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Environmental exposures to lead, mercury, cadmium, manganese, and arsenic and obesity in Korean adults: Korean National Environmental Health Survey 2009–2017 韩国成年人铅、汞、镉、锰和砷的环境暴露与肥胖:2009-2017年韩国国家环境健康调查
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-01 DOI: 10.1016/j.jtemb.2025.127771
Jeongwon Ock , Choong-Hee Park , Yoon-Hyeong Choi

Background

Obesity in adults has substantially increased, and the proportion of obese adults worldwide is estimated to exceed 50 % by 2030.

Objective

This study aims to evaluate the association between heavy metal exposure and obesity in the general adult population in Korea.

Methods

We used data from 14832 general adults from the Korean National Environmental Health Survey (KoNEHS) 2009–2017 with measures of heavy metals in blood and urine samples. Survey linear regression or survey logistic regression models were performed to assess the associations of blood lead, cadmium, and mercury, and urine arsenic and manganese with body mass index or obesity.

Results

After adjustment for confounders, participants in the highest quintile of blood lead and mercury had significantly higher odds of obesity compared to those in the lowest quintile (OR: 1.22 (95 % CI: 1.07–1.44); 2.17 (95 % CI: 1.87–2.51)) with dose-response relationships (both P for trend < 0.001). For blood manganese, participants in the third quintile had significantly higher odds of obesity (1.33 (95 % CI: 1.06–1.67)). There was a marginally significant increase in odds of underweight among those in the third quintile of urine arsenic compared to those in the lowest quintile (1.43 (95 % CI: 0.77–2.66)). There was no association between the quintiles of urine cadmium and arsenic levels and obesity.

Conclusion

We provide evidence of a dose-response association between lead and mercury exposure and an increased risk of obesity in Korean adults. Exposure to manganese at moderate concentrations was associated with obesity. In addition, exposure to arsenic was marginally associated with an increased risk of underweight. Additional prospective studies are required to elucidate the effects of heavy metals on obesity.
背景:成人肥胖已大幅增加,到2030年,全球肥胖成年人的比例估计将超过50% %。目的:本研究旨在评估韩国普通成年人重金属暴露与肥胖之间的关系。方法:我们使用了2009-2017年韩国国家环境健康调查(KoNEHS)中14832名普通成年人的数据,并测量了血液和尿液样本中的重金属。采用调查线性回归或调查逻辑回归模型来评估血铅、镉和汞、尿砷和锰与体重指数或肥胖的关系。结果:在调整混杂因素后,血铅和汞含量最高的五分位数的参与者与最低五分位数的参与者相比,肥胖的几率显著更高(OR: 1.22(95 % CI: 1.07-1.44);2.17(95 % CI: 1.87-2.51))与剂量-反应关系(趋势P均< 0.001)。对于血锰,第三个五分位数的参与者有显著更高的肥胖几率(1.33(95 % CI: 1.06-1.67))。与尿砷含量最低的五分之一组相比,尿砷含量第三五分之一组体重不足的几率略有显著增加(1.43(95 % CI: 0.77-2.66))。尿液中镉和砷含量的五分位数与肥胖之间没有关联。结论:我们提供的证据表明,铅和汞暴露与韩国成年人肥胖风险增加之间存在剂量反应关联。中等浓度的锰暴露与肥胖有关。此外,接触砷与体重不足的风险增加有轻微关联。需要更多的前瞻性研究来阐明重金属对肥胖的影响。
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引用次数: 0
Ferroptosis-targeting compounds modulate cancer cell cytotoxicity and migration: Insights from in vitro and in silico analyses 以凋亡铁为目标的化合物调节癌细胞的细胞毒性和迁移:来自体外和计算机分析的见解。
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-29 DOI: 10.1016/j.jtemb.2025.127770
Kalimuthu Kalishwaralal , Prajakta Patil , Aniket Mali

Objective

Ferroptosis is an iron-dependent, non-apoptotic form of metabolic cell death driven by lipid peroxidation. While Glutathione Peroxidase 4 (GPX4) is the canonical ferroptosis suppressor, recent evidence highlights additional selenoproteins, including Thioredoxin Reductase 1 (TXNRD1) and Peroxiredoxin 6 (PRDX6), as critical modulators of ferroptotic sensitivity. We compared three mechanistically distinct ferroptosis inducers, RSL3 (a covalent GPX4 inhibitor), auranofin (a TXNRD1 inhibitor), and artesunate (ART; a pro-oxidant derivative of artemisinin), in MDA-MB231, A549 and HepG2 cell lines.

Method

Cell viability (MTT) and wound-healing assays quantified cytotoxic and anti-migratory effects. Our inhibitor study using Ferrostatin-1(Ferro) and Liproxstatin-1(Lipo), in combination with ferroptosis inducers, confirmed the specificity of ferroptosis. Beyond GPX4, TXNRD1 and PRDX6 constitute a complementary selenium-dependent axis safeguarding cancer cells from ferroptosis. Dual targeting of GPX4 and TXNRD1, or disruption of PRDX6-mediated selenium trafficking, potentiates ferroptosis death and impedes metastatic traits.

Results

Using in silico methods, we confirmed the interaction between drug and protein molecules. Among the tested compounds, RSL3 and auranofin exhibited strong binding affinity towards all the targeted proteins, including GPX4, TXNRD1, and PRDX6, suggesting their potential as effective ferroptosis pathway inhibitors.

Conclusions

These findings nominate multi-selenoproteins inhibition as a promising strategy to overcome ferroptosis resistance.
目的:铁死亡是一种由脂质过氧化引起的铁依赖性、非凋亡形式的代谢性细胞死亡。虽然谷胱甘肽过氧化物酶4 (GPX4)是典型的铁下沉抑制因子,但最近的证据强调了其他硒蛋白,包括硫氧还蛋白还原酶1 (TXNRD1)和过氧化物还蛋白6 (PRDX6),是铁下沉敏感性的关键调节剂。我们在MDA-MB231、A549和HepG2细胞系中比较了三种机制不同的铁凋亡诱导剂,RSL3(一种共价GPX4抑制剂)、金嘌呤(一种TXNRD1抑制剂)和青蒿素(一种促氧化衍生物)。方法:细胞活力(MTT)和创面愈合测定定量细胞毒性和抗迁移作用。我们的抑制剂研究使用铁他汀-1(Ferro)和利普司他汀-1(Lipo)联合铁下垂诱导剂,证实了铁下垂的特异性。除了GPX4, TXNRD1和PRDX6构成了一个互补的硒依赖轴,保护癌细胞免于铁凋亡。GPX4和TXNRD1的双重靶向,或prdx6介导的硒运输中断,增强了铁中毒死亡并阻碍了转移特性。结果:用计算机方法证实了药物与蛋白质分子的相互作用。在所测试的化合物中,RSL3和金嘌呤与GPX4、TXNRD1和PRDX6等所有靶蛋白均表现出较强的结合亲和力,提示它们可能是有效的铁凋亡途径抑制剂。结论:这些发现表明多硒蛋白抑制是克服铁下垂耐药性的有希望的策略。
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引用次数: 0
Deciphering the impact of essential elements on spermatozoa quality and seminal protein integrity- an in vitro and in silico study 解读基本元素对精子质量和精液蛋白完整性的影响——体外和计算机研究。
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-27 DOI: 10.1016/j.jtemb.2025.127772
Parameswari R. , Jesu Jaya Sudan R. , Lesitha Jeeva Kumari J. , Madhan Kumar P. , Babujanarthanam R.
<div><h3>Background</h3><div>Essential Elements (EEs) such as calcium, zinc, selenium, magnesium, copper, sodium, and potassium are essential for spermatogenesis. They maintain seminal proteins, especially semenogelin and sperm morphology, which are followed by spermatozoa ejaculation to reach the egg for successful conception. In addition, these elements serve as nutrients/cofactors during ejaculation and enhance spermatogenic rapid progressive motility with sustained sperm integrity.</div></div><div><h3>Aim</h3><div>The current study sought to determine the relationship of essential elements (calcium, zinc, selenium, magnesium, copper, sodium, and potassium) between these three major components of sperm morphology, quality, and integrity via seminal proteins, as an <em>in vitro</em> and <em>in silico</em> study.</div></div><div><h3>Methodology</h3><div>With appropriate institutional approval, 116 individuals aged 25–39 were divided into normozoospermic (N = 58) and teratozoospermic (N = 58). The study volunteers were selected based on their andrology profile using Computer-Assisted Semen Analysis. This was followed by an atomic absorption spectrometer for essential element quantification, Enzyme Linked Immune Sorbent Assay (ELISA) for testosterone measurement, lipid peroxidation by malondialdehyde (MDA) analysis, sperm chromatin structure assay (SCSA) and acridine orange (AO) staining procedures were used for sperm DNA fragmentation index (DFI). In addition, computational analysis was done to predict ion binding sites on the seminal protein semenogelin.</div></div><div><h3>Results</h3><div>Our results showed the concentration of essential elements to be comparatively lower in teratozoospermic subjects than in normozoospermic (zinc> calcium >magnesium> selenium) individuals with a significant (p < 0.001 &p < 0.05) correlation. Morphological analysis revealed that teratozoospermia subjects have sperms with altered morphology, directly correlated (p < 0.001& p < 0.05) with reduced zinc, calcium, and selenium due to fragmented DNA and reduced motility. The correlation of semen parameters and essential elements revealed a direct impact of these elements on sperm motility, DNA profile, total antioxidant capacity (TAC), and testosterone levels. In addition, <em>an in silico</em> study confirms the presence of metal binding motifs like D-H-D, C-X-C, and G-K-[TS]-T for Zn, Mg, and Se ions in the seminal protein semenogelin in normozoospermic than teratozoospermic.</div></div><div><h3>Conclusion</h3><div>Our study's findings have significant implications for male reproductive health. We propose that the presence and adequate concentration of essential elements, notably zinc, calcium, magnesium, and selenium, are crucial for maintaining sperm morphology. The computational discovery of semenogelin sequences such as D-H-D, C-X-C, and G-K-[TS]-T, which promote robust sperm integrity, further supports this. These findings could gu
背景:必需元素(EEs)如钙、锌、硒、镁、铜、钠和钾是精子发生所必需的。它们维持精液蛋白,尤其是精胶质和精子形态,随后精子射精到达卵子,成功受孕。此外,这些元素在射精过程中作为营养/辅助因子,增强精子生成的快速进展动力,保持精子的完整性。目的:目前的研究旨在通过精子蛋白确定精子形态、质量和完整性的三个主要组成部分之间的基本元素(钙、锌、硒、镁、铜、钠和钾)之间的关系,作为体外和计算机研究。方法:经机构批准,将116例25-39岁的患者分为正常精子组(N = 58)和畸形精子组(N = 58)。研究志愿者是根据他们使用计算机辅助精液分析的男科特征来选择的。随后使用原子吸收光谱仪进行必需元素定量,酶联免疫吸附试验(ELISA)进行睾酮测定,丙二醛(MDA)脂质过氧化分析,精子染色质结构测定(SCSA)和吖啶橙(AO)染色程序进行精子DNA碎片指数(DFI)测定。此外,还进行了计算分析,预测了精液蛋白semenogelin上的离子结合位点。结果:我们的研究结果显示,畸形精子患者体内必需元素(锌b>钙>镁>硒)的浓度明显低于正常精子患者(p )。结论:我们的研究结果对男性生殖健康具有重要意义。我们认为必需元素的存在和足够的浓度,特别是锌、钙、镁和硒,对维持精子形态至关重要。精液凝胶序列如D-H-D、C-X-C和G-K-[TS]- t的计算发现进一步支持了这一观点。这些发现可以指导未来的研究和临床实践,强调了成功男性生殖的基本要素的重要性。
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引用次数: 0
Improvement of well-being and fish fillet nutrient value of a vulnerable minor carp, Puntius sarana (Hamilton, 1822): A result of incorporating Fe trace element in diet through α-Fe2O3 nanoparticles as dietary supplements α-Fe2O3纳米颗粒作为膳食补充剂,在饲料中添加微量铁元素,改善了脆弱的小鲤鱼Puntius sarana (Hamilton, 1822)的健康状况和鱼片营养价值。
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-26 DOI: 10.1016/j.jtemb.2025.127764
Sampa Mondal , Nilanjana Chatterjee , Baibaswata Bhattacharjee
Iron oxide (α-Fe2O3) nanoparticles (NPs) of different sizes are synthesized using a simple wet chemical method and are used as dietary supplements at rates of zero (control), 1, 2, 3, and 4 g/kg diet throughout the year in Puntius sarana to study its consequences on the growth, haematological parameters, biochemical or blood metabolic parameters, ionoregulatory characteristics, plasma lysozyme activity, antioxidant biomarkers, and fish flesh nutrient composition of the fish. The experiment is designed for bulk and nano iron oxides having particle sizes of 10, 12, 15, and 18 nm. When the concentration of NPs rises to 4 g/kg food and/or the size of the NPs is minimized up to 10 nm, the length, hemoglobin, red blood corpuscle, hematocrit, protein levels, plasma lysozyme, catalase, superoxidase dismutase, and glutathione peroxidase in the blood and crude protein of the fish flesh of P. sarana increase upto 32 cm, 9.73 g/dL, 3.22 million/mm3, 29.19 %, 7.78 g/dL, 0.97 ng/mL, 86.69 ng/mL, 39.81 μmol/min/mg protein, 44.96 U/mL, and 18.59 % respectively; and melanodialdehyde and Crude fat decrease upto 41.71 nmol TBARS/g tissue and 2.90 %, respectively. No significant changes in the values of survival rate, white blood cell, blood glucose, serum glutamic pyruvic transaminase, and serum glutamic oxaloacetic transaminase, sodium, potassium, chloride, crude moisture, and crude ash are observed between the control and treatments. Results indicate that NPs based dietary supplementations provide beneficial conditions of well-being of the fish due to increased absorption of iron in its nano form into the fish body via dietary supplements.
采用简单的湿化学方法合成了不同大小的氧化铁(α-Fe2O3)纳米颗粒(NPs),并在全年中将其作为无(对照)、1、2、3和4 g/kg饲料的膳食补充剂,研究其对鱼的生长、血液学参数、生化或血液代谢参数、离子调节特性、血浆溶菌酶活性、抗氧化生物标志物和鱼肉营养成分的影响。该实验设计用于颗粒尺寸为10、12、15和18 nm的大块和纳米氧化铁。当NPs的浓度上升到4 克/公斤食物和/或NPs是最小的大小10 纳米,长度,血红蛋白,红血细胞比容、蛋白质含量、血浆溶菌酶,过氧化氢酶,superoxidase歧化酶、谷胱甘肽过氧化物酶在鱼的血液和粗蛋白的肉p sarana增加到32 厘米,9.73 g / dL 322万/ mm3 % 29.19,7.78 g / dL  0.97 ng / mL, 86.69 ng / mL, 39.81μ摩尔/分钟/毫克蛋白44.96 U / mL,和分别为18.59 %;黑二醛和粗脂肪分别降低41.71 nmol TBARS/g组织和2.90 %。对照组与处理间存活率、白细胞、血糖、血清谷丙转氨酶、血清谷草转氨酶、钠、钾、氯、粗水分、粗灰分等指标均无显著变化。结果表明,基于NPs的膳食补充剂通过膳食补充剂增加了铁的纳米形式进入鱼类体内的吸收,为鱼类的健康提供了有益的条件。
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引用次数: 0
Zn2 + alleviates ischemia/reperfusion injury in H9c2 cells by modulating mitochondrial biogenesis and dynamics via MCU Zn2 +通过MCU调控线粒体生物发生和动力学,减轻H9c2细胞缺血再灌注损伤。
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-26 DOI: 10.1016/j.jtemb.2025.127769
Bingyu Wang , Bohan Xing , Luyao Huang , Xiaoyi Li , Xiyun Bian , Jinkun Xi

Background

Zinc is an essential nutrient implicated in cardiovascular health. This study investigates whether Zn2+ protects H9c2 cells by regulating mitochondrial biogenesis, dynamics, and calcium homeostasis via the mitochondrial calcium uniporter (MCU).

Methods

The I/R model were established using simulated ischemia and reoxygenation as previous reported, and cells were then treated with MCU siRNA. Biochemical kits, inductively coupled plasma mass spectrometry (ICP-MS), RT-qPCR, and transmission electron microscopy were used to assess the effects of Zn2+ on cell viability, cytotoxicity, Zn2+ and ATP content, NAD⁺/NADH ratio, mtDNA copy number, and mitochondrial morphological changes following myocardial I/R. Confocal microscopy and fluorescence microscopy were used to observe the fluorescence changes of Zn2+, mitochondrial membrane potential, protein expression, and mitochondrial Ca2+. The effects of Zn2+ on protein expression levels were evaluated using molecular docking and Western blot analysis.

Results

Compared to the Control group, the I/R group exhibited decreased cell viability, and increased cytotoxicity. Intracellular and mitochondrial Zn2+ levels were reduced, accompanied by mitochondrial dysfunction and an increase in mitochondrial Ca2+ content. The expression levels of mitochondrial biosynthesis proteins SIRT1, PGC-1α, NRF1, and TFAM, mitochondrial fusion proteins OPA1, MFN1, and MFN2, as well as MCUb gene and protein expression were downregulated. Conversely, the expression of mitochondrial fission proteins DRP1 and FIS1, along with MCU, MICU1, and MICU2 proteins, was upregulated. Exogenous Zn2+ treatment reversed these alterations. MCU silencing by siRNA further enhanced the protection effects of Zn2+.

Conclusions

I/R induced damage in H9c2 cells and mitochondrial dysfunction. Zn2+ protected H9c2 cells against I/R injury by regulating mitochondrial biogenesis, mitochondrial dynamics, and Ca2+ homeostasis via the MCU, with this protective effect potentially associated with the entire MCU complex.
背景:锌是一种涉及心血管健康的必需营养素。本研究探讨Zn2+是否通过线粒体钙单转运蛋白(MCU)调控线粒体生物发生、动力学和钙稳态来保护H9c2细胞。方法:采用先前报道的模拟缺血再氧化法建立I/R模型,并用MCU siRNA处理细胞。采用生化试剂盒、电感耦合等离子体质谱(ICP-MS)、RT-qPCR和透射电镜检测Zn2+对心肌I/R后细胞活力、细胞毒性、Zn2+和ATP含量、NAD + /NADH比值、mtDNA拷贝数和线粒体形态变化的影响。用共聚焦显微镜和荧光显微镜观察Zn2+、线粒体膜电位、蛋白表达和线粒体Ca2+的荧光变化。利用分子对接和Western blot分析Zn2+对蛋白表达水平的影响。结果:与对照组相比,I/R组细胞活力下降,细胞毒性增加。细胞内和线粒体Zn2+水平降低,并伴有线粒体功能障碍和线粒体Ca2+含量升高。线粒体生物合成蛋白SIRT1、PGC-1α、NRF1、TFAM表达水平下调,线粒体融合蛋白OPA1、MFN1、MFN2表达水平下调,MCUb基因及蛋白表达下调。相反,线粒体裂变蛋白DRP1和FIS1以及MCU、MICU1和MICU2蛋白的表达上调。外源Zn2+处理逆转了这些改变。siRNA对MCU的沉默进一步增强了Zn2+的保护作用。结论:I/R诱导H9c2细胞损伤和线粒体功能障碍。Zn2+通过MCU调节线粒体生物发生、线粒体动力学和Ca2+稳态,保护H9c2细胞免受I/R损伤,这种保护作用可能与整个MCU复合物有关。
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引用次数: 0
Antiviral activity of silver and selenium nanoparticles against SARS-CoV-2: A comprehensive systematic review of in vitro, in vivo, and clinical evidence 银和硒纳米颗粒对SARS-CoV-2的抗病毒活性:对体外、体内和临床证据的全面系统综述
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-25 DOI: 10.1016/j.jtemb.2025.127768
João Marcos Carvalho-Silva, Andréa Cândido dos Reis

Objectives

This systematic review aimed to answer the following question: "Do silver (AgNPs) and selenium (SeNPs) nanoparticles, either individually or incorporated into materials and products, exhibit antiviral activity against SARS-CoV-2 strains?"

Methods

This review was registered in PROSPERO and conducted following the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was performed in PubMed, Scopus, Embase, LILACS, ScienceDirect, Google Scholar, and ProQuest in March 2025 to identify studies evaluating the effects of isolated or material-incorporated AgNPs and SeNPs against SARS-CoV-2.

Results

AgNPs and SeNPs exhibit strong virucidal and antiviral activity against SARS-CoV-2 and its Spike glycoprotein, both as isolated nanoparticles and when incorporated into masks, goggles, polymers, sprays, coatings, mouthwashes, and solutions. High efficacy has been demonstrated across in vitro, in vivo, and clinical studies, with enhanced outcomes associated with smaller particle sizes, higher concentrations, and longer contact times.

Conclusion

Both isolated and material-integrated AgNPs and SeNPs exhibit high antiviral and virucidal effectiveness against multiple SARS-CoV-2 strains in vitro, in vivo, and in clinical studies.
本系统综述旨在回答以下问题:“银(AgNPs)和硒(SeNPs)纳米颗粒,无论是单独使用还是结合到材料和产品中,是否表现出对SARS-CoV-2菌株的抗病毒活性?”方法本综述在普洛斯彼罗杂志注册,并按照PRISMA 2020(系统评价和荟萃分析的首选报告项目)指南进行。我们于2025年3月在PubMed、Scopus、Embase、LILACS、ScienceDirect、谷歌Scholar和ProQuest中进行了全面检索,以确定评估分离或材料结合AgNPs和SeNPs对SARS-CoV-2效果的研究。结果agnps和SeNPs对SARS-CoV-2及其Spike糖蛋白均表现出较强的抗病毒活性,无论是作为分离的纳米颗粒,还是被纳入口罩、护目镜、聚合物、喷雾剂、涂料、漱口水和溶液中。在体外、体内和临床研究中都证明了高疗效,并且与更小的颗粒尺寸、更高的浓度和更长的接触时间相关的结果增强。结论分离的AgNPs和材料整合的SeNPs在体外、体内和临床研究中对多种SARS-CoV-2毒株均表现出较高的抗病毒和杀病毒效果。
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引用次数: 0
Ferroptosis and iron homeostasis in chronic obstructive pulmonary disease: Therapeutic opportunities of iron chelators 慢性阻塞性肺疾病的上铁和铁稳态:铁螯合剂的治疗机会
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.jtemb.2025.127766
Suresh Kumar Srinivasamurthy , Piyush Mittal , Ahsas Goyal , Suhas Ballal , Laxmidhar Maharana , Kavita Goyal , Mohit Rana , Haider Ali , Brian Gregory George Oliver , Keshav Raj Paudel , Kamal Dua , Gaurav Gupta

Purpose

To review the role of ferroptosis, an iron-dependent form of regulated cell death, in chronic obstructive pulmonary disease (COPD), and to explore the therapeutic opportunities of iron chelators in mitigating ferroptosis-driven lung injury.

Methods

We performed a structured search of PubMed, Scopus, and Web of Science from inception to Dec 31, 2024, using the terms “ferroptosis,” “iron homeostasis,” “iron chelators,” “lipid peroxidation,” and “COPD.” Of the 86 records identified, 45 met the predefined criteria (relevance to pulmonary iron metabolism, ferroptotic mechanisms, and therapeutic interventions) and were included in the narrative synthesis.

Results

Dysregulated iron handling in COPD leads to increased labile iron pools in airway epithelial cells and alveolar macrophages, promoting Fenton chemistry, reactive oxygen species generation, and lipid peroxidation cascades, which trigger ferroptosis. Classical iron chelators, such as deferoxamine, deferiprone, and deferasirox, have shown efficacy in preclinical models by sequestering redox-active iron and preserving mitochondrial integrity. Novel synthetic chelators and nanoparticle-based delivery systems offer lung-specific iron removal with improved safety. The integration of trace-element biomarkers, including serum ferritin, hepcidin, transferrin saturation, and lipid peroxidation products, provides potential tools for patient stratification and therapy monitoring.

Conclusion

Targeting iron dysregulation and ferroptosis through advanced chelation strategies holds promise as a novel therapeutic approach for COPD. Combining mechanistic insights with precision delivery technologies may enhance treatment efficacy and improve clinical outcomes by mitigating iron-driven oxidative lung injuries.
目的探讨铁中毒(一种铁依赖性的细胞死亡形式)在慢性阻塞性肺疾病(COPD)中的作用,并探讨铁螯合剂在减轻铁中毒引起的肺损伤中的治疗机会。方法我们对PubMed、Scopus和Web of Science从成立到2024年12月31日进行了结构化搜索,使用术语“铁中毒”、“铁稳态”、“铁螯合剂”、“脂质过氧化”和“COPD”。在确定的86例记录中,45例符合预先确定的标准(与肺铁代谢相关,铁下沉机制和治疗干预),并被纳入叙述综合。结果慢性阻塞性肺病患者铁处理失调导致气道上皮细胞和肺泡巨噬细胞中不稳定铁池增加,促进Fenton化学、活性氧生成和脂质过氧化级联反应,从而引发铁死亡。经典的铁螯合剂,如去铁胺、去铁素和去铁素,通过隔离氧化还原活性铁和保持线粒体完整性,在临床前模型中显示出疗效。新型合成螯合剂和纳米颗粒为基础的输送系统提供肺特异性铁去除与提高安全性。微量元素生物标志物的整合,包括血清铁蛋白、肝磷脂、转铁蛋白饱和度和脂质过氧化产物,为患者分层和治疗监测提供了潜在的工具。结论通过先进的螯合策略靶向铁调节失调和铁下垂有望成为COPD治疗的新途径。将机制见解与精确递送技术相结合,可以通过减轻铁驱动的氧化性肺损伤来提高治疗效果和改善临床结果。
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引用次数: 0
Cardiopulmonary injury in hypoxia and selenium: A review 缺氧和硒对心肺损伤的影响
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.jtemb.2025.127767
Lekang Han , Ting Huang , Zhongzhi Zhao , Zhancui Dang
Selenium (Se) is an essential trace element required by the human body, existing in selenium proteins as selenocysteine (Sec) and selenomethionine (SeMet). Through these proteins, Se exerts its biological effects such as free radical metabolism, antioxidant functions, immune response, reproductive functions, apoptosis, and endocrine hormone regulation. Both selenium deficiency and excess are can cause adverse effects on human health. A growing number of evidence highlights the involvement of selenium and its proteins in the development and progression of cardiovascular diseases (CVD). During hypoxia, the body undergoes a series of changes across all organ systems. Among these, the heart, lungs, and brain—due to their high oxygen demand and metabolic activity—demonstrate particularly prominent manifestations of injury. This review summarizes the effects of selenium/selenoproteins on the cardiovascular system, emphasizing new findings on their roles in hypoxic cardiorespiratory injury. This is to provide a scientific basis for preventing and treating high-altitude illnesses from both environmental and nutritional perspectives.
硒(Se)是人体必需的微量元素,以硒半胱氨酸(Sec)和硒代蛋氨酸(SeMet)的形式存在于硒蛋白中。硒通过这些蛋白发挥自由基代谢、抗氧化功能、免疫应答、生殖功能、细胞凋亡和内分泌激素调节等生物学作用。硒缺乏和过量都会对人体健康造成不良影响。越来越多的证据强调了硒及其蛋白质在心血管疾病(CVD)的发生和进展中的作用。在缺氧期间,身体所有器官系统都会发生一系列变化。其中,心脏、肺和大脑——由于它们的高需氧量和代谢活动——表现出特别突出的损伤表现。本文综述了硒/硒蛋白对心血管系统的影响,重点介绍了其在缺氧性心肺损伤中的新发现。从环境和营养两个方面为防治高原病提供科学依据。
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引用次数: 0
Biomarkers of total selenium and selenium species in paired serum and cerebrospinal fluid samples 配对血清和脑脊液样品中总硒和硒种的生物标志物
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.jtemb.2025.127765
Teresa Urbano , Tommaso Filippini , Barbara R. Cardoso , Lauren A. Wise , Giovanna Zamboni , Annalisa Chiari , Giulia Vinceti , Manuela Tondelli , Alessandro Marti , Marcella Malavolti , Marco Vinceti , Bernhard Michalke

Background

The validity of biomarkers to estimate exposure to selenium (Se) species and selenoproteins in the central nervous system (CNS) is not well studied.

Methods

Among 83 Italian participants with mild cognitive impairment, we estimated total Se and single Se species concentrations in paired serum and cerebrospinal fluid (CSF) samples using anion exchange chromatography-inductively coupled plasma-dynamic reaction cell-mass spectrometry. In each matrix (serum and CSF), we assessed associations between: 1) paired Se species and 2) total Se and Se species.

Results

The distribution of Se exposure was comparable to that generally found in European populations. We found few consistent patterns for most biomarkers, including total Se and some Se species. An exception was a positive association between the two matrices for selenoprotein-P-bound Se and the inorganic Se form selenate, and an unexpected inverse association for glutathione-peroxidase-bound Se. Total Se was positively associated with some Se species but inversely associated with other Se species in serum, while in CSF the positive association was stronger and more consistent across various Se species.

Conclusions

Concentrations of total Se and single Se species in serum were not strongly correlated with their respective concentrations in CSF, the gold standard to estimate CNS exposure. Furthermore, total Se and selected Se species showed consistent positive correlations within CSF but not serum. Our results suggest that relying on serum Se concentrations to assess CNS exposure can introduce error in human studies.
生物标志物用于评估硒(Se)种类和硒蛋白在中枢神经系统(CNS)中的暴露的有效性尚未得到很好的研究。方法在83名意大利轻度认知障碍患者中,我们使用阴离子交换色谱-电感耦合等离子体动力学反应细胞-质谱法估计配对血清和脑脊液(CSF)样品中的总硒和单一硒种浓度。在每种基质(血清和脑脊液)中,我们评估了:1)配对硒种和2)总硒和硒种之间的相关性。结果该地区硒暴露分布与欧洲人群相当。我们发现大多数生物标志物(包括总硒和某些硒种)的模式很少一致。一个例外是硒蛋白-p结合的硒和无机硒形成硒酸盐之间的正相关,而谷胱甘肽-过氧化物酶结合的硒出人意料地呈负相关。血清中总硒与某些硒种呈正相关,与其他硒种呈负相关,而脑脊液中各硒种之间的正相关更强且更一致。结论血清中总硒和单种硒浓度与脑脊液中硒浓度无明显相关性,脑脊液是判断中枢神经系统暴露的金标准。此外,总硒和选定硒种在脑脊液中呈一致的正相关,而在血清中没有。我们的研究结果表明,依靠血清硒浓度来评估中枢神经系统暴露可能会在人类研究中引入错误。
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引用次数: 0
Cardioprotective potential of azaleatin against sodium arsenite instigated sub-chronic cardiotoxicity via targeting TLR4/MyD88, JAK1/STAT3, and NF-κB in Sprague Dawley rats azaleatin通过靶向TLR4/MyD88、JAK1/STAT3和NF-κB对亚砷酸钠诱导的Sprague Dawley大鼠亚慢性心脏毒性的心脏保护作用
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-23 DOI: 10.1016/j.jtemb.2025.127763
Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream

Background

Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.

Objectives

The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.

Methodology

Thirty-two rats were apportioned into control, SA (10 mg kg−1), SA (10 mg kg−1) + AZA (25 mg kg−1), and AZA (25 mg kg−1) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.

Findings

SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.

Conclusion

SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.
背景:亚砷酸钠(SA)是一种强致癌物,可引起包括心脏在内的多个器官损伤。Azaleatin (AZA)是一种具有优良生物学特性的新型治疗剂。目的通过生化和组织学指标评价AZA对SA诱导的大鼠亚慢性心脏毒性的缓解作用。方法将32只大鼠分为对照组、SA (10 mg kg−1)、SA (10 mg kg−1)+ AZA (25 mg kg−1)和AZA (25 mg kg−1)暴露组。生化参数通过不同的技术进行评估,包括qRT-PCR, ELISA和已经报道的标准分析。组织学分析证实组织损伤。通过计算机方法重新验证了AZA的治疗潜力。结果发现,sa中毒可上调核因子-κB (NF-κB)、髓样分化初级反应88 (MyD88)、janus激酶1 (JAK1)、toll样受体4 (TLR4)、肿瘤坏死因子-α (TNF-α)、信号转导和转录激活因子3 (STAT3)、白细胞介素-1β (IL-1β)、白细胞介素-6 (IL-6)、环氧化酶-2 (COX-2)的表达,同时增加活性氧(ROS)和丙二醛(MDA)的水平。此外,SA暴露后,谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GSR)、谷胱甘肽s转移酶(GST)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、血红素加氧酶-1 (HO-1)和谷胱甘肽(GSH)活性降低,而肌钙蛋白I、ProBNP、c反应蛋白、LDH、肌钙蛋白-t、BNP和CPK水平升高。此外,SA中毒提高了Bax、Caspase-9和Caspase-3的水平,同时降低了Bcl-2的水平。给药后心脏组织出现组织学损伤。然而,由于其抗炎、抗氧化和抗凋亡的潜力,AZA治疗可以很好地改善心脏毒性。结论sa中毒通过破坏生物化学和组织学参数引起严重的心脏毒性,而AZA能很好地恢复心脏健康状况。总的来说,AZA可以作为一种心脏保护剂来对抗SA诱导的亚慢性心脏毒性。
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引用次数: 0
期刊
Journal of Trace Elements in Medicine and Biology
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