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Shino Manabe, Yoshiki Yamaguchi, Junpei Abe, Kana Matsumoto, Yukishige Ito
The endo-β- N -acetylglucosaminidase mutant endo-CC N180H transfers glycan from sialylglycopeptide (SGP) to various acceptors. The scope and limitations of low-molecular-weight acceptors were investigated. Several homogeneous glycan-containing compounds, especially those with potentially useful labels or functional moieties, and possible reagents in glycoscience were synthesized. The 1,3-diol structure is important in acceptor molecules in glycan transfer reactions mediated by endo-CC N180H as well as by endo-M-N175Q...
May 2018: Royal Society Open Science
Takashi Mino, Osamu Takeuchi
Cytokines are critical mediators of inflammation and host immune defense. Cytokine production is regulated at both transcriptional and post-transcriptional levels. Post-transcriptional damping of inflammatory mRNAs is mediated by a set of RNA binding proteins (RBPs) interacting with cis-elements, such as AU-rich elements (ARE) and stem-loop structures. Whereas ARE-binding proteins such as tristetraprolin and a stem-loop recognizing protein, Roquin, downregulate cytokine mRNA abundance by recruiting a CCR4-NOT deadenylase complex, another stem-loop RBP, Regnase-1, acts as an endoribonuclease, directly degrading target cytokine mRNAs...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Estefanía Armas-González, María Jesús Domínguez-Luis, Ana Díaz-Martín, Mayte Arce-Franco, Javier Castro-Hernández, Gabriela Danelon, Vanesa Hernández-Hernández, Sagrario Bustabad-Reyes, Alberto Cantabrana, Mariagrazia Uguccioni, Federico Díaz-González
BACKGROUND: B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. METHODS: Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients...
June 7, 2018: Arthritis Research & Therapy
Koichi Ohshima, Hiroaki Miyoshi, Kyohei Yamada
Angioimmunoblastic T-cell lymphoma (AITL) originates from follicular helper T cells and shows variable biological and clinical presentations. The survival rate of patients with AITL did not correlate with T-cell clonality, the presence of EBV-infected cells, EBV-DNA copy number, or IgH rearrangements. However, tumor-associated macrophage/M2 macrophages significantly correlated with worse overall survival (OS). Additionally, patients with composite lymphoma with diffuse large B cell lymphoma and AITL showed worse OS...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Zhaohui Wang, Nathan J Louras, Alexandre G Lellouch, Shannon G Pratts, Huiping Zhang, Haoyu Wang, Christene A Huang, Curtis L Cetrulo, Joren C Madsen, David H Sachs, Zhirui Wang
Recently we have developed a diphtheria toxin-based recombinant anti-human CCR4 immunotoxin for targeting CCR4+ tumors and Tregs. In this study, we further optimized the dosing schedule for improved CCR4+ Treg depletion. We have demonstrated that up to a 90% depletion was achieved and the depletion extended to approximately two weeks in the peripheral blood and more than 48 days in the lymph node at 25 μg/kg, BID for 8 consecutive days in cynomolgus monkeys. Expansion was observed including monocytes and NK cells...
June 5, 2018: Molecular Oncology
Elizabeth T Abshire, Jennifer Chasseur, Jennifer A Bohn, Paul A Del Rizzo, Peter L Freddolino, Aaron C Goldstrohm, Raymond C Trievel
The circadian protein Nocturnin (NOCT) belongs to the exonuclease, endonuclease and phosphatase superfamily and is most similar to the CCR4-class of deadenylases that degrade the poly-adenosine tails of mRNAs. NOCT-deficient mice are resistant to high-fat diet induced weight gain, and exhibit dysregulation of bone formation. However, the mechanisms by which NOCT regulates these processes remain to be determined. Here, we describe a pair of high-resolution crystal structures of the human NOCT catalytic domain...
June 1, 2018: Nucleic Acids Research
Peeyush K Lala, Pinki Nandi, Mousumi Majumder
Lymphangiogenesis (formation of new lymphatic vessels), unlike angiogenesis, has been a lesser-focused field in cancer biology, because of earlier controversy regarding whether lymphatic metastasis occurs via pre-existing or newly formed lymphatics. Recent evidence reveals that peri-tumoral or intra-tumoral lymphangiogenesis is a precursor for lymphatic metastasis in most carcinomas and melanomas. Two major lymphangiogenic factors, vascular endothelial growth factor (VEGF)-C and VEGF-D, are produced by cancer cells or immune cells such as macrophages in the tumor-stroma to promote sprouting of lymphatics from lymphatic endothelial cells (LEC) or LEC precursors (LECP) by binding to their primary (high affinity) receptor VEGF-R3 or secondary receptors VEGF-R2, neuropilin (NRP)2 and α9/β1 integrin...
June 1, 2018: Cancer Metastasis Reviews
Paula M van Mourik, Jannie de Jong, Sushma Sharma, Alan Kavšek, Andrei Chabes, Michael Chang
In 10-15% of cancers, telomere length is maintained by a telomerase-independent, recombination-mediated pathway called alternative lengthening of telomeres (ALT). ALT mechanisms were first seen, and have been best studied, in telomerase-null Saccharomyces cerevisiae cells called "survivors". There are two main types of survivors. Type I survivors amplify Y' subtelomeric elements while type II survivors, similar to the majority of human ALT cells, amplify the terminal telomeric repeats. Both types of survivors require Rad52, a key homologous recombination protein, and Pol32, a non-essential subunit of DNA polymerase δ...
May 30, 2018: G3: Genes—Genomes—Genetics
Hongfeng Chen, Tirupataiah Sirupangi, Zhao-Hui Wu, Daniel L Johnson, R Nicholas Laribee
The Ccr4-Not complex controls RNA polymerase II (Pol II) dependent gene expression and proteasome function. The Not4 ubiquitin ligase is a Ccr4-Not subunit that has both a RING domain and a conserved RNA recognition motif and C3H1 domain (referred to as the RRM-C domain) with unknown function. We demonstrate that while individual Not4 RING or RRM-C mutants fail to replicate the proteasomal defects found in Not4 deficient cells, mutation of both exhibits a Not4 loss of function phenotype. Transcriptome analysis revealed that the Not4 RRM-C affects a specific subset of Pol II-regulated genes, including those involved in transcription elongation, cyclin-dependent kinase regulated nutrient responses, and ribosomal biogenesis...
May 25, 2018: Scientific Reports
Julia Dai, Timothy H Almazan, Eric K Hong, Michael S Khodadoust, Sally Arai, Wen-Kai Weng, Youn H Kim
No abstract text is available yet for this article.
May 23, 2018: JAMA Dermatology
Wilfredo Alejandro González-Arriagada, Carlos Lozano-Burgos, Rodrigo Zúñiga-Moreta, Paulina González-Díaz, Ricardo Della Coletta
BACKGROUND: Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to access the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. METHODS: Immunohistochemical expression of chemokine receptors were evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma...
May 24, 2018: Journal of Oral Pathology & Medicine
Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Karolina Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M Shankar, Marie Larsson
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction...
2018: Frontiers in Immunology
Shigeo Fuji
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell lymphoma caused by the human T-cell lymphotropic virus type I. Patients with aggressive ATL show dismal prognoses, even with intensive dose-dense chemotherapy. Such patients often show chemo-refractoriness. Mogamulizumab (Moga) is a potent treatment option for patients with relapsed or refractory ATL. However, use of Moga before allo-HSCT could theoretically increase the risk of post-transplant complications like graft-versus-host disease (GVHD) as Moga depletes regulatory T-cells (Tregs)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Longqing Sun, Genlou Sun, Chenxia Shi, Dongfa Sun
BACKGROUND: 337S is a novel bi-pole-photo-thermo-sensitive genic male sterile line in wheat, and sensitive to both long day length/high temperature and short day length/low temperature condition. Although the regulatory function of MicroRNAs (miRNAs) in reproductive development has been increasingly studied, their roles in pre-meiotic and meiotic cells formation of plants have not been clearly explored. Here, we explored the roles of miRNAs in regulating male sterility of 337S at short day length/low temperature condition...
May 8, 2018: BMC Genomics
Lorenzo Cerroni
Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype...
March 2018: Seminars in Cutaneous Medicine and Surgery
Yang Zhang, Yinfang Wu, Hui Qi, Junhai Xiao, Hongwei Gong, Yan Zhang, Enquan Xu, Song Li, Dalong Ma, Ying Wang, Wen Li, Huahao Shen
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
April 26, 2018: Scientific Reports
Katelyn E Sadler, Katherine J Zappia, Crystal L O'Hara, Sarah N Langer, Andy D Weyer, Cheryl A Hillery, Cheryl L Stucky
Approximately one third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, SCD patients are also in a tonically pro-inflammatory state. Previous studies have revealed that there are elevated plasma levels of many inflammatory mediators including chemokine (c-c motif) ligand 2 (CCL2) in individuals with SCD. Using a transgenic mouse model of SCD, we investigated the contributions of CCL2 signaling to SCD-related pain...
April 23, 2018: Pain
Eszter Baricza, Nikolett Marton, Panna Királyhidi, Orsolya Tünde Kovács, Ilona Kovácsné Székely, Eszter Lajkó, Lászó Kőhidai, Bernadett Rojkovich, Barbara Érsek, Edit Irén Buzás, György Nagy
Background: The T-helper 17 (Th17) cells have a prominent role in inflammation as well as in bone and join destruction in both rheumatoid and psoriatic arthritis (RA and PsA). Here, we studied Th17 cell differentiation in RA and PsA. Methods: Blood samples from healthy donors, RA and PsA patients were collected. CD45RO- (naive) and CD45RO+ (memory) T cells were isolated from peripherial blood mononuclear cell by magnetic separation. Naive T cells were stimulated with anti-CD3, anti-CD28, and goat anti-mouse IgG antibodies and treated with transforming grow factor beta, interleukin (IL)-6, IL-1β , and IL-23 cytokines and also with anti-IL-4 antibody...
2018: Frontiers in Immunology
Mohamed Abdel-Mohsen, Leticia Kuri-Cervantes, Judith Grau-Exposito, Adam M Spivak, Racheal A Nell, Costin Tomescu, Surya Kumari Vadrevu, Leila B Giron, Carla Serra-Peinado, Meritxell Genescà, Josep Castellví, Guoxin Wu, Perla M Del Rio Estrada, Mauricio González-Navarro, Kenneth Lynn, Colin T King, Sai Vemula, Kara Cox, Yanmin Wan, Qingsheng Li, Karam Mounzer, Jay Kostman, Ian Frank, Mirko Paiardini, Daria Hazuda, Gustavo Reyes-Terán, Douglas Richman, Bonnie Howell, Pablo Tebas, Javier Martinez-Picado, Vicente Planelles, Maria J Buzon, Michael R Betts, Luis J Montaner
The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH 2 phenotype as defined by CXCR3, CCR4, and CCR6...
April 18, 2018: Science Translational Medicine
Yanchun Zhou, Xiuhua Meng, Shaoying Chen, Wei Li, Delin Li, Robert Singer, Wei Gu
BACKGROUND: Long noncoding RNAs (LncRNAs) represent a class of widespread and diverse endogenous RNAs that can posttranscriptionally regulate gene expression through the interaction with RNA-binding proteins and micro RNAs (miRNAs). Here, we report that in breast carcinoma cells, the insulin-like growth factor 2 messenger RNA binding protein (IMP1) binds to lncRNA urethral carcinoma-associated 1 (UCA1) and suppresses the UCA1-induced invasive phenotype. METHODS: RT-qPCR and RNA sequence assays were used to investigate the expression of UCA1 and miRNAs in breast cancer cells in response to IMP1 expression...
April 18, 2018: Breast Cancer Research: BCR
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