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https://www.readbyqxmd.com/read/28109039/nkx2-5-regulates-endothelin-converting-enzyme-1-during-pharyngeal-arch-patterning
#1
Jennifer M Iklé, Andre L P Tavares, Marisol King, Hailei Ding, Sophie Colombo, Beth A Firulli, Anthony B Fiulli, Kimara L Targoff, Deborah Yelon, David E Clouthier
In gnathostomes, dorsoventral (D-V) patterning of neural crest cells (NCC) within the pharyngeal arches is crucial for the development of hinged jaws. One of the key signals that mediates this process is Endothelin-1 (EDN1). Loss of EDN1 binding to the Endothelin-A receptor (EDNRA) results in loss of EDNRA signaling and subsequent facial birth defects in humans, mice and zebrafish. A rate-limiting step in this crucial signaling pathway is the conversion of immature EDN1 into a mature active form by Endothelin converting enzyme-1 (ECE1)...
January 20, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#2
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28108989/tigit-signaling-pathway-negatively-regulates-cd4-t-cell-responses-in-systemic-lupus-erythematosus
#3
Lie Mao, Hongyan Hou, Shiji Wu, Yu Zhou, Juan Wang, Jing Yu, Xiaohui Wu, Yanfang Lu, Liyan Mao, Munyemana Jean Bosco, Feng Wang, Ziyong Sun
B lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T cell-dependent, and CD4(+) T cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4(+) T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4(+) T cells. Here, we addressed the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4(+) T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28108607/insulin-like-growth-factor-binding-protein-1-could-improve-glucose-regulation-and-insulin-sensitivity-through-its-rgd-domain
#4
Natalie J Haywood, Paul A Cordell, Kar Yeun Tang, Natallia Makova, Nadira Y Yuldasheva, Helen Imrie, Hema Viswambharan, Alexander F Bruns, Richard M Cubbon, Mark T Kearney, Stephen B Wheatcroft
Low circulating levels of insulin-like growth factor binding protein 1 (IGFBP-1) are associated with insulin resistance and predict the development of type 2 diabetes. IGFBP-1 can affect cellular functions independently of IGF binding through an Arg-Gly-Asp (RGD) integrin-binding motif. Whether causal mechanisms underlie the favorable association of high IGFBP-1 levels with insulin sensitivity and whether these could be exploited therapeutically remain unexplored. We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complementary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion, and whole-body glucose regulation...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108557/low-level-mhc-class-ii-expression-leads-to-suboptimal-th-cell-response-increased-autoaggression-and-heightened-cytokine-inducibility
#5
Yi-Ting Chen, Yu-Chia Su, Mei-Ling Chang, Pi-Fang Tsai, John T Kung
The development and activation of MHC class II (MHC-II)-restricted CD4(+) T cells are distinct immunological processes that are strictly MHC-II-dependent. To address their relative dependence on MHC-II, we established a novel ENU-induced mutant mouse on the C57BL/6 background, named I-A(12%), with ∼8-fold reduced I-A expression on the surface of B cells, dendritic cells, cortical thymic epithelial cells, and medullary thymic epithelial cells. I-A(100%) and I-A(12%) mice are highly similar with respect to the numbers of double-positive thymocytes, CD4(+)CD8(-) T cells, regulatory T cells, CD4(+) T cell marker expression, lifespan, and Th/regulatory T cell function...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108506/biomarker-dynamics-in-b-cell-lymphoma-a-longitudinal-prospective-study-of-plasma-samples-up-to-25-years-before-diagnosis
#6
Florentin Späth, Carl Wibom, Esmeralda J M Krop, Ann-Sofie Johansson, Ingvar A Bergdahl, Roel Vermeulen, Beatrice Melin
The B-cell activation markers CXCL13, sCD23, sCD27, and sCD30 are associated with future lymphoma risk. However, a lack of information about the individual dynamics of marker-disease association hampers interpretation. In this study, we identified 170 individuals who had donated two pre-diagnostic blood samples before B-cell lymphoma diagnosis, along with 170 matched cancer-free controls from the Northern Sweden Health and Disease Study. Lymphoma risk associations were investigated by subtype and marker levels measured at baseline, at the time of the repeated sample, and with the rate of change in the marker level...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108486/regulation-of-the-immune-response-by-tgf-%C3%AE-from-conception-to-autoimmunity-and-infection
#7
Shomyseh Sanjabi, Soyoung A Oh, Ming O Li
Transforming growth factor β (TGF-β) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-β alters immunity under various conditions. Under steady-state conditions, TGF-β regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-β inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral (p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges...
January 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28108460/enhancer-remodeling-during-adaptive-bypass-to-mek-inhibition-is-attenuated-by-pharmacological-targeting-of-the-p-tefb-complex
#8
Jon S Zawistowski, Samantha M Bevill, Daniel R Goulet, Timothy J Stuhlmiller, Adriana S Beltran, Jose F Olivares-Quintero, Darshan Singh, Noah Sciaky, Joel S Parker, Naim U Rashid, Xin Chen, James S Duncan, Martin C Whittle, Steven P Angus, Sara Hanna Velarde, Brian T Golitz, Xiaping He, Charlene Santos, David B Darr, Kristalyn Gallagher, Lee M Graves, Charles M Perou, Lisa A Carey, H Shelton Earp, Gary L Johnson
Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment...
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28108389/development-of-clostridium-difficile-r20291%C3%AE-paloc-model-strains-and-in-vitro-methodologies-reveals-cdtr-is-required-for-the-production-of-cdt-to-cytotoxic-levels
#9
T W Bilverstone, N L Kinsmore, N P Minton, S A Kuehne
Assessing the regulation of Clostridium difficile transferase (CDT), is complicated by the presence of a Pathogenicity locus (PaLoc) which encodes Toxins A and B. Here we developed R20291ΔPaLoc model strains and cell-based assays to quantify CDT-mediated virulence. Their application demonstrated that the transcriptional regulator, CdtR, was required for CDT-mediated cytotoxicity.
January 17, 2017: Anaerobe
https://www.readbyqxmd.com/read/28108377/cucurbitacin-b-purified-from-ecballium-elaterium-l-a-rich-from-tunisia-inhibits-%C3%AE-5%C3%AE-1-integrin-mediated-adhesion-migration-proliferation-of-human-glioblastoma-cell-line-and-angiogenesis
#10
Imen Touihri-Barakati, Olfa Kallech-Ziri, Wiem Ayadi, Hervé Kovacic, Belgacem Hanchi, Karim Hosni, José Luis
Integrins are essential protagonists in the complex multistep process of cancer progression and are thus attractive targets for the development of anticancer agents. Cucurbitacin B, a triterpenoid purified from the leaves of Tunisian Ecballium elaterium exhibited an anticancer effect and displayed anti-integrin activity on human glioblastoma U87 cells, without being cytotoxic at concentrations up to 500nM. Here we show that cucurbitacin B affected the adhesion and migration of U87 cells to fibronectin in a dose-dependent manner with IC50 values of 86...
January 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28108365/neutrophil-subset-responses-in-infants-with-severe-viral-respiratory-infection
#11
Bart Cortjens, Sarah A Ingelse, Job C Calis, Alexander P Vlaar, Leo Koenderman, Reinout A Bem, Job B van Woensel
Neutrophils are the predominant inflammatory cells recruited to the respiratory tract as part of the innate immune response to viral infections. Recent reports indicate the existence of distinct functional neutrophil subsets in the circulatory compartment of adults, following severe inflammatory conditions. Here, we evaluated the occurrence of neutrophil subsets in blood and broncho-alveolar lavage fluid during severe viral respiratory infection in infants based on CD16/CD62L expression. We show that during the course of severe respiratory infection infants may develop four heterogeneous neutrophil subsets in blood (mature, immature, progenitor, and suppressive neutrophils), each with distinct activation states...
January 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28108242/evaluation-of-the-antimicrobial-activity-of-the-mastoparan-polybia-mpii-isolated-from-venom-of-the-social-wasp-pseudopolybia-vespiceps-testacea-vespidae-hymenoptera
#12
Juliana C Silva, Lázaro M Neto, Rogério C Neves, Jaqueline C Gonçalves, Monalisa M Trentini, Ricardo Mucury-Filho, Karina S Smidt, Isabel C Fensterseifer, Osmar N Silva, Lilian D Lima, Patricia B Clissa, Nathália Vilela, Fernanda Guilhelmelli, Luciano P Silva, Marisa Rangel, André Kipnis, Ildinete Silva-Pereira, Octavio L Franco, Ana P Junqueira-Kipnis, Anamelia L Bocca, Márcia R Mortari
Mastoparans, a class of peptides found in wasp venom, have significant effects following a sting as well as useful applications in clinical practice. Among these is their potential use in the control of micro-organisms that cause infectious diseases with a significant impact on society. Thus, the present study describes the isolation and identification of a mastoparan peptide from the venom of the social wasp Pseudopolybia vespiceps and evaluated its antimicrobial profile against bacteria (Staphylococcus aureus and Mycobacterium abscessus subsp...
January 9, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28108151/a-functional-genetic-screen-identifies-the-phosphoinositide-3-kinase-pathway-as-a-determinant-of-resistance-to-fibroblast-growth-factor-receptor-inhibitors-in-fgfr-mutant-urothelial-cell-carcinoma
#13
Liqin Wang, Tonći Šuštić, Rodrigo Leite de Oliveira, Cor Lieftink, Pasi Halonen, Marieke van de Ven, Roderick L Beijersbergen, Michel M van den Heuvel, René Bernards, Michiel S van der Heijden
Activating mutations and translocations of the FGFR3 gene are commonly seen in urothelial cell carcinoma (UCC) of the bladder and urinary tract. Several fibroblast growth factor receptor (FGFR) inhibitors are currently in clinical development and response rates appear promising for advanced UCC. A common problem with targeted therapeutics is intrinsic or acquired resistance of the cancer cells. To find potential drug targets that can act synergistically with FGFR inhibition, we performed a synthetic lethality screen for the FGFR inhibitor AZD4547 using a short hairpin RNA library targeting the human kinome in the UCC cell line RT112 (FGFR3-TACC3 translocation)...
January 17, 2017: European Urology
https://www.readbyqxmd.com/read/28107608/the-increased-expression-of-tcf3-is-correlated-with-poor-prognosis-in-chinese-patients-with-nasopharyngeal-carcinoma
#14
Xiaohe Shen, Jizhao Yuan, Mengjie Zhang, Wenhua Li, Bing Ni, Yuzhang Wu, Li Jiang, Weiping Fan, Zhiqiang Tian
OBJECTIVES: Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote cancer growth and progression. B-cell-specific transcription factor 3 (TCF3/E2A) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family that is central to regulating epidermal and embryonic stem cell identity. It has been reported that TCF3 was connected with the development and progression of a number of human cancers...
January 20, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28107482/a-circulating-microrna-signature-predicts-age-based-development-of-lymphoma
#15
Afshin Beheshti, Charles Vanderburg, J Tyson McDonald, Charusheila Ramkumar, Tatenda Kadungure, Hong Zhang, Ronald B Gartenhaus, Andrew M Evens
Extensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL) that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA) signatures in the host influence diffuse large B cell lymphoma (DLBCL) development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach...
2017: PloS One
https://www.readbyqxmd.com/read/28107431/characterization-of-a-broadly-reactive-anti-cd40-agonistic-monoclonal-antibody-for-potential-use-as-an-adjuvant
#16
Cameron Martin, Suryakant D Waghela, Shehnaz Lokhandwala, Andy Ambrus, Jocelyn Bray, Christina Vuong, Vanitha Vinodkumar, Paul J Dominowski, Sharath Rai, Duncan Mwangi, Dennis L Foss, Waithaka Mwangi
Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb), designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species...
2017: PloS One
https://www.readbyqxmd.com/read/28107180/identification-of-micrornas-implicated-in-the-late-differentiation-stages-of-normal-b-cells-suggests-a-central-role-for-mirna-targets-zeb1-and-tp53
#17
Giorgio Malpeli, Stefano Barbi, Simonetta Zupo, Gabriele Tosadori, Giovanni Scardoni, Anna Bertolaso, Silvia Sartoris, Stefano Ugel, Caterina Vicentini, Matteo Fassan, Annalisa Adamo, Mauro Krampera, Maria Teresa Scupoli, Carlo Maria Croce, Aldo Scarpa
In the late B cell differentiation stages, miRNAs expression modifications promoting or inhibiting key pathways are only partially defined. We isolated 29 CD19+ human B cell samples at different stages of differentiation: B cells from peripheral blood; naïve, germinal center (GC) and subepithelial (SE) B cells from tonsils. SE cells were further split in activated and resting B cell. The miRNA expression profile of these B cells was assessed by microarray analysis and selected miRNAs were validated by quantitative RT-PCR and in situ hybridization on normal tonsils...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106808/anti-fatigue-effects-of-the-unique-polysaccharide-marker-of-dendrobium-officinale-on-balb-c-mice
#18
Wei Wei, Zhi-Peng Li, Tong Zhu, Hau-Yee Fung, Tin-Long Wong, Xin Wen, Dik-Lung Ma, Chung-Hang Leung, Quan-Bin Han
Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D...
January 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106799/rna-editing-adar1-and-the-innate-immune-response
#19
REVIEW
Qingde Wang, Xiaoni Li, Ruofan Qi, Timothy Billiar
RNA editing, particularly A-to-I RNA editing, has been shown to play an essential role in mammalian embryonic development and tissue homeostasis, and is implicated in the pathogenesis of many diseases including skin pigmentation disorder, autoimmune and inflammatory tissue injury, neuron degeneration, and various malignancies. A-to-I RNA editing is carried out by a small group of enzymes, the adenosine deaminase acting on RNAs (ADARs). Only three members of this protein family, ADAR1-3, exist in mammalian cells...
January 18, 2017: Genes
https://www.readbyqxmd.com/read/28106517/traditional-invasive-and-synchrotron-based-non-invasive-assessments-of-3d-printed-hybrid-cartilage-constructs
#20
Adeola Deborah Olubamiji, Ning Zhu, Tuanjie Chang, Chijioke Nwankwo, Zohreh Izadifar, Ali Honaramooz, Daniel Chen, B Frank Eames
Three-dimensional (3D)-printed constructs made of polycaprolactone (PCL) and chondrocyte-impregnated alginate hydrogel (hybrid cartilage constructs) mimic the biphasic nature of articular cartilage, offering promise for cartilage tissue engineering (CTE) applications. However, the regulatory pathway for medical device development requires validation of such constructs through in vitro bench tests and in vivo preclinical examinations premarket approval. Furthermore, non-invasive imaging techniques are required for effective evaluation of the progress of these cartilage constructs, especially when implanted in animal models or human subjects...
January 20, 2017: Tissue Engineering. Part C, Methods
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