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https://www.readbyqxmd.com/read/29161347/pharmacological-blockage-of-the-cxcr4-cxcl12-axis-in-endometriosis-leads-to-contrasting-effects-in-proliferation-migration-and-invasion
#1
Abigail Ruiz, Lynnette Ruiz, Mariano Colón-Caraballo, Bryan J Torres-Collazo, Janice B Monteiro, Manuel Bayona, Asgerally T Fazleabas, Idhaliz Flores
High levels of inflammatory factors including chemokines have been reported in peritoneal fluid and blood of women with endometriosis. CXCL12 mediates its action by interaction with its specific receptor, CXCR4, which has been reported to be elevated in human endometriosis lesions and in the rat model of endometriosis. Activation of the CXCR4-CXCL12 axis increases cell proliferation, migration and invasion of cancer cells. To obtain insights into the CXCR4 expression profile in lesions and endometrium, as well as functionality of the CXCR4-CXCL12 axis in endometriosis we analysed the expression of CXCR4 in tissues on a human tissue array and studied CXCL12-mediated activation of proliferation, invasion, and migration in vitro...
November 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29160947/thymic-function-is-a-major-determinant-of-antibody-mediated-rejection-onset-in-heart-transplantation
#2
A Sannier, N Stroumza, G Caligiuri, M Le Borgne-Moynier, F Andreata, J Senemaud, L Louedec, G Even, A T Gaston, C Deschildre, A Couvelard, P Ou, R Cheynier, P Nataf, R Dorent, A Nicoletti
Thymic function progressively decreases with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether the thymic function was related to the onset of rejection. Twenty-eight antithymocyte globulin-treated heart transplant recipients were included. Patients diagnosed for an antibody-mediated rejection on endomyocardial biopsy had higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects...
November 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29160519/ex-vivo-t-lymphocyte-chemokine-receptor-phenotypes-in-patients-with-chronic-chagas-disease
#3
Matheus Barbosa de Miranda, Adriene Siqueira de Melo, Mariana Silva Almeida, Silvia Martins Marinho, Wilson Oliveira, Yara de Miranda Gomes
INTRODUCTION: Elucidating the molecules involved in the inflammatory process of chronic Chagas disease may allow identification of treatment targets. METHODS: The ex vivo phenotypic expression of chemokine receptors CCR1, CCR3, CCR4, CCR5, CXCR2, CXCR3, CXCR4, and CXCR5 on the CD4+ and CD8+ T-cells of patients with chronic Chagas cardiomyopathy of varying severity was evaluated using flow cytometry. RESULTS: Differential expression of CD4+CCR3+ and CD8+CCR4+ T-cells was observed in patients with mild cardiac involvement compared, respectively, with patients with severe cardiac and asymptomatic forms of Chagas disease...
September 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29160067/molecular-tension-probes-for-imaging-forces-at-the-cell-surface
#4
Yang Liu, Kornelia Galior, Victor Pui-Yan Ma, Khalid Salaita
Mechanical forces are essential for a variety of biological processes ranging from transcription and translation to cell adhesion, migration, and differentiation. Through the activation of mechanosensitive signaling pathways, cells sense and respond to physical stimuli from the surrounding environment, a process widely known as mechanotransduction. At the cell membrane, many signaling receptors, such as integrins, cadherins and T- or B-cell receptors, bind to their ligands on the surface of adjacent cells or the extracellular matrix (ECM) to mediate mechanotransduction...
November 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29159903/soluble-mhc-molecules-in-immune-regulation-highlighting-class-ii-antigens
#5
REVIEW
Katerina Bakela, Irene Athanassakis
The involvement of Major histocompatibility complex (MHC) antigens in the development and regulation of immune response has been well defined over the years, starting from maturation, antigenic peptide loading, migration to the cell membrane for recognition by the T cell receptor and recycling for immune response cessation. During this intracellular trafficking, MHC antigens find a way to be excreted by the cells, since they can be found as soluble MHC class I (sMHCI) and class II (sMHCII) molecules in all body fluids...
November 21, 2017: Immunology
https://www.readbyqxmd.com/read/29159902/histamine-enhanced-contractile-responses-of-gastric-smooth-muscle-via-interstitial-cells-of-cajal-in-the-syrian-hamster
#6
S Naganuma, T Shiina, S Yasuda, Y Suzuki, Y Shimizu
BACKGROUND: Gastric motility is controlled by the autonomic and enteric nervous systems and by interstitial cells of Cajal (ICCs). Although histamine is known to be released from enterochromaffin-like cells in the gastric mucosa, its regulatory roles in gastric motility are still controversial. Therefore, we investigated the functional roles of histamine in gastric motility. METHODS: Stomach preparations from hamsters were used because the stomach of hamsters can be easily separated into the forestomach and the glandular stomach...
November 21, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29159877/crystalline-structure-of-pulverized-dental-calculus-induces-cell-death-in-oral-epithelial-cells
#7
S M Ziauddin, A Yoshimura, J L Montenegro Raudales, Y Ozaki, K Higuchi, T Ukai, T Kaneko, T Miyazaki, E Latz, Y Hara
BACKGROUND AND OBJECTIVE: Dental calculus is a mineralized deposit attached to the tooth surface. We have shown that cellular uptake of dental calculus triggers nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, leading to the processing of the interleukin-1β precursor into its mature form in mouse and human phagocytes. The activation of the NLRP3 inflammasome also induced a lytic form of programmed cell death, pyroptosis, in these cells...
November 20, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29159714/regulatory-effects-of-dexamethasone-on-nk-and-t-cell-immunity
#8
Liying Chen, Mikael Jondal, Konstantin Yakimchuk
Glucocorticoids (GCs) act via the intracellular glucocorticoid receptor (GR), which can regulate the expression of target genes. With regard to the immune system, GCs may affect both innate and adaptive immunity. Our study analyzed the immunoregulatory effects of dexamethasone (Dex) treatment on splenic T, Treg, NK and NKT cells by treating C57Bl6 mice with various doses of Dex. We observed that treatment with Dex decreased the number of NK cells in the spleen and suppressed their activity. In particular, the expression of both Ly49G and NKG2D receptors was decreased by Dex...
November 20, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29159447/transcriptome-sequencing-of-the-long-nosed-bandicoot-perameles-nasuta-reveals-conservation-and-innovation-of-immune-genes-in-the-marsupial-order-peramelemorphia
#9
Katrina M Morris, Haylee J Weaver, Denis O'Meally, Marion Desclozeaux, Amber Gillett, Adam Polkinghorne
Bandicoots are omnivorous marsupials of the order Peramelemorphia. Conservation concerns and their unique biological characteristics suggest peramelomorphs are worthy research subjects, but knowledge of their genetics and immunology has lagged behind that of other high-profile marsupials. Here, we characterise the transcriptome of the long-nose bandicoot (Perameles nasuta), the first high-throughput data set from any peramelomorph. We investigate the immune gene repertoire of the bandicoot, with a focus on key immune gene families, and compare to previously characterised marsupial and mammalian species...
November 20, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29159173/corrigendum-dogs-with-acute-myeloid-leukemia-have-clonal-re-arrangements-in-t-and-b-cell-receptors
#10
Tracy Stokol, Gabrielle Nickerson, Martha Shuman, Nicole Belcher
[This corrects the article on p. 76 in vol. 4, PMID: 28620611.].
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/29158604/antiviral-cd8-t-cells-induce-zika-virus-associated-paralysis-in-mice
#11
Kellie A Jurado, Laura J Yockey, Patrick W Wong, Sarah Lee, Anita J Huttner, Akiko Iwasaki
Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly (1) and Guillain-Barré syndrome (2,3) as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis (4) , meningoencephalitis (5) and fatal encephalitis (6) . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 (-/-) ) mice, an infection model that exhibits high viral burden within the central nervous system...
November 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#12
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158482/structural-basis-for-the-unique-ganglioside-and-cell-membrane-recognition-mechanism-of-botulinum-neurotoxin-dc
#13
Sicai Zhang, Ronnie P-A Berntsson, William H Tepp, Liang Tao, Eric A Johnson, Pål Stenmark, Min Dong
Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158404/cd1b-restricted-gem-t-cell-responses-are-modulated-by-mycobacterium-tuberculosis-mycolic-acid-meromycolate-chains
#14
Andrew Chancellor, Anna S Tocheva, Chris Cave-Ayland, Liku Tezera, Andrew White, Juma'a R Al Dulayymi, John S Bridgeman, Ivo Tews, Susan Wilson, Nikolai M Lissin, Marc Tebruegge, Ben Marshall, Sally Sharpe, Tim Elliott, Chris-Kriton Skylaris, Jonathan W Essex, Mark S Baird, Stephan Gadola, Paul Elkington, Salah Mansour
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158376/leukemia-specific-delivery-of-mutant-notch1-targeted-therapy
#15
Giovanni Roti, Jun Qi, Samuel Kitara, Marta Sanchez-Martin, Amy Saur Conway, Anthony C Varca, Angela Su, Lei Wu, Andrew L Kung, Adolfo A Ferrando, James E Bradner, Kimberly Stegmaier
On-target drug delivery remains a challenge in cancer precision medicine; it is difficult to deliver a targeted therapy to cancer cells without incurring toxicity to normal tissues. The SERCA (sarco-endoplasmic reticulum Ca(2+) ATPase) inhibitor thapsigargin inhibits mutant NOTCH1 receptors compared with wild type in T cell acute lymphoblastic leukemia (T-ALL), but its administration is predicted to be toxic in humans. Leveraging the addiction of ALL to folic acid, we conjugated folate to an alcohol derivative of thapsigargin via a cleavable ester linkage...
November 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29158374/maternal-igg-immune-complexes-induce-food-allergen-specific-tolerance-in-offspring
#16
Asa Ohsaki, Nicholas Venturelli, Tess M Buccigrosso, Stavroula K Osganian, John Lee, Richard S Blumberg, Michiko K Oyoshi
The role of maternal immune responses in tolerance induction is poorly understood. To study whether maternal allergen sensitization affects offspring susceptibility to food allergy, we epicutaneously sensitized female mice with ovalbumin (OVA) followed by epicutaneous sensitization and oral challenge of their offspring with OVA. Maternal OVA sensitization prevented food anaphylaxis, OVA-specific IgE production, and intestinal mast cell expansion in offspring. This protection was mediated by neonatal crystallizable fragment receptor (FcRn)-dependent transfer of maternal IgG and OVA immune complexes (IgG-IC) via breast milk and induction of allergen-specific regulatory T (T reg) cells in offspring...
November 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29158348/galectin-1-a-jack-of-all-trades-in-the-resolution-of-acute-and-chronic-inflammation
#17
REVIEW
Victoria Sundblad, Luciano G Morosi, Jorge R Geffner, Gabriel A Rabinovich
Regulatory signals provide negative input to immunological networks promoting resolution of acute and chronic inflammation. Galectin-1 (Gal-1), a member of a family of evolutionarily conserved glycan-binding proteins, displays broad anti-inflammatory and proresolving activities by targeting multiple immune cell types. Within the innate immune compartment, Gal-1 acts as a resolution-associated molecular pattern by counteracting the synthesis of proinflammatory cytokines, inhibiting neutrophil trafficking, targeting eosinophil migration and survival, and suppressing mast cell degranulation...
December 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29158268/car-t-cell-therapies-in-glioblastoma-a-first-look
#18
Denis Migliorini, Pierre-Yves Dietrich, Roger Stupp, Gerald P Linette, Avery D Posey, Carl H June
Glioblastoma is an aggressive malignancy with a poor prognosis. The current standard of care for newly diagnosed glioblastoma patients includes surgery to the extent, temozolomide combined with radiotherapy, and alternating electric fields therapy. After recurrence, there is no standard therapy and survival is less than 9 months. Recurrent glioblastoma offers a unique opportunity to investigate new treatment approaches in a malignancy known for remarkable genetic heterogeneity, immunosuppressive microenvironment and partially permissive anatomical blood brain barrier (BBB)...
November 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29158203/p2x7-receptor-in-spinal-tuberculosis-gene-polymorphisms-and-protein-levels-in-chinese-han-population
#19
Ying Zhou, Chun-Yan Tan, Zhi-Jiang Mo, Qi-le Gao, Dan He, Jiong Li, Rong-Fu Huang, Yan-Bing Li, Chao-Feng Guo, Qiang Guo, Long-Jie Wang, Guan-Teng Yang, Hong-Qi Zhang
Spinal tuberculosis (TB) accounts for 1%-5% of all TB infections. Host genetic variation influences susceptibility to Mycobacterium tuberculosis (MTB). P2X7 receptor (P2X7R) expressed on cells has been identified as a regulatory molecule in cell death/apoptosis, killing of intercellular pathogens, and bone turnover. This study investigated the P2X7 gene polymorphisms and protein levels in spinal TB. P2X7 gene -762C>T and 489C>T polymorphisms were genotyped. The expression of P2X7R in bone or intervertebral disc (ID) tissues was analyzed by Western blot assay...
November 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29157617/the-role-of-interleukin-6-in-castleman-disease
#20
REVIEW
Kazuyuki Yoshizaki, Shinichi Murayama, Hiroki Ito, Tomohiro Koga
Since its discovery, improvements in treating Castleman disease and its variants have centered on interleukin-6 (IL-6). IL-6 was discovered from T-cell factors (BCDF or BSF-2), which induced B-cell maturation. Most symptoms of the plasma cell variant of Castleman disease are linked to the hyperfunction of IL-6, constitutively produced in the affected lymph nodes (1989), suggesting IL-6 is key in the pathogenesis of multicentric Castleman disease (MCD). The results of several studies have shown that most MCD symptoms and abnormal laboratory results are improved by anti-IL-6 MCD treatments, such as tocilizumab, a humanized anti-IL-6 receptor antibody, and siltuximab, an anti-IL-6 antibody...
February 2018: Hematology/oncology Clinics of North America
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