Heat stress targets and degrades BCR::ABL1 oncoproteins to overcome drug-resistance in Philadelphia chromosome-positive acute lymphoblastic leukemia.

BCR::ABL1 oncofusion protein drives Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL), making it a critical therapeutic target. Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have revolutionized the treatment of Ph+ ALL patients. However, mutations in the kinase domain of BCR::ABL1 commonly impair the sensitivity to TKIs, resulting in drug resistance and poor prognosis in Ph+ ALL.

Strontium and barium in deciduous teeth and infant feeding methods: A birth cohort adjunct study to the Japan environment and children's study.

Deciduous teeth are a unique medium that record exposure to various elements over time, as they are formed during fetal and infantile periods. We aimed to evaluate the association between infant feeding methods and changes in the distribution of Barium (Ba) and Strontium (Sr) in deciduous teeth of children. The current analysis included 216 children around 6-7 years of age whose deciduous central incisor teeth were provided between March 2018 and February 2020, as an adjunct study of the Japan Environment and Children's study.

Toxicological effects of Sb(III), Sb(V), and NMG-Sb(V) in human lung, kidney, and liver cells: cytotoxicity and fibrotic factor induction.

Antimony ecotoxicity studies are often hindered by the incorrect selection of Sb(III) standards and the application of concentrations that do not reflect real environmental exposure. In this study, we used environmentally relevant concentrations of inorganic Sb in its pentavalent [Sb(V)] and trivalent [Sb(III)] oxidation states, as well as the organic species NMG-Sb(V), which is present in Meglumine Antimoniate, to evaluate the effects of Sb on cell viability in human lung (A549), kidney (HEK293), and liver (HepG2) cell lines. Cell viability was assessed in these cells following treatment with 0.

The selenoprotein P/ApoER2 axis facilitates selenium accumulation in selenoprotein P-accepting cells and confers prolonged resistance to ferroptosis.

The essential trace element selenium (Se) plays a significant role in redox homeostasis, while Se is very reactive and has a potent toxicity. Understanding the molecular machinery that supports Se metabolism is important for the both physiological and pathophysiological context. Incorporated Se is translated/transformed in the liver into selenoprotein P (SeP; encoded by Selenop), an extracellular Se carrier protein that effectively transports Se to the cells via the binding to its receptor apolipoprotein E receptor 2 (ApoER2), which is taken up by cells.

Nutritional Availability of Methylated Selenometabolites in Gut Microbiota, Dimethyldiselenide and Dimethylselenide, in Rats.

Selenium (Se) is an essential micronutrient for animals. Various chemical forms of Se exist in nature, each with distinct physiological, nutritional, and toxicological properties. In this study, we aimed to determine whether dimethyldiselenide (DMDSe, a monomethylated Se (MMSe) compound) and dimethylselenide (DMSe, a dimethylated Se compound), known gut bacterial metabolites, could serve as Se sources in rats.

Enhancement of Sensitivity in Aggregation-Based Whole-Cell Arsenite Sensor Utilizing Arsenic Metabolism Regulation.

Arsenite [As(III)] is a toxic substance widely present on Earth, and the development of low-cost and simple microbial-based As(III) sensors has been attracting attention. Recently, we discovered that the protein LuxR, which contains multiple cysteine residues with high affinity for As(III), forms an insoluble structure upon binding to As(III) and exhibits OFF-switching properties as a quorum sensing transcriptional activator. Based on this property, the LuxR sensor operates on a new principle distinct from conventional whole-cell As(III) sensors; however, its sensitivity remains a challenge.

Evaluation of elemental impurities and particle size distribution in nanomedicine using asymmetric flow field-flow fractionation hyphenated to inductively coupled plasma mass spectrometry.

Nanomedicines, which consist of nanoparticles as active ingredients, have been developed and approved for pharmaceutical use. However, no method has been established to quantify ions and nanoparticles containing the same elements separately. We developed an asymmetric flow field-flow fractionation hyphenated to inductively coupled plasma mass spectrometry (AF4-ICP-MS) to assess elemental impurities from ions and nanoparticles of different sizes.

Conditional Binding of Arsenic Trioxide (ATO) to Cysteine-Rich Zinc Finger Motifs within RBCC Domain of PML Protein.

The arsenic trioxide (ATO)-based cure of acute promyelocytic leukemia is attributed to PML/RARα oncoprotein degradation through binding of its RBCC domain (i.e., consist of RING, B-box1, B-box2, and Coiled-coil) with arsenic.

The polar-localized borate exporter BOR1 facilitates boron transport in tapetal cells to the developing pollen grains.

Boron is an essential micronutrient required for plant cell wall integrity, as it is necessary for crosslinking the pectic polysaccharide rhamnogalacturonan II. Reproductive organs require a greater amount of boron for development and growth compared with vegetative organs. However, the mechanism by which plants distribute boron to specific organs is not fully understood.

Evaluation of Metal Accumulation in Expressing SPL2 by Single-Cell Inductively Coupled Plasma Mass Spectrometry.

Rare earth elements, comprising 17 elements including 15 lanthanides, are essential components in numerous high-tech applications. While physicochemical methods are commonly employed to remove toxic heavy metals (e.g.

Laser Ablation Coupled with LC-ICP-MS for Local Speciation of Trace Elements in Tissues.

The body mitigates the toxic effects of metals through diverse detoxification mechanisms that are activated depending on the chemical species and the burden of metals in each tissue. In this regard, analytical methods that can obtain information on the chemical form and the abundance of metals are required to elucidate the full range of detoxification mechanisms. Laser ablation (LA) is used to trim a specific microregion from tissue sections and visualize elements in it.

Analytical techniques for arsenic speciation.

Due to its toxicity, contamination with arsenic, a Group 1 carcinogen, is a significant environmental and public health issue. The toxicity of arsenic varies with its chemical form. For example, inorganic species like arsenite (AsO) and arsenate (AsO) are generally more toxic than organoarsenic compounds.

Determination of adalimumab by HPLC with fluorescence detection using the König reaction.

Monoclonal antibody drugs (mAb) are widely used to treat various diseases. Keeping quality of mAbs is crucial to maximize efficacy and minimize adverse effects. To this end, mAb content in the drug product must be precisely quantified.

Elucidation of γ-glutamyl-β-cyanoalanylglycine biosynthesis in mammalian cells by LC-QTOF-MS.

γ-Glutamyl-β-cyanoalanylglycine (gEcnAG) is a glutathione analog in which the cysteine moiety in glutathione is replaced with β-cyanoalanine, a known plant cyanide metabolite. Previously, gEcnAG was detected in the liver of rats and chicks exposed to β-cyanoalanine. We reported the detection of gEcnAG in naïve mammalian cells using liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).

Single-Cell Analysis of Elemental Contents by Laser Ablation-Inductively Coupled Plasma Mass Spectrometry.

Elemental analysis at the single-cell level is an emerging technique in the field of inductively coupled plasma mass spectrometry (ICP-MS). In comparison to the analysis of cell suspensions by fast time-resolved analysis, single-cell sampling by laser ablation (LA) allows the discriminatory analysis of single cells according to their size and morphology. In this study, we evaluated the changes in elemental contents in a single cell through differentiation of rat adrenal pheochromocytoma into neuron-like cells by LA-ICP-MS.

Development of a Biosafety Level 1 Cellular Assay for Identifying Small-Molecule Antivirals Targeting the Main Protease of SARS-CoV-2: Evaluation of Cellular Activity of GC376, Boceprevir, Carmofur, Ebselen, and Selenoneine.

While research has identified several inhibitors of the main protease (Mpro) of SARS-CoV-2, a significant portion of these compounds exhibit reduced activity in the presence of reducing agents, raising concerns about their effectiveness in vivo. Furthermore, the conventional biosafety level 3 (BSL-3) for cellular assays using viral particles poses a limitation for the widespread evaluation of Mpro inhibitor efficacy in a cell-based assay. Here, we established a BSL-1 compatible cellular assay to evaluate the in vivo potential of Mpro inhibitors.

Identification of Tellurium Metabolite in Broccoli Using Complementary Analyses of Inorganic and Organic Mass Spectrometry.

Tellurium (Te) is a chalcogen element like sulfur and selenium. Although it is unclear whether Te is an essential nutrient in organisms, unique Te metabolic pathways have been uncovered. We have previously reported that an unknown Te metabolite (UKTe) was observed in plants exposed to tellurate, a highly toxic Te oxyanion, by liquid chromatography-inductively coupled plasma mass spectrometer (LC-ICP-MS).

Protein-Labeling Reagents Selectively Activated by Copper(I).

Copper is an essential trace element that participates in many biological processes through its unique redox cycling between cuprous (Cu) and cupric (Cu) oxidation states. To elucidate the biological functions of copper, chemical biology tools that enable selective visualization and detection of copper ions and proteins in copper-rich environments are required. Herein, we describe the design of Cu-responsive reagents based on a conditional protein labeling strategy.

Subchronic toxicity study of indium-tin oxide nanoparticles following intratracheal administration into the lungs of rats.

Objectives: We aimed to analyze the subchronic toxicity and tissue distribution of indium after the intratracheal administration of indium-tin oxide nanoparticles (ITO NPs) to the lungs of rats.

Methods: Male Wistar rats were administered a single intratracheal dose of 10 or 20 mg In/kg body weight (BW) of ITO NPs. The control rats received only an intratracheal dose of distilled water.

Quantitative determination of the intracellular uptake of silica nanoparticles using asymmetric flow field flow fractionation coupled with ICP mass spectrometry and their cytotoxicity in HepG2 cells.

We established a size separation method for silica nanoparticles (SiNPs) measuring 10, 30, 50, 70, and 100 nm in diameter using asymmetric flow field flow fractionation hyphenated with inductively coupled plasma mass spectrometry (AF4-ICP-MS), and evaluated the cytotoxicity of SiNPs in human hepatoma HepG2 cells. Analysis of the mixture sample revealed that nanoparticles of different sizes were eluted at approximately 2-min intervals, with no effect on each elution time or percentage recovery. Compared with larger SiNPs, smaller SiNPs exhibited high cytotoxicity when the volume of SiNPs exposed to the cells was the same.