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https://www.readbyqxmd.com/read/29023488/transgenic-expression-of-human-cytokines-in-immunodeficient-mice-does-not-facilitate-myeloid-expansion-of-bcr-abl1-transduced-human-cord-blood-cells
#1
Maria Askmyr, Sofia von Palffy, Nils Hansen, Niklas Landberg, Carl Högberg, Marianne Rissler, Helena Ågerstam, Thoas Fioretos
Several attempts have been made to model chronic myeloid leukemia (CML) in a xenograft setting but expansion of human myeloid cells in immunodeficient mice has proven difficult to achieve. Lack of cross-reacting cytokines in the microenvironment of the mice has been proposed as a potential reason. In this study we have used NOD/SCID IL2-receptor gamma deficient mice expressing human SCF, IL-3 and GM-CSF (NSGS mice), that should be superior in supporting human, and particularly, myeloid cell engraftment, to expand BCR-ABL1 expressing human cells in order to model CML...
2017: PloS One
https://www.readbyqxmd.com/read/28956210/identification-of-drought-responsive-micrornas-in-tomato-using-high-throughput-sequencing
#2
Minmin Liu, Huiyang Yu, Gangjun Zhao, Qiufeng Huang, Yongen Lu, Bo Ouyang
Drought is a major abiotic stress affecting crop productivity and quality. As a class of noncoding RNA, microRNA (miRNA) plays important roles in plant growth, development, and stress response. However, their response and roles in tomato drought stress is largely unknown. Here, by using high-throughput sequencing, we compared the miRNA profiles before and after drought treatment in two tomato genotypes: M82, a drought-sensitive cultivated tomato (Solanum lycopersicum), and IL2-5, a drought-tolerant introgression line derived from M82 and the tomato wild species S...
September 28, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28951527/ethanol-stimulates-locomotion-via-a-g%C3%AE-s-signalling-pathway-in-il2-neurons-in-caenorhabditis-elegans
#3
James R Johnson, Mark R Edwards, Huw Davies, Daniel Newman, Whitney Holden, Rosalind E Jenkins, Robert D Burgoyne, Robert J Lucas, Jeff W Barclay
Alcohol is a potent pharmacological agent when consumed acutely at sufficient quantities and repeated overuse can lead to addiction and deleterious effects on health. Alcohol is thought to modulate neuronal function through low affinity interactions with proteins, in particular with membrane channels and receptors. Paradoxically, alcohol acts as both a stimulant and a sedative. The exact molecular mechanisms for the acute effects of ethanol on neurons, as either a stimulant or a sedative, however remain unclear...
September 26, 2017: Genetics
https://www.readbyqxmd.com/read/28916655/tethering-il2-to-its-receptor-il2r%C3%AE-enhances-anti-tumor-activity-and-expansion-of-natural-killer-nk92-cells
#4
Youssef Jounaidi, Joseph F Cotten, Keith W Miller, Stuart A Forman
Interleukin-2 (IL2) is an immunostimulatory cytokine for key immune cells including T cells and natural killer (NK) cells. Systemic IL2 supplementation could enhance NK-mediated immunity in a variety of diseases ranging from neoplasms to viral infection. However, its systemic use is restricted by its serious side effects and limited efficacy due to activation of T regulatory cells (Tregs). IL2 signaling is mediated through interactions with a multi-subunit receptor complex containing IL2Rα, IL2Rβ and IL2Rγ...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28912468/cytokine-based-predictive-models-to-estimate-the-probability-of-chronic-periodontitis-development-of-diagnostic-nomograms
#5
I Tomás, N Arias-Bujanda, M Alonso-Sampedro, M A Casares-de-Cal, C Sánchez-Sellero, D Suárez-Quintanilla, C Balsa-Castro
Although a distinct cytokine profile has been described in the gingival crevicular fluid (GCF) of patients with chronic periodontitis, there is no evidence of GCF cytokine-based predictive models being used to diagnose the disease. Our objectives were: to obtain GCF cytokine-based predictive models; and develop nomograms derived from them. A sample of 150 participants was recruited: 75 periodontally healthy controls and 75 subjects affected by chronic periodontitis. Sixteen mediators were measured in GCF using the Luminex 100™ instrument: GMCSF, IFNgamma, IL1alpha, IL1beta, IL2, IL3, IL4, IL5, IL6, IL10, IL12p40, IL12p70, IL13, IL17A, IL17F and TNFalpha...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899730/a-green-tea-polyphenol-epigallocatechin-3-gallate-enhances-neuroregeneration-after-spinal-cord-injury-by-altering-levels-of-inflammatory-cytokines
#6
Lucia Machova Urdzikova, Jiri Ruzicka, Kristyna Karova, Anna Kloudova, Barbora Svobodova, Anubhav Amin, Jana Dubisova, Meic Schmidt, Sarka Kubinova, Meena Jhanwar-Uniyal, Pavla Jendelova
Spinal cord injury (SCI) is a debilitating condition which is characterized by an extended secondary injury due to the presence of inflammatory local milieu. Epigallocatechin gallate (EGCG) appears to possess strong neuroprotective properties. Here, we evaluated the beneficial effect of EGCG on recovery from SCI. Male Wistar rats were given either EGCG or saline directly to the injured spinal cord and thereafter a daily IP injection. Behavior recovery was monitored by BBB, plantar, rotarod and flat-beam tests...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28892206/il-33-and-ige-stimulate-mast-cell-production-of-il-2-and-regulatory-t-cells-expansion-in-allergic-dermatitis
#7
Pazit Salamon, Irit Shefler, Itay Moshkovits, Ariel Munitz, Deborah Horwitz Klotzman, Yoseph A Mekori, Alon Y Hershko
BACKGROUND: We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. OBJECTIVE: To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. METHODS: Isolated murine bone marrow derived-MCs (BMMCs) were incubated with various stimulators and IL-2 production was assessed by RT-PCR and ELISA...
September 11, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28878331/the-immunosuppressive-effect-of-the-tick-protein-salp15-is-long-lasting-and-persists-in-a-murine-model-of-hematopoietic-transplant
#8
Julen Tomás-Cortázar, Itziar Martín-Ruiz, Diego Barriales, Miguel Ángel Pascual-Itoiz, Virginia Gutiérrez de Juan, Alfredo Caro-Maldonado, Nekane Merino, Alberto Marina, Francisco J Blanco, Juana María Flores, James D Sutherland, Rosa Barrio, Adriana Rojas, María Luz Martínez-Chantar, Arkaitz Carracedo, Carolina Simó, Virginia García-Cañas, Leticia Abecia, José Luis Lavín, Ana M Aransay, Héctor Rodríguez, Juan Anguita
Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869563/synergic-anti-pruritus-mechanisms-of-action-for-the-radix-sophorae-flavescentis-and-fructus-cnidii-herbal-pair
#9
Jiali Zhong, Zhihong Liu, Xinxin Zhou, Jun Xu
Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the main active ingredients for the RSF and FC herbal pair. We demonstrate that the RSF-FC herbal pair can be elucidated by mining the chemical structures of compounds derived from RSF and FC. Based on chemical structure data, the putative targets for RSF and FC were predicted...
September 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28861943/surface-engineering-of-red-blood-cells-as-artificial-antigen-presenting-cells-promising-for-cancer-immunotherapy
#10
Xiaoqi Sun, Xiao Han, Ligeng Xu, Min Gao, Jun Xu, Rong Yang, Zhuang Liu
The development of artificial antigen presenting cells (aAPCs) to mimic the functions of APCs such as dendritic cells (DCs) to stimulate T cells and induce antitumor immune responses has attracted substantial interests in cancer immunotherapy. In this work, a unique red blood cell (RBC)-based aAPC system is designed by engineering antigen peptide-loaded major histocompatibility complex-I and CD28 activation antibody on RBC surface, which are further tethered with interleukin-2 (IL2) as a proliferation and differentiation signal...
September 1, 2017: Small
https://www.readbyqxmd.com/read/28836262/immune-status-of-patients-with-haemophilia-a-before-exposure-to-factor-viii-first-results-from-the-hemfil-study
#11
MULTICENTER STUDY
Letícia L Jardim, Daniel G Chaves, Amanda C O Silveira-Cassette, Ana Cristina Simões E Silva, Marcio P Santana, Monica H Cerqueira, Alessandra Prezotti, Claudia Lorenzato, Vivian Franco, Johanna G van der Bom, Suely M Rezende
Previous cross-sectional studies showed that some patients with haemophilia A (HA) without inhibitor presented a pro-inflammatory profile during factor VIII (FVIII) replacement therapy. Furthermore, an anti-inflammatory/regulatory state was described in HA patients after inhibitor development. However, no study investigated the levels of these biomarkers before exposure to exogenous FVIII. This study investigated the immunological profile of previously untreated patients (PUPs) with HA in comparison with non-haemophiliac boys...
September 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28821531/cd28-and-41bb-costimulation-enhances-the-effector-function-of-cd19-specific-engager-t-cells
#12
Mireya Paulina Velasquez, Arpad Szoor, Abishek Vaidya, Aarohi Thakkar, Phuong Nguyen, Meng-Fen Wu, Hao Liu, Stephen Gottschalk
T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies. Besides CD19-specific CARs, other approaches are actively being pursued to redirect T cells to CD19, including recombinant bispecific T-cell engager (BiTE) proteins or T cells genetically modified to express BiTEs [engager (ENG) T cells]. As BiTEs provide no costimulation, we investigated here if provision of costimulation through CD28 and 41BB enhances the effector function of CD19-ENG T cells...
October 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28774835/current-and-emerging-biomarkers-in-tumors-of-the-central-nervous-system-possible-diagnostic-prognostic-and-therapeutic-applications
#13
REVIEW
Ishaq N Khan, Najeeb Ullah, Deema Hussein, Kulvinder S Saini
Recent investments in research associated with the discovery of specific tumor biomarkers important for efficient diagnosis and prognosis are beginning to bear fruit. Key biomarkers could potentially outweigh traditional radiological or pathological methods by enabling specificity of early detection, when coupled with tumor molecular profiling and clinical associations. Only few biomarkers are approved by regulatory authorities for Central Nervous System Tumors (CNSTs), despite the evaluation of a large number of CNST related markers during clinical trials...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28768877/immunodominance-of-adenovirus-derived-cd8-t-cell-epitopes-interferes-with-the-induction-of-transgene-specific-immunity-in-adenovirus-based-immunization
#14
Dominik Schöne, Camilla Patrizia Hrycak, Sonja Windmann, Dennis Lapuente, Ulf Dittmer, Matthias Tenbusch, Wibke Bayer
Adenovirus (Ad)-based immunization is a popular approach in vaccine development, and Ad-based vectors are renowned for their potential to induce strong CD8(+) T cell responses to the encoded transgene. Surprisingly, we previously found in the mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8(+) T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL85-93 We show now that induction of GagL85-93-specific CD8(+) T cells was highly effective when leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad-derived epitopes in mediating unresponsiveness...
October 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28716814/potency-matched-dual-cytokine-antibody-fusion-proteins-for-cancer-therapy
#15
Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
A novel biopharmaceutical, consisting of the F8 monoclonal antibody (specific to a splice isoform of fibronectin) simultaneously fused to both tumor necrosis factor and interleukin-2, was found to react with the majority of solid tumors and hematological malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNF(mut)) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody-cytokine fusion proteins or by standard doxorubicin treatment...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28713365/what-s-normal-immune-profiling-of-human-milk-from-healthy-women-living-in-different-geographical-and-socioeconomic-settings
#16
Lorena Ruiz, Irene Espinosa-Martos, Cristina García-Carral, Susana Manzano, Michelle K McGuire, Courtney L Meehan, Mark A McGuire, Janet E Williams, James Foster, Daniel W Sellen, Elizabeth W Kamau-Mbuthia, Egidioh W Kamundia, Samwel Mbugua, Sophie E Moore, Linda J Kvist, Gloria E Otoo, Kimberly A Lackey, Katherine Flores, Rossina G Pareja, Lars Bode, Juan M Rodríguez
Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28702029/inflammation-related-gene-polymorphisms-associated-with-primary-immune-thrombocytopenia
#17
Ju Li, Sai Ma, Linlin Shao, Chunhong Ma, Chengjiang Gao, Xiao-Hui Zhang, Ming Hou, Jun Peng
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226, FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1, in the pathogenesis and treatment response of ITP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28686482/outer-membrane-vesicles-blebbing-contributes-to-b-vulgatus-mpk-mediated-immune-response-silencing
#18
Jan Kevin Maerz, Alex Steimle, Anna Lange, Annika Bender, Birgit Fehrenbacher, Julia-Stefanie Frick
The Gram negative intestinal symbiont Bacteroides vulgatus mpk is able to prevent from induction of colonic inflammation in Rag1(-/-) mice and promotes immune balance in Il2(-/-) mice. These inflammation-silencing effects are associated with B. vulgatus mpk-mediated induction of semi-mature dendritic cells, especially in the colonic lamina propria (cLP). However the beneficial interaction of bacteria with host immune cells is limited due to the existence of a large mucus layer covering the intestinal epithelium...
July 7, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28686294/nfat-regulated-cytokine-gene-expression-during-tacrolimus-therapy-early-after-renal-transplantation
#19
Sara Bremer, Nils T Vethe, Morten Skauby, Margrete Kasbo, Elisabet D Johansson, Karsten Midtvedt, Stein Bergan
AIMS: Despite pharmacokinetic monitoring of calcineurin inhibitors, the long-term outcome after transplantation (Tx) is still hampered by the side effects of these drugs. The aim of this study was to characterize the nuclear factor of activated T cells (NFAT)-regulated gene expression as a potential pharmacodynamic biomarker for further individualization of tacrolimus (Tac) therapy. METHODS: In 29 renal allograft recipients samples were drawn once pre-Tx, and before and 1...
July 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28679475/cik-as-therapeutic-agents-against-tumors
#20
REVIEW
M Introna
Cytokine Induced Killer (CIK) cells are ex vivo expanded and activated T lymphocytes obtained by sequential incubation of Peripheral Blood Mononuclear cells (PBMNC) with Interferon γ (IFNG), anti CD3 monoclonal antibody OKT3 and IL2. These cells, while retaining few characteristics of the Effector memory T cells subpopulation, acquired during culture CD56 expression, as well as non specific, Natural Killer like, anti tumoral cytotoxicity. CIK cells from human are equivalent to expanded NKT cells in mouse...
July 2, 2017: Journal of Autoimmunity
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