure caused marked retinal degeneration, elevated oxidative and inflammatory markers (mTOR, COX-2, Caspase-3, MDA, and NO), and significant gut microbiota dysbiosis. ZnO NPs treatment ameliorated these effects, improving retinal structure, reducing inflammatory and apoptotic markers, restoring dopamine and serotonin levels, and partially normalizing gut microbial composition by decreasing pathogenic Escherichia coli and Enterococcus devriesei.
Conclusion
ZnO NPs exert both protective and therapeutic effects against LPS-induced retinal injury in mother rats and their offspring, potentially through modulation of oxidative stress, suppression of inflammatory signaling, and rebalancing of gut microbiota. These findings highlight their promise as a novel therapeutic approach for retinal disorders associated with systemic inflammation.
{"title":"The therapeutic effect of zinc oxide nanoparticles against lipopolysaccharides on the rats' retina","authors":"Eman M. Emara , Hassan IH El-Sayyad , Amr M. Mowafy , Heba A. El-Ghaweet","doi":"10.1016/j.jtemb.2025.127783","DOIUrl":"10.1016/j.jtemb.2025.127783","url":null,"abstract":"<div><h3>Background</h3><div>Lipopolysaccharide (LPS), a potent endotoxin, triggers oxidative stress and inflammatory cascades that contribute to retinal degeneration and disruption of the gut–retina axis. Zinc oxide nanoparticles (ZnO NPs) have emerged as promising agents owing to their strong antioxidant and anti-inflammatory activities, yet their role in retinal protection remains underexplored.</div></div><div><h3>Objective</h3><div>This study investigated the protective and therapeutic effects of ZnO NPs against LPS-induced retinal injury, with emphasis on their impact on oxidative stress, inflammatory responses, and gut microbiota composition in mother rats and their offspring.</div></div><div><h3>Methods</h3><div>Eight males and forty female albino rats were used. Pregnant rats were divided into four groups: control, LPS-exposed, ZnO NP-treated, and combined treatment. ZnO NPs were administered four times (three doses during gestation and one post-delivery), whereas LPS was injected twice during gestation. Retinal tissues were examined histologically and immunohistochemically for markers of oxidative stress, inflammation, and apoptosis (including PCNA, p53, and vimentin), while gut microbiota composition was assessed by 16S rRNA sequencing.</div></div><div><h3>Results</h3><div>LPS exposure caused marked retinal degeneration, elevated oxidative and inflammatory markers (mTOR, COX-2, Caspase-3, MDA, and NO), and significant gut microbiota dysbiosis. ZnO NPs treatment ameliorated these effects, improving retinal structure, reducing inflammatory and apoptotic markers, restoring dopamine and serotonin levels, and partially normalizing gut microbial composition by decreasing pathogenic <em>Escherichia coli</em> and <em>Enterococcus devriesei</em>.</div></div><div><h3>Conclusion</h3><div>ZnO NPs exert both protective and therapeutic effects against LPS-induced retinal injury in mother rats and their offspring, potentially through modulation of oxidative stress, suppression of inflammatory signaling, and rebalancing of gut microbiota. These findings highlight their promise as a novel therapeutic approach for retinal disorders associated with systemic inflammation.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127783"},"PeriodicalIF":3.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Micronutrient deficiencies (MiNDs) during pregnancy contribute to anemia, preeclampsia, and poor fetal outcomes. We assessed the prevalence of MiNDs and their association with anemia among pregnant women in northern India.
Methods
A prospective cross-sectional study was conducted on 322 first-trimester pregnant women from low- to middle socioeconomic backgrounds. Haematology indices were measured on an automated analyser; vitamins (A, B1, B9, B12, D3) by LC-MS/MS; and trace elements (Fe, Zn, Cu, Se, Mn) by ICP-MS.
Results
Anaemia prevalence was 46.5 %. Anemic women had significantly lower levels of manganese (50.3 %), copper (32.8 %), zinc (41.9 %), and iron (51.1 %) (p < 0.0001) and vitamins A (14.8 %), B1 (59.3 %), B9 (46.4 %), and B12 (71.3 %) (p < 0.0001). Selenium (p = 0.752) and vitamin D3 (p = 0.340) were not associated with anemia. Among anaemic women, 14 % had multiple micronutrient deficiencies.
Anemia increased the risk of low vitamin A (<900 pg/mL; OR 2.06, CI: 1.32–3.21, p = 0.001), B1 (<70 ng/mL; OR 4.30, CI: 2.68–6.89, p < 0.0001), B9 (<3 ng/mL; OR 5.91, CI: 3.64–9.59, p < 0.0001), and B12 (<200 pg/mL; OR 5.53, CI: 3.43–8.93, p < 0.0001) respectively. Similarly, the risk of low iron (<80 µg/dL; OR 8.01, 95 % CI: 4.85–13.23, p < 0.0001), zinc (<600 µg/L; OR 5.18, 95 % CI: 3.22–8.34, p < 0.0001), copper (<700 µg/L; OR 4.30, 95 % CI: 2.68–6.89, p < 0.0001), and manganese (<4.0 µg/L; OR 2.25, 95 % CI: 1.44–3.51, p = 0.004) was significantly associated with higher risk of anemia.
Univariate analysis showed significant correlations between hemoglobin and vitamins A, B1, B12, manganese; copper; and iron (p < 0.05). In multivariate analysis, B1, B9, B12, Fe, Cu, and Zn were independent predictors of Hb levels.
Conclusions
Anemia during pregnancy is strongly linked to multiple micronutrient deficiencies. Findings support antenatal strategies that extend beyond iron–folate to address multiple micronutrient deficiencies.
{"title":"Impact of hidden hunger on pregnant women from underserved communities and its role in anaemia","authors":"Anumesh K. Pathak , Dhruv Agarwal , Shivani Singh , Rupita Kulshresthra , Manish Raj Kulshrestha , Vandana Tiwari","doi":"10.1016/j.jtemb.2025.127794","DOIUrl":"10.1016/j.jtemb.2025.127794","url":null,"abstract":"<div><h3>Background</h3><div>Micronutrient deficiencies (MiNDs) during pregnancy contribute to anemia, preeclampsia, and poor fetal outcomes. We assessed the prevalence of MiNDs and their association with anemia among pregnant women in northern India.</div></div><div><h3>Methods</h3><div>A prospective cross-sectional study was conducted on 322 first-trimester pregnant women from low- to middle socioeconomic backgrounds. Haematology indices were measured on an automated analyser; vitamins (A, B1, B9, B12, D3) by LC-MS/MS; and trace elements (Fe, Zn, Cu, Se, Mn) by ICP-MS.</div></div><div><h3>Results</h3><div>Anaemia prevalence was 46.5 %. Anemic women had significantly lower levels of manganese (50.3 %), copper (32.8 %), zinc (41.9 %), and iron (51.1 %) (p < 0.0001) and vitamins A (14.8 %), B1 (59.3 %), B9 (46.4 %), and B12 (71.3 %) (p < 0.0001). Selenium (p = 0.752) and vitamin D3 (p = 0.340) were not associated with anemia. Among anaemic women, 14 % had multiple micronutrient deficiencies.</div><div>Anemia increased the risk of low vitamin A (<900 pg/mL; OR 2.06, CI: 1.32–3.21, p = 0.001), B1 (<70 ng/mL; OR 4.30, CI: 2.68–6.89, p < 0.0001), B9 (<3 ng/mL; OR 5.91, CI: 3.64–9.59, p < 0.0001), and B12 (<200 pg/mL; OR 5.53, CI: 3.43–8.93, p < 0.0001) respectively. Similarly, the risk of low iron (<80 µg/dL; OR 8.01, 95 % CI: 4.85–13.23, p < 0.0001), zinc (<600 µg/L; OR 5.18, 95 % CI: 3.22–8.34, p < 0.0001), copper (<700 µg/L; OR 4.30, 95 % CI: 2.68–6.89, p < 0.0001), and manganese (<4.0 µg/L; OR 2.25, 95 % CI: 1.44–3.51, p = 0.004) was significantly associated with higher risk of anemia.</div><div>Univariate analysis showed significant correlations between hemoglobin and vitamins A, B1, B12, manganese; copper; and iron (p < 0.05). In multivariate analysis, B1, B9, B12, Fe, Cu, and Zn were independent predictors of Hb levels.</div></div><div><h3>Conclusions</h3><div>Anemia during pregnancy is strongly linked to multiple micronutrient deficiencies. Findings support antenatal strategies that extend beyond iron–folate to address multiple micronutrient deficiencies.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127794"},"PeriodicalIF":3.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.jtemb.2025.127793
Yan Chen , Wenlong Li , Dian Zhao , Chong Huang , Chengyun Xu
Background
Cisplatin-induced acute kidney injury (CP-AKI) is a major complication of cisplatin chemotherapy that is mechanistically linked to ferroptosis, an iron-dependent form of cell death. However, the epigenetic and post-transcriptional factors regulating ferroptosis in CP-AKI, particularly those mediated by N6-methyladenosine (m6A) RNA methylation, remain insufficiently defined. This study investigated the role of methyltransferase-like 14 (METTL14)-mediated m6A RNA methylation and its downstream targets in ferroptosis regulation during CP-AKI.
Methods
We established an in vitro model of CP-AKI using cisplatin-treated human renal proximal tubular epithelial cells (HK-2). The expressions of gene and protein were tested by qRT-PCR, western blot, and immunofluorescence. Cell viability was detected by CCK-8 assay. The total m6A methylation and ferroptosis markers were measured by the kits. MeRIP-PCR was performed to detect m6A modifications on ERFE mRNA. The binding relationship between METTL14/insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and erythroferrone (ERFE) was analyzed by RIP assay. ERFE mRNA stability was determined by Actinomycin D chase assay.
Results
Cisplatin treatment upregulated METTL14, IGF2BP3, and ERFE in HK-2 cells, coinciding with increased m6A methylation and ferroptosis induction. METTL14 knockdown attenuated cisplatin-induced ferroptosis in HK-2 cells by downregulating ERFE. Mechanistically, METTL14 stabilized ERFE mRNA through IGF2BP3-dependent m6A modification. As expected, IGF2BP3 overexpression reversed the effect of METTL14 knockdown on cisplatin-induced ferroptosis in HK-2 cells, while concomitant ERFE depletion abrogated this reversal.
Conclusion
METTL14 upregulation promotes ferroptosis in CP-AKI by stabilizing ERFE mRNA through IGF2BP3-dependent m6A modification. Targeting the METTL14/IGF2BP3/ERFE axis offers a promising strategy for mitigating cisplatin-induced kidney injury.
{"title":"METTL14 promotes ferroptosis during the development of cisplatin-induced kidney injury by stabilizing ERFE through IGF2BP3-dependent m6A methylation","authors":"Yan Chen , Wenlong Li , Dian Zhao , Chong Huang , Chengyun Xu","doi":"10.1016/j.jtemb.2025.127793","DOIUrl":"10.1016/j.jtemb.2025.127793","url":null,"abstract":"<div><h3>Background</h3><div>Cisplatin-induced acute kidney injury (CP-AKI) is a major complication of cisplatin chemotherapy that is mechanistically linked to ferroptosis, an iron-dependent form of cell death. However, the epigenetic and post-transcriptional factors regulating ferroptosis in CP-AKI, particularly those mediated by N6-methyladenosine (m<sup>6</sup>A) RNA methylation, remain insufficiently defined. This study investigated the role of methyltransferase-like 14 (METTL14)-mediated m<sup>6</sup>A RNA methylation and its downstream targets in ferroptosis regulation during CP-AKI.</div></div><div><h3>Methods</h3><div>We established an in vitro model of CP-AKI using cisplatin-treated human renal proximal tubular epithelial cells (HK-2). The expressions of gene and protein were tested by qRT-PCR, western blot, and immunofluorescence. Cell viability was detected by CCK-8 assay. The total m<sup>6</sup>A methylation and ferroptosis markers were measured by the kits. MeRIP-PCR was performed to detect m<sup>6</sup>A modifications on ERFE mRNA. The binding relationship between METTL14/insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and erythroferrone (ERFE) was analyzed by RIP assay. ERFE mRNA stability was determined by Actinomycin D chase assay.</div></div><div><h3>Results</h3><div>Cisplatin treatment upregulated METTL14, IGF2BP3, and ERFE in HK-2 cells, coinciding with increased m6A methylation and ferroptosis induction. METTL14 knockdown attenuated cisplatin-induced ferroptosis in HK-2 cells by downregulating ERFE. Mechanistically, METTL14 stabilized ERFE mRNA through IGF2BP3-dependent m<sup>6</sup>A modification. As expected, IGF2BP3 overexpression reversed the effect of METTL14 knockdown on cisplatin-induced ferroptosis in HK-2 cells, while concomitant ERFE depletion abrogated this reversal.</div></div><div><h3>Conclusion</h3><div>METTL14 upregulation promotes ferroptosis in CP-AKI by stabilizing ERFE mRNA through IGF2BP3-dependent m<sup>6</sup>A modification. Targeting the METTL14/IGF2BP3/ERFE axis offers a promising strategy for mitigating cisplatin-induced kidney injury.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127793"},"PeriodicalIF":3.6,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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