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https://www.readbyqxmd.com/read/28607601/evaluation-of-attenuated-tumor-antigens-and-the-implications-for-peptide-based-cancer-vaccine-development
#1
J S Berry, T J Vreeland, D F Hale, D O Jackson, A F Trappey, J M Greene, M O Hardin, G S Herbert, G T Clifton, G E Peoples
INTRODUCTION: Peptide vaccines offer anti-tumor efficacy with very low toxicity. However, repeat stimulation with an immunogenic peptide leads to activation induced cell death (AICD), decreasing efficacy. We engineered variants of an immunogenic peptide (E39) and tested their ability to induce a robust, sustainable immune response. METHODS: Multiple variants of E39 were created by exchanging 1 or 2 amino acids. We tested the PBMC proliferation, cytokine production and cytolytic activity induced by each variant peptide...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28587768/small-things-matter-implications-of-app-intracellular-domain-aicd-nuclear-signaling-in-the-progression-and-pathogenesis-of-alzheimer-s-disease
#2
REVIEW
Hassan Bukhari, Annika Glotzbach, Katharina Kolbe, Gregor Leonhardt, Christina Loosse, Thorsten Müller
Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus...
June 3, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28587718/%C3%AE-amyloid-precursor-protein-intracellular-domain-controls-mitochondrial-function-by-modulating-phosphatase-and-tensin-homolog-induced-kinase-1-transcription-in-cells-and-in-alzheimer-mice-models
#3
Thomas Goiran, Eric Duplan, Mounia Chami, Alexandre Bourgeois, Wejdane El Manaa, Lila Rouland, Julie Dunys, Inger Lauritzen, Han You, Vuk Stambolic, Maria-Grazia Biféri, Martine Barkats, Sanjay W Pimplikar, Nicolas Sergeant, Morvane Colin, Vanessa A Morais, Raphaelle Pardossi-Piquard, Frédéric Checler, Cristine Alves da Costa
BACKGROUND: Mitophagy and mitochondrial dynamics alterations are two major hallmarks of neurodegenerative diseases. Dysfunctional mitochondria accumulate in Alzheimer's disease-affected brains by yet unexplained mechanisms. METHODS: We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which presenilins control phosphatase and tensin homolog-induced kinase 1 (Pink-1) expression and transcription. In vivo approaches were carried out on various transgenic and knockout animals as well as in adeno-associated virus-infected mice...
May 3, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28553201/fe65-ptb2-dimerization-mimics-fe65-app-interaction
#4
Lukas P Feilen, Kevin Haubrich, Paul Strecker, Sabine Probst, Simone Eggert, Gunter Stier, Irmgard Sinning, Uwe Konietzko, Stefan Kins, Bernd Simon, Klemens Wild
Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28428882/differential-phenotypes-of-memory-cd4-and-cd8-t-cells-in-the-spleen-and-peripheral-tissues-following-immunostimulatory-therapy
#5
Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy
BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28400856/glossogyne-tenuifolia-hsiang-ju-extract-suppresses-t-cell-activation-by-inhibiting-activation-of-c-jun-n-terminal-kinase
#6
Jer-Yiing Houng, Tzong-Shyuan Tai, Shu-Ching Hsu, Hsia-Fen Hsu, Tzann-Shun Hwang, Chih-Jiun Lin, Li-Wen Fang
BACKGROUND: Glossogyne tenuifolia (GT) (Hsiang-ju) is a Chinese herbal medicine previously exhibited an anti-inflammatory activity. This study aimed to investigate the effect of GT ethanol extract (GTE) on T cell-mediated adaptive immunity. METHODS: Human peripheral blood mononuclear cells (PBMCs) and Jurkat T cells were activated by phytohemagglutinin in the presence of various doses (3.13-50 μg/mL) of GTE. The effect of GTE on T cell activation was examined by a proliferation assay of activated PBMCs and the level of the activation marker CD69 on the surface of activated Jurkat T cells...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28362092/spiro-metallaaromatics-of-pd-pt-rh-synthesis-and-characterization
#7
Yongliang Zhang, Junnian Wei, Yue Chi, Xuan Zhang, Wen-Xiong Zhang, Zhenfeng Xi
Since the concept of aromaticity represents one of the most funda-mental principles in chemistry, the search for unprecedented and exciting aromatic systems, therefore, continues to drive research in this area. Herein we report the synthesis and characterization of spiro metallaaromatics, in which the transition metal (Pd, Pt, or Rh) is the spiro atom, that cross-conjugates two aromatic five-membered metallacycles. These spiro metallaaromatics tend to take square planar geometries, with the dihedral angle being influenced by the steric repulsion between the α-positioned substituents...
March 31, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28360125/cellular-levels-of-grb2-and-cytoskeleton-stability-are-correlated-in-a-neurodegenerative-scenario
#8
Piyali Majumder, Kasturi Roy, Brijesh Kumar Singh, Nihar Ranjan Jana, Debashis Mukhopadhyay
Alzheimer's disease (AD) manifests as neuronal loss. On the premise of Grb2 overexpression in AD mouse brain and brain tissues of AD patients, our study primarily focuses on the stability of cytoskeletal proteins in the context of degenerative AD-like conditions. Two predominant molecular features of AD, extracellular accumulation of β-amyloid oligomers and intracellular elevation of amyloid precursor protein intracellular domain levels, have been used to closely inspect the series of signalling events. In their presence, multiple signalling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton, and Grb2 partially counterbalances the cytoskeletal loss...
May 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28359846/long-term-effect-of-neonatal-inhibition-of-app-gamma-secretase-on-hippocampal-development-in-the-ts65dn-mouse-model-of-down-syndrome
#9
Fiorenza Stagni, Alessandra Raspanti, Andrea Giacomini, Sandra Guidi, Marco Emili, Elisabetta Ciani, Alessandro Giuliani, Andrea Bighinati, Laura Calzà, Jacopo Magistretti, Renata Bartesaghi
Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed...
July 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28344547/app-function-and-lipids-a-bidirectional-link
#10
REVIEW
Marcus O W Grimm, Janine Mett, Heike S Grimm, Tobias Hartmann
Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28243115/rnai-for-contactin-2-inhibits-proliferation-of-u87-glioma-stem-cells-by-downregulating-aicd-egfr-and-hes1
#11
Yang Guo, Peidong Zhang, Hongtian Zhang, Peng Zhang, Ruxiang Xu
Glioblastoma is the most common form of malignant brain tumors and has a poor prognosis. Glioma stem cells (GSCs) are thought to be responsible for the aberrant proliferation and invasion. Targeting the signaling pathways that promote proliferation in GSCs is one of the strategies for glioma treatment. In this study, we found increased expression of contactin 2 (CNTN2) and amyloid β precursor protein (APP) in U87-derived GSCs (U87-GSCs). RNA interference (RNAi) for CNTN2 downregulated the expression of APP intracellular domain (AICD), which is the proteolytic product of APP...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28171770/forecasting-state-level-premature-deaths-from-alcohol-drugs-and-suicides-using-google-trends-data
#12
Jason Parker, Courtney Cuthbertson, Scott Loveridge, Mark Skidmore, Will Dyar
BACKGROUND: Vital statistics on the number of, alcohol-induced death (AICD) drug-induced death (DICD), and suicides at the local-level are only available after a substantial lag of up to two years after the events occur. We (1) investigate how well Google Trends search data explain variation in state-level rates in the US, and (2) use this method to forecast these rates of death for 2015 as official data are not yet available. METHODS: We tested the degree to which Google Trends data on 27 terms can be fit to CDC data using L1-regularization on AICD, DICD, and suicide...
April 15, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28164545/plasma-zonulin-and-its-association-with-kidney-function-severity-of-heart-failure-and-metabolic-inflammation
#13
Thomas B Dschietzig, Felix Boschann, Jana Ruppert, Franz P Armbruster, Andreas Meinitzer, Dragic Bankovic, Veselin Mitrovic, Christoph Melzer
BACKGROUND: The tight junction regulator zonulin has attracted clinical attention as a biomarker of increased gastrointestinal permeability. Recent work also suggests zonulin to represent a general regulator of tissue barriers and a player in metabolic inflammation. Here, we investigated the associations of zonulin with chronic heart failure (CHF), kidney function, and metabolic inflammation. METHODS: Using multiple linear regression (Generalized Linear Model), this study determined the association of plasma zonulin with different laboratory and clinical parameters in 225 patients carrying automatic implantable cardioverters/defibrillators (AICD) for primary or secondary prevention...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28135203/ellagic-acid-inhibits-the-proliferation-of-human-pancreatic-carcinoma-panc-1-cells-in-vitro-and-in-vivo
#14
Hao Cheng, Chenglin Lu, Ribo Tang, Yiming Pan, Shanhua Bao, Yudong Qiu, Min Xie
Ellagic aicd (EA), a dietary polyphenolic compound found in plants and fruits, possesses various pharmacological activities. This study investigated the effect of EA on human pancreatic carcinoma PANC-1 cells both in vitro and in vivo; and defined the associated molecular mechanisms. In vitro, the cell growth and repairing ability were assessed by CCK-8 assay and wound healing assay. The cell migration and invasion activity was evaluated by Tanswell assay. In vivo, PANC-1 cell tumor-bearing mice were treated with different concentrations of EA...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106772/neuroprotective-and-anti-apoptotic-effects-of-csp-1103-in-primary-cortical-neurons-exposed-to-oxygen-and-glucose-deprivation
#15
Vanessa Porrini, Ilenia Sarnico, Marina Benarese, Caterina Branca, Mariana Mota, Annamaria Lanzillotta, Arianna Bellucci, Edoardo Parrella, Lara Faggi, Pierfranco Spano, Bruno Pietro Imbimbo, Marina Pizzi
CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer's disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28078580/in-vitro-evaluation-of-the-apoptosis-function-in-human-activated-t-cells
#16
Aude Magerus-Chatinet, Frédéric Rieux-Laucat
The apoptosis function can be monitored on human lymphocytes by quantifying the induced-death upon apoptotic stimuli involving either the extrinsic or the intrinsic pathway on in vitro activated T cells. Her, we describe an in vitro assay allowing the monitoring of three different apoptosis pathways: (1) the FAS-induced pathway, (2) the activation-induced cell death (AICD), and (3) the death induced by starvation of the cells, called activated-cell autonomous death (ACAD).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987381/hypoxia-ischemia-activate-processing-of-amyloid-precursor-protein-impact-of-vascular-dysfunction-in-the-pathogenesis-of-alzheimer-s-disease
#17
REVIEW
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
Alzheimer's disease (AD) is associated with deficiencies in cerebrovascular functions, e.g. reduced cerebral blood flow and capillary amyloid angiopathy, both of which are evident during the early phase of AD, thus local hypoxia/ischemia could augment the pathogenesis of AD. There is abundant literature revealing that exposures to hypoxia/ischemia increase the amyloidogenic processing of amyloid-β precursor protein (APP) leading to the accumulation of amyloid-β peptides in brain. This hypoxia-induced response has been attributed to a significant increase in the activities of β- and γ-secretases, whereas α-secretase activity decreases in hypoxia...
December 17, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27935327/activation-induced-cell-death-aicd-of-human-melanoma-antigen-specific-tcr-engineered-cd8-t-cells-involves-jnk-bim-and-p53
#18
Arvind Chhabra, Bijay Mukherji, Deepika Batra
OBJECTIVES: Adoptive cancer immunotherapy (ACT) with transgenic T cell receptor (TCR) engineered (TCReng) anti-tumor T cells has produced encouraging results, however, efficacy of these approaches need improvement. Since premature activation induced cell death (AICD) of adoptively administered T cells could be a major impediment, we examined the mechanism(s) underlying AICD in TCReng CD8+ cytolytic T lymphocytes (CTL). METHODS: AICD in human tumor antigen-specific MHC class I restricted TCR engineered CD8+ CTL was induced by exposing them to cognate peptide epitope...
February 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27928425/synthesis-of-acyl-oleanolic-acid-uracil-conjugates-and-their-anti-tumor-activity
#19
Wei-Bin Mo, Chun-Hua Su, Jia-Yan Huang, Jun Liu, Zhen-Feng Chen, Ke-Guang Cheng
BACKGROUND: Oleanolic acid, which can be isolated from many foods and medicinal plants, has been reported to possess diverse biological activities. It has been found that the acylation of the hydroxyl groups of the A-ring in the triterpene skeleton of oleanolic acid could be favorable for biological activities. The pyrimidinyl group has been constructed in many new compounds in various anti-tumor studies. RESULTS: Five acyl oleanolic acid-uracil conjugates were synthesized...
2016: Chemistry Central Journal
https://www.readbyqxmd.com/read/27877154/immununochemical-markers-of-the-amyloid-cascade-in-the-hippocampus-in-motor-neuron-diseases
#20
Ulises Gómez-Pinedo, Rocio N Villar-Quiles, Lucia Galán, Jordi A Matías-Guiu, Maria S Benito-Martin, Antonio Guerrero-Sola, Teresa Moreno-Ramos, Jorge Matías-Guiu
BACKGROUND: Several findings suggest that the amyloid precursor protein (APP) and the amyloid cascade may play a role in motor neuron disease (MND). OBJECTIVE: Considering that dementia is one of the most frequent non-motor symptoms in amyotrophic lateral sclerosis (ALS) and that hippocampus is one of the brain areas with greater presence of amyloid-related changes in neurodegenerative diseases, our aim was to analyze the molecular markers of the amyloid cascade of APP in pathology studies of the hippocampus of autopsied patients with ALS and ALS-frontotemporal dementia (FTD)...
2016: Frontiers in Neurology
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