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Rag da Silva, C P Churchward, A V Karlyshev, O Eleftheriadou, A K Snabaitis, M R Longman, A Ryan, R Griffin
BACKGROUND AND PURPOSE: The level of cell surface expression of the meningococcal vaccine antigen, Factor H binding protein (FHbp) varies between and within strains and this limits the breadth of strains that can be targeted by FHbp-based vaccines. The molecular pathway dictating expression of FHbp at the cell surface, including its lipidation, sorting to the outer membrane and export, and the potential regulation of this pathway have not been investigated until now. This knowledge will aid our evaluation of FHbp vaccines...
October 26, 2016: British Journal of Pharmacology
Li Cheng, Jun Zhang, Xin-Yi Li, Li Yuan, Yan-Fang Pan, Xiao-Rong Chen, Tian-Ming Gao, Jian-Tian Qiao, Jin-Shun Qi
Amyloid β protein (Aβ) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in Aβ molecule is an effective active center responsible for Aβ neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid β protein, and investigated the neuroprotection of the anti-Aβ31-35 antibody against Aβ1-42 -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats...
October 26, 2016: Hippocampus
B K Singleton, M Ahmed, C A Green, H Heimpel, M J Woźniak, L Ranjha, F Seeney, A Bomford, P Mehta, A Guest, R Mushens, M-J King
BACKGROUND: Bone marrow examination has been the confirmatory test for congenital dyserythropoietic anemia type II (CDAII). Occasional spherocytes on peripheral blood smear can confound the diagnosis. Since a screening test is still unavailable, we explored the feasibility of using flow cytometry as a preliminary screening method. METHODS: Thirteen monoclonal antibodies with specificities for eight erythrocyte membrane proteins were used in FACS analysis to probe the cellular features of red cells from CDAII, normal adults, hereditary spherocytosis (HS), and cord red cells...
October 26, 2016: Cytometry. Part B, Clinical Cytometry
Cyrill Wehling, Oliver Amon, Martin Bommer, Bernd Hoppe, Karim Kentouche, Gesa Schalk, Rolf Weimer, Michael Wiesener, Bernd Hohenstein, Burkhard Tönshoff, Rainer Büscher, Henry Fehrenbach, Ömer-Necmi Gök, Michael Kirschfink
Various complement-mediated renal disorders are currently treated with the complement inhibitor eculizumab. By blocking the cleavage of C5 this monoclonal antibody prevents cell damage caused by complement-mediated inflammation. We included 23 patients with atypical hemolytic uremic syndrome (aHUS, n=12), C3 glomerulopathies (C3G, n=9) and acute antibody-mediated renal graft rejection (AMR, n=2), treated with eculizumab in 12 hospitals in Germany. We explored the course of complement activation biomarkers and the benefit of therapeutic drug monitoring of eculizumab...
October 26, 2016: Clinical and Experimental Immunology
Norihiro Suzuki, Yoshio Hirano, Taneto Tomiyasu, Yuya Esaki, Akiyoshi Uemura, Tsutomu Yasukawa, Munenori Yoshida, Yuichiro Ogura
Purpose: This study evaluates the retinal hemodynamics using optical coherence tomography angiography (OCTA) before and after anti-vascular endothelial growth factor (VEGF) therapy in patients with macular edema associated with retinal vein occlusion (RVO). Methods: Twelve patients (23 eyes; mean age, 64 years) were included (eight eyes with branch RVO, four with central RVO, and 11 unaffected fellow eyes. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before and 6 months after treatment...
October 1, 2016: Investigative Ophthalmology & Visual Science
Ying Xiong, Li Liu, Jiajun Wang, Wei Xi, Yu Xia, Qi Bai, Yang Qu, Qilai Long, Jiejie Xu, Jianming Guo
BACKGROUND: Chemokine (C-C motif) ligand 21 (CCL21), a ligand of the chemokine (C-C motif) receptor 7, has recently been identified as an immuno-based anti-cancer molecule for its dendritic cells and T lymphocytes chemoattractant function. The aim of this study was to investigate prognostic values of CCL21 expression in metastatic renal cell carcinoma patients treated with targeted therapy. METHODS: This study included 111 patients with metastatic renal cell carcinoma receiving targeted therapy...
October 23, 2016: Oncotarget
Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
Wankun Chen, Yajun Xu, Jing Zhong, Huihui Wang, Meilin Weng, Qian Cheng, Qichao Wu, Zhirong Sun, Hui Jiang, Minmin Zhu, Yu Ren, Pingbo Xu, Jiawei Chen, Changhong Miao
Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underlying pathways require to be elucidated. In this study, we detected a positive association between MFHAS1 expression in TAMs and human colorectal cancer (CRC) TNM stage...
October 21, 2016: Oncotarget
Lorena P Suarez-Kelly, Gregory M Kemper, Megan C Duggan, Andrew Stiff, Tiffany C Nole, Joseph Markowitz, Eric A Luedke, Vedat O Yildiz, Lianbo Yu, Alena Cristina Jaime-Ramirez, Volodymyr Karpa, Xiaoli Zhang, William E Carson
The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed...
October 21, 2016: Oncotarget
Hriday Bera, Sridevi Chigurupati
Thymidine phosphorylase (TP, EC, an enzyme involved in pyrimidine salvage pathway, is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is extremely upregulated in a variety of solid tumours. The TP amplification is associated with concomitant overexpression of many angiogenic factors such as matrix metalloproteases (MMPs), interleukins (ILs), vascular endothelial growth factor (VEGF) etc., resulting in promotion of angiogenesis and cancer metastasis. In addition, overshooting TP level protects tumour cells from apoptosis and helps cell survival...
October 17, 2016: European Journal of Medicinal Chemistry
Dror Alishekevitz, Svetlana Gingis-Velitski, Orit Kaidar-Person, Lilach Gutter-Kapon, Sandra D Scherer, Ziv Raviv, Emmanuelle Merquiol, Yael Ben-Nun, Valeria Miller, Chen Rachman-Tzemah, Michael Timaner, Yelena Mumblat, Neta Ilan, David Loven, Dov Hershkovitz, Ronit Satchi-Fainaro, Galia Blum, Jonathan P Sleeman, Israel Vlodavsky, Yuval Shaked
While chemotherapy strongly restricts or reverses tumor growth, the response of host tissue to therapy can counteract its anti-tumor activity by promoting tumor re-growth and/or metastases, thus limiting therapeutic efficacy. Here, we show that vascular endothelial growth factor receptor 3 (VEGFR3)-expressing macrophages infiltrating chemotherapy-treated tumors play a significant role in metastasis. They do so in part by inducing lymphangiogenesis as a result of cathepsin release, leading to VEGF-C upregulation by heparanase...
October 25, 2016: Cell Reports
Katherine A Muratore, Heather M Grundhofer, Edgar A Arriaga
Macroautophagy is a cellular degradation process responsible for the clearance of excess intracellular cargo. Existing methods for bulk quantification of autophagy rely on organelle markers that bind to multiple autophagy organelle types, making it difficult to tease apart the subcellular mechanisms implicated in autophagy dysfunction in liver and other pathologies. To address this issue, methods based on individual organelle measurements are needed. Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was previously used to count and determine properties of individual autophagy organelles isolated from an LC3-GFP expressing cell line, but has never been used on autophagy organelles originating from a tissue sample...
October 26, 2016: Analytical Chemistry
Hirokazu Taniguchi, Shinji Takeuchi, Koji Fukuda, Takayuki Nakagawa, Sachiko Arai, Shigeki Nanjo, Tadaaki Yamada, Hiroyuki Yamaguchi, Hiroshi Mukae, Seiji Yano
Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement...
October 26, 2016: Cancer Science
Laura Denise Mendes da Silva, Mariana Gatto, Mariana Miziara de Abreu Teodoro, Marjorie de Assis Golim, Érika Alessandra Pelisson Nunes da Costa, Francilene Capel Tavares Carvalho, Daniela Ramos Rodrigues, Paulo Câmara Marques Pereira, Ângela Maria Victoriano de Campos Soares, Sueli Aparecida Calvi
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi is a serious public health issue. Its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30 to 40% of them become symptomatic presenting the cardiac or digestive disease. Host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. The pro-inflammatory cytokines are crucial in host resistance. However, a fine control of this inflammatory process, by action of anti-inflammatory cytokines, is necessary to avoid tissue injury...
October 26, 2016: Scandinavian Journal of Immunology
T J Mai, R Ma, Z Li, S C Bi
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Kaisy Pereira Martins, Tatiana Ferreira da Costa, Thayris Mariano de Medeiros, Maria das Graças Melo Fernandes, Inácia Sátiro Xavier de França, Kátia Nêyla de Freitas Macêdo Costa
This study aimed at evaluating the internal structure of Family Health Units in relation to the access of people with physical and/or sensory disabilities. It is a descriptive, exploratory, population-based research, held in Family Health Units of the municipality of João Pessoa, Paraíba, Brazil. For the collection of data, a checklist based on Technical Standard 9050 was used. For the analysis, the descriptive and exploratory analysis of the data and the Chi-square test were applied. As a result, of the 90 buildings evaluated, only 47...
October 2016: Ciência & Saúde Coletiva
Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan Kumar Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice...
October 2016: PLoS Pathogens
Chwan Hong Foo, Christina L Rootes, Karla Cowley, Glenn A Marsh, Cathryn M Gould, Celine Deffrasnes, Christopher J Cowled, Reuben Klein, Sarah J Riddell, Deborah Middleton, Kaylene J Simpson, Lin-Fa Wang, Andrew G D Bean, Cameron R Stewart
Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs) impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection...
October 2016: PLoS Pathogens
Alexandra Sufit, Alisa B Lee-Sherick, Deborah DeRyckere, Manali Rupji, Bhakti Dwivedi, Marileila Varella-Garcia, Angela M Pierce, Jeanne Kowalski, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Amy K Keating, Douglas K Graham
BACKGROUND: MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. METHODS: Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database...
2016: PloS One
Olga Volotskova, Larisa Dubrovsky, Michael Keidar, Michael Bukrinsky
Cold atmospheric plasma (CAP) is a specific type of partially ionized gas that is less than 104°F at the point of application. It was recently shown that CAP can be used for decontamination and sterilization, as well as anti-cancer treatment. Here, we investigated the effects of CAP on HIV-1 replication in monocyte-derived macrophages (MDM). We demonstrate that pre-treatment of MDM with CAP reduced levels of CD4 and CCR5, inhibiting virus-cell fusion, viral reverse transcription and integration. In addition, CAP pre-treatment affected cellular factors required for post-entry events, as replication of VSV-G-pseudotyped HIV-1, which by-passes HIV receptor-mediated fusion at the plasma membrane during entry, was also inhibited...
2016: PloS One
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