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https://www.readbyqxmd.com/read/28428882/differential-phenotypes-of-memory-cd4-and-cd8-t-cells-in-the-spleen-and-peripheral-tissues-following-immunostimulatory-therapy
#1
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
#2
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
#3
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-growth-factor-receptor-bound-protein-2-grb2-and-cytoskeleton-stability-are-correlated-in-a-neurodegenerative-scenario
#4
Piyali Majumder, Kasturi Roy, Brijesh Kumar Singh, Nihar Ranjan Jana, Debashis Mukhopadhyay
Alzheimer's Disease (AD) manifests neuronal loss. On the premises 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 Aβ oligomers and intracellular elevation of AICD levels, have been used to closely inspect the series of signaling events. In their presence, multiple signaling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton and Grb2 partially counterbalances the cytoskeletal loss...
March 30, 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
#5
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...
March 28, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28344547/app-function-and-lipids-a-bidirectional-link
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
December 20, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27928425/synthesis-of-acyl-oleanolic-acid-uracil-conjugates-and-their-anti-tumor-activity
#15
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
#16
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
https://www.readbyqxmd.com/read/27871938/the-role-of-gpi-anchored-axonal-glycoproteins-in-neural-development-and-neurological-disorders
#17
REVIEW
Gianfranco Gennarini, Antonella Bizzoca, Sabrina Picocci, Daniela Puzzo, Patrizia Corsi, Andrew J W Furley
This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49...
November 18, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27742673/efficacy-of-adoptive-t-cell-therapy-is-improved-by-treatment-with-the-antioxidant-n-acetyl-cysteine-which-limits-activation-induced-t-cell-death
#18
Matthew J Scheffel, Gina Scurti, Patricia Simms, Elizabeth Garrett-Mayer, Shikhar Mehrotra, Michael I Nishimura, Christina Voelkel-Johnson
Although adoptive transfer of autologous tumor antigen-specific T-cell immunotherapy can produce remarkable clinical efficacy, most patients do not achieve durable complete responses. We hypothesized that reducing susceptibility of T cells to activation-induced cell death (AICD), which increases during the rapid in vitro expansion of therapeutic T cells before their infusion, might improve the persistence of adoptively transferred cells. Our investigations revealed that repetitive stimulation of the T-cell receptor (TCR) induced AICD, as a result of activating the DNA damage response pathway through ATM-mediated Ser15 phosphorylation of p53...
October 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27645989/a-novel-method-for-epicardial-defibrillator-lead-placement-in-young-children-coil-between-the-great-arteries
#19
Raghav Murthy, Matthew R Williams, James C Perry, Suzanne Shepard, Daniel DiBardino
The primary and secondary prevention of sudden cardiac death resulting from malignant arrhythmia, channelopathy, and hypertrophic cardiomyopathy often requires the implantation of automatic internal cardiac defibrillators (AICDs) in the pediatric population. In young patients, the small size of the systemic veins, complex anatomy of congenital heart disease, and body habitus often preclude safe and durable transvenous placement of the AICD coil, requiring innovative methods to circumvent this problem. This report describes the technique used at Rady Children's Hospital San Diego/UCSD for the epicardial placement of an ICD system with a transvenous ICD coil placed between the aorta and pulmonary artery, thereby producing a stable location and excellent coil-to-can vector for successful defibrillation...
October 2016: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/27629285/autophagy-inhibition-and-mitochondrial-remodeling-join-forces-to-amplify-apoptosis-in-activation-induced-cell-death
#20
Corrado Mauro, Campello Silvia
Mitochondrial structural and functional changes and the autophagy pathway crosstalk under several stress conditions. However, their interplay under physiological cell death stimulation has been unclear. In our recent report, we show that during activation-induced cell death (AICD), the T-cell receptor (TCR)-dependent pathway that controls immune tolerance, autophagy is inhibited at an early stage. Further, we found that this inhibition is coupled with mitochondria fragmentation and cristae remodeling to unleash the apoptotic program...
December 2016: Autophagy
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