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https://www.readbyqxmd.com/read/28324651/line-activity-of-ganglioside-gm1-regulates-raft-size-distribution-in-a-cholesterol-dependent-manner
#1
Timur R Galimzyanov, Anna S Lyushnyak, Veronika V Aleksandrova, Liudmila A Shilova, Ilya I Mikhalyov, Irina M Molotkovskaya, Sergey A Akimov, Oleg V Batishchev
Liquid-ordered lipid domains, also called rafts, are assumed to be important players in different cellular processes, mainly signal transduction and membrane trafficking. They are thicker than the disordered part of the membrane and are thought to form for compensating the hydrophobic mismatch between transmembrane proteins and lipid environment. Despite the existence of such structures in vivo is still an open question, they are observed in model systems of multicomponent lipid bilayers. Moreover, the predictions obtained from model experiments allow explaining different physiological processes possibly involving rafts...
March 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#2
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318770/expression-of-cathepsin-s-in-bcg-converts-it-into-a-pro-apoptotic-and-highly-immunogenic-strain
#3
Alice Lau, Vijender Singh, Hafid Soualhine, Zakaria Hmama
BACKGROUND: BCG vaccine, introduced almost 100years ago, is the only option to prevent TB disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#4
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
March 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28317875/chd7-is-indispensable-for-mammalian-brain-development-through-activation-of-a-neuronal-differentiation-programme
#5
Weijun Feng, Daisuke Kawauchi, Huiqin Körkel-Qu, Huan Deng, Elisabeth Serger, Laura Sieber, Jenna Ariel Lieberman, Silvia Jimeno-González, Sander Lambo, Bola S Hanna, Yassin Harim, Malin Jansen, Anna Neuerburg, Olga Friesen, Marc Zuckermann, Vijayanad Rajendran, Jan Gronych, Olivier Ayrault, Andrey Korshunov, David T W Jones, Marcel Kool, Paul A Northcott, Peter Lichter, Felipe Cortés-Ledesma, Stefan M Pfister, Hai-Kun Liu
Mutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), frequently associated with CHARGE syndrome, is indispensable for normal cerebellar development. Genetic inactivation of Chd7 in cerebellar granule neuron progenitors leads to cerebellar hypoplasia in mice, due to the impairment of granule neuron differentiation, induction of apoptosis and abnormal localization of Purkinje cells, which closely recapitulates known clinical features in the cerebella of CHARGE patients...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28317413/mesenchymal-stromal-cells-enhance-the-suppressive-effects-ofmyeloid-derived-suppressor-cells-of-multiple-myeloma
#6
Yinhui Xu, Xiaoying Zhang, Hongbo Liu, Pan Zhao, Yafang Chen, Yimin Luo, Limin Luo, Zhiqing Zhang, Xiaofang Wang
Both mesenchymal stromal cells (MSCs) and myeloid-derived suppressor cells (MDSCs) have immunosuppressive properties, and their presence may confer a worse prognosis upon cancer patients. However, whether MSCs can enhance the immunosuppressive effects of MDSCs in MM remains unknown. We evaluated the influence of MSCs on MDSCs growth, apoptosis, and functions. Our results show that MSCs promote proliferation and inhibit apoptosis in MDSCs. Additionally, MSCs enhance the ability of MDSCs by inhibiting T-cell proliferation and IFN-γ production...
March 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28316997/sildenafil-can-affect-innate-and-adaptive-immune-system-in-both-experimental-animals-and-patients
#7
REVIEW
Monika Kniotek, Agnieszka Boguska
Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28315436/nocardia-rubra-cell-wall-skeleton-promotes-cd4-t-cell-activation-and-drives-th1-immune-response
#8
Guangchuan Wang, Jie Wu, Miao Miao, Heng Dou, Ning Nan, Mingsheng Shi, Guang Yu, Fengping Shan
Several lines of evidences have shown that Nocardia rubra cell wall skeleton (Nr-CWS) has immunoregulatory and anti-tumor activities. However, there is no information about the effect of Nr-CWS on CD4(+) T cells. The aim of this study was to explore the effect of Nr-CWS on the phenotype and function of CD4(+) T cells. Our results of in vitro experiments showed that Nr-CWS could significantly up-regulate the expression of CD69 and CD25 on CD4(+) T cells, promote the proliferation of CD4(+) T cells, increase the production of IFN-γ, TNF-α and IL-2 in the supernatants, but has no significant effect on the apoptosis and death of CD4(+) T cells...
March 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28314856/ubc9-is-required-for-positive-selection-and-late-stage-maturation-of-thymocytes
#9
Aibo Wang, Xiao Ding, Maud Demarque, Xindong Liu, Deng Pan, Huawei Xin, Bo Zhong, Xiaohu Wang, Anne Dejean, Wei Jin, Chen Dong
SUMOylation is an important posttranslational modification that regulates protein function in diverse biological processes. However, its role in early T cell development has not been genetically studied. UBC9 is the only E2 enzyme for all SUMOylation. In this study, by selectively deleting Ubc9 gene in T cells, we have investigated the functional roles of SUMOylation in T cell development. Loss of Ubc9 results in a significant reduction of CD4 and CD8 single-positive lymphocytes in both thymus and periphery...
March 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28314844/abituzumab-targeting-of-alphav-class-integrins-inhibits-prostate-cancer-progression
#10
Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller
Integrins that contain an integrin alpha V subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine if abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin alpha V impacts, prostate cancer (PCa) progression. To evaluate this, PCa cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt and ERK were determined...
March 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28314315/pd-l1-expression-is-a-prognostic-factor-in-patients-with-thoracic-esophageal-cancer-treated-without-adjuvant-chemotherapy
#11
Akiyuki Wakita, Satoru Motoyama, Hiroshi Nanjo, Yusuke Sato, Kei Yoshino, Tomohiko Sasaki, Yuta Kawakita, Jiajia Liu, Kazuhiro Imai, Hajime Saito, Yoshihiro Minamiya
BACKGROUND/AIM: Programmed death-1 ligand 1 (PD-L1) induces apoptosis of tumor-reactive T-cells, that enables tumors to evade immune defense and thus furthers their growth. Our aim was to determine whether PD-L1 expression status correlates with prognosis in patients with advanced thoracic esophageal squamous cell carcinoma. PATIENTS AND METHODS: The PD-L1 expression status of 177 patients treated with esophagectomy without preoperative therapy was evaluated immunohistochemically using tissue microarray...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314156/an-explant-of-heifer-mammary-gland-to-study-the-immune-response-of-the-organ
#12
Giada Magro, Tiziana A L Brevini, Marcella De Maglie, Giulietta Minozzi, Eugenio Scanziani, Renata Piccinini
Continuous or primary epithelial cell lines have been extensively used to study the mammary gland immune response, but they are constituted by a single cell population. Our aim was to test whether an explant of heifer gland, where the tissue structure is maintained, might be a valid model to investigate the innate immune response to infection. The study was carried out on 2mm(3)-sections of heifer udders, in 2 consecutive trials, using LPS or LTA in the first trial and two different concentrations of Staphylococcus aureus (Staph...
March 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28303901/mutual-reinforcement-between-telomere-capping-and-canonical-wnt-signalling-in-the-intestinal-stem-cell-niche
#13
Ting-Lin B Yang, Qijun Chen, Jennifer T Deng, Geetha Jagannathan, John W Tobias, David C Schultz, Shan Wang, Christopher J Lengner, Anil K Rustgi, John P Lynch, F Brad Johnson
Critical telomere shortening (for example, secondary to partial telomerase deficiency in the rare disease dyskeratosis congenita) causes tissue pathology, but underlying mechanisms are not fully understood. Mice lacking telomerase (for example, mTR(-/-) telomerase RNA template mutants) provide a model for investigating pathogenesis. In such mice, after several generations of telomerase deficiency telomeres shorten to the point of uncapping, causing defects most pronounced in high-turnover tissues including intestinal epithelium...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#14
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28303124/identification-and-characterization-of-mirnas-in-response-to-leishmania-donovani-infection-delineation-of-their-roles-in-macrophage-dysfunction
#15
Neeraj Tiwari, Vinod Kumar, Mallikarjuna Rao Gedda, Ashish K Singh, Vijay K Singh, Sreenivas Gannavaram, Surya P Singh, Rakesh K Singh
The outcome of Leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. Despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. Micro RNAs (miRNAs) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding RNA gene products, described to participate in the regulation of almost every cellular process investigated so far...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28302921/deciphering-the-acute-cellular-phosphoproteome-response-to-irradiation-with-x-rays-protons-and-carbon-ions
#16
Martin Winter, Ivana Dokic, Julian Schlegel, Uwe Warnken, Jürgen Debus, Amir Abdollahi, Martina Schnölzer
Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive. Here, we present the first comprehensive proteomic and phosphoproteomic study applying stable isotope labeling by amino acids in cell culture (SILAC) in combination with high-resolution mass spectrometry to decipher cellular response to irradiation with X-rays, protons and carbon ions...
March 16, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28301594/daxx-plays-a-novel-role-in-t-cell-survival-but-is-dispensable-in-fas-induced-apoptosis
#17
Jinghe Li, Liangyue Qian, John P Dowling, Christine Curcione, Drishya Kurup, Jianke Zhang
Daxx was originally isolated as a Fas-binding protein. However, the in vivo function of Daxx in Fas-induced apoptosis has remained enigmatic. Fas plays an important role in homeostasis in the immune system. Fas gene mutations lead to autoimmune-lymphoproliferation (lpr) diseases characterized by hyperplasia of secondary lymphoid organs. It is well established that the FADD adaptor binds to Fas, and recruits/activates caspase 8. However, additional proteins including Daxx have also been indicated to associate with Fas...
2017: PloS One
https://www.readbyqxmd.com/read/28300831/immunoproteomic-identification-and-characterization-of-ni-2-regulated-proteins-implicates-ni-2-in-the-induction-of-monocyte-cell-death
#18
Annika Jakob, Franz Mussotter, Stefanie Ohnesorge, Lisa Dietz, Julian Pardo, Ian D Haidl, Hermann-Josef Thierse
Nickel allergy is the most common cause of allergic reactions worldwide, with cutaneous and systemic effects potentially affecting multiple organs. Monocytes are precursors of not only macrophages but also dendritic cells, the most potent activators of nickel hypersensitivity. Monocytes are themselves important antigen-presenting cells, capable of nickel-specific T-cell activation in vivo and in vitro, in addition to being important for immediate innate immune inflammation. To elucidate early Ni(2+)-dependent inflammatory molecular mechanisms in human monocytes, a Ni(2+)-specific proteomic approach was applied...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28299574/physiological-and-pathological-roles-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2-in-the-central-nervous-system-and-neurological-diseases
#19
REVIEW
Tatsurou Yagami, Yasuhiro Yamamoto, Hiromi Koma
Prostaglandins (PGs) are divided into conventional PGs, e.g., PGD2, and cyclopentenone-type PGs, e.g., 15-deoxy-Δ(12,14) prostaglandin J2 (15d-PGJ2). PGD2 is non-enzymatically metabolized to PGJ2, Δ(12)-PGJ2, and 15d-PGJ2. In the central nervous system, 15d-PGJ2 differentiates embryonic midbrain cells into dopaminergic neuronal cells via its nuclear peroxysome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 exerts conflict actions: proinflammatory and anti-inflammatory activities. In the brain, 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain...
March 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28296676/histopathologic-features-of-colitis-due-to-immunotherapy-with-anti-pd-1-antibodies
#20
Jonathan H Chen, Maryam K Pezhouh, Gregory Y Lauwers, Ricard Masia
Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis...
March 14, 2017: American Journal of Surgical Pathology
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