Journal of Trace Elements in Medicine and Biology最新文献_第2页

Dual protection by naringin and dexrazoxane against iron-induced erythrocyte damage: Exploring their synergistic regulation of ferroptosis and eryptosis 柚皮苷和右唑嗪对铁致红细胞损伤的双重保护作用：探讨它们对铁下垂和铁萎的协同调节作用

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2026-01-07 DOI: 10.1016/j.jtemb.2026.127818

Gamaleldin I. Harisa , Ahmed H. Bakheit , Amsha S. Alsegiani , Sheikh F. Ahmad , Sabry M. Attia

Iron cellular accumulation is linked to ferroptosis, which induces cell injury. Conventional iron chelators often elicit side effects and encourage the exploration of naringin (NAR) as a potential protective agent against ferroptosis. Erythrocytes are a simple cellular model for exploring the beneficial effects of bioactive compounds. This study aims to investigate the protective effects of NAR against ferrous sulfate (FeSO4) induced ferroptosis. FeSO₄ and hydrogen peroxide were applied to erythrocytes to induce ferroptosis either in the presence or absence of NAR, dexrazoxane (DEX), or their combination and compared to control cells. Key indicators of ferroptosis, including reactive oxygen species (ROS) production, GPX4 activity, glutathione (GSH) levels, malondialdehyde (MDA) levels, GPX4, GRD, and erythrocyte cytolysis, and eryptosis were analyzed using spectrophotometric and flow cytometric methods. Molecular docking studies with AutoDock Vina assessed the interactions between DEX, NAR, GPX4, GRD, HO-1, GST, SDH, AChE, and NOS. The present results displayed that both DEX and NAR significantly mitigates FeSO₄-induced ROS production and lipid peroxidation while preserving GSH levels and enhancing GPX and GRD activities compared to the FeSO₄-treated group. DEX and NAR also effectively prevented iron-induced erythrocyte cytolysis and eryptosis. The DEX and NAR combination produced pronounced effect of the measured parameters compared to other groups. Docking analysis indicated stronger binding affinities of NAR to GPX4, GRD, HO-1, GST, SDH, AChE, and NOS compared to DEX, suggesting NAR may be a more effective modulator. These findings concluded that NAR is a potential alternative to traditional DEX as iron chelators. Moreover, NAR is a promising therapy for disorders connected with iron overloading.

铁细胞积累与铁下垂有关，铁下垂引起细胞损伤。传统的铁螯合剂经常引起副作用，并鼓励探索柚皮苷（NAR）作为一种潜在的保护剂对铁下垂。红细胞是探索生物活性化合物有益作用的简单细胞模型。本研究旨在探讨NAR对硫酸亚铁（FeSO4）诱导的铁下垂的保护作用。将FeSO4和过氧化氢作用于红细胞，在NAR、dexrazoxane （DEX）或它们的组合存在或不存在的情况下诱导铁凋亡，并与对照细胞进行比较。采用分光光度法和流式细胞术分析铁死亡的关键指标，包括活性氧（ROS）产生、GPX4活性、谷胱甘肽（GSH）水平、丙二醛（MDA）水平、GPX4、GRD、红细胞溶解和赤霉素。与AutoDock Vina的分子对接研究评估了DEX、NAR、GPX4、GRD、HO-1、GST、SDH、AChE和NOS之间的相互作用。目前的研究结果表明，与feso4处理组相比，DEX和NAR均能显著减轻feso4诱导的ROS产生和脂质过氧化，同时保持GSH水平，增强GPX和GRD活性。DEX和NAR还能有效预防铁诱导的红细胞溶解和红细胞淤血。与其他组相比，DEX和NAR联合使用对测量参数的影响明显。对接分析表明，与DEX相比，NAR对GPX4、GRD、HO-1、GST、SDH、AChE和NOS的结合亲和力更强，表明NAR可能是一种更有效的调节剂。这些发现表明，NAR是替代传统DEX作为铁螯合剂的潜在选择。此外，NAR是一种有希望的治疗与铁超载有关的疾病的方法。

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引用次数: 0

Association of iodine nutritional status with thyroid nodules and papillary thyroid carcinoma in women from an iodine-sufficient region in Brazil: A cross-sectional center study 巴西缺碘地区妇女碘营养状况与甲状腺结节和甲状腺乳头状癌的关系：一项横断面中心研究

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2026-01-07 DOI: 10.1016/j.jtemb.2026.127816

Ivia Fonseca , Aline Larcher de Almeida , Patrícia Borges dos Santos , Natalia Treistman , Tales Aprigio , Mario Vaisman , Ana Paula Aguiar Vidal , Patrícia de Fátima dos Santos Teixeira , Nathalie Silva de Morais

Objectives

This study aimed to evaluate the association of iodine nutritional status with TNs, and papillary thyroid carcinoma (PTC) in women attending an outpatient clinic at a university hospital in an iodine-sufficient region of Brazil. Additionally, the urinary iodine status was evaluated in patients with PTC and BRAF mutation.

Methods

Cross-sectional study including 133 women who underwent thyroid ultrasound and urinary iodine concentration (UIC) measurement. The diagnosis of PTC was confirmed by histopathology, and the BRAF V600E mutation was assessed through immunohistochemistry in patients with classical PTC.

Results

A UIC > 300 µg/L was an independent risk factor for the presence of TNs (odds ratio [OR] 3.42, 95 % confidence interval [CI] 1.10–10.66 p = 0.033) and for the occurrence of PTC (OR 3.90, 95 % CI 1.00–15.42, p = 0.05). The BRAF V600E mutation was present in 50 % of the analyzed PTCs, with frequencies of 33.3 %, 50.0 %, and 75.0 % among participants with insufficient, adequate, and more than adequate iodine levels, respectively. The median UIC was higher in patients with the follicular subtype of PTC compared with those with the classical subtype (318.1 µg/L vs. 207.1 µg/L, respectively; p = 0.048). A high frequency of UIC values ≥ 300 µg/L also was found in patients with the follicular subtype of PTC (83.3 %).

Conclusion

In an iodine-sufficient area, UIC values ≥ 300 µg/L suggested an association with the presence of TNs and PTC. A high frequency of iodine excessive status was observed in patients with follicular subtype. However, none of the patients with presence of the BRAFV 600E mutation presented excessive iodine status.

目的：本研究旨在评估在巴西一个碘充足地区的大学医院门诊就诊的妇女的碘营养状况与甲状腺乳头状癌（PTC）的关系。此外，还评估了PTC和BRAF突变患者的尿碘状态。方法133例妇女行甲状腺超声和尿碘浓度（UIC）测定的横断面研究。通过组织病理学证实PTC的诊断，并通过免疫组织化学评估经典PTC患者的BRAF V600E突变。结果UIC >； 300 µg/L是TNs发生的独立危险因素（比值比[OR] 3.42, 95 %可信区间[CI] 1.10 ~ 10.66 p = 0.033）和PTC发生的独立危险因素（比值比[OR] 3.90, 95 % CI 1.00 ~ 15.42, p = 0.05）。BRAF V600E突变存在于50% %所分析的ptc中，在碘水平不足、充足和过量的参与者中，其频率分别为33.3% %、50.0% %和75.0% %。滤泡型PTC患者的中位UIC高于经典型PTC患者（分别为318.1 µg/L和207.1 µg/L; p = 0.048）。滤泡型PTC患者UIC值≥ 300 µg/L的频率也很高（83.3 %）。结论在足碘区，UIC≥ 300 µg/L提示与TNs和PTC存在相关。滤泡型患者碘过量状态发生率高。然而，存在BRAFV 600E突变的患者均未出现碘过量状态。

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引用次数: 0

An overview of lead toxicity and its therapeutic strategies 铅毒性及其治疗策略综述

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2026-01-06 DOI: 10.1016/j.jtemb.2026.127815

Pushkar Singh Rawat , Shalini Singh

Lead (Pb) is recognized as one of the most prevalent metals found in the Earth’s crust. Its affordability and easy accessibility have led to its extensive use in various industrial applications. Over recent decades, the global issue of heavy metal pollution has escalated, despite increased awareness. This situation is particularly concerning in developing nations, where Pb toxicity poses a significant threat to public health. A critical challenge in addressing Pb toxicity lies in its diagnosis, as it often presents asymptomatically, with many symptoms overlapping with other medical conditions. Blood Pb levels (BLLs) serve as a primary diagnostic test, while additional screening methods assess hematological alteration, including the breakdown of RBCs, elevated coproporphyrin levels, zinc protoporphyrin, and urinary porphyrins, among others. This review intends to outline the systemic toxicity of Pb, emphasizing its impact on various systems, including the Respiratory, Hematological, Nervous, Cardiovascular, Hepatic, Renal, Skeletal, and Reproductive systems. Additionally, this article also examines its genotoxic effect and associated cancer risks. Consequently, there is an urgent need to investigate alternative prevention strategies against Pb toxicity, particularly through dietary supplementation. This review focuses on the vital role of dietary supplements in mitigating Pb toxicity and highlights advanced management approaches. It thoroughly examines the protective effects of phytochemicals, vitamins, probiotics, essential metals, edible plants, and other nutritional supplements in combating Pb toxicity. Furthermore, it discusses advanced chelation therapies utilizing various chelating agents such as CaNa₂EDTA, DMPS, succimer, D-penicillamine, and dimercaprol in a dedicated section. The findings of the present review work indicate that incorporating nutrient supplements into regular diet plans is both straightforward and cost-effective, with fewer side effects compared to alternative treatments. Therefore, these protective strategies are deemed effective and beneficial in reducing the impact of Pb toxicity.

铅（Pb）被认为是地壳中发现的最普遍的金属之一。它的可负担性和易获取性使其在各种工业应用中得到广泛应用。近几十年来，尽管人们对重金属污染的认识有所提高，但全球重金属污染问题已经升级。这种情况在发展中国家尤其令人担忧，因为铅毒性对这些国家的公众健康构成了重大威胁。解决铅中毒的一个关键挑战在于其诊断，因为它通常表现为无症状，许多症状与其他医疗条件重叠。血铅水平（bll）可作为主要诊断测试，而其他筛查方法可评估血液学改变，包括红细胞分解、高比例卟啉水平、原卟啉锌和尿卟啉等。本文旨在概述铅的全身毒性，强调其对各种系统的影响，包括呼吸系统、血液系统、神经系统、心血管系统、肝脏、肾脏、骨骼和生殖系统。此外，本文还研究了其基因毒性作用和相关的癌症风险。因此，迫切需要研究预防铅中毒的替代策略，特别是通过膳食补充。本文综述了膳食补充剂在减轻铅毒性中的重要作用，并重点介绍了先进的管理方法。它彻底检查了植物化学物质、维生素、益生菌、必需金属、可食用植物和其他营养补充剂在对抗铅毒性方面的保护作用。此外，它讨论了先进的螯合疗法利用各种螯合剂，如can2edta， DMPS，琥珀酸，d -青霉胺和二巯基醇在一个专门的部分。目前的研究结果表明，将营养补充剂纳入常规饮食计划既直接又经济，而且与其他治疗方法相比副作用更少。因此，这些保护策略对减少铅毒性的影响是有效和有益的。

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引用次数: 0

Aluminium adjuvants and childhood health: a call for science 铝佐剂与儿童健康：呼唤科学。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2025-12-25 DOI: 10.1016/j.jtemb.2025.127810

Guillemette Crépeaux , Jeremy R. Hammond , Jonathan B. Handley , Brian Hooker , Karl Jablonowski , Lluís Luján , James Lyons-Weiler , Marika Nosten-Bertrand , Christopher A. Shaw , Yehuda Shoenfeld , Lucija Tomljenovic , Christopher Exley

In July 2025, Andersson et al. reported in Annals of Internal Medicine that early-life exposure to Aluminium (Al)-adjuvanted vaccines was not associated with increased risk of 50 chronic diseases, based on a Danish cohort of 1.2 million children. While widely cited as reassuring evidence of Al-Based Adjuvant (ABA) safety, closer scrutiny reveals major methodological and conceptual flaws. Specifically, the study demonstrates limited understanding of Al toxicology, weaknesses in cohort design and statistical analysis, and insufficient transparency regarding potential conflicts of interest. We argue that these shortcomings prevent meaningful conclusions about ABA safety, particularly in relation to neurodevelopmental and autoimmune outcomes, and highlight the need for more rigorous, transparent, and scientifically grounded investigations.

2025年7月，Andersson等人在《内科学年鉴》（Annals of Internal Medicine）上报道，基于丹麦120万儿童队列研究，早期接触铝（Al）佐剂疫苗与50种慢性疾病的风险增加无关。虽然被广泛引用为al基佐剂（ABA）安全性的可靠证据，但更仔细的审查揭示了主要的方法和概念缺陷。具体而言，该研究表明对Al毒理学的了解有限，队列设计和统计分析存在弱点，潜在利益冲突的透明度不足。我们认为，这些缺陷阻碍了对ABA安全性的有意义的结论，特别是与神经发育和自身免疫结果相关的结论，并强调需要更严格、透明和有科学依据的调查。

引用次数: 0

Manganese supplementation in aquafeed: Current knowledge, research gaps, and future prospects for growth and health optimization 水产饲料中锰的补充：目前的知识，研究差距，以及未来的发展前景和健康优化。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2025-12-23 DOI: 10.1016/j.jtemb.2025.127813

Rubina Hayat , Syed Zakir Hussain Shah , Mahroze Fatima , Wazir Ali , Areej Farooq

Trace elements are important for improving the productivity and health of aquatic animals. Manganese (Mn) is a micronutrient that supports various physiological functions. It plays a key role in enzyme production, hormone formation, the immune response, reproductive processes, metabolic activity and antioxidant functions. Some aquafeed ingredients naturally provide Mn to meet the requirements of aquatic animals, but supplementation may be necessary for optimal growth. However, both excess and deficiency of Mn can disrupt metabolic functions and overall health. This review evaluates the role of Mn supplementation in the feed of fishes and crustaceans in improving growth performance, feed utilization, antioxidant defense, tissue accumulation, proximate composition and enzyme activity.

微量元素对提高水生动物的生产力和健康具有重要意义。锰（Mn）是一种支持多种生理功能的微量营养素。它在酶的产生、激素的形成、免疫反应、生殖过程、代谢活性和抗氧化功能中起着关键作用。一些水产饲料成分天然提供锰以满足水生动物的需求，但为了获得最佳生长，可能需要补充锰。然而，锰的过量和缺乏都会破坏代谢功能和整体健康。本文综述了在鱼类和甲壳类动物饲料中添加锰在提高生长性能、饲料利用率、抗氧化防御、组织积累、近似组成和酶活性方面的作用。

引用次数: 0

Influence of feeding zones and seasonal dynamics on metal bioaccumulation and human health risk assessment in riverine fish 饵料带和季节动态对河流鱼类金属生物积累和人体健康风险评价的影响

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2025-12-23 DOI: 10.1016/j.jtemb.2025.127814

Javed Ahmed Ujan , Madeeha Arshad , Fariha Latif , Abdur Rahim , Saira Naz , Mohamed Mohany , Salim S. Al-Rejaie

Metal pollution poses a significant ecological and public health concern due to its persistence, non-biodegradability, and potential for biomagnification through aquatic food webs. This study investigated the influence of feeding zones and seasonal variations on metal bioaccumulation in six fish species (Sperata seenghala, Cyprinus carpio, Labeo rohita, Hypophthalmichthys nobilis, Catla catla, and Hypophthalmichthys molitrix), collected seasonally (December 2023-November 2024) from the Jinnah Barrage on the Indus River, Pakistan, using different nets. Concentrations of Pb, Cd, Ni, Cr, Zn, and Hg were analyzed in fish muscle, water, and sediment using ICP-MS and CV-AAS. Statistical analyses, including two-way ANOVA and Principal Component Analysis (PCA), were used to evaluate the effects of season and feeding zone on metal accumulation patterns. Results revealed that the bottom feeders accumulated significantly (p < 0.05) higher levels of Pb, Cd, Ni, and Cr than column and surface feeders, reflecting greater sediment exposure. Concentrations of Pb and Cd exceeded the WHO/FAO permissible limits in all seasons across different feeding zones, while Cr levels were higher during winter, spring, and autumn in bottom-feeding species. Seasonal variations were also significant (p < 0.05), with metal levels in fish peaking during winter and autumn and declining in summer. In contrast, water and sediment exhibited the highest metal concentrations during summer, likely due to low flow and higher metal retention in fish during colder months. PCA revealed apparent seasonal clustering between biotic and abiotic compartments. Bioconcentration factors were highest for Hg and Cr, particularly in bottom feeders during summer. Health risk assessment showed Hazard Index (HI) > 1 in winter and autumn for several species (mainly due to Hg, Pb, and Cd), with children at highest risk. The findings revealed that both feeding habits and seasonal conditions regulate metal accumulation in fish, necessitating ongoing monitoring and mitigation strategies for consumer safety.

金属污染由于其持久性、不可生物降解性和通过水生食物网进行生物放大的潜力，引起了重大的生态和公共卫生问题。研究了2023年12月~ 2024年11月在巴基斯坦印度河真纳拦河坝不同季节采集的6种鱼类（Sperata seenghala、Cyprinus carpio、Labeo rohita、Hypophthalmichthys nobilis、Catla Catla和Hypophthalmichthys molitrix）的取食区和季节变化对金属生物积累的影响。采用ICP-MS和CV-AAS分析了鱼类肌肉、水和沉积物中Pb、Cd、Ni、Cr、Zn和Hg的浓度。采用双因素方差分析和主成分分析（PCA）评价季节和投食区对金属积累模式的影响。结果表明，冬季和秋季，几种底栖动物的累积量显著（p  1），主要原因是汞、铅和镉，其中儿童的风险最高。研究结果表明，摄食习惯和季节条件都能调节鱼类体内的金属积累，因此有必要对其进行持续监测，并制定消费者安全缓解战略。

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引用次数: 0

Thallium accumulation and transfer through developmental stages of the common green bottle fly, Lucilia sericata, exposed to Tl(I) and Tl(III) species 常见绿瓶蝇暴露于Tl(I)和Tl（III）种后铊在发育阶段的积累和转移。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2025-12-22 DOI: 10.1016/j.jtemb.2025.127812

Julita Malejko , Krzysztof Deoniziak , Kinga Sulej , Justyna Adamska , Beata Godlewska-Żyłkiewicz

Background

Thallium accumulation in insects, which is relevant to both environmental and forensic toxicology, is poorly understood. Thallium toxicity is related to its chemical speciation. Objective: Study of thallium bioaccumulation by the green bottle fly Lucilia sericata exposed to different thallium compounds (TlCH₃COO and Tl(CH₃COO)₃) and doses. Method: The content of thallium, potassium, and sodium in feeding substrate, larvae, puparial cases, and adult flies was determined by inductively coupled plasma mass spectrometry (ICP-MS). Results: The bioaccumulation factors (BAFs) of Tl(I) remained stable across doses (0.28–0.30 for larvae, 0.10–0.13 for adults and 0.4–0.5 for puparial cases), while BAFs of Tl(III) decreased with increasing dose from 0.38 to 0.27 in larvae and from 0.15 to 0.07 in adults but increased with increasing dose from 0.5 to 0.8 in puparial cases. The 46–49 % of Tl(I) and 50–94 % of Tl(III) accumulated in larvae were eliminated by deposition in puparial cases. Larval weight and mortality were unaffected by the presence of Tl(I) or Tl(III) in the feeding substrate at the doses tested. Conclusion: Thallium accumulation in the life stages of L. sericata depends on its chemical form (Tl(I) and Tl(III)) and content in the insect diet. Its main elimination route is the deposition in puparial cases. Potassium naturally present in the feed may mitigate Tl toxicity to the larvae. Our study demonstrates the usefulness of L. sericata as a reliable model organism for monitoring environmental thallium pollution and thallium poisoning in forensic entomotoxicological investigations.

背景：昆虫体内铊的积累与环境毒理学和法医毒理学都有关系，但人们对其了解甚少。铊的毒性与其化学形态有关。目的：研究不同铊化合物（TlCH3COO和Tl(CH3COO)3）及剂量对绿瓶蝇铊生物蓄积的影响。方法：采用电感耦合等离子体质谱法（ICP-MS）测定取食底物、幼虫、蛹和成蝇中铊、钾、钠的含量。结果：Tl(I)的生物积累因子（baf）在不同剂量下保持稳定（幼虫为0.28 ~ 0.30，成虫为0.10 ~ 0.13，蛹期为0.4 ~ 0.5），而Tl（III）的生物积累因子（baf）随剂量增加而降低，幼虫为0.38 ~ 0.27，成虫为0.15 ~ 0.07，蛹期为0.5 ~ 0.8，随剂量增加而升高。幼虫体内积累的46- 49% %的Tl(I)和50- 94% %的Tl（III）通过沉积消除。在试验剂量下，取食基质中是否存在Tl(I)或Tl（III）对幼虫体重和死亡率没有影响。结论：丝毛假蝇生命阶段铊的积累取决于其化学形态(Tl（I)和Tl(III)）和在昆虫食粮中的含量。它的主要消除途径是在阴道病例中沉积。饲料中天然存在的钾可以减轻对幼虫的毒性。我们的研究证明了丝毛拟合蝇作为一种可靠的模式生物在法医昆虫毒理学调查中监测环境铊污染和铊中毒的有效性。

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引用次数: 0

X-ray fluorescence analysis of elemental concentrations in human tongue tissues: Distinguishing healthy from carcinoma profiles 人舌组织中元素浓度的x射线荧光分析：区分健康与癌剖面

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2025-12-20 DOI: 10.1016/j.jtemb.2025.127811

Luísa Zagalo , Luísa L. Gonçalves , Carlos Zagalo , Maria João Oliveira , Pedro Oliveira , José A.A. Brito

This study explores the feasibility of Wavelength Dispersive X-ray Fluorescence (WDXRF) to distinguish between healthy and carcinoma tongue tissues based on elemental concentration profiles. The concentrations of six chemical elements (phosphorus, sulphur, calcium, iron, zinc and copper) were determined in formalin-fixed and paraffin-embedded tissue samples from both tumour regions and histologically validated healthy margins in 31 patients with tongue squamous cell carcinoma. Mean concentrations for every sample were calculated from three replicate measurements and analysed using discriminant analysis and mixed linear models. Although the discriminant model lacked statistical relevance, the structural matrix suggested iron, copper and zinc contributed the most to the differentiation between tissue types. These elements were subsequently investigated further by using mixed linear models, which confirmed they had significantly reduced concentrations in carcinoma tissues (p < 0.001), having maintained significant results after Bonferroni correction. Furthermore, a decreased iron concentration in carcinoma tissue of patients who reported frequent alcohol consumption was observed (p = 0.003), while tobacco use showed no significant effect on the element’s concentrations. Although exploratory, our results show changes in specific elemental concentrations, something that may help define oral cancer and support the incorporation of X-ray fluorescence into complementary diagnostic means.

本研究探讨了波长色散x射线荧光（WDXRF）基于元素浓度谱区分健康和癌舌组织的可行性。对31例舌鳞癌患者肿瘤区域和经组织学验证的健康边缘的福尔马林固定和石蜡包埋组织样本中六种化学元素（磷、硫、钙、铁、锌和铜）的浓度进行了测定。每个样品的平均浓度通过三个重复测量计算，并使用判别分析和混合线性模型进行分析。虽然判别模型缺乏统计相关性，但结构矩阵表明铁、铜和锌对组织类型的分化贡献最大。随后使用混合线性模型进一步研究了这些元素，证实它们在癌组织中的浓度显著降低（p <； 0.001），在Bonferroni校正后保持了显著的结果。此外，观察到经常饮酒的患者癌组织中的铁浓度降低（p = 0.003），而吸烟对该元素的浓度没有显着影响。虽然是探索性的，但我们的结果显示了特定元素浓度的变化，这可能有助于定义口腔癌，并支持将x射线荧光纳入辅助诊断手段。

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引用次数: 0

Therapeutic effects of newly synthesized boron compounds (BPM and BPD) on Mycobacterium tuberculosis and A549 cells 新合成硼化合物（BPM和BPD）对结核分枝杆菌和A549细胞的治疗作用

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2025-12-16 DOI: 10.1016/j.jtemb.2025.127809

Elif AYDIN , Melda BOLAT , Meliha KOLDEMIR GUNDUZ , Dursun Ali KOSE

In this study, the cytotoxic and antimycobacterial effects of two newly synthesized boron-based compounds, boron phenylalanine monoester (BPM) and boron phenylalanine diester (BPD), were investigated in human lung adenocarcinoma cells (A549) and Mycobacterium tuberculosis H37Rv strain. MTT assays revealed dose-dependent antiproliferative activity, with IC₅₀ values of 1.5 mM for BPM and 1.16 mM for BPD, indicating greater potency of BPD at lower concentrations. To contextualize potency, we report MICs in both mM and µg/mL. While the current MICs are higher than typical literature benchmarks for front-line comparators, these chemotypes provide a starting point for optimization. Gene expression analysis after 48-hour treatment showed significant upregulation of TNF-α, p53, and Bax, and downregulation of IL-6 and Bcl-2 (p < 0.05). The increase in TNF-α expression (p = 0.0159 for BPM; p = 0.0095 for BPD) suggests immune pathway activation, while the rise in p53 levels supports apoptotic induction. In antimicrobial assays, BPD demonstrated superior efficacy with a MIC value of 25 mM, compared to 50 mM for BPM. Collectively, these findings indicate that BPM and especially BPD show preliminary activity that warrants further optimization for dual anticancer and antimycobacterial applications.

本研究研究了两种新合成的硼基化合物硼苯丙氨酸单酯（BPM）和硼苯丙氨酸二酯（BPD）对人肺腺癌细胞（A549）和结核分枝杆菌H37Rv株的细胞毒和抑菌作用。MTT试验显示了剂量依赖性的抗增殖活性，BPM的IC₅0值为1.5 mM， BPD的IC₅0值为1.16 mM，表明BPD在较低浓度下的效力更大。为了将效力背景化，我们报告了mic单位为mM和µg/mL。虽然目前的mic高于一线比较器的典型文献基准，但这些化学型为优化提供了起点。治疗48小时后基因表达分析显示，TNF-α、p53、Bax表达上调，IL-6、Bcl-2表达下调（p <； 0.05）。TNF-α表达升高（BPM p = 0.0159;BPD p = 0.0095）提示免疫通路激活，而p53水平升高支持诱导凋亡。在抗菌试验中，BPD表现出更好的功效，MIC值为25 mM，而BPM为50 mM。总的来说，这些发现表明BPM，特别是BPD显示出初步的活性，值得进一步优化双重抗癌和抗细菌应用。

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引用次数: 0

Manganese-induced neurotoxicity and its role in frontotemporal dementia: Insights from the frontotemporal cortex of BALB/c mice 锰诱导的神经毒性及其在额颞叶痴呆中的作用：来自BALB/c小鼠额颞叶皮层的见解。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2025-12-15 DOI: 10.1016/j.jtemb.2025.127807

Olumayowa Kolawole Idowu , Grace Ayobami Fajemidagba , Ileje Inelo Ukwubile , Damilare Adedayo Adekomi

Background

Manganese (Mn), an essential trace metal, has been identified as a potential contributor to neurotoxicity when misregulated, with implications for cognitive decline and motor dysfunctions. Frontotemporal dementia (FTD) is a devastating neurological condition that causes increasing cognitive, behavioral, and linguistic deficits in the frontal and temporal lobes of the brain. The specific mechanisms behind FTD remain unknown. This study investigates Mn-induced neurotoxicity as it affects frontotemporal cortex of BALB/c mice as a model for FTD.

Methods

BALB/c mice were given varying doses of Mn—low (50 mg/kg body weight), medium (100 mg/kg), and high (200 mg/kg)—for eight weeks, while the control group received distilled water. The Morris Water Maze Test (MWMT) and the Open Field Test (OFT) were used to test cognitive abilities. Brain tissue was examined for oxidative stress markers (GSH, MDA, SOD, CAT, NO), neurotransmitters (glutamate, GABA, ACh), AChE, inflammatory and apoptotic markers (IL-6, TNF-α, caspase-3), Mn concentration, and histopathological alterations (H and E, Bielschowsky, and Golgi staining).

Results

Mn exposure, specifically to the medium and high doses, significantly impairs cognition and memory function, resulting in decreased locomotion and increased freezing time in the OFT and increased escape latency in the MWMT. Oxidative stress markers showed increased MDA and NO levels but decreased GSH, SOD, and CAT. Neurotransmitter dysfunction was obvious, with increased glutamate and AChE activity and decreased GABA and ACh levels. Mn increased IL-6, TNF-α, and caspase-3 levels, and histology showed neuronal vacuolation, neurofibrils, and axonal/dendritic injury, especially in medium- and high-dose groups.

Conclusion

Mn exposure induces oxidative stress, neurotransmitter dysfunction, neuroinflammation, and neurodegeneration in the frontotemporal cortex, contributing to FTD pathogenesis.

背景：锰（Mn）是一种必需的微量金属，当调节不当时，已被确定为神经毒性的潜在贡献者，可能导致认知能力下降和运动功能障碍。额颞叶痴呆（FTD）是一种破坏性的神经系统疾病，会导致大脑额叶和颞叶的认知、行为和语言缺陷增加。FTD背后的具体机制尚不清楚。本研究将mn对BALB/c小鼠额颞叶皮层的神经毒性作为FTD的模型进行研究。方法：给予BALB/c小鼠不同剂量的mn -低（50 mg/kg体重）、中（100 mg/kg）和高（200 mg/kg），持续8周，对照组给予蒸馏水。采用Morris水迷宫测验（MWMT）和Open Field测验（OFT）测试认知能力。脑组织检测氧化应激标志物（GSH、MDA、SOD、CAT、NO）、神经递质（谷氨酸、GABA、乙酰胆碱）、乙酰胆碱酯酶（AChE）、炎症和凋亡标志物（IL-6、TNF-α、caspase-3）、Mn浓度和组织病理学改变（H和E、Bielschowsky和高尔基染色）。结果：锰暴露，特别是中剂量和高剂量，显著损害认知和记忆功能，导致前脑运动减少，冻结时间增加，后脑区逃避潜伏期增加。氧化应激标志物显示MDA和NO水平升高，GSH、SOD和CAT水平降低。神经递质功能障碍明显，谷氨酸和乙酰胆碱酯酶活性升高，氨基丁酸和乙酰胆碱酯酶水平降低。Mn增加了IL-6、TNF-α和caspase-3水平，组织学表现为神经元空泡化、神经原纤维和轴突/树突损伤，特别是在中、高剂量组。结论：Mn暴露诱导额颞叶皮层氧化应激、神经递质功能障碍、神经炎症和神经退行性变，参与FTD的发病机制。

{"title":"Manganese-induced neurotoxicity and its role in frontotemporal dementia: Insights from the frontotemporal cortex of BALB/c mice","authors":"Olumayowa Kolawole Idowu , Grace Ayobami Fajemidagba , Ileje Inelo Ukwubile , Damilare Adedayo Adekomi","doi":"10.1016/j.jtemb.2025.127807","DOIUrl":"10.1016/j.jtemb.2025.127807","url":null,"abstract":"<div><h3>Background</h3><div>Manganese (Mn), an essential trace metal, has been identified as a potential contributor to neurotoxicity when misregulated, with implications for cognitive decline and motor dysfunctions. Frontotemporal dementia (FTD) is a devastating neurological condition that causes increasing cognitive, behavioral, and linguistic deficits in the frontal and temporal lobes of the brain. The specific mechanisms behind FTD remain unknown. This study investigates Mn-induced neurotoxicity as it affects frontotemporal cortex of BALB/c mice as a model for FTD.</div></div><div><h3>Methods</h3><div>BALB/c mice were given varying doses of Mn—low (50 mg/kg body weight), medium (100 mg/kg), and high (200 mg/kg)—for eight weeks, while the control group received distilled water. The Morris Water Maze Test (MWMT) and the Open Field Test (OFT) were used to test cognitive abilities. Brain tissue was examined for oxidative stress markers (GSH, MDA, SOD, CAT, NO), neurotransmitters (glutamate, GABA, ACh), AChE, inflammatory and apoptotic markers (IL-6, TNF-α, caspase-3), Mn concentration, and histopathological alterations (H and E, Bielschowsky, and Golgi staining).</div></div><div><h3>Results</h3><div>Mn exposure, specifically to the medium and high doses, significantly impairs cognition and memory function, resulting in decreased locomotion and increased freezing time in the OFT and increased escape latency in the MWMT. Oxidative stress markers showed increased MDA and NO levels but decreased GSH, SOD, and CAT. Neurotransmitter dysfunction was obvious, with increased glutamate and AChE activity and decreased GABA and ACh levels. Mn increased IL-6, TNF-α, and caspase-3 levels, and histology showed neuronal vacuolation, neurofibrils, and axonal/dendritic injury, especially in medium- and high-dose groups.</div></div><div><h3>Conclusion</h3><div>Mn exposure induces oxidative stress, neurotransmitter dysfunction, neuroinflammation, and neurodegeneration in the frontotemporal cortex, contributing to FTD pathogenesis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"93 ","pages":"Article 127807"},"PeriodicalIF":3.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784229","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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