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https://www.readbyqxmd.com/read/28934717/expression-of-c-ebp%C3%AE-in-myeloid-progenitors-during-sepsis-promotes-immunosuppression
#1
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs...
September 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28934595/copd-alters-immune-cell-composition-and-immune-checkpoint-inhibitor-efficacy-in-nsclc
#2
Nicholas M Mark, Julia Kargl, Stephanie E Busch, Grace H Y Yang, Heather E Metz, Huajia Zhang, Jesse J Hubbard, Sudhakar N J Pipavath, David K Madtes, A McGarry Houghton
RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality; the pathogenesis of both involves aberrant immune functioning. OBJECTIVE: To profile the immune cell composition and function in patients with NSCLC and describe the effect of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC...
September 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28934563/hemophagocytic-lymphohistiocytosis
#3
Hanny Al-Samkari, Nancy Berliner
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immunemediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger)...
September 13, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28934503/a-novel-requirement-for-drosha-in-maintenance-of-mammalian-cg-methylation
#4
Athanasia Stathopoulou, Jyoti B Chhetri, John C Ambrose, Pierre-Olivier Estève, Lexiang Ji, Hediye Erdjument-Bromage, Guoqiang Zhang, Thomas A Neubert, Sriharsa Pradhan, Javier Herrero, Robert J Schmitz, Steen K T Ooi
In mammals, faithful inheritance of genomic methylation patterns ensures proper gene regulation and cell behaviour, impacting normal development and fertility. Following establishment, genomic methylation patterns are transmitted through S-phase by the maintenance methyltransferase Dnmt1. Using a protein interaction screen, we identify Microprocessor component DROSHA as a novel DNMT1-interactor. Drosha-deficient embryonic stem (ES) cells display genomic hypomethylation that is not accounted for by changes in the levels of DNMT proteins...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934489/antisense-oligonucleotides-targeting-translation-inhibitory-elements-in-5-utrs-can-selectively-increase-protein-levels
#5
Xue-Hai Liang, Hong Sun, Wen Shen, Shiyu Wang, Joyee Yao, Michael T Migawa, Huynh-Hoa Bui, Sagar S Damle, Stan Riney, Mark J Graham, Rosanne M Crooke, Stanley T Crooke
A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#6
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934106/biosensor-technology-reveals-the-disruption-of-the-endothelial-barrier-function-and-the-subsequent-death-of-blood-brain-barrier-endothelial-cells-to-sodium-azide-and-its-gaseous-products
#7
Dan T Kho, Rebecca H Johnson, Simon J O'Carroll, Catherine E Angel, E Scott Graham
Herein we demonstrate the sensitive nature of human blood-brain barrier (BBB) endothelial cells to sodium azide and its gaseous product. Sodium azide is known to be acutely cytotoxic at low millimolar concentrations, hence its use as a biological preservative (e.g., in antibodies). Loss of barrier integrity was noticed in experiments using Electric Cell-substrate Impedance Sensing (ECIS) biosensor technology, to measure endothelial barrier integrity continuously in real-time. Initially the effect of sodium azide was observed as an artefact where it was present in antibodies being employed in neutralisation experiments...
September 21, 2017: Biosensors
https://www.readbyqxmd.com/read/28933920/multi-tissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#8
Akul Singhania, Joshua C Wallington, Caroline G Smith, Daniel Horowitz, Karl J Staples, Peter H Howarth, Stephan D Gadola, Ratko Djukanović, Christopher H Woelk, Timothy Sc Hinks
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma, and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3+ T cells from sputum and bronchoalveolar lavage were obtained from healthy subjects (N=19) and asthmatic patients (mild, moderate and severe asthma; N=46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips and results were validated by real-time quantitative PCR...
September 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28933828/latent-porosity-in-alkali-metal-m2b12f12-salts-structures-and-rapid-room-temperature-hydration-dehydration-cycles
#9
Dmitry V Peryshkov, Eric V Bukovsky, Matthew R Lacroix, Hui Wu, Wei Zhou, W Matthew Jones, Matic Lozinšek, Travis C Folsom, D Luke Heyliger, Terrence J Udovic, Steven H Strauss
Structures of the alkali-metal hydrates Li2(H2O)4Z, LiK(H2O)4Z, Na2(H2O)3Z, and Rb2(H2O)2Z, unit cell parameters for Rb2Z and Rb2(H2O)2Z, and the density functional theory (DFT)-optimized structures of K2Z, K2(H2O)2Z, Rb2Z, Rb2(H2O)2Z, Cs2Z, and Cs2(H2O)Z are reported (Z(2-) = B12F12(2-)) and compared with previously reported X-ray structures of Na2(H2O)0,4Z, K2(H2O)0,2,4Z, and Cs2(H2O)Z. Unusually rapid room-temperature hydration/dehydration cycles of several M2Z/M2(H2O)nZ salt hydrate pairs, which were studied by isothermal gravimetry, are also reported...
September 21, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28933657/a-novel-immunization-approach-for-dengue-infection-based-on-conserved-t-cell-epitopes-formulated-in-calcium-phosphate-nanoparticles
#10
Xiaofang Huang, Aykan Karabudak, Joseph D Comber, Mohan Philip, Tulin Morcol, Ramila Philip
Dengue virus (DV) is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans. Most DV vaccine approaches are focused on generating antibody mediated responses; one such DV vaccine is approved for use in humans but its efficacy is limited. While it is clear that T cell responses play important role in DV infection and subsequent disease manifestations, fewer studies are aimed at developing vaccines that induce robust T cells responses. Potent T cell based vaccines require two critical components: the identification of specific T cell stimulating MHC associated peptides, and an optimized vaccine delivery vehicle capable of simultaneously delivering the antigens and any required adjuvants...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28932937/foxn1-deficiency-from-the-discovery-to-novel-therapeutic-approaches
#11
REVIEW
Vera Gallo, Emilia Cirillo, Giuliana Giardino, Claudio Pignata
Since the discovery of FOXN1 deficiency, the human counterpart of the nude mouse, a growing body of evidence investigating the role of FOXN1 in thymus and skin, has been published. FOXN1 has emerged as fundamental for thymus development, function, and homeostasis, representing the master regulator of thymic epithelial and T cell development. In the skin, it also plays a pivotal role in keratinocytes and hair follicle cell differentiation, although the underlying molecular mechanisms still remain to be fully elucidated...
September 21, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28932920/microrna-30a-inhibits-colorectal-cancer-metastasis-through-down-regulation-of-type-i-insulin-like-growth-factor-receptor
#12
Y C Liu, Y R Park, S L Kim, S T Lee, S W Kim
BACKGROUND: miR-30a expression is down-regulated and regulates tumor suppressors in various cancers. AIM: We investigated the mechanisms underlying the biological role of miR-30a in CRC. METHODS: MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a...
September 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28932817/designing-biomaterials-with-immunomodulatory-properties-for-tissue-engineering-and-regenerative-medicine
#13
REVIEW
James I Andorko, Christopher M Jewell
Recent research in the vaccine and immunotherapy fields has revealed that biomaterials have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. Intriguingly, new studies reveal these responses are influenced by the physicochemical properties of the material. Nearly all of this work has been done in the vaccine and immunotherapy fields, but there is tremendous opportunity to apply this same knowledge to tissue engineering and regenerative medicine. This review discusses recent findings that reveal how material properties-size, shape, chemical functionality-impact immune response, and links these changes to emerging opportunities in tissue engineering and regenerative medicine...
June 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28932723/anaphase-promoting-complex-7-is-a-prognostic-factor-in-human-colorectal-cancer
#14
Ik Yong Kim, Hye Yeon Kwon, Kwang Hwa Park, Dae Sung Kim
PURPOSE: The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity and is required for ubiquitination of securin and cyclin-B. Several APC-targeting molecules are reported to be oncogenes. Dysregulation of APC may be associated with tumorigenesis. This study examines the relationship between APC expression and clinicopathological factors and evaluates the possibility of an aberrant APC function in colorectal carcinomas (CRCs). METHODS: To determine whether the loss of APC7 expression is related to tumorigenesis, we used tissue micro-arrays in 114 resected CRCs to scrutinize the expressions of APC7 and Ki-67 immunohistochemistry and to find relations with clinocopathologic parameters...
August 2017: Annals of Coloproctology
https://www.readbyqxmd.com/read/28932646/reconstitution-of-multifunctional-cd56-low-cd16-low-natural-killer-cell-subset-in-children-with-acute-leukemia-given-%C3%AE-%C3%AE-t-cell-depleted-hla-haploidentical-haematopoietic-stem-cell-transplantation
#15
Stabile Helena, Nisti Paolo, Peruzzi Giovanna, Fionda Cinzia, Pagliara Daria, Pomonia Brescia Letizia, Merli Pietro, Locatelli Franco, Angela Santoni, Angela Gismondi
We recently described the CD56(low)CD16(low) subset of Natural Killer (NK) cells that both mediate cytotoxic activity and produce IFNγ, being more abundant in bone marrow (BM) than in peripheral blood (PB) of pediatric normal subjects. Given the multifunctional properties of this subset, we examined its development and functional recovery in a cohort of children undergoing α/β T-cell depleted HLA-haploidentical haematopoietic stem cell transplantation (HSCT). The results obtained indicate that CD56(low)CD16(low) NK cells are present in both PB and BM already at one month post-HSCT, with an increased frequency in BM of graft recipients as compared with normal subjects...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932639/soluble-nkg2d-ligands-in-the-ovarian-cancer-microenvironment-are-associated-with-an-adverse-clinical-outcome-and-decreased-memory-effector-t-cells-independent-of-nkg2d-downregulation
#16
Maulik Vyas, Silke Reinartz, Nathalie Hoffmann, Katrin S Reiners, Sonja Lieber, Julia M Jansen, Uwe Wagner, Rolf Müller, Elke Pogge von Strandmann
The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932637/muc1-c-promotes-the-suppressive-immune-microenvironment-in-non-small-cell-lung-cancer
#17
Audrey Bouillez, Dennis Adeegbe, Caining Jin, Xiufeng Hu, Ashujit Tagde, Maroof Alam, Hasan Rajabi, Kwok-Kin Wong, Donald Kufe
The cancer immune microenvironment is of importance for the effectiveness of immunotherapy; however, its dysregulation is poorly understood. The MUC1-C oncoprotein is aberrantly overexpressed in non-small cell lung cancer (NSCLC) and has been linked to the induction of PD-L1. The present work investigated the effects of targeting MUC1-C in an immuno-competent MUC1 transgenic (MUC1.Tg) mouse model. We show that Lewis Lung Carcinoma cells expressing MUC1-C (LLC/MUC1) exhibit upregulation of PD-L1 and suppression of interferon-γ (IFN-γ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932631/tadalafil-has-biologic-activity-in-human-melanoma-results-of-a-pilot-trial-with-tadalafil-in-patients-with-metastatic-melanoma-tame
#18
Jessica C Hassel, Huanhuan Jiang, Carolin Bender, Julia Winkler, Alexandra Sevko, Ivan Shevchenko, Niels Halama, Antonia Dimitrakopoulou-Strauss, Walter E Haefeli, Dirk Jäger, Alexander Enk, Jochen Utikal, Viktor Umansky
Myeloid-derived suppressor cells (MDSCs) are known to play a critical role in the suppression of T cell antitumor responses. Our preclinical data showed that the phosphodiesterase (PDE)-5 inhibitor sildenafil impaired MDSC functions, enhanced intratumoral T cell activity and prolonged survival of melanoma-bearing mice. In this study, we evaluated biologic effects, safety and efficacy of palliative treatment with the PDE-5 inhibitor tadalafil in metastatic melanoma patients. We conducted an open-label, dose de-escalation trial with tadalafil in pretreated metastatic melanoma patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932625/vascular-aging-implications-for-cardiovascular-disease-and-therapy
#19
Yohannes T Ghebre, Eduard Yakubov, Wing Tak Wong, Prasanna Krishnamurthy, Nazish Sayed, Andrew G Sikora, Mark D Bonnen
The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function...
December 2016: Translational Medicine: Current Research
https://www.readbyqxmd.com/read/28932225/expression-and-function-of-the-cholinergic-system-in-immune-cells
#20
REVIEW
Takeshi Fujii, Masato Mashimo, Yasuhiro Moriwaki, Hidemi Misawa, Shiro Ono, Kazuhide Horiguchi, Koichiro Kawashima
T and B cells express most cholinergic system components-e.g., acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Using ChAT(BAC)-eGFP transgenic mice, ChAT expression has been confirmed in T and B cells, dendritic cells, and macrophages. Moreover, T cell activation via T-cell receptor/CD3-mediated pathways upregulates ChAT mRNA expression and ACh synthesis, suggesting that this lymphocytic cholinergic system contributes to the regulation of immune function...
2017: Frontiers in Immunology
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