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Juan S Naranjo-Gómez, Andrés Castillo, Mauricio Rojas, Bertha N Restrepo, Francisco J Diaz, Paula A Velilla, Diana Castaño
Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients than in controls...
October 13, 2018: Immunology
Gertrude Ecklu-Mensah, Rebecca W Olsen, Anja Bengtsson, Michael F Ofori, Lars Hviid, Anja T R Jensen, Yvonne Adams
The lack of suitable animal models for the study of cytoadhesion of P. falciparum-infected erythrocytes (IEs) has necessitated in vitro studies employing a range of cell lines of either human tumour origin (e.g., BeWo and C32 cells) or non-human origin (e.g., CHO cells). Of the human cells available, many were isolated from adults, or derived from a pool of donors (e.g., HBEC-5i). Here we demonstrate, for the first time, the successful isolation of blood outgrowth endothelial cells (BOECs) from frozen stabilates of peripheral blood mononuclear cells obtained from small-volume peripheral blood samples from paediatric malaria patients...
2018: PloS One
Ahmed Al-Qaissi, Maria Papageorgiou, Harshal Deshmukh, Leigh A Madden, Alan Rigby, Eric S Kilpatrick, Stephen L Atkin, Thozhukat Sathyapalan
AIMS: Endothelial microparticles (EMPs) are novel surrogate markers of endothelial injury and dysfunction that may be differentially produced in response to acute insulin-induced hypoglycaemia in adults with and without type 2 diabetes. MATERIALS AND METHODS: A prospective, parallel study was conducted in individuals with type 2 diabetes (n=23) and controls (n=22). Hypoglycaemia (<2.2mmol/l: <40mg/dl) was achieved by intravenous infusion of soluble insulin...
September 28, 2018: Diabetes, Obesity & Metabolism
Xi Chen, Xiaojie Ai, Chunlian Wu, Heyong Wang, Gang Zeng, Peixin Yang, Gentao Liu
IL-2 is critical to the activation, growth, and survival of T cells and NK cells, and maintains the delicate balance between auto-immunity and anti-neoplasm surveillance. High IL-2 doses have clear antitumor capabilities, but also have severe side effects that limit its clinical use. Side effects include the vascular leak syndrome (VLS), which results in lung edema and liver damage. Therefore, a new version of IL-2 that does not induce organ toxicity would improve IL-2-based immunotherapy. We conducted a systematic screening by changing one amino acid at a time at the interaction area of IL-2 with its receptor IL-2R to select one particular mutant IL-2, FSD13, in which the proline at position 65 was substituted by lysine (P65L)...
September 24, 2018: Cell Death & Disease
Erika Moravcikova, E Michael Meyer, Mirko Corselli, Vera S Donnenberg, Albert D Donnenberg
Human culture-expanded mesenchymal stromal cells (MSC) are being considered for multiple therapeutic applications because of their regenerative and anti-inflammatory properties. Although a large number of MSC can be propagated from a small initial sample, several lines of evidence indicate that MSC lose their immunosuppressive and regenerative potency aftaer multiple passages. In this report, we use the FACSCAP Lyoplate proteomic analysis system to detect changes in cell surface protein expression of CD45- /CD31- /CD34- /CD73+ /CD105+ stromal cells in unpassaged bone marrow (BM) and through 10 serial culture passages...
July 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Lisa M Kronstad, Christof Seiler, Rosemary Vergara, Susan P Holmes, Catherine A Blish
In human and murine studies, IFN-γ is a critical mediator immunity to influenza. IFN-γ production is critical for viral clearance and the development of adaptive immune responses, yet excessive production of IFN-γ and other cytokines as part of a cytokine storm is associated with poor outcomes of influenza infection in humans. As NK cells are the main population of lung innate immune cells capable of producing IFN-γ early in infection, we set out to identify the drivers of the human NK cell IFN-γ response to influenza A viruses...
October 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Christian Schwabe, Bernd Rosenstock, Thi Doan, Paul Hamilton, P Rod Dunbar, Anastasia G Eleftheraki, David Joseph, James Hilbert, Corinna Schoelch, Steven J Padula, Jürgen Steffgen
BI 655064 is a humanized antagonistic anti-cluster of differentiation (CD) 40 monoclonal antibody that selectively blocks the CD40-CD40L interaction. The CD40-CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and lupus nephritis. The safety, tolerability, pharmacokinetics, and pharmacodynamics of repeated once-weekly BI 655064 subcutaneous dosing over 4 weeks were evaluated in a multiple-dose study in healthy subjects. Subjects (N = 40) were randomized 4:1 to four sequential BI 655064 dose groups (80, 120, 180, 240 mg) or to placebo...
August 16, 2018: Journal of Clinical Pharmacology
Marsha S Russell, Abenaya Muralidharan, Louise Larocque, Jingxin Cao, Yvon Deschambault, Jessie Varga, Sathya N Thulasi Raman, Xuguang Li
Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses...
2018: PloS One
Eun-Jung Park, Hong-Soo Lee, Sang Jin Lee, Yoo-Jin Park, Son-Il Park, Jaerak Chang, Kyuhong Lee
Considering that cigarette smoke condensate (CSC) is primarily absorbed through the alveoli in the lungs, herein, we used a mouse alveolar macrophage cell line (MH-S cells). After 24 h exposure, CSC decreased dose-dependently cell viability accompanying an increase in intracellular ROS and NO level. CSC structurally or functionally damaged organelles including mitochondria, ER and lysosome and enhanced the expression of proteins related to apoptosis, ER stress and DNA damage accompanying an elevated proportion of annexin V-bound cells...
October 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Kenneth P Hough, Landon S Wilson, Jennifer L Trevor, John G Strenkowski, Njeri Maina, Young-Il Kim, Marion L Spell, Yong Wang, Diptiman Chanda, Jose Rodriguez Dager, Nirmal S Sharma, Miranda Curtiss, Veena B Antony, Mark T Dransfield, David D Chaplin, Chad Steele, Stephen Barnes, Steven R Duncan, Jeevan K Prasain, Victor J Thannickal, Jessy S Deshane
Asthma is a chronic inflammatory disease process involving the conductive airways of the human lung. The dysregulated inflammatory response in this disease process may involve multiple cell-cell interactions mediated by signaling molecules, including lipid mediators. Extracellular vesicles (EVs) are lipid membrane particles that are now recognized as critical mediators of cell-cell communication. Here, we compared the lipid composition and presence of specific lipid mediators in airway EVs purified from the bronchoalveolar lavage (BAL) fluid of healthy controls and asthmatic subjects with and without second-hand smoke (SHS) exposure...
July 9, 2018: Scientific Reports
Katharina Heinzelmann, Mareike Lehmann, Michael Gerckens, Nina Noskovičová, Marion Frankenberger, Michael Lindner, Rudolf Hatz, Jürgen Behr, Anne Hilgendorff, Melanie Königshoff, Oliver Eickelberg
Fibroblasts play an important role in lung homeostasis and disease. In lung fibrosis, fibroblasts adopt a proliferative and migratory phenotype, with increased expression of α-smooth muscle actin (αSMA) and enhanced secretion of extracellular matrix components. Comprehensive profiling of fibroblast heterogeneity is limited, due to a lack of specific cell-surface markers. We have previously profiled the surface proteome of primary human lung fibroblasts. Here, we sought to define and quantify a panel of cluster of differentiation markers in primary human lung fibroblasts and IPF lung tissue, using immunofluorescence and FACS analysis...
June 28, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
L-Q Li, D Pan, S-W Zhang, D -Y-Xie, X-L Zheng, H Chen
OBJECTIVE: Gastric cancer is the most common gastrointestinal malignancy and the leading cause of cancer-related deaths in East Asia. Increasing evidence has revealed that autophagy is closely associated with tumor initiation and progression. The present work aimed to investigate the role of autophagy in adjuvant chemotherapy for gastric cancer. MATERIALS AND METHODS: Gastric cancer stem cells (CSCs) were isolated from gastric cancer cell lines using the cell surface markers CD44 and CD54 and cultured in a three-dimensional cell culture system...
June 2018: European Review for Medical and Pharmacological Sciences
Alexander Edwards, Lottie Roscoe, Christopher Longmore, Fiona Bailey, Bushra Sim, Carol Treasure
Skin sensitisers are substances that can elicit allergic responses following skin contact and the process by which this occurs is described as skin sensitisation. Skin sensitisation is defined as a series of key events, that form an adverse outcome pathway (AOP). Key event three in the AOP is dendritic cell activation that can be modelled by the human Cell Line Activation Test (h-CLAT) and is typified by changes in cell surface markers CD54 and CD86 in dendritic cells. The h-CLAT is accepted at a regulatory level (OECD Test-Guideline (TG)442E) and can be used to assess skin sensitisation potential as part of an integrated approach to testing and assessment (IATA)...
June 13, 2018: ALTEX
Aldana Trotta, Lis N Velásquez, M Ayelén Milillo, M Victoria Delpino, Ana M Rodríguez, Verónica I Landoni, Guillermo H Giambartolomei, Roberto G Pozner, Paula Barrionuevo
Brucellosis is an infectious disease elicited by bacteria of the genus Brucella . Platelets have been extensively described as mediators of hemostasis and responsible for maintaining vascular integrity. Nevertheless, they have been recently involved in the modulation of innate and adaptive immune responses. Although many interactions have been described between Brucella abortus and monocytes/macrophages, the role of platelets during monocyte/macrophage infection by these bacteria remained unknown. The aim of this study was to investigate the role of platelets in the immune response against B...
2018: Frontiers in Immunology
Theresa El-Murr, Ankita Patel, Carrie Sedlak, Bernadette D'Souza-Lobo
Immunotherapy approaches targeting dendritic cells (DCs) are being studied as treatment options in cancer. This project focused on utilizing DCs as a valuable in vitro screening tool for efficacious microparticle formulations containing tumor associated antigens (TAAs) and adjuvants as immunotherapy alternatives. The innate immune system, including DCs, distinctly responds to the particulate matter and adjuvants in these formulations which stimulates the adaptive immune system to eliminate resident cancer cells...
August 2018: Journal of Immunological Methods
Luciana P Ruas, Livia M Genaro, Amauri S Justo-Junior, Lilian O Coser, Lívia F de Castro, Plinio Trabasso, Ronei L Mamoni, Maria-Cristina Roque-Barreira, Maria-Heloisa S L Blotta
Infections caused by fungi are prominent in our environment and can be potentially fatal. paracoccidioidomycosis (PCM), caused by fungi of the Paracoccidioides genus, is the most frequent systemic mycosis in Brazil and the main cause of death among immunocompetent individuals. The antifungal therapy for PCM is usually effective but side effects and relapses are often reported. The latter could be avoided with alternative or complementary therapies aimed at boosting the immune response to combat this pathogen...
2018: Frontiers in Microbiology
Vahid Bagheri, Bahram Memar, Ramezan Behzadi, Mohsen Aliakbarian, Ali Jangjoo, Mostafa Mehrabi Bahar, Samaneh Talebi, Mehran Gholamin, Mohammad R Abbaszadegan
Gastric cancer (GC) is the third and fifth cause of cancer-associated mortality for men and women throughout the world, respectively. Despite the use of surgery and chemotherapy for GC therapy, there are no efficient therapeutic protocols for it to date. Cancer stem cells (CSCs) due to their pivotal role in tumor initiation, growth, progression, invasion, distant metastasis, recurrence and resistance to anticancer drugs are very appealing targets for cancer therapies. Here, we isolated and identified CSCs from a chemotherapy-treated patient...
October 2018: Journal of Cellular Physiology
Takafumi Mitachi, Minori Mezaki, Kunihiko Yamashita, Hiroshi Itagaki
To evaluate the sensitization potential of chemicals in cosmetics, using non-animal methods, a number of in vitro safety tests have been designed. Current assays are based on the expression of cell surface markers, such as CD86 and CD54, which are associated with the activation of dendritic cells, in skin sensitization tests. However, these markers are influenced by culture conditions through activating danger signals. In this study, we investigated the relationship between extracellular pH and the expression of the skin sensitization test human cell line activation test (h-CLAT) markers CD86 and CD54...
2018: Journal of Toxicological Sciences
Elaine Coustan-Smith, Guangchun Song, Sheila Shurtleff, Allen Eng-Juh Yeoh, Wee Joo Chng, Siew Peng Chen, Jeffrey E Rubnitz, Ching-Hon Pui, James R Downing, Dario Campana
BACKGROUND: Optimal management of acute myeloid leukemia (AML) requires monitoring of treatment response, but minimal residual disease (MRD) may escape detection. We sought to identify distinctive features of AML cells for universal MRD monitoring. METHODS: We compared genome-wide gene expression of AML cells from 157 patients with that of normal myeloblasts. Markers encoded by aberrantly expressed genes, including some previously associated with leukemia stem cells, were studied by flow cytometry in 240 patients with AML and in nonleukemic myeloblasts from 63 bone marrow samples...
May 3, 2018: JCI Insight
Lauren A Thurgood, Karen M Lower, Cindy Macardle, Bryone J Kuss
The cryopreservation of peripheral blood mononuclear cells (PBMCs) is a routine research laboratory process, enabling long-term storage of primary patient blood samples. Retrospective analysis of these samples has the potential to identify markers that may be associated with prognosis and response to treatment. To draw valid biological conclusions from this type of analysis, it is essential to ensure that any observed changes are directly related to the pathology of the disease rather than the preservation process itself...
July 2018: Experimental Hematology
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