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https://www.readbyqxmd.com/read/28654435/myasthenia-gravis-new-developments-in-research-and-treatment
#1
Amelia Evoli
PURPOSE OF REVIEW: Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than as a single disease. This review summarizes recent advances in pathophysiology which confirm the disease heterogeneity, and may help find disease-targeted and patient-targeted therapies. RECENT FINDINGS: Antibodies to the acetylcholine receptor, the muscle-specific tyrosine kinase and the lipoprotein receptor protein 4, characterize disease subtypes with distinct clinical traits and immune-pathogenic mechanisms...
June 24, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28654219/a-comparative-study-of-hepatitis-b-virus-x-protein-mutants-k130m-v131i-and-kv130-131mi-to-investigate-their-roles-in-fibrosis-cirrhosis-and-hepatocellular-carcinoma
#2
Zaheenul Islam Siddiqui, Sabihur Rahman Farooqui, Syed Ali Azam, Masarrat Afroz, Saima Wajid, Shama Parveen, Syed Naqui Kazim
Hepatitis B virus (HBV) genomic mutations A1762T, G1764A and AG1762/1764TA cause production of HBV X protein (HBx) mutants, namely K130M, V131I and KV130/131MI. These mutations are important biomarkers for the development of cirrhosis and hepatocellular carcinoma (HCC) in chronic HBV patients. The present study comparatively analyzes the impact of intracellular expression of HBx mutants on HCC cell line Huh7. It was found that expression of KV130/131MI induced: cell proliferation; altered expression of cell cycle regulatory genes in favor of cell proliferation; intracellular reactive oxygen species (ROS) production and mitochondrial depolarization...
June 27, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28653862/optimal-response-to-dimethyl-fumarate-associates-in-ms-with-a-shift-from-an-inflammatory-to-a-tolerogenic-blood-cell-profile
#3
Silvia Medina, Noelia Villarrubia, Susana Sainz de la Maza, José Lifante, Lucienne Costa-Frossard, Ernesto Roldán, Carmen Picón, José C Álvarez-Cermeño, Luisa M Villar
BACKGROUND: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. OBJECTIVE: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. METHODS: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28653569/the-mutable-vaccine-for-mutable-viruses
#4
Marilia Cascalho, Samuel J Balin, Jeffrey L Platt
Mutable viruses, such as HIV, pose difficult obstacles to prevention and/or control by vaccination. Mutable viruses rapidly diversify in populations and in individuals, impeding development of effective vaccines. We devised the 'mutable vaccine' to appropriate the properties of mutable viruses that undermine conventional strategies. The vaccine consists of a DNA construct encoding viral antigen and regulatory sequences that upon delivery to B cells target the enzymatic apparatus of 'somatic hypermutation' causing the construct to mutate one million-times baseline rates and allowing production and presentation of antigen variants...
June 2017: Immunotherapy
https://www.readbyqxmd.com/read/28652580/immunological-phenotype-of-the-murine-lrba-knockout
#5
Laura Gámez-Díaz, Julika Neumann, Fiona Jäger, Michele Proietti, Felicitas Felber, Pauline Soulas-Sprauel, Lisa Perruzza, Fabio Grassi, Tamara Kögl, Peter Aichele, Manfred Kilimann, Bodo Grimbacher, Sophie Jung
Biallelic mutations in the human Lipopolysaccharide Responsive Beige-like Anchor (LRBA) gene lead to a primary immunodeficiency known as LRBA deficiency, characterized by a broad range of clinical manifestations including autoimmunity, organomegaly, hypogammaglobulinemia and recurrent infections. Considering the phenotypic heterogeneity in patients and the severity of the disease, our aim was to assess the role of LRBA in immune cells and to understand the underlying pathomechanisms through the study of a Lrba knockout (Lrba(-/-)) mouse model...
June 27, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28650848/ser-thr-protein-kinase-b2-nadph-oxidase-2-signaling-in-thromboinflammation
#6
Jing Li, Jaehyung Cho
PURPOSE OF REVIEW: Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)2-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. RECENT FINDINGS: Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently...
June 24, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28650473/testes-specific-protease-50-promotes-cell-proliferation-via-inhibiting-activin-signaling
#7
Z-B Song, P Wu, J-S Ni, T Liu, C Fan, Y-L Bao, Y Wu, L-G Sun, C-L Yu, Y-X Huang, Y-X Li
Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649611/lrrk2-levels-in-immune-cells-are-increased-in-parkinson-s-disease
#8
D A Cook, G T Kannarkat, A F Cintron, Laura M Butkovich, Kyle B Fraser, J Chang, N Grigoryan, S A Factor, Andrew B West, J M Boss, M G Tansey
Mutations associated with leucine-rich repeat kinase 2 are the most common known cause of Parkinson's disease. The known expression of leucine-rich repeat kinase 2 in immune cells and its negative regulatory function of nuclear factor of activated T cells implicates leucine-rich repeat kinase 2 in the development of the inflammatory environment characteristic of Parkinson's disease. The aim of this study was to determine the expression pattern of leucine-rich repeat kinase 2 in immune cell subsets and correlate it with the immunophenotype of cells from Parkinson's disease and healthy subjects...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28648331/il-35-as-a-newly-proposed-homeostasis-associated-molecular-pattern-plays-three-major-functions-including-anti-inflammatory-initiator-effector-and-blocker-in-cardiovascular-diseases
#9
Xinyuan Li, Pu Fang, William Y Yang, Hong Wang, Xiaofeng Yang
IL-35 is a new anti-inflammatory cytokine identified in 2007, which inhibits inflammation and immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. The unique initiator and effector anti-inflammatory properties of IL-35 bring tremendous interest in investigating its role during cardiovascular disease (CVD) development, in which inflammatory processes are firmly established as central to its development and complications. In this review, we update recent understanding of how IL-35 is produced and regulated in the cells...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#10
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28646220/angiotensin-ii-synergizes-with-baff-to-promote-atheroprotective-regulatory-b-cells
#11
Padmapriya Ponnuswamy, Jeremie Joffre, Olivier Herbin, Bruno Esposito, Ludivine Laurans, Christoph J Binder, Thomas F Tedder, Lynda Zeboudj, Xavier Loyer, Andreas Giraud, Yujiao Zhang, Alain Tedgui, Ziad Mallat, Hafid Ait-Oufella
Angiotensin II (AngII) promotes hypertension, atherogenesis, vascular aneurysm and impairs post-ischemic cardiac remodeling through concerted roles on vascular cells, monocytes and T lymphocytes. However, the role of AngII in B lymphocyte responses is largely unexplored. Here, we show that chronic B cell depletion (Baffr deficiency) significantly reduces atherosclerosis in Apoe (-/-) mice infused with AngII. While adoptive transfer of B cells in Apoe (-/-) /Baffr (-/-) mice reversed atheroprotection in the absence of AngII, infusion of AngII in B cell replenished Apoe (-/-) /Baffr (-/-) mice unexpectedly prevented the progression of atherosclerosis...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645851/nanotubes-connecting-b-lymphocytes-high-impact-of-differentiation-dependent-lipid-composition-on-their-growth-and-mechanics
#12
Eszter A Tóth, Ádám Oszvald, Mária Péter, Gábor Balogh, Anikó Osteikoetxea-Molnár, Tamás Bozó, Edina Szabó-Meleg, Miklós Nyitrai, Imre Derényi, Miklós Kellermayer, Toshiyuki Yamaji, Kentaro Hanada, László Vígh, János Matkó
Nanotubes (NTs) are thin, long membranous structures forming novel, yet poorly known communication pathways between various cell types. Key mechanisms controlling their growth still remained poorly understood. Since NT-forming capacity of immature and mature B cells was found largely different, we investigated how lipid composition and molecular order of the membrane affect NT-formation. Screening B cell lines with various differentiation stages revealed that NT-growth linearly correlates with membrane ganglioside levels, while it shows maximum as a function of cholesterol level...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28644763/methyltransferase-g9a-regulates-osteogenesis-via-twist-gene-repression
#13
N Higashihori, B Lehnertz, A Sampaio, T M Underhill, F Rossi, J M Richman
Here we investigate the role of epigenetic factors in controlling the timing of cranial neural crest cell differentiation. The gene coding for histone H3 lysine 9 methyltransferase G9A was conditionally deleted in neural crest cells with Wnt1-Cre. The majority of homozygous-null animals survived to birth but thereafter failed to thrive. Phenotypic analysis of postnatal animals revealed that the mutants displayed incomplete ossification and 20% shorter jaws as compared to their wild-type littermates. At E13...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28643924/exosomes-novel-regulators-of-bone-remodelling-and-potential-therapeutic-agents-for-orthodontics
#14
REVIEW
L S Holliday, K P McHugh, J Zuo, J I Aguirre, J K Neubert, W J Rody
Recent studies suggest that exosomes are involved in intercellular communication required for the maintenance of healthy bone. Exosomes are small (30-150 nm in diameter) extracellular vesicles that are formed in multivesicular bodies and are released from cells as the multivesicular bodies fuse with the plasma membrane. Regulatory exosomes have the capacity to exert profound control over target cells. They can stimulate plasma membrane receptors and are also internalized by the target cell delivering proteins, lipids, small molecules and functional RNAs from the cell of origin...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28642254/redox-regulation-of-a-guard-cellsnf1-relatedprotein-kinase-in-brassica-napus-%C3%A2-an-oilseed-crop
#15
Menmeng Zhu, Tong Zhang, Wei Ji, Cecilia Silva-Sanchez, Wenyuan Song, Sarah M Assmann, Alice C Harmon, Sixue Chen
Kinase-mediated phosphorylation is a pivotal regulatory process in stomatal responses to stresses. Through a redox proteomics study, a sucrose non-fermenting 1-related protein kinase (SnRK2.4) was identified to be redox regulated in Brassica napus guard cells upon abscisic acid (ABA) treatment. There are six genes encoding SnRK2.4 paralogs in B. napus Here we show that recombinant BnSnRK2.4-1C exhibited autophosphorylation activity and preferentially phosphorylated the N-terminal region of B. napus slow anion channel (BnSLAC1-NT) over generic substrates...
June 22, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28640862/a-biosystems-approach-to-identify-the-molecular-signaling-mechanisms-of-tmem30a-during-tumor-migration
#16
Jiao Wang, Qian Wang, Dongfang Lu, Fangfang Zhou, Dong Wang, Ruili Feng, Kai Wang, Robert Molday, Jiang Xie, Tieqiao Wen
Understanding the molecular mechanisms underlying cell migration, which plays an important role in tumor growth and progression, is critical for the development of novel tumor therapeutics. Overexpression of transmembrane protein 30A (TMEM30A) has been shown to initiate tumor cell migration, however, the molecular mechanisms through which this takes place have not yet been reported. Thus, we propose the integration of computational and experimental approaches by first predicting potential signaling networks regulated by TMEM30A using a) computational biology methods, b) our previous mass spectrometry results of the TMEM30A complex in mouse tissue, and c) a number of migration-related genes manually collected from the literature, and subsequently performing molecular biology experiments including the in vitro scratch assay and real-time quantitative polymerase chain reaction (qPCR) to validate the reliability of the predicted network...
2017: PloS One
https://www.readbyqxmd.com/read/28640191/phenotypic-plasticity-and-cell-fate-decisions-in-cancer-insights-from-dynamical-systems-theory
#17
REVIEW
Dongya Jia, Mohit Kumar Jolly, Prakash Kulkarni, Herbert Levine
Waddington's epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of "landscape" in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype is considered as an "attractor" that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes...
June 22, 2017: Cancers
https://www.readbyqxmd.com/read/28639950/reactive-oxygen-species-generation-and-increase-in-mitochondrial-copy-number-new-insight-into-the-potential-mechanism-of-cytotoxicity-induced-by-aurora-kinase-inhibitor-azd1152-hqpa
#18
Ali Zekri, Yashar Mesbahi, Samad Ghanizadeh-Vesali, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Aurora-B kinase overexpression plays important roles in the malignant progression of prostate cancer (PCa). AZD1152-HQPA, as an inhibitor of Aurora-B, has recently emerged as a promising agent for cancer treatment. In this study, we aimed to investigate the effects of AZD1152-HQPA on reactive oxygen species (ROS) generation and mitochondrial function in PCa. We used AZD1152-HQPA (Barasertib), a highly potent and selective inhibitor of Aurora-B kinase. The effects of AZD1152-HQPA on cell viability, DNA content, cell morphology, and ROS production were studied in the androgen-independent PC-3 PCa cell line...
June 21, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#19
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637621/gata2-deficiency-and-related-myeloid-neoplasms
#20
Marcin W Wlodarski, Matthew Collin, Marshall S Horwitz
The GATA2 gene codes for a hematopoietic transcription factor that through its two zinc fingers (ZF) can occupy GATA-DNA motifs in a countless number of genes. It is crucial for the proliferation and maintenance of hematopoietic stem cells. During the past 5 years, germline heterozygous mutations in GATA2 were reported in several hundred patients with various phenotypes ranging from mild cytopenia to severe immunodeficiency involving B cells, natural killer cells, CD4(+) cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia...
April 2017: Seminars in Hematology
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