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Richard P Tobin, Kimberly R Jordan, William A Robinson, Dana Davis, Virginia F Borges, Rene Gonzalez, Karl D Lewis, Martin D McCarter
BACKGROUND: Immune checkpoint inhibitors have improved overall survival rates for many cancers, yet the majority of patients do not respond to treatment and succumb to disease progression. One tumor-related mechanism limiting the efficacy of immunotherapies in melanoma is the recruitment and expansion of myeloid-derived suppressor cells (MDSCs). Therefore, targeting MDSCs in combination with immunotherapies is an attractive strategy to improve response rates and effectiveness. METHODS: We tested this strategy by designing a randomized phase II clinical trial treating advanced melanoma patients with either Ipilimumab monotherapy or Ipilimumab plus all-trans retinoic acid (ATRA)...
August 16, 2018: International Immunopharmacology
Rupinder Kaur, Sukhbir Kaur
BACKGROUND: The available drugs for treating visceral leishmaniasis are limited. Moreover, the disease is associated with suppression of immune function. Therefore, therapies with effective immunomodulatory agents are needed which can decrease parasitic burden and enhance adaptive immunity. OBJECTIVES: The present study was planned to evaluate the antileishmanial efficacy of crude ethanolic extract of roots of Chlorophytum borivilianum (CBREE) against murine visceral leishmaniasis through immunomodulation...
August 14, 2018: Journal of Ayurveda and Integrative Medicine
Manohar Prasad Koduri, Venkanagouda S Goudar, Yu-Wei Shao, John A Hunt, James Henstock, Judith Curran, Fan-Gang Tseng
Closed-loop artificial pancreas systems have recently been proposed as a solution for treating stage I diabetes by reproducing the function of the pancreas. However, there are many unresolved issues associated with their development, including monitoring and controlling oxygen, immune responses and the optimization of glucose. All of which need to be monitored and controlled to produce an efficient and viable artificial organ, that can become integrated in the patient and maintain homeostasis. This research focused on monitoring oxygen concentration, specifically achieving this kinetically as the oxygen gradient in an artificial pancreas made of alginate spheres containing islet cells...
August 17, 2018: ACS Applied Materials & Interfaces
Susan A Safley, Norma S Kenyon, Dora M Berman, Graham F Barber, Melissa Willman, Stephanie Duncanson, Neal Iwakoshi, Robert Holdcraft, Lawrence Gazda, Peter Thompson, I Raul Badell, Athanassios Sambanis, Camillo Ricordi, Collin J Weber
BACKGROUND: Xenogeneic donors would provide an unlimited source of islets for the treatment of type 1 diabetes (T1D). The goal of this study was to assess the function of microencapsulated adult porcine islets (APIs) transplanted ip in streptozotocin (STZ)-diabetic non-human primates (NHPs) given targeted immunosuppression. METHODS: APIs were encapsulated in: (a) single barium-gelled alginate capsules or (b) double alginate capsules with an inner, islet-containing compartment and a durable, biocompatible outer alginate layer...
August 17, 2018: Xenotransplantation
Heather M Gibson, Brooke N McKnight, Agnes Malysa, Gregory Dyson, Wendy Wiesend, Claire E McCarthy, Joyce Reyes, Wei-Zen Wei, Nerissa T Viola-Villegas
Interferon-gamma (IFN-gamma) is an attractive target for imaging active anti-tumor immunity due to its function in the T cell signaling axis. Here we test an IFN-gamma immuno-positron emission tomography (immunoPET) probe for its capacity to identify adaptive immunotherapy (ITx) response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse mammary tumors. IFN-gamma immunoPET detected elevated cytokine levels in situ post-vaccination, which inversely correlated with tumor growth rate, an indicator of response to therapy...
August 16, 2018: Cancer Research
Luca Trotta, Anna Norberg, Mervi Taskinen, Vivien Béziat, Sofie Degerman, Ulla Wartiovaara-Kautto, Hannamari Välimaa, Kirsi Jahnukainen, Jean-Laurent Casanova, Mikko Seppänen, Janna Saarela, Minna Koskenvuo, Timi Martelius
BACKGROUND: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs...
August 17, 2018: Orphanet Journal of Rare Diseases
Emma Nilsson, Anna Benrick, Milana Kokosar, Anna Krook, Eva Lindgren, Thomas Källman, Mihaela M Martis, Kurt Højlund, Charlotte Ling, Elisabet Stener-Victorin
Context: Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective: To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate to phenotypic variation. Design/Participants: In a case-control study, skeletal muscle biopsies from women with PCOS (n=17) and age, weight and BMI matched controls (n=14) were analyzed by array-based DNA methylation and mRNA expression profiling...
August 2, 2018: Journal of Clinical Endocrinology and Metabolism
Jenny Rubin, Sharmineh Mansoori, Kristin Blom, Malin Berglund, Lena Lenhammar, Claes Andersson, Angelica Loskog, Mårten Fryknäs, Peter Nygren, Rolf Larsson
Mebendazole (MBZ) was recently shown to induce a tumor suppressive M1 phenotype in THP-1 monocytes and macrophages. In the present study the immune effects of MBZ was further investigated using human peripheral blood mononuclear cells (PBMCs) co-cultured with tumour cells. The Biomap platform was used to screen for biomarkers induced from MBZ exposed co-cultures of T-cell receptor activated PBMCs, HT29 colon cancer cells and either human fibroblasts or human umbilical vein endothelial cells (HUVEC) cells. In these co-culture systems MBZ at 0...
July 20, 2018: Oncotarget
Taku Hatano, Masashi Takanashi, Hitoshi Tsuchihashi, Shin-Ichi Ueno, Arisa Hayashida, Yutaka Tsukune, Kazuaki Kanai, Yasushi Shimo, Nobutaka Hattori
BACKGROUND: Cutaneous and systemic plasmacytosis are skin disorders characterized by cutaneous polyclonal plasma cell infiltration accompanied by polyclonal hypergammaglobulinemia. Cutaneous plasmacytosis involvement is limited to the skin, mainly on the face and trunk, while systemic plasmacytosis also involves 2 or more organ systems. However, there have been no reports of inflammatory myositis due to plasmacytosis. Here, we report a patient with plasmacytosis who developed myalgia and easy fatigability due to inflammatory myositis...
August 14, 2018: BMC Neurology
B Gutiérrez-Gil, C Esteban-Blanco, A Suarez-Vega, J J Arranz
This study presents a scan of the ovine genome to identify quantitative trait loci (QTL) influencing the somatic cell score (SCS), a classical indicator of subclinical mastitis in sheep, and a subsequent high-resolution analysis of one of the identified QTL regions based on the analysis of whole-genome sequence data sets. A half-sib commercial population of Churra sheep genotyped with a 50K SNP-Chip was analyzed using linkage analysis (LA) and combined linkage and linkage disequilibrium analysis (LDLA). By LA, 2 5% chromosome-wide significant QTL on OAR5 and OAR25 and one 5% genome-wide significant QTL on ovine chromosome 20 (OAR20) were detected, whereas 22 significant associations were identified by LDLA...
August 9, 2018: Journal of Dairy Science
Zongguo Yang, Yuquan Tao, Xin Xu, Feng Cai, Yongchun Yu, Lifang Ma
OBJECTIVE: This study aimed to evaluate functions of APOBEC3F gene in biological process of hepatocellular carcinoma (HCC) and anti-tumor mechanisms of bufalin. METHODS: Effect of APOBEC3F and bufalin on cell proliferation and migration abilities were evaluated by CCK-8, wounding healing tests and transwell assays in SK-Hep1 and Bel-7404 cells. Bioinformatic analysis were also used to compare APOBEC3F expression levels, detect coexpressed genes and enrichment of pathways...
August 6, 2018: Biochemical and Biophysical Research Communications
Weifeng Xu, Michael Sank, Jennifer Cummings, Stephen Carl, Marina Juhel, Carol Gleason, Robert Dodge, Binodh S DeSilva, Gerry Kolaitis, Renuka Pillutla
Biological therapeutics are foreign antigens and can potentially induce immune response resulting in the formation of anti-drug antibodies (ADA), which in turn may lead to a wide range of side effects. Neutralizing Ab (NAb) is a subset of ADA that can bind to the pharmacological activity regions of therapeutic to inhibit or complete neutralize its clinical efficacy. A cell-based functional NAb assay is preferred to characterize its neutralization activity. However, cell-based NAb assays are often vulnerable to drug interference, as well as interference from numerous serum factors, including but not limited to growth factors and disease-related cytokines...
August 9, 2018: Journal of Immunological Methods
Katrin Richter, Christian Koch, Alexander Perniss, Philipp M Wolf, Elke K H Schweda, Sven Wichmann, Sigrid Wilker, Ilona Magel, Michael Sander, J Michael McIntosh, Winfried Padberg, Veronika Grau
Phosphocholine-modified bacterial cell wall components are virulence factors enabling immune evasion and permanent colonization of the mammalian host, by mechanisms that are poorly understood. Recently, we demonstrated that free phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from Haemophilus influenzae , an opportunistic pathogen of the upper and lower airways, function as unconventional nicotinic agonists and efficiently inhibit the ATP-induced release of monocytic IL-1β. We hypothesize that H...
August 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Mengju Liu, Jian Peng, Ningwen Tai, James A Pearson, Changyun Hu, Junhua Guo, Lin Hou, Hongyu Zhao, F Susan Wong, Li Wen
AIMS/HYPOTHESIS: Innate immune effectors interact with the environment to contribute to the pathogenesis of the autoimmune disease, type 1 diabetes. Although recent studies have suggested that innate immune Toll-like receptors (TLRs) are involved in tissue development, little is known about the role of TLRs in tissue development, compared with autoimmunity. We aimed to fill the knowledge gap by investigating the role of TLR9 in the development and function of islet beta cells in type 1 diabetes, using NOD mice...
August 9, 2018: Diabetologia
Monica Maijo, Kamal Ivory, Sarah J Clements, Jack R Dainty, Amy Jennings, Rachel Gillings, Susan Fairweather-Tait, Massimo Gulisano, Aurelia Santoro, Claudio Franceschi, Simon R Carding, Claudio Nicoletti
Amongst the major features of aging are chronic low grade inflammation and a decline in immune function. The Mediterranean diet (MedDiet) is considered to be a valuable tool to improve health status, and although beneficial effects have been reported, to date, immunological outcomes have not been extensively studied. We aimed to test the hypothesis that 1 year of a tailored intervention based on the MedDiet with vitamin D (10 μg/day) would improve innate immune responses in healthy elderly subjects (65-79 years) from the English cohort (272 subjects recruited) of the NU-AGE randomized, controlled study (clinicaltrials...
2018: Frontiers in Physiology
Takuya Osada, Zachary C Hartman, Junping Wei, Gangjun Lei, Amy C Hobeika, William R Gwin, Marcio A Diniz, Neil Spector, Timothy M Clay, Wei Chen, Michael A Morse, H Kim Lyerly
BACKGROUND: Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), but also exposes HER3 as a target for immune attack. We generated an adenovirus encoding full length human HER3 (Ad-HER3) to serve as a cancer vaccine. Previously we reported the anti-tumor efficacy and function of the T cell response to this vaccine...
August 9, 2018: Breast Cancer Research: BCR
Raya Al Maskari, Iris Hardege, Sarah Cleary, Nicki Figg, Ye Li, Keith Siew, Ashraf Khir, Yong Yu, Pentao Liu, Ian Wilkinson, Kevin O'Shaughnessy, Yasmin
The recent genome-wide analysis of carotid-femoral pulse wave velocity (PWV) identified a significant locus within the 14q32.2 gene desert. Gene regulatory elements for the transcriptional regulator B-cell CLL/lymphoma 11B (BCL11B) are within this locus and an attractive target for the gene association. We investigated the functional impact of these gene desert SNPs on BCL11B transcript in human aorta to characterize further its role in aortic stiffness. To do this, we used a large repository of aortic tissues (n = 185) from an organ transplant program and assessed ex vivo stiffness of the aortic rings...
August 8, 2018: European Journal of Human Genetics: EJHG
Yasuhiro Murata, Keigo Kawashima, Knvul Sheikh, Yasuhito Tanaka, Masanori Isogawa
CD8+ T cells are the key cellular effectors mediating the clearance of hepatitis B virus (HBV) infections. However, early immunological events surrounding the priming of HBV-specific CD8+ T cell responses remain poorly understood. This study examined the importance of priming location and the relative contribution of endogenous antigen presentation by hepatocytes versus cross-presentation by bone-marrow derived cells to the induction of functional HBV-specific CD8+ T cell responses using the animal models of acute and chronic HBV infection...
August 8, 2018: Journal of Virology
Bonnie Phillips, Koen K A Van Rompay, Jennifer Rodriguez-Nieves, Clarisse Lorin, Marguerite Koutsoukos, Mark Tomai, Christopher B Fox, Josh Eudailey, Maria Dennis, S Munir Alam, Michael Hudgens, Genevieve Fouda, Justin Pollara, Anthony Moody, Xiaoying Shen, Guido Ferrari, Sallie Permar, Kristina De Paris
Towards the goal of developing an effective HIV vaccine that can be administered in infancy to protect against postnatal and life-long sexual HIV transmission risks, the current pilot study was designed to compare the effect of novel adjuvants on the induction of HIV Env-specific antibody responses in infant macaques. Aligning our studies with the adjuvanted proteins evaluated in a prime-boost schedule with ALVAC in the ongoing HVTN 702 efficacy trial, we selected the bivalent clade C Env immunogens gp120 C...
August 8, 2018: Journal of Virology
Xiaohong Li, Eric C Rouchka, Guy N Brock, Jun Yan, Timothy E O'Toole, David A Tieri, Nigel G F Cooper
Breast cancer (BC) is increasing in incidence and resistance to treatment worldwide. The challenges in limited therapeutic options and poor survival outcomes in BC subtypes persist because of its molecular heterogeneity and resistance to standard endocrine therapy. Recently, high throughput RNA sequencing (RNA-seq) has been used to identify biomarkers of disease progression and signaling pathways that could be amenable to specific therapies according to the BC subtype. However, there is no single generally accepted pipeline for the analysis of RNA-seq data in biomarker discovery due, in part, to the needs of simultaneously satisfying constraints of sensitivity and specificity...
2018: PloS One
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