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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...
July 18, 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
Lucía Melguizo-Rodríguez, Javier Ramos-Torrecillas, Francisco Javier Manzano-Moreno, Rebeca Illescas-Montes, Ana Rivas, Concepción Ruiz, Elvira De Luna-Bertos, Olga García-Martínez
The reported incidence of osteoporosis is lower in countries in which the Mediterranean diet predominates, and this apparent relationship may be mediated by the phenolic compounds present in olive oil. The objective of this study was to determine the effect of phenolic extracts from different varieties of extra-virgin olive oil (Picual, Arbequina, Picudo, and Hojiblanca) on the differentiation, antigenic expression, and phagocytic capacity of osteoblast-like MG-63 cells. At 24 h of treatment a significant increase in phosphatase alkaline activity and significant reductions in CD54, CD80, and HLA-DR expression and in phagocytic activity were observed in comparison to untreated controls...
2018: PloS One
Akemi Toyoda, Hiroshi Itagaki
Photoreactive compounds that may experience exposure to ultraviolet (UV) radiation can lead to the intracellular production of reactive oxygen species (ROS), which may cause phototoxic and photoallergenic responses. Here, we developed a novel in vitro photosafety assay and investigated whether it could be used to predict phototoxicity and photosensitivity by measuring changes in intracellular ROS production. THP-1 cells that had previously taken up 5-(and-6)-carboxy-2',7'-difluorodihydrofluorescein diacetate (carboxy-H2 DFFDA), a ROS-sensitive fluorescent reagent, were exposed to photoreactive substances such as phototoxic and photoallergenic materials and then subjected to with UV-A irradiation (5 J/cm2 )...
2018: Journal of Toxicological Sciences
Yongxi Li, Haiyang Yu, Yan Jin, Min Li, Caijie Qu
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the interplay between multiple genetic and environmental factors. The pathogenesis of AD remains incompletely understood. Treatment with topical steroids for chronic AD symptoms has severe side effects and so a new treatment is required. Verbascoside is a hydrophilic phenylethanoid glycoside with antioxidant, anti-inflammatory properties. METHODS: Verbascoside was evaluated in AD-like lesions induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice...
2018: International Archives of Allergy and Immunology
Xing-Xing Yu, Ting-Ting Han, Ling-Ling Xu, Ying-Jun Chang, Xiao-Jun Huang, Xiang-Yu Zhao
Granulocyte colony-stimulating factor (G-CSF) has been widely used in the field of allogeneic haematopoietic stem cell transplantation (allo-HSCT) for priming donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect stem cells more conveniently. Donor-derived natural killer (NK) cells have important antitumour functions and immune regulatory roles post-allo-HSCT. The aim of this study was to evaluate the effect of G-CSF on donors' NK cells in BM and PB. The percentage of NK cells among nuclear cells and lymphocyte was significantly decreased and led to increased ratio of T and NK cells in BM and PB post-G-CSF in vivo application...
June 2018: Journal of Cellular and Molecular Medicine
Xue-Juan Bai, Hong-Min Li, You-Rong Yang, Jun-Xian Zhang, Yan Liang, Xue-Qiong Wu
Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment...
August 2018: Cytokine
Xiang Song, Yan Zhang, Li Zhang, Wengang Song, Lixin Shi
Hypoxia-associated metabolic reprogramming modulates the biological functions of many immune and non-immune cells, and affects immune response types and intensities. Adenosine and indoleamine 2,3-dioxygenase (IDO) are known immunosuppressors, and adenosine is a hypoxia-associated product. We investigated the impact of hypoxia on IDO production in dendritic cells (DCs). We found that hypoxia (1% O2 ) enhances IDO production in DCs, and this increase was dependent on the adenosine A3 receptor (A3R), but not A2aR or A2bR...
February 20, 2018: Oncotarget
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