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https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28637496/mir21-sensitized-b-lymphoma-cells-to-abt-199-via-icos-icosl-mediated-interaction-of-treg-cells-with-endothelial-cells
#12
Zhong Zheng, Peng-Peng Xu, Li Wang, Hui-Jin Zhao, Xiang-Qin Weng, Hui-Juan Zhong, Bin Qu, Jie Xiong, Yan Zhao, Xue-Feng Wang, Anne Janin, Wei-Li Zhao
BACKGROUND: MicroRNAs (miRs) are involved in tumor progression by regulating tumor cells and tumor microenvironment. MiR21 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological impact on tumor microenvironment remains unclear. METHODS: MiR21 was assessed by quantitative RT-PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR21 on lymphoma progression and tumor angiogenesis was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model...
June 21, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28637181/crosstalk-between-histone-modifications-indicates-that-inhibition-of-arginine-methyltransferase-carm1-activity-reverses-hiv-latency
#13
Zheng Zhang, Bryan C Nikolai, Leah A Gates, Sung Yun Jung, Edward B Siwak, Bin He, Andrew P Rice, Bert W O'Malley, Qin Feng
In eukaryotic cells, the gene expression status is strictly controlled by epigenetic modifications on chromatin. The repressive status of chromatin largely contributes to HIV latency. Studies have shown that modification of histone H3K27 acts as a key molecular switch for activation or suppression of many cellular genes. In this study, we found that K27-acetylated histone H3 specifically recruited Super Elongation Complex (SEC), the transcriptional elongation complex essential for HIV-1 long terminal repeat (LTR)-mediated and general cellular transcription...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28636198/actin-filament-reorganisation-controlled-by-the-scar-wave-complex-mediates-stomatal-response-to-darkness
#14
Jean-Charles Isner, Zaoxu Xu, Joaquim Miguel Costa, Fabien Monnet, Thomas Batstone, Xiaobin Ou, Michael J Deeks, Bernard Genty, Kun Jiang, Alistair M Hetherington
Stomata respond to darkness by closing to prevent excessive water loss during the night. Although the reorganisation of actin filaments during stomatal closure is documented, the underlying mechanisms responsible for dark-induced cytoskeletal arrangement remain largely unknown. We used genetic, physiological and cell biological approaches to show that reorganisation of the actin cytoskeleton is required for dark-induced stomatal closure. The opal5 mutant does not close in response to darkness but exhibits wild-type (WT) behaviour when exposed to abscisic acid (ABA) or CaCl2 ...
June 21, 2017: New Phytologist
https://www.readbyqxmd.com/read/28634857/computational-modelling-of-cancer-development-and-growth-modelling-at-multiple-scales-and-multiscale-modelling
#15
Zuzanna Szymańska, Maciej Cytowski, Elaine Mitchell, Cicely K Macnamara, Mark A J Chaplain
In this paper, we present two mathematical models related to different aspects and scales of cancer growth. The first model is a stochastic spatiotemporal model of both a synthetic gene regulatory network (the example of a three-gene repressilator is given) and an actual gene regulatory network, the NF-[Formula: see text]B pathway. The second model is a force-based individual-based model of the development of a solid avascular tumour with specific application to tumour cords, i.e. a mass of cancer cells growing around a central blood vessel...
June 20, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28631561/proinflammatory-follicular-helper-t-cells-promote-immunoglobulin-g-secretion-suppress-regulatory-b-cell-development-and-correlate-with-worse-clinical-outcomes-in-gastric-cancer
#16
Hong Zhang, Rongxi Yue, Pengfei Zhao, Xuetao Yu, Junguo Li, Guoqing Ma, Jiahong Tang, Lixin Zhang, Liying Feng, Lidong Sun, Zongchang Song, Chunliang Guo, Ning Wang
Gastric cancer is one of the most common and aggressive malignancies. Both bacterial virulence factors and host chronic inflammation are thought to promote gastric cancer development. In this study, we investigated the potential involvement of follicular helper T cells in gastric cancer. Functions of follicular helper T subsets were examined in Helicobacter pylori-infected gastric cancer patients and H. pylori-infected but asymptomatic individuals. We found that the follicular helper T cells in gastric cancer individuals were skewed toward the Th1 and Th17 subsets compared to those in H...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631500/pancreatic-%C3%AE-cell-survival-and-proliferation-are-promoted-by-protein-kinase-g-type-i%C3%AE-and-downstream-regulation-of-akt-foxo1
#17
Janica C Wong, Van Vo, Priyatham Gorjala, Ronald R Fiscus
Early studies showed nitric oxide as a pro-inflammatory-cytokine-induced toxin involved in pancreatic β-cell destruction during pathogenesis of type-1 diabetes. However, nitric oxide has both cytotoxic and cytoprotective effects on mammalian cells, depending on concentration and micro-environmental surroundings. Our studies have shown that low/physiological-level nitric oxide selectively activates protein kinase G type Iα isoform, promoting cytoprotective/pro-cell-survival effects in many cell types. In bone marrow-derived stromal/mesenchymal stem cells, protein kinase G type Iα mediates autocrine effects of nitric oxide and atrial natriuretic peptide, promoting DNA-synthesis/proliferation and cell survival...
June 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28631093/myelin-regulatory-factor-drives-remyelination-in-multiple-sclerosis
#18
Greg J Duncan, Jason R Plemel, Peggy Assinck, Sohrab B Manesh, Fraser G W Muir, Ryan Hirata, Matan Berson, Jie Liu, Michael Wegner, Ben Emery, G R Wayne Moore, Wolfram Tetzlaff
Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may be disrupted in chronic MS lesions. The expression of few transcription factors has been differentially compared between remyelinating lesions and lesions refractory to remyelination...
June 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28631092/rituximab-treatment-in-pemphigus-vulgaris-effect-on-circulating-tregs
#19
Bakr El-Zawahry, Dalia Bassiouny, Rehab Hegazy, Heba Gawdat, Suzan Shalaby, Mervat Khorshied, Marwah Adly Saleh
Rituximab (RTX) has been used successfully to treat refractory pemphigus. We aimed to assess the response of pemphigus vulgaris (PV) cases to RTX therapy and its effect on CD4(+)CD25(+) (T regulatory) cells level. Sixteen PV patients were included in this study, each received one cycle of two RTX infusions (1000 mg on days 1 and 15). Five PV patients served as controls. All cases were on prednisolone ± adjuvant therapy. Pemphigus disease area index (PDAI), autoimmune bullous skin intensity score (ABSIS), anti-desmoglein antibodies, CD4, CD8, CD20 and CD4(+)CD25(+) levels were assessed at baseline, 3, 6 and 12 months after therapy...
June 19, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28629373/blimp-1-impairs-t-cell-function-via-upregulation-of-tigit-and-pd-1-in-patients-with-acute-myeloid-leukemia
#20
Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F Claxton, W Christopher Ehmann, Witold B Rybka, Neil D Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D Schell, Raymond J Hohl, Hui Zeng, Hong Zheng
BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML...
June 19, 2017: Journal of Hematology & Oncology
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