Characterization of the mechanisms underlying sulfasalazine-induced ferroptotic cell death: role of protein disulfide isomerase-mediated NOS activation and NO accumulation.

Sulfasalazine (SAS), a clinically utilized anti-inflammatory drug, has been shown to induce ferroptosis by inhibiting system Xc activity, thereby causing cellular glutathione depletion. Recently, protein disulfide isomerase (PDI) was shown to be an upstream mediator of the oxidative cell death (oxytosis/ferroptosis) induced by glutamate, erastin, RSL3 and SAS. The present study aims to further characterize the detailed biochemical and cellular mechanisms of SAS-induced ferroptosis in two cell lines, .

Sodium formate-induced mitochondrial impairment and cytotoxicity in neuronal cells reveal crucial pathogenic mechanisms underlying diabetic neuropathy and retinopathy.

Formic acid, a toxic one-carbon metabolite formed from methanol and formaldehyde in the body, can cause neuronal dysfunctions. It was recently hypothesized that metabolic formation of toxic one-carbon metabolites (particularly formic acid) under hyperglycemic conditions may contribute to the pathogenesis of diabetic complications in humans. The present study aims to investigate the mechanism of formic acid-induced neurotoxicity using immortalized HT22 mouse hippocampal neurons as an in-vitro model.

Complete biosynthesis of salicylic acid from phenylalanine in plants.

Salicylic acid (SA) is a pivotal phytohormone for plant responses to biotic and abiotic stresses. Plants have evolved two pathways to produce SA: the isochorismate synthase and phenylalanine ammonia lyase (PAL) pathways. Whereas the isochorismate synthase pathway has been fully identified, the PAL pathway remains incomplete.

Nontarget Screening Analysis Combined with Computational Toxicology: A Promising Solution for Identification and Risk Assessment of Environmental Pollutants in the Big Data Era.

Synthetic chemicals are intensively utilized in modern societies, and their mixtures pose significant health and ecological threats. Nontarget screening (NTS) analysis allows for the simultaneous chemical identification and quantitative reporting of tens of thousands of chemicals in complex environmental matrices, whereas the computational toxicology (CT) serves as another high-throughput means of rapidly and comprehensively screening chemicals for toxicity. To date, there has been a lack of guidance on how to combine NTS experiments and CT for the risk assessment of chemical mixtures and the prioritization of pollutants.

Administrative pressure, interpersonal relationships, and teachers' professional identity.

Understanding teachers' professional identity is significant for promoting their professional development, cultivating a high-quality teaching force, and achieving a high-quality education system. This paper empirically analyzes the impact of administrative pressure on teachers' understanding of professional identity based on data from the China Education Panel Survey using the order probit model to reveal the mechanisms at play in this relationship. Administrative pressure was found to inhibit teachers' professional identity significantly.

N-Methyldopamine and ibopamine can prevent chemically-induced oxidative ferroptosis in vitro and in vivo.

Oxidative ferroptotic cell death can be selectively induced in cultured cells by chemicals like erastin (an inhibitor of system Xc) and RSL3 (an inhibitor of glutathione peroxidase 4). It was recently revealed that protein disulfide isomerase (PDI) is an upstream mediator of chemically-induced ferroptosis and thus also a drug target for ferroptosis protection. Here, we report that N-methyldopamine (MD), a metabolite of dopamine, can protect against erastin- and RSL3-induced ferroptosis in cultured cells, including rat hepatocytes and rat cardiomyocytes.

Development of Ga-NOTA-cRGD Probe Mediated by Sulfenic Acid for Prolonging Tumor Imaging.

High reactive oxygen species (ROS) serve as important signaling molecules in the tumor microenvironment, and their excessive generation is closely associated with tumor growth, drug resistance, and metastasis of tumors. Rrecently, probes based on 1,3-cyclohexanedione have been proposed, enabling real-time monitoring of ROS levels in the tumor microenvironment. Herein, as a proof of concept, we aimed at synthesizing a novel tumor diagnostic probe, Ga-NOTA-cRGD, by connecting NOTA and the tumor-targeting peptide cRGD with a 1,3-cyclohexanedione group that specifically undergoes cross-linking with sulfenic acid, to enhance the targeting and prolong the imaging time of the probe in tumors.

Facile Biological Oxidation of Dopamine to 6-Hydroxydopamine -Quinone in a Sequential Two-Step Process: Implications for Parkinson's Disease.

6-Hydroxydopamine (6-OHDA), a hydroxyl-derivative of the endogenous neurotransmitter dopamine, can selectively induce Parkinsonian symptoms in animal models. At present, most researchers consider 6-OHDA a man-made neurotoxicant, due to the lack of strong evidence for its presence and/or formation in biological systems. The present study aims to determine whether 6-OHDA can be formed under physiologically relevant conditions.

Protective effect of norepinephrine, dopamine and N-methyldopamine against chemically-induced oxidative ferroptosis in HT22 neuronal cells: Protein disulfide isomerase as a mechanistic target for protection.

Under pathogenic conditions, the endogenous neurotransmitters dopamine and norepinephrine can readily undergo auto-oxidation to generate reactive oxygen species (ROS), culminating in glutathione depletion and oxidative neuronal injury. Recently, we have revealed that protein disulfide isomerase (PDI) is a mediator of glutathione depletion-associated oxidative ferroptosis, which is also a novel target for ferroptosis protection. In this study, we identify that three chemicals of the endogenous catecholamine family, i.

Strong protection by bazedoxifene against chemically-induced ferroptotic neuronal death in vitro and in vivo.

Ferroptosis, a form of regulated cell death associated with glutathione depletion and excess lipid peroxidation, can be induced in cultured cells by chemicals (e.g., erastin and RSL3).

Assessment of myocardial dysfunction of patients with systemic lupus erythematosus based on myocardial perfusion imaging and analysis of potential influencing factors.

The incidence and prevalence of systemic lupus erythematosus (SLE) have increased annually over the past decade. The involvement of myocardium is one of the main reasons for the poor prognosis of patients with SLE. Identifying myocardial involvement in patients with autoimmune diseases and providing early targeted treatment can improve patient outcomes.

Rap2B drives tumorigenesis and progression of colorectal cancer through intestinal cytoskeleton remodeling.

Ras family protein plays a key role in transducing signals involved in cytoskeletal remodeling and cell adhesion, which are particularly important in the development of colorectal cancer (CRC). While Rap2B, a member of the Ras superfamily, has been linked to cancer malignancy in vitro, its exact role in tumorigenesis remains unclear. In this study, we demonstrated that intestine-specific knockout of Rap2B suppresses the initiation and progression of CRC.

Establishment of GDF15 time-resolved fluorescence immunoassay and its clinical application in colorectal cancer.

Objective: This study aimed to develop a highly sensitive time-resolved fluoroimmunoassay for growth differentiation factor 15 (GDF15-TRFIA) and investigate its clinical applicability in colorectal cancer (CRC).

Methods: Using the principle of double-antibody sandwich immunity, the GDF15-TRFIA was established by solid-phase capture antibody and labeled detection antibody with europium as a tracer, the levels of serum GDF15 were quantified in healthy controls (HCs) and patients, and the value of GDF15 in the diagnosis of CRC was analyzed.

Results: The established method has a wide measurement range and good linearity.

Protective effect of 2-hydroxyestrone and 2-hydroxyestradiol against chemically induced hepatotoxicity in vitro and in vivo.

Ferroptosis is a form of regulated cell death closely associated with glutathione depletion and accumulation of reactive lipid peroxides. In this study, we seek to determine whether 2-hydroxyestrone (2-OH-E) and 2-hydroxyestradiol (2-OH-E), 2 major metabolites of endogenous estrone (E) and 17β-estradiol (E) formed by cytochrome P450 in the liver, can protect against erastin- and RSL3-induced ferroptosis in hepatoma cells (H-4-II-E and HuH-7) in vitro and acetaminophen-induced mouse liver injury in vivo. We find that 2-OH-E and 2-OH-E can protect, in a dose-dependent manner, H-4-II-E hepatoma cells against erastin/RSL3-induced ferroptosis.

Role of protein disulfide isomerase in mediating sulfasalazine-induced ferroptosis in HT22 cells: The PDI-NOS-NO-ROS/lipid-ROS cascade.

Ferroptosis is a form of regulated cell death resulting from excessive lipid peroxidation. Sulfasalazine (SAS), an anti-inflammatory drug, can induce ferroptosis through inhibiting the system Xc and triggering glutathione depletion. SAS has attracted considerable interest in recent years because of its potential for repurposing as an anticancer agent.

Further exploration of the quantitative distance-energy and contact number-energy relationships for predicting the binding affinity of protein-ligand complexes.

Accurate estimation of the strength of the protein-ligand interaction is important in the field of drug discovery. The binding strength can be determined by using experimental binding affinity assays which are both time and labor consuming and costly. Predicting the binding affinity/energy in silico is an alternative approach, particularly for virtual screening of large data sets.

4-Hydroxyestrogen metabolites strongly prevent chemically-induced ferroptotic hepatocyte injury in vitro and in vivo.

Ferroptosis is a regulated cell death characterized by excessive accumulation of toxic lipid reactive oxygen species (ROS). Ferroptosis is an underlying cause in some human diseases, including the drug-induced liver injury. The present study aims to determine whether 4-hydroxyestrone (4-OH-E) and 4-hydroxyestradiol (4-OH-E), two endogenous catechol estrogens, can prevent chemically-induced ferroptotic hepatocyte injury in vitro and in vivo.

Binding of Selected Ligands to Human Protein Disulfide Isomerase and Microsomal Triglyceride Transfer Protein Complex and the Associated Conformational Changes: A Computational Molecular Modelling Study.

Human protein disulfide isomerase (PDI) is a multifunctional protein, and also serves as the β subunit of the human microsomal triglyceride transfer protein (MTP) complex, a lipid transfer machinery. Dysfunction of the MTP complex is associated with certain disease conditions such as abetalipoproteinemia and cardiovascular diseases. It is known that the functions of PDI or the MTP complex can be regulated by the binding of a small-molecule ligand to either of these two proteins.

Establishment of Time-Resolved Fluorescence Immunoassay for Thyrotropin Receptor Antibodies and Clinical Application.

Thyroid-stimulating hormone receptor antibody (TRAb) is a specific marker for Graves' disease (GD) and the measurement of which can improve the accuracy of GD diagnosis. Current detection methods utilize porcine-derived polyclonal-TRAb, which is unstable and is a source of significant inter-assay variability. This study aims to establish a time-resolved fluorescence immunoassay (TRFIA) method based on stable source of recombinant human TSHR and TRAb for the detection of serum TRAb.

FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology.

Immunoglobulin G (IgG) is traditionally recognized as a plasma protein that neutralizes antigens for immune defense. However, our research demonstrates that IgG predominantly accumulates in adipose tissue during obesity development, triggering insulin resistance and macrophage infiltration. This accumulation is governed by neonatal Fc receptor (FcRn)-dependent recycling, orchestrated in adipose progenitor cells and macrophages during the early and late stages of diet-induced obesity (DIO), respectively.

Mechanism of RSL3-induced ferroptotic cell death in HT22 cells: crucial role of protein disulfide isomerase.

Protein disulfide isomerase (PDI) was recently shown to be an upstream mediator of erastin-induced, glutathione depletion-associated ferroptosis through its catalysis of nitric oxide synthase (NOS) dimerization and nitric oxide (NO) accumulation. A recent study reported that RSL3, a known ferroptosis inducer and glutathione peroxidase 4 (GPX4) inhibitor, can inhibit thioredoxin reductase 1 (TrxR1). The present study seeks to test the hypothesis that RSL3 may, through its inhibition of TrxR1, facilitate PDI activation ( .

Protection of HT22 neuronal cells against chemically-induced ferroptosis by catechol estrogens: protein disulfide isomerase as a mechanistic target.

Ferroptosis is a form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Biochemically, ferroptosis can be selectively induced by erastin through glutathione depletion or through inhibition of glutathione peroxidase 4 by RSL3, which leads to accumulation of cytotoxic lipid reactive oxygen species (ROS). Protein disulfide isomerase (PDI) was recently shown to mediate erastin/RSL3-induced ferroptosis and thus also become a new target for protection against chemically-induced ferroptosis.

Raloxifene Prevents Chemically-Induced Ferroptotic Neuronal Death In Vitro and In Vivo.

Ferroptosis, a regulated form of cell death characterized by excessive iron-dependent lipid peroxidation, can be readily induced in cultured cells by chemicals such as erastin and RSL3. Protein disulfide isomerase (PDI) has been identified as an upstream mediator of chemically induced ferroptosis and also a target for ferroptosis protection. In this study, we discovered that raloxifene (RAL), a selective estrogen receptor modulator known for its neuroprotective actions in humans, can effectively inhibit PDI function and provide robust protection against chemically induced ferroptosis in cultured HT22 neuronal cells.