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https://www.readbyqxmd.com/read/28334626/label-free-electrochemiluminescent-biosensor-for-rapid-and-sensitive-detection-of-pseudomonas-aeruginosa-using-phage-as-highly-specific-recognition-agent
#1
Huan Yue, Yong He, Enci Fan, Lin Wang, Shuguang Lu, Zhifeng Fu
A virulent phage named as PaP1 was isolated from hospital sewage based on a lambda phage isolation protocol. This phage showed a strong and highly specific binding ability to Pseudomonas aeruginosa (P. aeruginosa). Using this isolated phage as a recognition agent, a novel electrochemiluminescent (ECL) biosensor was developed for label-free detection of P. aeruginosa. The biosensor was fabricated through depositing phage-conjugated carboxyl graphene onto the surface of a glass carbon electrode. After specific binding of the host bacteria through the adsorption of P...
March 18, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28333137/the-mtor-signal-regulates-myeloid-derived-suppressor-cells-differentiation-and-immunosuppressive-function-in-acute-kidney-injury
#2
Chao Zhang, Shuo Wang, Jiawei Li, Weitao Zhang, Long Zheng, Cheng Yang, Tongyu Zhu, Ruiming Rong
The mammalian target of rapamycin (mTOR) signal controls innate and adaptive immune response in multiple immunoregulatory contexts. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells of potent immunosuppressive capacity. In this study, we aimed to investigate the role of MDSCs in the protection of acute kidney injury (AKI) and the regulation of mTOR signal on MDSC's protective role in this context. In mice AKI model, rapamycin administration was associated with improved renal function, restored histological damage and decreased CD4(+) and CD8(+) T-cell infiltration in kidney tissue...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28331616/ex-vivo-akt-inhibition-promotes-the-generation-of-potent-cd19car-t-cells-for-adoptive-immunotherapy
#3
Ryan Urak, Miriam Walter, Laura Lim, ChingLam W Wong, Lihua E Budde, Sandra Thomas, Stephen J Forman, Xiuli Wang
BACKGROUND: Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation. We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331613/systematic-evaluation-of-immune-regulation-and-modulation
#4
REVIEW
David F Stroncek, Lisa H Butterfield, Michael A Cannarile, Madhav V Dhodapkar, Tim F Greten, Jean Charles Grivel, David R Kaufman, Heidi H Kong, Firouzeh Korangy, Peter P Lee, Francesco Marincola, Sergio Rutella, Janet C Siebert, Giorgio Trinchieri, Barbara Seliger
Cancer immunotherapies are showing promising clinical results in a variety of malignancies. Monitoring the immune as well as the tumor response following these therapies has led to significant advancements in the field. Moreover, the identification and assessment of both predictive and prognostic biomarkers has become a key component to advancing these therapies. Thus, it is critical to develop systematic approaches to monitor the immune response and to interpret the data obtained from these assays. In order to address these issues and make recommendations to the field, the Society for Immunotherapy of Cancer reconvened the Immune Biomarkers Task Force...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28321811/interleukin-2-old-and-new-approaches-to-enhance-immune-therapeutic-efficacy
#5
Pooja Dhupkar, Nancy Gordon
Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. Systemic delivery of IL-2 has shown clinical benefit in renal cell carcinoma and melanoma patients. However, its use has been limited by the numerous toxicities encountered with the systemic delivery. Intravenous IL-2 causes the well-known "capillary leak syndrome," or the leakage of fluid from the circulatory system to the interstitial space resulting in hypotension (low blood pressure), edema, and dyspnea that can lead to circulatory shock and eventually cardiopulmonary collapse and multiple organ failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28320933/activin-a-co-opts-irf4-and-ahr-signaling-to-induce-human-regulatory-t-cells-that-restrain-asthmatic-responses
#6
Sofia Tousa, Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Aikaterini I Trochoutsou, Tess M Brodie, Nikolaos Poulos, Konstantinos Samitas, Maria Kapasa, Dimitris Konstantopoulos, Giannis Paraskevopoulos, Mina Gaga, Catherine M Hawrylowicz, Federica Sallusto, Georgina Xanthou
Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4(+) T cells that express the Tr1-cell-associated molecules IL-10, inducible T-Cell costimulator (ICOS), lymphocyte activation gene 3 protein (LAG-3), and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320753/do-memory-b-cells-form-secondary-germinal-centers-impact-of-antibody-class-and-quality-of-memory-t-cell-help-at-recall
#7
Louise J McHeyzer-Williams, Chad Dufaud, Michael G McHeyzer-Williams
Antigen recall can clearly induce a germinal center (GC) reaction. What has become an issue for debate are the origins of the antigen-specific B cells that form memory-response GCs (mGCs). Using antigen labeling and adoptive transfer, memory B cells expressing different antibody class can give rise to mGCs with differing efficiency. Here, we will argue that the range of class-specific memory responses reported across multiple systems represents the spectrum of memory B-cell fate and function. While the formulation of recall immunogen and location of mGCs have an important role, we propose that effective cognate regulation is the key variable influencing recall outcome...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28320593/spore-photoproduct-within-dna-is-a-surprisingly-poor-substrate-for-its-designated-repair-enzyme-the-spore-photoproduct-lyase
#8
Linlin Yang, Yajun Jian, Peter Setlow, Lei Li
DNA repair enzymes typically recognize their substrate lesions with high affinity to ensure efficient lesion repair. In UV irradiated endospores, a special thymine dimer, 5-thyminyl-5,6-dihydrothymine, termed the spore photoproduct (SP), is the dominant DNA photolesion, which is rapidly repaired during spore outgrowth mainly by spore photoproduct lyase (SPL) using an unprecedented protein-harbored radical transfer process. Surprisingly, our in vitro studies using SP-containing short oligonucleotides, pUC 18 plasmid DNA, and E...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28320444/ox40-signaling-is-involved-in-the-autoactivation-of-cd4-cd28-t-cells-and-contributes-to-the-pathogenesis-of-autoimmune-arthritis
#9
Juean Jiang, Cuiping Liu, Mi Liu, Yu Shen, Xiaohan Hu, Qin Wang, Jian Wu, Min Wu, Qi Fang, Xueguang Zhang
BACKGROUND: CD4(+)CD28(-) T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of this study was to investigate the costimulatory effects of OX40 on CD4(+)CD28(-) T cells in autoimmune arthritis...
March 21, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28318626/the-leukotriene-b4-leukotriene-b4-receptor-axis-promotes-cisplatin-induced-acute-kidney-injury-by%C3%A2-modulating-neutrophil-recruitment
#10
Bo Deng, Yuli Lin, Shuai Ma, Yin Zheng, Xuguang Yang, Bingji Li, Wenyan Yu, Qingqing Xu, Tingyan Liu, Chuanming Hao, Rui He, Feng Ding
Cisplatin is an effective chemotherapeutic agent and widely used in treatment of various solid organ malignancies, including head and neck, ovarian, and testicular cancers. However, the induction of acute kidney injury (AKI) is one of its main side effects. Leukotriene B4 receptor 1 (BLT1) mediates the majority of physiological effects of leukotriene B4 (LTB4), a potent lipid chemoattractant generated at inflammation sites, but the role of the LTB4-BLT1 axis in cisplatin-induced AKI remains unknown. Here we found upregulated LTB4 synthesis and BLT1 expression in the kidney after cisplatin administration...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#11
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28318408/bone-marrow-derived-mesenchymal-stem-cells-attenuate-immune-mediated-liver-injury-and-compromise-virus-control-during-acute-hepatitis-b-virus-infection-in-mice
#12
Mengmeng Qu, Xu Yuan, Dan Liu, Yuhong Ma, Jun Zhu, Jun Cui, Mengxue Yu, Changyong Li, Deyin Guo
Mesenchymal stem cells (MSCs) have been used as therapeutic tools not only for their ability to differentiate toward different cells, but also for their unique immunomodulatory properties. However, it is still unknown how MSCs may affect immunity during hepatitis B virus (HBV) infection. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in a mouse model of acute HBV infection. Mice were injected with 1 × 10(6) BM-MSCs, which stained with chloromethyl derivatives of fluorescein diacetate fluorescent probe, 24 h before hydrodynamic injection of viral DNA (pHBV1...
February 2, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#13
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28315676/the-major-histocompatibility-complex-class-iii-haplotype-ltab-ncr3-regulates-adjuvant-induced-but-not-antigen-induced-autoimmunity
#14
Anthony C Y Yau, Jonatan Tuncel, Rikard Holmdahl
Rheumatoid arthritis is a complex disease associated with >100 risk loci, with the strongest association from the major histocompatibility complex (MHC) region. Here, we analyzed a new genetic association in the MHC class-III region (MHC-III) using adjuvant- and antigen-induced arthritis models. In addition, we used models for multiple sclerosis for comparison and dissected the MHC-III-mediated mechanisms of importance for antibody and T-cell responses to antigens. With the use of a panel of MHC-III recombinant inbred strains, we found that the 33-kb Ltab-Ncr3 haplotype in MHC-III was linked to the induction of arthritis with incomplete Freund's adjuvant, with similar effects in arthritis induced by several oil adjuvants (hexadecane, heptadecane, squalene, arlacel)...
March 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28301559/synergy-between-the-classical-and-alternative-pathways-of-complement-is-essential-for-conferring-effective-protection-against-the-pandemic-influenza-a-h1n1-2009-virus-infection
#15
Ajitanuj Rattan, Shailesh D Pawar, Renuka Nawadkar, Neeraja Kulkarni, Girdhari Lal, Jayati Mullick, Arvind Sahu
The pandemic influenza A(H1N1) 2009 virus caused significant morbidity and mortality worldwide thus necessitating the need to understand the host factors that influence its control. Previously, the complement system has been shown to provide protection during the seasonal influenza virus infection, however, the role of individual complement pathways is not yet clear. Here, we have dissected the role of intact complement as well as of its individual activation pathways during the pandemic influenza virus infection using mouse strains deficient in various complement components...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28296576/competition-for-amino-acid-flux-among-translation-growth-and-detoxification-in-bacteria
#16
Iolanda Ferro, Irina Chelysheva, Zoya Ignatova
Transfer RNAs (tRNAs) are central entities for translation that deliver amino acids to the ribosome to translate genetic information in an mRNA-template dependent manner. Recent discoveries from our laboratory show that in E. coli and B. licheniformis, some tRNAs are poorly charged despite the plentiful intracellular cognate amino acid. Specifically, tRNAs carrying amino acids that exert toxicity and inhibit bacterial growth when added separately to the growth medium are poorly charged. Here, we discuss various evolutionary strategies different bacterial cells have adopted to precisely hone the competition between amino acid utilization for translation and proliferation and combat the inhibitory effect towards maximizing bacterial fitness...
March 15, 2017: RNA Biology
https://www.readbyqxmd.com/read/28295019/m2e-tetramer-specific-memory-cd4-t-cells-are-broadly-protective-against-influenza-infection
#17
D G Eliasson, A Omokanye, K Schön, U A Wenzel, V Bernasconi, M Bemark, A Kolpe, K El Bakkouri, T Ysenbaert, L Deng, W Fiers, X Saelens, N Lycke
Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A(d) restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection...
March 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28291388/lymphoma-remissions-caused-by-anti-cd19-chimeric-antigen-receptor-t-cells-are-associated-with-high-serum-interleukin-15-levels
#18
James N Kochenderfer, Robert P T Somerville, Tangying Lu, Victoria Shi, Adrian Bot, John Rossi, Allen Xue, Stephanie L Goff, James C Yang, Richard M Sherry, Christopher A Klebanoff, Udai S Kammula, Marika Sherman, Arianne Perez, Constance M Yuan, Tatyana Feldman, Jonathan W Friedberg, Mark J Roschewski, Steven A Feldman, Lori McIntyre, Mary Ann Toomey, Steven A Rosenberg
Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells...
March 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28290464/blocking-the-recruitment-of-naive-cd4-t-cells-reverses-immunosuppression-in-breast-cancer
#19
Shicheng Su, Jianyou Liao, Jiang Liu, Di Huang, Chonghua He, Fei Chen, LinBing Yang, Wei Wu, Jianing Chen, Ling Lin, Yunjie Zeng, Nengtai Ouyang, Xiuying Cui, Herui Yao, Fengxi Su, Jian-Dong Huang, Judy Lieberman, Qiang Liu, Erwei Song
The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4(+) T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4(+) T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients...
March 14, 2017: Cell Research
https://www.readbyqxmd.com/read/28288125/regulatory-t-cells-promote-myelin-regeneration-in-the-central-nervous-system
#20
Yvonne Dombrowski, Thomas O'Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, George Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard Perbal, Anna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin, Denise C Fitzgerald
Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg...
March 13, 2017: Nature Neuroscience
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