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https://www.readbyqxmd.com/read/29684377/biphasic-modulation-of-camp-levels-by-the-contraceptive-nomegestrol-acetate-impact-on-p-glycoprotein-expression-and-activity-in-hepatic-cells
#1
Guillermo Nicolás Tocchetti, Camila Juliana Domínguez, Felipe Zecchinati, Maite Rocío Arana, María Laura Ruiz, Silvina Stella Maris Villanueva, Johanna Weiss, Aldo Domingo Mottino, Juan Pablo Rigalli
ABC transporters are key players in drug excretion with alterations in their expression and activity by therapeutic agents potentially leading to drug-drug interactions. The interaction potential of nomegestrol acetate (NMGA), a synthetic progestogen increasingly used as oral contraceptive, had never been explored. In this work we evaluated (1) the effect of NMGA on ABC transporters in the human hepatic cell line HepG2 and (2) the underlying molecular mechanism. NMGA (5, 50 and 500 nM) increased P-glycoprotein (P-gp) expression at both protein and mRNA levels and reduced intracellular calcein accumulation, indicating an increase also in transporter activity...
April 20, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29675004/the-fast-growing-brucella-suis-biovar-5-depends-on-phosphoenolpyruvate-carboxykinase-and-pyruvate-phosphate-dikinase-but-not-on-fbp-and-glpx-fructose-1-6-bisphosphatases-or-isocitrate-lyase-for-full-virulence-in-laboratory-models
#2
Amaia Zúñiga-Ripa, Thibault Barbier, Leticia Lázaro-Antón, María J de Miguel, Raquel Conde-Álvarez, Pilar M Muñoz, Jean J Letesson, Maite Iriarte, Ignacio Moriyón
Bacteria of the genus Brucella infect a range of vertebrates causing a worldwide extended zoonosis. The best-characterized brucellae infect domestic livestock, behaving as stealthy facultative intracellular parasites. This stealthiness depends on envelope molecules with reduced pathogen-associated molecular patterns, as revealed by the low lethality and ability to persist in mice of these bacteria. Infected cells are often engorged with brucellae without signs of distress, suggesting that stealthiness could also reflect an adaptation of the parasite metabolism to use local nutrients without harming the cell...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29668066/mait-cell-mediated-cytotoxicity-roles-in-host-defense-and-therapeutic-potentials-in-infectious-diseases-and-cancer
#3
REVIEW
Patrick T Rudak, Joshua Choi, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29656544/an-overview-on-the-identification-of-mait-cell-antigens
#4
Lars Kjer-Nielsen, Alexandra J Corbett, Zhenjun Chen, Ligong Liu, Jeffrey Y W Mak, Dale I Godfrey, Jamie Rossjohn, David P Fairlie, James McCluskey, Sidonia B G Eckle
Mucosal Associated Invariant T (MAIT) cells are restricted by the monomorphic MHC class I-like molecule, MHC-related protein-1 (MR1). Until 2012, the origin of the MAIT cell antigens (Ags) was unknown, although it was established that MAIT cells could be activated by a broad range of bacteria and yeasts, possibly suggesting a conserved Ag. Using a combination of protein chemistry, mass spectrometry, cellular biology, structural biology and chemistry, we discovered MAIT cell ligands derived from folic acid (vitamin B9) and from an intermediate in the microbial biosynthesis of riboflavin (vitamin B2)...
April 14, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29629900/recipient-mucosal-associated-invariant-t-cells-control-gvhd-within-the-colon
#5
Antiopi Varelias, Mark D Bunting, Kate L Ormerod, Motoko Koyama, Stuart D Olver, Jasmin Straube, Rachel D Kuns, Renee J Robb, Andrea S Henden, Leanne Cooper, Nancy Lachner, Kate H Gartlan, Olivier Lantz, Lars Kjer-Nielsen, Jeffrey Yw Mak, David P Fairlie, Andrew D Clouston, James McCluskey, Jamie Rossjohn, Steven W Lane, Philip Hugenholtz, Geoffrey R Hill
Mucosal-associated invariant T (MAIT) cells are a unique innate-like T cell subset that responds to a wide array of bacteria and yeast through recognition of riboflavin metabolites presented by the MHC class I-like molecule MR1. Here, we demonstrate using MR1 tetramers that recipient MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD) target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Consistent with their preferential juxtaposition to microbial signals in the colon, recipient MAIT cells generate large amounts of IL-17A, promote gastrointestinal tract integrity, and limit the donor alloantigen presentation that in turn drives donor Th1 and Th17 expansion specifically in the colon after BMT...
April 9, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29618662/human-mait-cells-exit-peripheral-tissues-and-recirculate-via-lymph-in-steady-state-conditions
#6
Valentin Voillet, Marcus Buggert, Chloe K Slichter, Julia D Berkson, Florian Mair, Mary M Addison, Yoav Dori, Gregory Nadolski, Maxim G Itkin, Raphael Gottardo, Michael R Betts, Martin Prlic
Mucosal-associated invariant T cells (MAIT cells) recognize bacterial metabolites as antigen and are found in blood and tissues, where they are poised to contribute to barrier immunity. Recent data demonstrate that MAIT cells located in mucosal barrier tissues are functionally distinct from their blood counterparts, but the relationship and circulation of MAIT cells between blood and different tissue compartments remains poorly understood. Previous studies raised the possibility that MAIT cells do not leave tissue and may either be retained or undergo apoptosis...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29616020/hyper-expression-of-pd-1-is-associated-with-the-levels-of-exhausted-and-dysfunctional-phenotypes-of-circulating-cd161-tcr-iv%C3%AE-7-2-mucosal-associated-invariant-t-cells-in-chronic-hepatitis-b-virus-infection
#7
Yean K Yong, Alireza Saeidi, Hong Y Tan, Mohamed Rosmawati, Philip F Enström, Rami Al Batran, V Vasuki, Indranil Chattopadhyay, Amudhan Murugesan, Ramachandran Vignesh, Adeeba Kamarulzaman, Jayakumar Rajarajeswaran, Abdul W Ansari, Jamuna Vadivelu, James E Ussher, Vijayakumar Velu, Marie Larsson, Esaki M Shankar
Mucosal-associated invariant T (MAIT) cells, defined as CD161++ TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+ CD161++ TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29597306/biocompatibility-of-gd-loaded-chitosan-hyaluronic-acid-nanogels-as-contrast-agents-for-magnetic-resonance-cancer-imaging
#8
Cecilia Virginia Gheran, Guillaume Rigaux, Maité Callewaert, Alexandre Berquand, Michael Molinari, Françoise Chuburu, Sorina Nicoleta Voicu, Anca Dinischiotu
Although the research on nanogels incorporating Gd chelates for theranostic applications has grown exponentially in recent years, knowledge about their biocompatibility is limited. We compared the biocompatibility of Gd-loaded hyaluronic acid-chitosan-based nanogels (GdCA⊂CS-TPP/HA) with two chitosan concentrations (2.5 and 1.5 mg·mL-1 respectively) using SVEC4-10 murine lymph node endothelial cells. The sulforhodamine B method and released lactate dehydrogenase (LDH) activity were used as cell viability tests...
March 28, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29582588/altered-lactate-metabolism-in-huntington-s-disease-is-dependent-on-glut3-expression
#9
Macarena Solís-Maldonado, María Paz Miró, Aníbal I Acuña, Adriana Covarrubias-Pinto, Anitsi Loaiza, Gonzalo Mayorga, Felipe A Beltrán, Carlos Cepeda, Michael S Levine, Ilona I Concha, Luis Federico Bátiz, Mónica A Carrasco, Maite A Castro
AIMS: Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive abnormalities in cognitive function, mental state, and motor control. HD is characterized by a failure in brain energy metabolism. It has been proposed that monocarboxylates, such as lactate, support brain activity. During neuronal synaptic activity, ascorbic acid released from glial cells stimulates lactate and inhibits glucose transport. The aim of this study was to evaluate the expression and function of monocarboxylate transporters (MCTs) in two HD models...
April 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29582333/influence-of-post-transplant-mucosal-associated-invariant-t-cell-recovery-on-the-development-of-acute-graft-versus-host-disease-in-allogeneic-bone-marrow-transplantation
#10
Koji Kawaguchi, Katsutsugu Umeda, Eitaro Hiejima, Atsushi Iwai, Masamitsu Mikami, Seishiro Nodomi, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Takahiro Yasumi, Ryuta Nishikomori, Tadakazu Kondo, Akifumi Takaori-Kondo, Toshio Heike, Souichi Adachi
Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) cells are T cell subpopulations that possess innate-like properties. We examined the impact of post-hematopoietic stem cell transplantation (HSCT) MAIT and iNKT cell recovery on the clinical outcomes of 69 patients who underwent allogeneic HSCT at Kyoto University Hospital. Multivariate analyses identified the absolute number of MAIT cells (< 0.48/μL on day 60 post-HSCT) as the sole independent risk factor for grade I-IV and grade II-IV acute graft-versus-host disease (aGVHD) among patients who underwent bone marrow transplantation; no correlation was observed between post-HSCT iNKT cell recovery and the development of aGVHD...
March 26, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29569752/development-of-mucosal-associated-invariant-t-mait-cells
#11
Hui-Fern Koay, Dale I Godfrey, Daniel G Pellicci
MAIT cells develop in the thymus and migrate into the periphery to become the largest antigen-specific αβ T cell population in the human immune system. However, the frequency of MAIT cells varies widely between human individuals, and the basis for this is unclear. While MAIT cells are highly conserved through evolution and are phenotypically similar between humans and mice, they represent a much smaller proportion of total T cells in mice. In this review, we discuss how MAIT cells transition through a three-stage development pathway in both mouse and human thymus, and continue to mature and expand after they leave the thymus...
March 23, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29569417/dermoscopy-features-of-atypical-fibroxanthoma-a-multicenter-study-of-the-international-dermoscopy-society
#12
Elvira Moscarella, Simonetta Piana, Francesca Specchio, Athanassios Kyrgidis, Gianluca Nazzaro, Maite L Eliceche, Francesco Savoia, Leonardo Bugatti, Giorgio Filosa, Iris Zalaudek, Federica Scarfi, Mike Inskip, Cliff Rosendahl, John H Pyne, Graeme Siggs, Arzu K Toğral, Horatio Cabo, Lubomir Drlik, Aimilios Lallas, Caterina Longo, Giuseppe Argenziano
BACKGROUND/OBJECTIVES: Little is known about the dermoscopic features of atypical fibroxanthoma. METHODS: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer. RESULTS: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%)...
March 23, 2018: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/29562195/unconventional-t-cell-targets-for-cancer-immunotherapy
#13
REVIEW
Dale I Godfrey, Jérôme Le Nours, Daniel M Andrews, Adam P Uldrich, Jamie Rossjohn
Most studies on the immunotherapeutic potential of T cells have focused on CD8 and CD4 T cells that recognize peptide antigens (Ag) presented by polymorphic major histocompatibility complex (MHC) class I and MHC class II molecules, respectively. However, unconventional T cells, which interact with MHC class Ib and MHC-I like molecules, are also implicated in tumor immunity, although their role therein is unclear. These include unconventional T cells targeting MHC class Ib molecules such as HLA-E and its murine ortholog Qa-1b, natural killer T (NKT) cells, mucosal associated invariant T (MAIT) cells, and γδ T cells...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29543654/il-7-treatment-supports-cd8-mucosa-associated-invariant-t-cell-restoration-in-hiv-1-infected-patients-on-antiretroviral-therapy
#14
Ornella Sortino, Elizabeth Richards, Joana Dias, Edwin Leeansyah, Johan K Sandberg, Irini Sereti
: Chronic HIV-1 infection is associated with lower frequencies and functional impairment of mucosa-associated invariant T (MAIT) cells. We evaluated IL-7 treatment to restore MAIT cells in peripheral blood of chronically HIV-1-infected individuals on antiretroviral therapy. IL-7 led to increased relative and absolute levels of MAIT cells, and this expansion occurred primarily in the CD8 subset. These results suggest that IL-7 may represent a therapeutic intervention for the restoration of MAIT cells in chronic HIV-1 infection...
March 27, 2018: AIDS
https://www.readbyqxmd.com/read/29525444/a-peptidogalactomannan-isolated-from-cladosporium-herbarum-induces-defense-related-genes-in-by-2-tobacco-cells
#15
Bianca Braz Mattos, Caroline Montebianco, Elisson Romanel, Tatiane da Franca Silva, Renato Barroso Bernabé, Fernanda Simas-Tosin, Lauro M Souza, Guilherme L Sassaki, Maite F S Vaslin, Eliana Barreto-Bergter
Cladosporium herbarum is a plant pathogen associated with passion fruit scab and mild diseases in pea and soybean. In this study, a peptidogalactomannan (pGM) of C. herbarum mycelium was isolated and structurally characterized, and its role in plant-fungus interactions was evaluated. C. herbarum pGM is composed of carbohydrates (76%) and contains mannose, galactose and glucose as its main monosaccharides (molar ratio, 52:36:12). Methylation and13 C-nuclear magnetic resonance (13 C-NMR) spectroscopy analysis have shown the presence of a main chain containing (1 → 6)-linked α-D-Manp residues, and β-D-Galf residues are present as (1 → 5)-interlinked side chains...
March 2, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29525282/characterization-of-the-immune-response-elicited-by-the-vaccinia-virus-l3-protein-delivered-as-naked-dna
#16
Maite Ramírez, Saritza Santos, Osmarie Martínez, Ricardo Rodríguez, Eric Miranda, Willy D Ramos-Perez, Miguel Otero
Poxviruses are complex dsDNA viruses with over 200 genes, many of them with unknown role in the stimulation of immune responses. Among these, the vaccinia virus (VACV) L3L ORF encodes an essential protein for the transcription of the VACV early genes. To the best of our knowledge, the immune response elicited by L3 has not been characterized. In this regard, our data describes a DNA L3-coding plasmid (pL3L) that stimulates both, humoral- and cell-mediated immune responses in a mouse model. Cell-mediated immune responses were measured by IFN-γ and IL-4 ELISPOT assays...
March 7, 2018: Vaccine
https://www.readbyqxmd.com/read/29520610/atp-binding-cassette-abc-transporters-expression-and-clinical-value-in-glioblastoma
#17
Antonin Dréan, Shai Rosenberg, François-Xavier Lejeune, Larissa Goli, Aravindan Arun Nadaradjane, Jérémy Guehennec, Charlotte Schmitt, Maïté Verreault, Franck Bielle, Karima Mokhtari, Sanson Marc, Alexandre Carpentier, Delattre Jean-Yves, Ahmed Idbaih
ATP-binding cassette transporters (ABC transporters) regulate traffic of multiple compounds, including chemotherapeutic agents, through biological membranes. They are expressed by multiple cell types and have been implicated in the drug resistance of some cancer cells. Despite significant research in ABC transporters in the context of many diseases, little is known about their expression and clinical value in glioblastoma (GBM). We analyzed expression of 49 ABC transporters in both commercial and patient-derived GBM cell lines as well as from 51 human GBM tumor biopsies...
March 8, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29515123/enumeration-functional-responses-and-cytotoxic-capacity-of-mait-cells-in-newly-diagnosed-and-relapsed-multiple-myeloma
#18
Nicholas A Gherardin, Liyen Loh, Lorenztino Admojo, Alexander J Davenport, Kelden Richardson, Amy Rogers, Phillip K Darcy, Misty R Jenkins, H Miles Prince, Simon J Harrison, Hang Quach, David P Fairlie, Katherine Kedzierska, James McCluskey, Adam P Uldrich, Paul J Neeson, David S Ritchie, Dale I Godfrey
Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors. Furthermore, there was no evidence that MAIT cells accumulated at the disease site (bone marrow) of these patients...
March 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29507084/il-18-is-critical-for-mait-cell-ifn-%C3%AE-responses-to-francisella-species-in-vitro-but-not-in-vivo
#19
Eric Jesteadt, Irma Zhang, Huifeng Yu, Anda Meierovics, Wei-Jen Chua Yankelevich, Siobhan Cowley
Mucosa-associated invariant T (MAIT) cells are an innate T cell subset that expresses a semi-invariant Vα chain paired with limited Vβ chains. MAIT cells are activated by riboflavin metabolite derivatives presented by MR1. The precise mechanisms required to activate MAIT cells are an area of intense interest. Here we used two closely related intracellular pathogens with distinct inflammasome activation phenotypes to probe the role of innate cytokines in MAIT cell activation. Using an in vitro assay containing transgenic murine MAIT cells, we show that macrophages infected with Francisella novicida , a strong inflammasome activator, released high levels of IL-18 and stimulated high levels of MAIT cell IFN-γ through a partially MR1-independent pathway...
March 5, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29501962/rgd-functionalized-fe-3-o-4-nanoparticles-for-magnetic-hyperthermia
#20
Oihane K Arriortua, Maite Insausti, Luis Lezama, Izaskun Gil de Muro, Eneko Garaio, Jesus Martínez de la Fuente, Raluca M Fratila, Maria P Morales, Rocío Costa, Maite Eceiza, Maialen Sagartzazu-Aizpurua, Jesus M Aizpurua
To improve the selectivity of magnetic nanoparticles for tumor treatment by hyperthermia, Fe3 O4 nanoparticles have been functionalized with a peptide of the type arginine-glycine-aspartate (RGD) following a "click" chemistry approach. The RGD peptide was linked onto the previously coated nanoparticles in order to target αv β3 integrin receptors over-expressed in angiogenic cancer cells. Different coatings have been analyzed to enhance the biocompatibility of magnetic nanoparticles. Monodispersed and homogeneous magnetite nanoparticles have been synthesized by the seed growth method and have been characterized using X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, transmission electron microscopy and magnetic measurements...
February 15, 2018: Colloids and Surfaces. B, Biointerfaces
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