Revealing mercury species-specific transfer and toxicity mechanisms in placental trophoblasts.

Environmental mercury (Hg) follows a biogeochemical cycle resulting in a variety of Hg species. Therefore, human exposure to the three Hg species inorganic Hg via crops and air, methyl Hg through fish consumption and ethyl Hg due to the use as antiseptic agent in medical applications is a rising concern. Especially pregnant women and their developing fetus present a vulnerable population.

α-Tocopherol Long-Chain Metabolite α-T-13'-COOH Exhibits Biphasic Effects on Cell Viability, Induces ROS-Dependent DNA Damage, and Modulates Redox Status in Murine RAW264.7 Macrophages.

Scope: The α-tocopherol long-chain metabolite α-tocopherol-13'-hydroxy-chromanol (α-T-13'-COOH) is a proposed regulatory intermediate of endogenous vitamin E metabolism. Effects of α-T-13'-COOH on cell viability and adaptive stress response are not well understood. The present study aims to investigate the concentration-dependent effects of α-T-13'-COOH on cellular redox homeostasis, genotoxicity, and cytotoxicity in murine RAW264.

Standardizing Nutritional Care for Cancer Patients: Implementation and Evaluation of a Malnutrition Risk Screening.

Introduction: Cancer-related malnutrition is a highly prevalent, yet often overlooked concern in clinical practice. Although cancer-related management guidelines recommend standardized nutritional care, its implementation is scarce. The aim of this study was to investigate the prevalence of malnutrition and the medical need for nutrition counseling in cancer patients employing a novel standardized nutritional management program (containing malnutrition risk screening, nutritional assessment, and counseling).

NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium.

Background: Selenium and zinc are essential trace elements known to regulate cellular processes including redox homeostasis. During inflammation, circulating selenium and zinc concentrations are reduced in parallel, but underlying mechanisms are unknown. Accordingly, we modulated the zinc and selenium supply of HepG2 cells to study their relationship.

Transcriptomics pave the way into mechanisms of cobalt and nickel toxicity: Nrf2-mediated cellular responses in liver carcinoma cells.

Cobalt (Co) and Nickel (Ni) are used nowadays in various industrial applications like lithium-ion batteries, raising concerns about their environmental release and public health threats. Both metals are potentially carcinogenic and may cause neurological and cardiovascular dysfunctions, though underlying toxicity mechanisms have to be further elucidated. This study employs untargeted transcriptomics to analyze downstream cellular effects of individual and combined Co and Ni toxicity in human liver carcinoma cells (HepG2).

Selenium-Enriched Bacteria Mitigate the Age-Associated Degeneration of Cholinergic Neurons in .

Selenium (Se) is an essential trace element for humans and animals, but high-dose supplementation with Se compounds, most notably selenite, may exert cytotoxic and other adverse effects. On the other hand, bacteria, including (), are capable of reducing selenite to red elemental Se that may serve as a safer Se source. Here, we examined how a diet of Se-enriched bacteria affected vital parameters and age-associated neurodegeneration in the model organism ().

Determination of copper status by five biomarkers in serum of healthy women.

Background: The essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism.

Long-term suboptimal dietary trace element supply does not affect trace element homeostasis in murine cerebellum.

The ageing process is associated with alterations of systemic trace element (TE) homeostasis increasing the risk, e.g. neurodegenerative diseases.

Temporal dynamics of muscle mitochondrial uncoupling-induced integrated stress response and ferroptosis defense.

Mitochondria play multifaceted roles in cellular function, and impairments across domains of mitochondrial biology are known to promote cellular integrated stress response (ISR) pathways as well as systemic metabolic adaptations. However, the temporal dynamics of specific mitochondrial ISR related to physiological variations in tissue-specific energy demands remains unknown. Here, we conducted a comprehensive 24-hour muscle and plasma profiling of male and female mice with ectopic mitochondrial respiratory uncoupling in skeletal muscle (m-transgenic, TG).

Selenium, Zinc, and Copper Status of Vegetarians and Vegans in Comparison to Omnivores in the Nutritional Evaluation (NuEva) Study.

Plant-based diets usually contain more nutrient-dense foods such as vegetables, legumes, whole grains, and fruits than a standard Western diet. Yet, the amount and especially the bioavailability of several nutrients, such as trace elements, is supposed to be lower in comparison to diets with consumption of animal-derived foods. Based on this, the Nutritional Evaluation (NuEva) study (172 participants) was initiated to compare the trace element status of omnivores, flexitarians, vegetarians, and vegans.

Selenium-binding protein 1 (SELENBP1) is a copper-dependent thiol oxidase.

Selenium-binding protein 1 (SELENBP1) was reported to act as a methanethiol oxidase (MTO) in humans, catalyzing the conversion of methanethiol to hydrogen peroxide, hydrogen sulfide and formaldehyde. Here, we identify copper ions as essential to this novel MTO activity. Site-directed mutagenesis of putative copper-binding sites in human SELENBP1 produced as recombinant protein in E.

Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P.

Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain.

Simultaneous quantitation of oxidized and reduced glutathione via LC-MS/MS to study the redox state and drug-mediated modulation in cells, worms and animal tissue.

Alterations in reduced and oxidized glutathione (GSH/GSSG) levels represent an important marker for oxidative stress and potential disease progression in toxicological research. Since GSH can be oxidized rapidly, using a stable and reliable method for sample preparation and GSH/GSSG quantification is essential to obtain reproducible data. Here we describe an optimised sample processing combined with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, validated for different biological matrices (lysates from HepG2 cells, C.

Measurement of trace elements in murine liver tissue samples: Comparison between ICP-MS/MS and TXRF.

Background: Trace elements exhibit essential functions in many physiological processes. Thus, for research focusing on trace element homeostasis and metabolism analytical methods allowing for multi-element analyses are fundamental. Small sample amounts may be a big challenge in trace element analyses especially if also other end points want to be addressed in the same sample.

Selenium homeostasis in human brain cells: Effects of copper (II) and Se species.

Background: Both essential trace elements selenium (Se) and copper (Cu) play an important role in maintaining brain function. Homeostasis of Cu, which is tightly regulated under physiological conditions, seems to be disturbed in Alzheimer´s (AD) and Parkinson´s disease (PD) patients. Excess Cu promotes the formation of oxidative stress, which is thought to be a major cause for development and progression of neurological diseases (NDs).

Ferroptosis-modulating small molecules for targeting drug-resistant cancer: Challenges and opportunities in manipulating redox signaling.

Ferroptosis is an iron-dependent cell death program that is characterized by excessive lipid peroxidation. Triggering ferroptosis has been proposed as a promising strategy to fight cancer and overcome drug resistance in antitumor therapy. Understanding the molecular interactions and structural features of ferroptosis-inducing compounds might therefore open the door to efficient pharmacological strategies against aggressive, metastatic, and therapy-resistant cancer.

Side-by-side comparison of recombinant human glutathione peroxidases identifies overlapping substrate specificities for soluble hydroperoxides.

Five out of eight human glutathione peroxidases (GPXs) are selenoproteins, representing proteins that contain selenium as part of the amino acid selenocysteine. The GPXs are important for reducing hydroperoxides in a glutathione-consuming manner and thus regulate cellular redox homeostasis. GPX1, GPX2, and GPX4 represent the three main cytosolic GPXs, but they differ in their expression patterns with GPX1 and GPX4 being expressed ubiquitously, whereas GPX2 is mainly expressed in epithelial cells.

Patient-reported experiences with side effects of kidney cancer therapies and corresponding information flow.

Background: Treatment options for metastatic renal cell carcinoma (mRCC) have improved over recent years. Various therapies for metastatic renal cell carcinoma are currently approved for first and successive lines. Having various treatment options makes it important to reflect how patients experience side effects in the real-world setting.

Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling.

The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear.

The Nutritional Supply of Iodine and Selenium Affects Thyroid Hormone Axis Related Endpoints in Mice.

Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones but additional trace elements such as iron, zinc, and copper are also involved. To compare the primary effects of inadequate intake of selenium and iodine on the thyroid gland, as well as the target organs of thyroid hormones such as liver and kidney, mice were subjected to an eight-week dietary intervention with low versus adequate selenium and iodine supply. Analysis of trace element levels in serum, liver, and kidney demonstrated a successful intervention.

The Trace Element Selenium Is Important for Redox Signaling in Phorbol Ester-Differentiated THP-1 Macrophages.

Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping the immunoregulatory cytokine and lipid mediator profile. How exactly differentiation of monocytes into macrophages influences the expression of the selenoproteome in concert with the Se supply remains obscure. THP-1 monocytes were differentiated with phorbol 12-myristate 13-acetate (PMA) into macrophages and (i) the expression of selenoproteins, (ii) differentiation markers, (iii) the activity of NF-κB and NRF2, as well as (iv) lipid mediator profiles were analyzed.

Ageing-associated effects of a long-term dietary modulation of four trace elements in mice.

Trace elements (TEs) are essential for diverse processes maintaining body function and health status. The complex regulation of the TE homeostasis depends among others on age, sex, and nutritional status. If the TE homeostasis is disturbed, negative health consequences can result, e.

Are trace element concentrations suitable biomarkers for the diagnosis of cancer?

Despite advances in cancer research, cancer is still one of the leading causes of death worldwide. An early diagnosis substantially increases the survival rate and treatment success. Thus, it is important to establish biomarkers which could reliably identify cancer patients.