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https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#1
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28214833/nogo-b-facilitates-lps-mediated-immune-responses-by-up-regulation-of-tlr4-signaling-in-macrophage-raw264-7
#2
Ying Zhu, Qiang Tong, Jia Ye, Yunye Ning, Ye Xiong, Meng Yang, Hua Xiao, Jian Lu, Wujian Xu, Jiandong Li, Qiang Li
BACKGROUND/AIMS: Nogo-B, a member of the reticulon family of proteins, is mainly located in the endoplasmic reticulum (ER). Here, we investigate the function and mechanism of Nogo-B in the regulation of TLR4-associated immune responses in the macrophage cell line of RAW264.7. METHODS: Nogo-B was up- and down-regulated through the use of appropriate adenoviral vectors or siRNA, and the effects of Nogo-B on macrophages under liposaccharide (LPS) stimulation were evaluated via western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), flow cytometric analysis, and transwell assay...
January 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213978/estrogens-and-androgens-inhibit-association-of-rankl-with-the-pre-osteoblast-membrane-through-post-translational-mechanisms
#3
Anthony Martin, Jiali Yu, Jian Xiong, Aysha B Khalid, Benita Katzenellenbogen, Sung Hoon Kim, John A Katzenellenbogen, Suchinda Malaivijitnond, Yankel Gabet, Susan A Krum, Baruch Frenkel
We have recently demonstrated that RUNX2 promoted, and 17-β-Estradiol (E2) diminished, association of RANKL with the cell membrane in pre-osteoblast cultures. Here we show that, similar to E2, dihydrotestosterone (DHT) diminishes association of RANKL and transiently transfected GFP-RANKL with the pre-osteoblast membrane without decreasing total RANKL mRNA or protein levels. Diminution of membrane-associated RANKL was accompanied with marked suppression of osteoclast differentiation from co-cultured pre-osteoclasts, even though DHT increased, not decreased, RANKL concentrations in pre-osteoblast conditioned media...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213930/antibiotic-administration-alleviates-the-aggravating-effect-of-orthodontic-force-on-ligature-induced-experimental-periodontitis-bone-loss-in-mice
#4
J Shi, Z Liu, T Kawai, Y Zhou, X Han
BACKGROUND AND OBJECTIVES: It is recognized that orthodontic force (OF) has an aggravating effect on the progression of destructive periodontitis if periodontitis have not been well controlled. However, the underlying mechanism is not completely clear. This study was to investigate the effect of antibiotic administration on OF-aggravated, ligature-induced experimental periodontitis in mice. MATERIAL AND METHODS: C57BL/6 mice (male, 8 wk old) were divided into three groups (n = 8)...
February 18, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#5
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213501/immature-lymphocytes-inhibit-rag1-and-rag2-transcription-and-v-d-j-recombination-in-response-to-dna-double-strand-breaks
#6
Megan R Fisher, Adrian Rivera-Reyes, Noah B Bloch, David G Schatz, Craig H Bassing
Mammalian cells have evolved a common DNA damage response (DDR) that sustains cellular function, maintains genomic integrity, and suppresses malignant transformation. In pre-B cells, DNA double-strand breaks (DSBs) induced at Igκ loci by the Rag1/Rag2 (RAG) endonuclease engage this DDR to modulate transcription of genes that regulate lymphocyte-specific processes. We previously reported that RAG DSBs induced at one Igκ allele signal through the ataxia telangiectasia mutated (ATM) kinase to feedback-inhibit RAG expression and RAG cleavage of the other Igκ allele...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#7
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
February 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28213469/insulin-signaling-via-the-pi3k-akt-pathway-regulates-airway-glucose-uptake-and-barrier-function-in-a-cftr-dependent-manner
#8
Samuel A Molina, Hannah K Moriarty, Danny T Infield, Barry R Imhoff, Rachel J Vance, Agnes H Kim, Jason M Hansen, William R Hunt, Michael Koval, Nael A McCarty
Cystic fibrosis-related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF) and correlates with increased rates of lung function decline. Since glucose is a nutrient present in the airways of patients with bacterial airway infections and since insulin controls glucose metabolism, the effect of insulin on CF airway epithelia was investigated to determine the role of insulin receptors and glucose transport in regulating glucose availability in the airway. The response to insulin by human airway epithelial cells was characterized by qPCR, immunoblot, immunofluorescence, and glucose uptake assays...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213271/woodchuck-sodium-taurocholate-cotransporting-polypeptide-supports-low-level-hepatitis-b-and-d-virus-entry
#9
Liran Fu, Hongjie Hu, Yang Liu, Zhiyi Jing, Wenhui Li
Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck (Marmota monax), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP...
February 14, 2017: Virology
https://www.readbyqxmd.com/read/28213267/ferulic-acid-inhibits-neuro-inflammation-in-mice-exposed-to-chronic-unpredictable-mild-stress
#10
Ya-Min Liu, Ji-Duo Shen, Li-Ping Xu, Han-Bing Li, Yu-Cheng Li, Li-Tao Yi
Ferulic acid is a hydroxycinnamic acid that widely presents in plant cell wall components. It has been demonstrated that ferulic acid can attenuate depressive-like behaviors in both forced swimming test and tail suspension test. Considering that depression is an inflammatory related mental disease, our present study was aimed to investigate the role of ferulic acid in the regulation of microglia activation, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in mice exposed to chronic unpredictable mild stress (CUMS)...
February 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#11
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212895/the-influence-of-enteral-obestatin-administration-to-suckling-rats-on-intestinal-contractility
#12
M Słupecka, P Grzesiak, J Kwiatkowski, M Gajewska, A Kuwahara, I Kato, J Woliński
This study investigated the effect of enteral administration of obestatin on the contractility of whole-thickness preparations of duodenum and middle jejunum, as well as on the morphology of the enteric nervous system (ENS). Suckling rats were assigned to 3 groups (n=12) treated with: C- saline solution; LO- obestatin (125 nmol/kg b.wt); HO-obestatin (250 nmol/kg b.wt). Saline solution or obestatin were administered twice daily, from the 14(th) to the 21(st) day of life. Sections were studied in an organ bath, for isometric recording in the presence of acetylocholine (ACh), atropine (ATR) and tetradotoxin (TTX)...
February 14, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28212447/diffuse-large-b-cell-lymphoma-with-concurrent-high-myc-and-bcl2-expression-shows-evidence-of-active-b-cell-receptor-signaling-by-quantitative-immunofluorescence
#13
Agata M Bogusz, Alexandra E Kovach, Long P Le, Derek Feng, Richard H G Baxter, Aliyah R Sohani
B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28212352/rta-occupancy-of-the-origin-of-lytic-replication-during-murine-gammaherpesvirus-68-reactivation-from-b-cell-latency
#14
Alexis L Santana, Darby G Oldenburg, Varvara Kirillov, Laraib Malik, Qiwen Dong, Roman Sinayev, Kenneth B Marcu, Douglas W White, Laurie T Krug
RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS)/toll-like receptor (TLR)4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB) signaling during murine gammaherpesvirus 68 (MHV68) infection: a latent B cell line (HE-RIT) inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio) that enabled in vivo biotinylation of RTA in BirA transgenic mice...
February 16, 2017: Pathogens
https://www.readbyqxmd.com/read/28211903/activating-killer-immunoglobulin-receptors-and-hla-c-a-successful-combination-providing-hiv-1-control
#15
Mauro S Malnati, Elisabetta Ugolotti, Maria Cristina Monti, Davide De Battista, Irene Vanni, Domenico Bordo, Francesca Sironi, Patrizia Larghero, Eddi Di Marco, Priscilla Biswas, Guido Poli, Elisa Vicenzi, Agostino Riva, Maciej Tarkowski, Giuseppe Tambussi, Silvia Nozza, Gino Tripodi, Francesco Marras, Andrea De Maria, Angela Pistorio, Roberto Biassoni
Several studies demonstrated a relevant role of polymorphisms located within the HLA-B and -C loci and the Killer Immunoglobulin Receptors (KIRs) 3DL1 and 3DS1 in controlling HIV-1 replication. KIRs are regulatory receptors expressed at the surface of NK and CD8+ T-cells that specifically bind HLA-A and -B alleles belonging to the Bw4 supratype and all the -C alleles expressing the C1 or C2 supratype. We here disclose a novel signature associated with the Elite Controller but not with the long-term nonprogressor status concerning 2DS activating KIRs and HLA-C2 alleles insensitive to miRNA148a regulation...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211154/kir2dl3-and-the-kir-ligand-groups-hla-a-bw4-and-hla-c2-predict-the-outcome-of-hepatitis-b-virus-infection
#16
Danilo Di Bona, Anna Aiello, Claudia Colomba, Massimo Bilancia, Giulia Accardi, Raffaella Rubino, Lidia Giannitrapani, Antonino Tuttolomondo, Antonio Cascio, Maria Filomena Caiaffa, Sergio Rizzo, Gabriele Di Lorenzo, Giuseppina Candore, Luigi Macchia, Giuseppe Montalto, Calogero Caruso
Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands...
February 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#17
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
: Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209719/adaptive-nk-cells-can-persist-in-patients-with-gata2-mutation-depleted-of-stem-and-progenitor-cells
#18
Heinrich Schlums, Moonjung Jung, Hongya Han, Jakob Theorell, Venetia Bigley, Samuel C C Chiang, David S J Allan, Jan K Davidson-Moncada, Rachel E Dickinson, Tim D Holmes, Amy P Hsu, Danielle Townsley, Thomas Winkler, Weixin Wang, Pål Aukrust, Ingvild Nordøy, Katherine R Calvo, Steve M Holland, Matthew Collin, Cynthia E Dunbar, Yenan T Bryceson
Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and NK cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor PLZF, as well as expression of intracellular signaling proteins FcϵRγ, SYK, and EAT-2 in a variegated manner...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28208600/invariant-chain-complexes-and-clusters-as-platforms-for-mif-signaling
#19
REVIEW
Robert Lindner
Invariant chain (Ii/CD74) has been identified as a surface receptor for migration inhibitory factor (MIF). Most cells that express Ii also synthesize major histocompatibility complex class II (MHC II) molecules, which depend on Ii as a chaperone and a targeting factor. The assembly of nonameric complexes consisting of one Ii trimer and three MHC II molecules (each of which is a heterodimer) has been regarded as a prerequisite for efficient delivery to the cell surface. Due to rapid endocytosis, however, only low levels of Ii-MHC II complexes are displayed on the cell surface of professional antigen presenting cells and very little free Ii trimers...
February 10, 2017: Cells
https://www.readbyqxmd.com/read/28207921/pneumatic-stimulation-of-c-elegans-mechanoreceptor-neurons-in-a-microfluidic-trap
#20
Adam L Nekimken, Holger Fehlauer, Anna A Kim, Sandra N Manosalvas-Kjono, Purim Ladpli, Farah Memon, Divya Gopisetty, Veronica Sanchez, Miriam B Goodman, Beth L Pruitt, Michael Krieg
New tools for applying force to animals, tissues, and cells are critically needed in order to advance the field of mechanobiology, as few existing tools enable simultaneous imaging of tissue and cell deformation as well as cellular activity in live animals. Here, we introduce a novel microfluidic device that enables high-resolution optical imaging of cellular deformations and activity while applying precise mechanical stimuli to the surface of the worm's cuticle with a pneumatic pressure reservoir. To evaluate device performance, we compared analytical and numerical simulations conducted during the design process to empirical measurements made with fabricated devices...
February 16, 2017: Lab on a Chip
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