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

Elucidation of molecular mechanisms, pathways, and diseases modulated by arsenicals through toxogenomics and multi-omics analysis 通过毒物基因组学和多组学分析，阐明砷化物调节的分子机制、途径和疾病。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-11-09 DOI: 10.1016/j.jtemb.2024.127561

Seema Zargar , Nojood Altwaijry , Humidah Alanazi , Atekah Hazzaa Alshammari , Hamad M. Alkahtani , Tanveer A. Wani

Arsenic compounds exist in inorganic and organic forms with inorganic form confirmed as a potent carcinogen. Toxogenomics and multi-omics analysis were used to explore the molecular mechanisms of carcinogenecity induced by arsenicals. Comparative toxogenomics revealed sodium arsenite and arsenate as the most toxic arsenicals to humans, interacting with various genes and altering gene expression through mRNA binding proteins. Both metalloids were classified as Class II toxins by the ProTox II prediction tool, with a lethal dose (LD50) of 149 mg/kg body weight. The most frequently interacting genes were HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM. Analysis of TCGA pan-cancer data revealed that 46 % of hepatocellular carcinoma patients exhibited alterations in the genes HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM, suggesting their significant role in the development of this disease. The alteration in the gene list decreased the overall patient survival but insignificantly in the Kaplan-Meier curves revealing insignificant role in survival. GSEA suggested significant enrichment of the gene list in pathways involved in the G2M checkpoint, apoptosis, hypoxia, TNFA signaling via NFKB, PI3K AKTMTOR signaling, P53, IFN gamma and inflammatory response pathways revealing the involvement of these pathways. Ten microRNAs (miRNAs) regulated the expressions of the genes involved in the above-mentioned pathways with the significant enrichment in miR-21–3p, miR-206 and mir486a-5p. The relevant pathway and graphical representation of the network of miRNA-target interactions identified by the enrichment analysis along with disease ontologies were predicted. This study will be helpful insight into setting of laboratory experiments.

砷化合物有无机和有机两种形式，其中无机形式已被证实是一种强致癌物。毒物基因组学和多组学分析被用来探索砷化物致癌的分子机制。比较毒物基因组学发现，亚砷酸钠和砷酸盐是对人类毒性最大的砷化物，它们与各种基因相互作用，并通过 mRNA 结合蛋白改变基因表达。根据 ProTox II 预测工具，这两种金属物质都被列为二级毒素，致死剂量（LD50）为 149 毫克/千克体重。最常发生相互作用的基因是HMOX1、CAT、NFE2L2、CASP3、MAPK1、CXCL8、PARP1、TNF和PYGM。对 TCGA 泛癌症数据的分析表明，46% 的肝细胞癌患者的基因 HMOX1、CAT、NFE2L2、CASP3、MAPK1、CXCL8、PARP1、TNF 和 PYGM 发生了改变，这表明它们在该疾病的发展中起着重要作用。基因列表中的改变降低了患者的总生存率，但在 Kaplan-Meier 曲线中并不显著，这表明基因改变对生存率的影响并不明显。GSEA 显示，基因列表在涉及 G2M 检查点、细胞凋亡、缺氧、通过 NFKB 的 TNFA 信号转导、PI3K AKTMTOR 信号转导、P53、IFN γ 和炎症反应通路中显着富集，揭示了这些通路的参与。10个微小RNA（miRNA）调控了参与上述通路的基因的表达，其中miR-21-3p、miR-206和mir486a-5p显著富集。通过富集分析确定的 miRNA-靶点相互作用网络的相关通路和图示与疾病本体一起进行了预测。这项研究将有助于深入了解实验室实验的设置。

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引用次数: 0

Association between urinary arsenic levels and kidney damage in US adults: NHANES 2007–2018 美国成年人尿砷水平与肾损伤之间的关系：Nhanes 2007-2018。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-11-07 DOI: 10.1016/j.jtemb.2024.127559

Nishat Tasnim Hasan , Xiaohui Xu , Daikwon Han , Garett Sansom , Taehyun Roh

Background

Chronic arsenic exposure is known to be associated with various diseases by inducing multiple organ dysfunctions. Despite the high prevalence of kidney diseases in the US and globally, population-level research on the link between inorganic arsenic and kidney damage remains limited. In our study, we assessed the association between urinary arsenic levels and kidney damage among US adults using a multi-marker approach.

Methods

We analyzed data from the National Health and Nutrition Examination Survey (2007–2018). Multivariable logistic regression models were employed to estimate the odds ratios (ORs) for kidney damage based on total urinary arsenic levels and multiple kidney biomarkers, including albuminuria, low estimated glomerular filtration rate (eGFR), hyperuricemia, and elevated blood urea nitrogen (BUN), while adjusting for demographic, socioeconomic, and other risk factors. Total urinary arsenic levels were calculated by summing the levels of arsenous acid (As3), arsenic acid (As5), and their methylated metabolites, monomethylarsinic acid (MMA), and dimethylarsinic acid (DMA). Dimethylarsinic acid (DMA) was calibrated for arsenobetaine using a residual regression method to minimize the influence of seafood-related exposure.

Results

After adjusting for covariates, we observed 1.29-fold higher odds (95 % CI 1.01, 1.64) of kidney damage in the highest quartile of urinary arsenic compared to the lowest quartile. Specifically, the odds of albuminuria and hyperuricemia were 1.49-fold (95 % CI 1.09, 2.03) and 1.38-fold (95 % CI 1.01, 1.88) higher, respectively, in the highest quartile. Additionally, for every one-unit increase in the natural log of arsenic levels, significant associations were observed for overall kidney damage (OR 1.10, 95 % CI 1.01, 1.20), albuminuria (OR 1.15, 95 % CI 1.03, 1.29), and hyperuricemia (OR 1.12, 95 % CI 1.02, 1.24) when considering arsenic levels in drinking water as a continuous variable.

Conclusion

Our study concludes that higher urinary arsenic levels are positively associated with kidney damage. Further prospective studies are needed to confirm these findings.

背景：众所周知，长期接触砷会诱发多种器官功能障碍，从而导致多种疾病。尽管肾脏疾病在美国和全球的发病率都很高，但有关无机砷与肾脏损伤之间关系的人群研究仍然有限。在我们的研究中，我们采用多指标方法评估了美国成年人尿砷水平与肾损伤之间的关联：我们分析了美国国家健康与营养调查（2007-2018 年）的数据。采用多变量逻辑回归模型，根据总尿砷水平和多种肾脏生物标志物（包括白蛋白尿、估计肾小球滤过率（eGFR）低、高尿酸血症和血尿素氮（BUN）升高）估算肾脏损伤的几率比（ORs），同时对人口、社会经济和其他风险因素进行调整。尿砷总含量的计算方法是将砷酸（As3）、砷酸（As5）及其甲基化代谢产物单甲基胂酸（MMA）和二甲基胂酸（DMA）的含量相加。采用残差回归法对二甲基胂酸（DMA）进行了砷甜菜碱校准，以尽量减少与海产品有关的暴露的影响：结果：在对协变量进行调整后，我们发现尿砷含量最高的四分位数与最低的四分位数相比，肾脏受损的几率高出 1.29 倍（95 % CI 1.01，1.64）。具体来说，最高四分位数人群出现白蛋白尿和高尿酸血症的几率分别高出 1.49 倍（95 % CI 1.09，2.03）和 1.38 倍（95 % CI 1.01，1.88）。此外，当将饮用水中的砷含量视为连续变量时，砷含量的自然对数每增加一个单位，整体肾脏损害（OR 1.10，95 % CI 1.01，1.20）、白蛋白尿（OR 1.15，95 % CI 1.03，1.29）和高尿酸血症（OR 1.12，95 % CI 1.02，1.24）就会出现显著的相关性：我们的研究得出结论，尿砷水平较高与肾损伤呈正相关。需要进一步的前瞻性研究来证实这些发现。

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引用次数: 0

Metallomic analysis of urine from individuals with and without Covid-19 infection reveals extensive alterations in metal homeostasis 对感染 Covid-19 和未感染 Covid-19 的人的尿液进行金属原子分析，发现金属平衡发生了广泛变化

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-28 DOI: 10.1016/j.jtemb.2024.127557

Ketolly Natanne da Silva Leal , Ana Beatriz Santos da Silva , Elisânia Kelly Barbosa Fonseca , Olívia Brito de Oliveira Moreira , Lúcio Marco de Lemos , Marcone Augusto Leal de Oliveira , Alan J. Stewart , Marco Aurélio Zezzi Arruda

Background

Metal ions perform important functions in the body and their concentrations in cells and tissues are tightly controlled. Alterations in metal homeostasis can occur in certain disease states including infection. In this study urinary excretion of several metals including calcium, cadmium, cobalt, copper, iron, magnesium, nickel, selenium, and zinc in Covid-19 patients (n=35) and control (n=60) individuals, spanning ages and sexes.

Methods

Urinary samples were analysed using ICP-MS and the differences in metal concentrations between the Covid-19-infected and control groups were assessed using multivariate data analysis and univariate data analysis employing Student's t-test and Pearson's correlation, with significance set at p<0.05.

Results

The urinary concentrations of all metals analysed were significantly higher in the Covid-infected group (compared to controls), with the exception of copper, which was markedly reduced. The increase in calcium excretion was lower and magnesium excretion greater in Covid-19-positive individuals aged 41 or over compared to those aged 40 or lower. Whilst the increase in iron excretion was lower, and cobalt excretion greater in Covid-19-positive males compared to females.

Conclusions

The study highlights significant alterations in the handling of a range of metals in the body during Covid-19 infection. It also highlights both age and sex-specific differences in metal homeostasis. The results suggest an important role for copper in the body during Covid-19 infection and suggests that urinary concentrations of copper and other metals may serve as markers to predict progression of the disease.

背景金属离子在人体内发挥着重要功能，它们在细胞和组织中的浓度受到严格控制。在某些疾病（包括感染）状态下，金属平衡会发生改变。在这项研究中，Covid-19 患者（35 人）和对照组（60 人）不同年龄和性别的尿液中排出了多种金属，包括钙、镉、钴、铜、铁、镁、镍、硒和锌。方法使用 ICP-MS 分析尿液样本，使用多变量数据分析和单变量数据分析评估 Covid-19 感染组和对照组之间金属浓度的差异，使用学生 t 检验和皮尔逊相关性，显著性设定为 p<0.05。与 40 岁或 40 岁以下的人相比，41 岁或 41 岁以上的 Covid-19 阳性者的钙排泄量增加较少，镁排泄量增加较多。结论该研究强调了在 Covid-19 感染期间，体内一系列金属的处理发生了显著变化。该研究还强调了金属稳态的年龄和性别差异。研究结果表明，铜在 Covid-19 感染期间在体内发挥着重要作用，并表明尿液中铜和其他金属的浓度可作为预测疾病进展的标志物。

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引用次数: 0

Zinc deficiency impairs the development of human regulatory B cells from purified B cells 缺锌会影响纯化 B 细胞中人类调节性 B 细胞的发育。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-20 DOI: 10.1016/j.jtemb.2024.127556

Mary-Ann Puppa , Sabrina B. Bennstein , Henrike J. Fischer, Lothar Rink

Zinc is a vital trace element, important for many different immune processes and adequate functionality. B cell development is known to be dependent on sufficient zinc supply. Recently a regulatory B cell (Breg) population has been identified, as CD19⁺IL-10⁺ B cells, able to regulate immune responses by secretion of anti-inflammatory cytokines, such as IL-10. Due to their promotion of an anti-inflammatory milieu, Bregs could reduce or might even prevent excessive pro-inflammatory responses. Hence, having and maintaining Bregs could be interesting for patients suffering from allergies, asthma, and autoimmune diseases. Therefore, understanding Breg generation, required signaling, and their developmental requirements are important. Since our group could previously show that zinc is important for regulatory T cells, we aimed to determine the effect of zinc deficiency on Breg development from human peripheral blood CD19⁺ B cells. We observed highest Breg generation with a combined stimulus of CD40L and the toll like receptor (TLR) ligand, CpG-ODN2006. Using this stimulus, we observed that zinc deficient medium significantly decreased Breg generation from purified B cells. This was not seen in Bregs generated from peripheral blood mononuclear cells (PBMCs) without B cell enrichment suggesting a compensatory mechanism. In line with literature, our data also confirms Bregs develop from CD19⁺ B cells, since total CD19⁺ frequencies remained unchanged, while Breg frequencies varied between stimuli and zinc media conditions. Our study shows for the first time that zinc deficiency significantly impairs Breg development, which provides an important new perspective for clinical applications and therapeutic strategies.

锌是一种重要的微量元素，对许多不同的免疫过程和充分发挥功能非常重要。众所周知，B 细胞的发育依赖于充足的锌供应。最近发现了一种调节性 B 细胞（Breg）群，即 CD19+IL-10+ B 细胞，它们能够通过分泌 IL-10 等抗炎细胞因子来调节免疫反应。由于 Bregs 能促进抗炎环境，因此可以减少甚至防止过度的促炎反应。因此，拥有并维持 Bregs 对过敏、哮喘和自身免疫性疾病患者很有意义。因此，了解 Breg 的生成、所需的信号传导及其发育要求非常重要。由于我们的研究小组之前已经证明锌对调节性 T 细胞很重要，因此我们的目的是确定缺锌对人类外周血 CD19+ B 细胞 Breg 发育的影响。我们观察到，在 CD40L 和类收费受体（TLR）配体 CpG-ODN2006 的联合刺激下，Breg 的生成量最高。利用这种刺激，我们观察到缺锌培养基显著减少了纯化 B 细胞的 Breg 生成。而在未进行 B 细胞富集的外周血单核细胞（PBMCs）中生成的 Bregs 则没有出现这种情况，这表明存在一种补偿机制。与文献一致，我们的数据也证实了 Bregs 是由 CD19+ B 细胞发展而来的，因为 CD19+ 的总频率保持不变，而 Breg 的频率则因刺激和锌培养基条件的不同而不同。我们的研究首次表明，缺锌会显著影响 Breg 的发育，这为临床应用和治疗策略提供了一个重要的新视角。

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引用次数: 0

Zinc-modulated bidirectional copper transfer across the blood-brain barrier in a porcine brain capillary endothelial cell culture model system 在猪脑毛细血管内皮细胞培养模型系统中，锌调控铜在血脑屏障上的双向转移。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-19 DOI: 10.1016/j.jtemb.2024.127547

Denny Pellowski , Franziska Ebert , Julia Bornhorst , Tanja Schwerdtle

The blood-brain barrier (BBB) serves as a crucial interface, regulating the transfer of trace elements (TEs) such as copper (Cu) and zinc (Zn) between the bloodstream and the brain. Cu and Zn are essential for maintaining neural function and enzymatic processes. Understanding the interplay of Cu and Zn with the BBB is crucial for elucidating their roles in neurological health and disease. This study investigates the bidirectional transfer of Cu across the BBB and examines the impact of Zn supplementation on this process using a porcine brain capillary endothelial cell (PBCEC) model. Transendothelial electrical resistance (TEER) and capacitance measurements confirmed barrier integrity upon TE exposure, while quantification of Cu and Zn concentrations via inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS) in the culture medium provided essential baseline data. Transfer studies revealed significant increases in basolateral (brain side) Cu concentrations after apical (blood side) Cu incubation, with additional Zn supplementation reducing Cu transfer from apical to basolateral compartments. Conversely, Zn incubation showed no effect on basolateral-to-apical Cu transfer. Surprisingly, it was found that Cu also transferred significantly to the apical compartments when incubated basolaterally, and with slightly higher permeability coefficients than vice versa, indicating a potential role of PBCECs in regulating Cu transport both from blood to brain and from brain to blood. These findings suggest a bidirectional Cu trafficking across PBCECs, only slightly influenced unidirectionally by Zn supplementation, highlighting the intricate interplay between TEs at the BBB. Importantly, no alterations in barrier integrity were observed, underscoring the physiological relevance of the experimental conditions. Overall, this study sheds light on the complex dynamics of Cu and Zn transfer at the BBB, emphasizing the need for comprehensive investigations into TE interactions for a deeper understanding of brain TE homeostasis.

血脑屏障（BBB）是一个重要的界面，它调节着铜（Cu）和锌（Zn）等微量元素（TE）在血液和大脑之间的转移。铜和锌对维持神经功能和酶过程至关重要。了解铜和锌与 BBB 的相互作用对于阐明它们在神经系统健康和疾病中的作用至关重要。本研究利用猪脑毛细血管内皮细胞（PBCEC）模型研究了铜在 BBB 上的双向转移，并探讨了补充锌对这一过程的影响。经内皮电阻（TEER）和电容测量证实了暴露于 TE 时屏障的完整性，而通过电感耦合等离子体串联质谱法（ICP-MS/MS）对培养基中的铜和锌浓度进行定量则提供了重要的基线数据。转移研究显示，顶端（血液侧）铜培养后，基底侧（大脑侧）铜浓度明显增加，额外的锌补充减少了铜从顶端向基底侧的转移。相反，锌孵育对基底侧到顶端的铜转移没有影响。令人惊讶的是，研究发现，当铜在基底侧培养时，也会显著转移到顶端区室，而且渗透系数略高于基底侧培养，这表明 PBCECs 在调节铜从血液到大脑以及从大脑到血液的转运中发挥了潜在作用。这些研究结果表明，铜在 PBCECs 上的运输是双向的，而单向运输只受到锌补充的轻微影响，这突显了 BBB 中 TEs 之间错综复杂的相互作用。重要的是，没有观察到屏障完整性的改变，这强调了实验条件的生理相关性。总之，这项研究揭示了铜和锌在 BBB 转移的复杂动态，强调了全面研究 TE 相互作用的必要性，以加深对脑 TE 平衡的理解。

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引用次数: 0

Unveiling the interaction and combined effects of multiple metals/metalloids exposure to TNF-α and kidney function in adults using bayesian kernel machine regression and quantile-based G-computation 利用贝叶斯核机器回归和基于量子的G计算揭示多种金属/金属化合物暴露对成人TNF-α和肾功能的相互作用和综合影响

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-19 DOI: 10.1016/j.jtemb.2024.127552

Kuei-Hau Luo , Hung-Pin Tu , Yong-Chuan Chung , Min-Hsin Huang , Chen-Cheng Yang , Tzu-Hua Chen , Cheng-Hong Yang , Hung-Yi Chuang

Background

Exposure to multiple metals may cause adverse effects, particularly in the kidneys. However, studies on the combined and interaction effects of metal mixtures on human health remain limited.

Objective

The study aims to evaluate the interaction between metals and assess the combined effects of exposure to metal mixtures on tumor necrosis factor-alpha (TNF-α) levels and kidney function

Methods

Particular emphasis has been placed on the impact of various metals, including arsenic (As), cadmium (Cd), lead (Pb), as well as essential trace elements, such as cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn), on human health and their potential collective influence on both TNF-α and kidney function. This cross-sectional study analyzed the data of 421 adults who underwent a health examination. Generalized linear model (GLM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation (qgcomp) were used to evaluate the association and joint effects between the metals and TNF-α, as well as kidney function.

Results

Increased concentrations of As (β = 0.11, 95 % CI = 0.05, 0.17) and Pb (β = 0.30, 95 % CI = 0.23, 0.37) in the blood were associated with elevated levels of TNF-α, while elevated Cu (β = −0.42, 95 % CI = −0.77, −0.07) levels were linked to a significant reduction in TNF-α. The overall effect of metals mixture showed a significant association with a decline in eGFR and an increase TNF-α in the BKMR model. Qgcomp analysis of the metals mixture (β = −0.06, 95 % CI = −0.07, −0.05) indicated that As, Pb, and Zn were the primary contributors to the reduction in eGFR, while As and Pb were the major contributors in metals mixture (β = 0.12, 95 % CI = 0.08, 0.15) to the elevation of TNF-α levels.

Conclusion

Exposure to multiple metals could have joint association with the TNF-α levels and kidney function. Furthermore, TNF-α could act as a mediator between metal mixtures and eGFR.

背景接触多种金属可能会造成不良影响，尤其是对肾脏的影响。然而，有关金属混合物对人体健康的综合影响和相互作用的研究仍然有限。本研究旨在评估金属之间的相互作用，并评估暴露于金属混合物对肿瘤坏死因子-α（TNF-α）水平和肾功能的综合影响、砷 (As)、镉 (Cd)、铅 (Pb) 以及钴 (Co)、铜 (Cu)、硒 (Se) 和锌 (Zn) 等必需微量元素对人体健康的影响及其对 TNF-α 和肾功能的潜在共同影响。这项横断面研究分析了 421 名接受健康检查的成年人的数据。研究采用了广义线性模型（GLM）、贝叶斯核机器回归（BKMR）和基于量子的 G 计算（qgcomp）来评估金属与 TNF-α 和肾功能之间的关联和联合效应。结果血液中砷（β = 0.11，95 % CI = 0.05，0.17）和铅（β = 0.30，95 % CI = 0.23，0.37）浓度的升高与 TNF-α 水平的升高有关，而铜（β = -0.42，95 % CI = -0.77，-0.07）浓度的升高与 TNF-α 水平的显著降低有关。在 BKMR 模型中，金属混合物的总体效应与 eGFR 的下降和 TNF-α 的增加有显著关联。对金属混合物的Qgcomp分析（β = -0.06，95 % CI = -0.07，-0.05）表明，砷、铅和锌是导致eGFR下降的主要因素，而砷和铅是导致TNF-α水平升高的主要因素（β = 0.12，95 % CI = 0.08，0.15）。此外，TNF-α可能是金属混合物与肾小球滤过率之间的媒介。

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引用次数: 0

Chemical elemental composition and human taphonomy: A comparative analysis between skeletonised and preserved individuals from six Portuguese public cemeteries 化学元素组成与人类的出土研究：对葡萄牙六个公共墓地的骸骨和保存下来的个体进行比较分析。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-18 DOI: 10.1016/j.jtemb.2024.127551

Angela Silva-Bessa , Rui Azevedo , Agostinho Almeida , Lorna Dawson , Shari L. Forbes , Maria Teresa Ferreira , Ricardo Jorge Dinis-Oliveira

Introduction

In Portugal, it is common practice to reuse burial graves in cemeteries with exhumations occurring after a minimum period of three years after entombment. However, if the human remains still retain soft tissues when the grave is opened, inhumations must continue for successive periods of two years until complete skeletonization is achieved. For the past decade, several Portuguese public cemeteries have been struggling with the lack of burial space mainly due to a slow cadaveric decomposition. As such, this work aims to understand if the chemical elemental concentrations found in the depositional environment of deceased individuals is influencing human taphonomy.

Methods

A total of 112 soil samples were collected from graves of five Portuguese public cemeteries and the concentration of 28 chemical elements was measured by inductively coupled plasma mass spectrometry (ICP-MS). A total of 56 head hair samples and 19 fingernail samples were also collected from cadaveric remains and analysed for the same purpose.

Results

Overall, all matrices showed statistically significant differences (p < 0.05) between skeletonised and preserved individuals. Although it was considered that the preserved bodies would display higher elemental concentrations than the skeletonised ones, this hypothesis was not confirmed.

Conclusions

The authors believe that changes in the burial conditions over time may have enable the disintegration of soft tissues even if they were initially preserved due to the presence of chemical elements. Similar studies on a global scale should be considered as they could bring together distinct perspectives and lead to more comprehensive and innovative solutions for cemetery management.

导言：在葡萄牙，墓地中的墓穴通常在埋葬后至少三年后才进行挖掘。但是，如果在打开墓穴时遗骸仍保留软组织，则必须连续两年进行掘墓，直到完全骨骼化为止。在过去十年中，葡萄牙的几个公共墓地一直在为缺乏埋葬空间而苦苦挣扎，这主要是由于尸体分解缓慢造成的。因此，这项工作旨在了解死者沉积环境中的化学元素浓度是否会影响人类的岩石学：方法：从葡萄牙五个公共墓地的坟墓中收集了 112 份土壤样本，并通过电感耦合等离子体质谱法（ICP-MS）测量了 28 种化学元素的浓度。此外，还从尸体遗骸中采集了 56 个头发样本和 19 个指甲样本，并进行了同样的分析：总体而言，骸骨化个体和保存完好的个体之间在所有基质上都存在显著的统计学差异（p < 0.05）。尽管人们认为保存下来的遗体会比骸骨化的遗体显示出更高的元素浓度，但这一假设并未得到证实：作者认为，随着时间的推移，埋葬条件的变化可能会使软组织解体，即使它们最初因化学元素的存在而被保存下来。应考虑在全球范围内开展类似的研究，因为这些研究可以汇集不同的观点，为墓地管理提供更全面、更创新的解决方案。

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引用次数: 0

Lithium affects sodium balance but not intestinal microbiota - studies in Drosophila melanogaster 锂会影响钠平衡，但不会影响肠道微生物群--黑腹果蝇研究

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-18 DOI: 10.1016/j.jtemb.2024.127548

Katharina Jans , Tobias Jöckel , Jakob von Frieling , Ignacio R. Ipharraguerre , Thomas Roeder , Kai Lüersen , Gerald Rimbach

Background

The trace element lithium (Li) is known for its therapeutic mood-stabilizing application in humans, but also for its various bioactivities, which have been uncovered in model organisms. According to the literature, Li may interfere with the homeostasis of other minerals in mammals, namely sodium, calcium and magnesium. In addition, Li was found to influence the composition and diversity of the intestinal microbiota in vertebrates, an observation that may be related to the many bioactivities of Li.

Methods

Based on these previous findings, we employed the model organism Drosophila melanogaster to decipher whether Li exhibits similar bioactivities in invertebrates. First, we examined the influence of increasing dietary Li supply (0 −100 mM LiCl) on the status of Li and ten other minerals via Inductively coupled plasma - mass spectrometry (ICP-MS) in heads and remaining body parts of the three wildtype strains w¹¹¹⁸, Oregon-R-C and Canton-S. In addition, we investigated the potential impact of Li feeding (0, 0.1, 1 mM LiCl) on the total bacterial load, α- and β-diversity via real-time quantitative polymerase chain reaction (RT q-PCR) and 16S rDNA sequencing in the intestines of female w¹¹¹⁸.

Results

Our observations revealed that Li accumulates linearly in both sexes and all body parts of the three Drosophila strains as the dietary Li supply increases. While the status of most elements remained unchanged, the sodium levels of the fly also correlated positively with the Li content of the diet. The intestinal microbiota, however, remained largely unaffected by Li feeding in terms of both, bacterial load and diversity.

Conclusion

These findings support the hypothesis that elevating the Li supply affects sodium homeostasis in Drosophila, a finding coherent with observations in mammals. Furthermore, our data opposes a possible involvement of the bacterial intestinal colonization in the bioactivity of Li in Drosophila.

背景：微量元素锂（Li）因其对人类稳定情绪的治疗作用而闻名，同时也因其在模式生物体中发现的各种生物活性而闻名。根据文献记载，锂可能会干扰哺乳动物体内其他矿物质（即钠、钙和镁）的平衡。此外，研究还发现锂会影响脊椎动物肠道微生物群的组成和多样性，这可能与锂的多种生物活性有关：方法：基于这些先前的发现，我们利用黑腹果蝇这一模式生物来解读 Li 是否在无脊椎动物中具有类似的生物活性。首先，我们通过电感耦合等离子体质谱法（ICP-MS）检测了w1118、俄勒冈-R-C和Canton-S三个野生型品系的头部和其余身体部位中锂离子和其他十种矿物质的状况。此外，我们还通过实时定量聚合酶链式反应（RT q-PCR）和 16S rDNA 测序研究了喂食锂（0、0.1、1 mM 氯化锂）对雌性 w1118 肠道中细菌总数、α- 和 β-多样性的潜在影响：我们的观察结果表明，随着膳食中锂离子供应量的增加，锂离子在三种果蝇品系的雌雄和所有身体部位都呈线性累积。虽然大多数元素的状态保持不变，但果蝇体内的钠含量也与膳食中的锂含量呈正相关。然而，肠道微生物群在细菌负荷和多样性方面基本不受锂饲喂的影响：这些发现支持了提高锂供应量会影响果蝇体内钠稳态的假设，这一发现与在哺乳动物体内的观察结果一致。此外，我们的数据反对细菌肠道定植可能参与果蝇体内 Li 的生物活性。

{"title":"Lithium affects sodium balance but not intestinal microbiota - studies in Drosophila melanogaster","authors":"Katharina Jans , Tobias Jöckel , Jakob von Frieling , Ignacio R. Ipharraguerre , Thomas Roeder , Kai Lüersen , Gerald Rimbach","doi":"10.1016/j.jtemb.2024.127548","DOIUrl":"10.1016/j.jtemb.2024.127548","url":null,"abstract":"<div><h3>Background</h3><div>The trace element lithium (Li) is known for its therapeutic mood-stabilizing application in humans, but also for its various bioactivities, which have been uncovered in model organisms. According to the literature, Li may interfere with the homeostasis of other minerals in mammals, namely sodium, calcium and magnesium. In addition, Li was found to influence the composition and diversity of the intestinal microbiota in vertebrates, an observation that may be related to the many bioactivities of Li.</div></div><div><h3>Methods</h3><div>Based on these previous findings, we employed the model organism <em>Drosophila melanogaster</em> to decipher whether Li exhibits similar bioactivities in invertebrates. First, we examined the influence of increasing dietary Li supply (0 −100 mM LiCl) on the status of Li and ten other minerals via Inductively coupled plasma - mass spectrometry (ICP-MS) in heads and remaining body parts of the three wildtype strains <em>w</em><sup><em>1118</em></sup>, Oregon-R-C and Canton-S. In addition, we investigated the potential impact of Li feeding (0, 0.1, 1 mM LiCl) on the total bacterial load, α- and β-diversity via real-time quantitative polymerase chain reaction (RT q-PCR) and 16S rDNA sequencing in the intestines of female <em>w</em><sup><em>1118</em></sup>.</div></div><div><h3>Results</h3><div>Our observations revealed that Li accumulates linearly in both sexes and all body parts of the three <em>Drosophila</em> strains as the dietary Li supply increases. While the status of most elements remained unchanged, the sodium levels of the fly also correlated positively with the Li content of the diet. The intestinal microbiota, however, remained largely unaffected by Li feeding in terms of both, bacterial load and diversity.</div></div><div><h3>Conclusion</h3><div>These findings support the hypothesis that elevating the Li supply affects sodium homeostasis in <em>Drosophila</em>, a finding coherent with observations in mammals. Furthermore, our data opposes a possible involvement of the bacterial intestinal colonization in the bioactivity of Li in <em>Drosophila</em>.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127548"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nephropathy induced by cisplatin results from mitochondrial disruption, impaired energy metabolism, altered expression of renal transporters, and accumulation of urinary toxins 顺铂诱发的肾病是线粒体破坏、能量代谢受损、肾脏转运体表达改变和尿毒素积累的结果。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-18 DOI: 10.1016/j.jtemb.2024.127553

Mingkang Zhang , Jianping Zhang , Yanrong Ma , Yongwen Jin , Yile Li , Xin’an Wu

Background

The administration of platinum-based drugs such as cisplatin and its derivatives, which are frequently used during clinical chemotherapy, is highly restricted due to the incidence of nephrotoxicity. The present study focused on investigating cisplatin-induced nephrotoxicity from the perspective of energy metabolism, renal transporter expression and urinary toxin accumulation.

Methods

This study investigated cisplatin's toxic effects, including nephrotoxicity, cardiotoxicity, hepatotoxicity, pulmonary toxicity, and splenotoxicity. We used transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to characterize the accumulation of cisplatin in the kidney and the structure of renal mitochondria. The production of reactive oxygen species (ROS) induced by cisplatin in renal tubular epithelial cells was evaluated by in vitro experiments, and apoptosis of renal tubular epithelial cells and alterations to the renal microvasculature were assessed. Metabolites associated with the glycolytic and tricarboxylic acid pathways were measured, and renal transporters expression, autophagy, and urinary toxins (UTs) accumulation were also assessed.

Results

Our results reveal that cisplatin-induced varying degrees of damage to the heart, liver, spleen, lungs, and kidneys, including inflammatory and fibrotic damage. Accumulation of cisplatin in renal mitochondria disrupted mitochondrial structure and mitochondrial function, as evidenced by decreased levels of glucose 6-phosphate and ribose 5-phosphate and elevated levels of isocitric acid. Cisplatin-induced accumulation of ROS in renal tubular epithelial cells led to apoptosis and, ultimately, constriction or loss of renal microvasculature. Furthermore, dysregulation of renal transporter expression, activation of autophagy and increased accumulation of UTs was observed.

Conclusion

Accumulation of cisplatin in the kidney led to damage to mitochondrial structure and function, apoptosis of renal tubular epithelial cells, constriction or loss of renal microvasculature, dysfunction of renal transporters, activation of autophagy, and accumulation of UTs.

背景：顺铂及其衍生物等铂类药物是临床化疗中经常使用的药物，但由于其肾毒性的发生率较高，因此其用药受到很大限制。本研究主要从能量代谢、肾脏转运体表达和尿毒素蓄积的角度研究顺铂诱导的肾毒性：本研究探讨了顺铂的毒性作用，包括肾毒性、心脏毒性、肝毒性、肺毒性和脾毒性。我们使用透射电子显微镜（TEM）和扫描电子显微镜（SEM）分析了顺铂在肾脏中的蓄积和肾线粒体的结构。体外实验评估了顺铂在肾小管上皮细胞中诱导产生的活性氧（ROS），并评估了肾小管上皮细胞的凋亡和肾微血管的改变。测定了与糖酵解和三羧酸途径相关的代谢物，还评估了肾脏转运体的表达、自噬和尿毒素（UTs）的积累：结果：我们的研究结果表明，顺铂会对心脏、肝脏、脾脏、肺脏和肾脏造成不同程度的损伤，包括炎症和纤维化损伤。顺铂在肾线粒体中的蓄积破坏了线粒体结构和线粒体功能，表现为 6-磷酸葡萄糖和 5-磷酸核糖水平的降低以及异柠檬酸水平的升高。顺铂诱导的 ROS 在肾小管上皮细胞中积累，导致细胞凋亡，最终导致肾微血管收缩或丧失。此外，还观察到肾脏转运体表达失调、自噬激活和UTs积累增加：结论：顺铂在肾脏中的蓄积导致线粒体结构和功能受损、肾小管上皮细胞凋亡、肾微血管收缩或丧失、肾转运体功能失调、自噬激活和UTs蓄积。

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引用次数: 0

The integrated effect of roflumilast and selenium nanoparticles on nephrotoxicity generated by cisplatin through the regulation of the antioxidant and apoptotic pathways 罗氟司特和纳米硒粒子通过调节抗氧化和细胞凋亡途径对顺铂产生的肾毒性的综合影响

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology

Pub Date : 2024-10-18 DOI: 10.1016/j.jtemb.2024.127555

Nashwa Barakat , Ehab Ismail , Faten Zahran

Aim

The current investigations aimed to investigate the potential synergistic effect of Roflumilast (ROF) and Selenium nanoparticles (SeNPs) administration on Cisplatin (Cis) -induced nephrotoxicity.

Materials and methods

Fifty male rats were divided into five groups; Control group: animals were administered 0.9 % saline solution. Cis group: animals were injected with a single dose of 6 mg/kg. ROF group: Rats received a dosage of 1.2 mg/kg orally daily for 11 days. SeNPs group: animals orally received 0.5 mg/kg of ROF daily for 11 days. The ROF + SeNPs group was administered both after receiving a Cis injection for 11 days. Animals were sacrificed at 5 and 11 days, and the urine and blood samples were collected on day 5 and day 11 for chemical analysis, while kidney samples were obtained for molecular, histological, and immunohistochemical studies.

Results

The levels of serum creatinine, Blood urea nitrogen (BUN), and total protein were elevated in the Cis group compared to the control group (p < 0.05). While the combination of ROF and SeNPs dramatically decreased these values after 5 and 11 days (p < 0.05). In addition, Cis caused renal oxidative stress by elevating MDA levels and suppressing the activities of SOD, GSH, and CAT. Similarly, these effects were modulated by ROF and SeNPs after 11 days (p < 0.05). Furthermore, the concurrent administration of ROF and SeNPs resulted in a significant increase in the expression of HO-1, Nrf2, and Bcl2, while decreasing the expression of BAX and IL-6 compared to the Cis group after 11 days (P < 0.05).

Conclusion

The study showed that both ROF and SeNPs had significant therapeutic potential in reducing the pathological alterations caused by Cis.

目的：本研究旨在探讨服用罗氟司特（ROF）和纳米硒颗粒（SeNPs）对顺铂（Cis）诱导的肾毒性的潜在协同作用：将 50 只雄性大鼠分为 5 组：对照组：给动物注射 0.9 % 的生理盐水。顺铂组：动物注射单剂量 6 毫克/千克。ROF 组：大鼠每天口服 1.2 毫克/千克，连续 11 天。SeNPs 组：动物每天口服 0.5 毫克/千克 ROF，共 11 天。ROF + SeNPs 组在接受顺式注射 11 天后同时给药。动物分别在第 5 天和第 11 天被处死，并在第 5 天和第 11 天采集尿液和血液样本进行化学分析，同时采集肾脏样本进行分子、组织学和免疫组化研究：结果：与对照组相比，顺式组的血清肌酐、血尿素氮（BUN）和总蛋白水平升高（P < 0.05）。而在 5 天和 11 天后，ROF 和 SeNPs 的组合能显著降低这些数值（P < 0.05）。此外，Cis 通过提高 MDA 水平和抑制 SOD、GSH 和 CAT 的活性引起肾脏氧化应激。同样，在 11 天后，ROF 和 SeNPs 也能调节这些效应（p < 0.05）。此外，与顺式组相比，同时给予 ROF 和 SeNPs 11 天后，HO-1、Nrf2 和 Bcl2 的表达量显著增加，而 BAX 和 IL-6 的表达量则有所减少（P < 0.05）：研究表明，ROF 和 SeNPs 在减轻 Cis 引起的病理改变方面具有显著的治疗潜力。

{"title":"The integrated effect of roflumilast and selenium nanoparticles on nephrotoxicity generated by cisplatin through the regulation of the antioxidant and apoptotic pathways","authors":"Nashwa Barakat , Ehab Ismail , Faten Zahran","doi":"10.1016/j.jtemb.2024.127555","DOIUrl":"10.1016/j.jtemb.2024.127555","url":null,"abstract":"<div><h3>Aim</h3><div>The current investigations aimed to investigate the potential synergistic effect of Roflumilast (ROF) and Selenium nanoparticles (SeNPs) administration on Cisplatin (Cis) -induced nephrotoxicity.</div></div><div><h3>Materials and methods</h3><div>Fifty male rats were divided into five groups; Control group: animals were administered 0.9 % saline solution. Cis group: animals were injected with a single dose of 6 mg/kg. ROF group: Rats received a dosage of 1.2 mg/kg orally daily for 11 days. SeNPs group: animals orally received 0.5 mg/kg of ROF daily for 11 days. The ROF + SeNPs group was administered both after receiving a Cis injection for 11 days. Animals were sacrificed at 5 and 11 days, and the urine and blood samples were collected on day 5 and day 11 for chemical analysis, while kidney samples were obtained for molecular, histological, and immunohistochemical studies.</div></div><div><h3>Results</h3><div>The levels of serum creatinine, Blood urea nitrogen (BUN), and total protein were elevated in the Cis group compared to the control group <em>(p < 0.05).</em> While the combination of ROF and SeNPs dramatically decreased these values after 5 and 11 days <em>(p < 0.05).</em> In addition, Cis caused renal oxidative stress by elevating MDA levels and suppressing the activities of SOD, GSH, and CAT. Similarly, these effects were modulated by ROF and SeNPs after 11 days <em>(p < 0.05).</em> Furthermore, the concurrent administration of ROF and SeNPs resulted in a significant increase in the expression of HO-1, Nrf2, and Bcl2, while decreasing the expression of BAX and IL-6 compared to the Cis group after 11 days <em>(P < 0.05).</em></div></div><div><h3>Conclusion</h3><div>The study showed that both ROF and SeNPs had significant therapeutic potential in reducing the pathological alterations caused by Cis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127555"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515474","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}

引用次数: 0