Targeting of CYP2E1 by miRNAs in alcohol-induced intestine injury.

Although binge alcohol-induced gut leakage has been studied extensively in the context of reactive oxygen species-mediated signaling, it was recently revealed that post-transcriptional regulation plays an essential role as well. Ethanol (EtOH)-inducible cytochrome P450-2E1 (CYP2E1), a key enzyme in EtOH metabolism, promotes alcohol-induced hepatic steatosis and inflammatory liver disease, at least in part by mediating changes in intestinal permeability. For instance, gut leakage and elevated intestinal permeability to endotoxins have been shown to be regulated by enhancing CYP2E1 mRNA and CYP2E1 protein levels.

Autoimmune Limbic Encephalitis in Patients with Hematologic Malignancies after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020.

Peripheral Blood from Rheumatoid Arthritis Patients Shows Decreased T CD25 Expression and Reduced Frequency of Effector T Subpopulation.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by immune cell infiltration of the synovium, leading to the loss of cartilage, bone, and joint function. Although regulatory T (T) cells are thought to modulate the initiation and progression of RA, a consensus has yet to be reached regarding the function and composition of T cells in RA patients. To address these discrepancies, we analyzed not only the total T frequency but also that of T subpopulations in the peripheral blood of RA patients and healthy controls by flow cytometry.

Impact of pre-transplant use of antibiotics on the graft-versus-host disease in adult patients with hematological malignancies.

Objectives: Changes in fecal microbiota affect the incidence and extent of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Most patients with hematological malignancies receive antibiotics for the treatment of febrile neutropenia prior to allogeneic HSCT, and pre-transplant use of antibiotics may influence the fecal microbiota and GVHD.

Methods: We retrospectively analysed consecutive adult patients with hematological malignancies who received allogeneic HSCT at Chungnam National University Hospital between 2007 and 2018.

Adherence of to SiHa Cells is Inhibited by Diphenyleneiodonium.

Microbial adhesion is critical for parasitic infection and colonization of host cells. To study the host-parasite interaction in vitro, we established a flow cytometry-based assay to measure the adherence of to epithelial cell line SiHa. SiHa cells and were detected as clearly separated, quantifiable populations by flow cytometry.

Carrot Pomace Polysaccharide (CPP) Improves Influenza Vaccine Efficacy in Immunosuppressed Mice via Dendritic Cell Activation.

Despite the advancements in vaccination research and practices, influenza viruses remain a global health concern. Inducing a robust immune response by vaccination is especially challenging in the elderly, the immunocompromised, and persons with chronic illnesses. Polysaccharides derived from food may act as a safe and readily accessible means to boost the immune system during vaccination.

A Mouse Homolog of a Human TP53 Germline Mutation Reveals a Lipolytic Activity of p53.

The physiological effects of the many germline mutations of TP53, encoding the tumor suppressor protein p53, are poorly understood. Here we report generating a p53 R178C knockin mouse modeling the human TP53 R181C mutation, which is notable for its prevalence and prior molecular characterization. Consistent with its weak cancer penetrance in humans, homozygous p53 mice show a modest increase in tumorigenesis but, surprisingly, are lean with decreased body fat content.

Dipenyleneiodonium Induces Growth Inhibition of Toxoplasma gondii through ROS Induction in ARPE-19 Cells.

Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investigated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the intracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, followed by suppression of T.

Duox1 Regulates Primary B Cell Function under the Influence of IL-4 through BCR-Mediated Generation of Hydrogen Peroxide.

Engagement of the BCR with Ags triggers signaling pathways for commitment of B lymphocyte responses that can be regulated, in part, by reactive oxygen species. To investigate the functional relevance of reactive oxygen species produced in primary B cells, we focused on the role of the hydrogen peroxide generator Duox1 in stimulated splenic B cells under the influence of the T2 cytokine IL-4. We found that HO production in wild type (WT) and Nox2-deficient CD19 B cells was boosted concomitantly with enhanced expression of Duox1 following costimulation with BCR agonists together with IL-4, whereas stimulated Duox1 cells showed attenuated HO release.

TNFα and IL-1β in the synovial fluid facilitate mucosal-associated invariant T (MAIT) cell migration.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood.

NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an important family of catalytic enzymes that generate reactive oxygen species (ROS), which mediate the regulation of diverse cellular functions. Although phagocyte Nox2/gp91phox is closely associated with the activation of host innate immune responses, the roles of Nox family protein during Toxoplasma gondii (T. gondii) infection have not been fully investigated.

Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration.

Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family exhibiting both glutathione peroxidase and phospholipase A2 activities.

Low ambient oxygen prevents atherosclerosis.

Large population studies have shown that living at higher altitudes, which lowers ambient oxygen exposure, is associated with reduced cardiovascular disease mortality. However, hypoxia has also been reported to promote atherosclerosis by worsening lipid metabolism and inflammation. We sought to address these disparate reports by reducing the ambient oxygen exposure of ApoE-/- mice.

Intracellular Networks of the PI3K/AKT and MAPK Pathways for Regulating Toxoplasma gondii-Induced IL-23 and IL-12 Production in Human THP-1 Cells.

Interleukin (IL)-23 and IL-12 are closely related in structure, and these cytokines regulate both innate and adaptive immunity. However, the precise signaling networks that regulate the production of each in Toxoplasma gondii-infected THP-1 monocytic cells, particularly the PI3K/AKT and MAPK signaling pathways, remain unknown. In the present study, T.

Trichonomas vaginalis metalloproteinase induces apoptosis of SiHa cells through disrupting the Mcl-1/Bim and Bcl-xL/Bim complexes.

To elucidate the roles of metalloproteinases and the Bcl-2 family of proteins in Trichovaginalis. vaginalis-induced apoptosis in human cervical cancer cells (SiHa cells) and vaginal epithelial cells (MS74 cells), SiHa cells and MS74 cells were incubated with live T. vaginalis, T.

Decreased STAT5 phosphorylation and GATA-3 expression in NOX2-deficient T cells: role in T helper development.

Absence of phagocyte NADPH oxidase (NOX2) activity causes chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent bacterial infections. In contrast to this innate immune deficit, CGD patients and animal models display a predisposition toward autoimmune disease and enhanced response to Helicobacter pylori and influenza virus infection. These data imply an altered, perhaps augmented, adaptive immune response in CGD.

Zinc finger protein tristetraprolin interacts with CCL3 mRNA and regulates tissue inflammation.

Zinc finger protein tristetraprolin (TTP) modulates macrophage inflammatory activity by destabilizing cytokine mRNAs. In this study, through a screen of TTP-bound mRNAs in activated human macrophages, we have identified CCL3 mRNA as the most abundantly bound TTP target mRNA and have characterized this interaction via conserved AU-rich elements. Compared to the wild-type cells, TTP(-/-) macrophages produced higher levels of LPS-induced CCL3.

The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling.

Production of reactive oxygen species, often by NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidases, plays a role in the signaling responses of cells to many receptor stimuli. Here, we describe the function of the calcium-dependent, nonphagocytic NADPH oxidase Duox1 in primary human CD4(+) T cells and cultured T cell lines. Duox1 bound to inositol 1,4,5-trisphosphate receptor 1 and was required for early T cell receptor (TCR)-stimulated production of hydrogen peroxide (H(2)O(2)) through a pathway that was dependent on TCR-proximal kinases.

Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP.

Receptor-stimulated generation of intracellular reactive oxygen species (ROS) modulates signal transduction, although the mechanism(s) is unclear. One potential basis is the reversible oxidation of the active site cysteine of protein tyrosine phosphatases (PTPs). Here, we show that activation of the antigen receptor of T cells (TCR), which induces production of ROS, induces transient inactivation of the SH2 domain-containing PTP, SHP-2, but not the homologous SHP-1.

Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors.

Stimulation of cells with various peptide growth factors induces the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) through activation of phosphatidylinositol 3-kinase. The action of this enzyme is reversed by that of the tumor suppressor PTEN. With the use of cells overexpressing NADPH oxidase 1 or peroxiredoxin II, we have now shown that H2O2 produced in response to stimulation of cells with epidermal growth factor or platelet-derived growth factor potentiates PIP3 generation and activation of the protein kinase Akt induced by these growth factors.

T cell receptor stimulation, reactive oxygen species, and cell signaling.

In the immune system, much of the focus on reactive oxygen species (ROS) has been regarding their role in antimicrobial defense as part of the innate immune system. In addition to this role, it is now becoming clear that ROS are used by cells of the adaptive immune system as regulators of signal transduction by cell surface receptors. The activation of T lymphocytes through their specific antigen receptor [T cell receptor (TCR)] is vital in regulating the immune response.

T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation.

T cell receptor (TCR) stimulation induces rapid generation of reactive oxygen species, although the mechanisms for this are unclear. Here we found that T cells expressed a functional phagocyte-type nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. TCR crosslinking induced oxidase activation through the recruitment of preformed Fas ligand and Fas.

Oxidation of thioredoxin reductase in HeLa cells stimulated with tumor necrosis factor-alpha.

Stimulation of cells with tumor necrosis factor-alpha (TNF-alpha) results in the increase in generation of H(2)O(2) in mitochondria that leads to apoptosis. The effect of H(2)O(2) produced by TNF-alpha on the redox status of selenocysteine (SeCys) residue essential for mitochondrial thioredoxin reductase (TrxR2) was investigated in HeLa cells. TNF-alpha caused accumulation of oxidized TrxR2 with a thioselenide bond.