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https://www.readbyqxmd.com/read/28238890/time-lapse-imaging-of-p65-and-i%C3%AE%C2%BAb%C3%AE-translocation-kinetics-following-ca-2-induced-neuronal-injury-reveals-biphasic-translocation-kinetics-in-surviving-neurons
#1
Robert Schwamborn, Heiko Düssmann, Hans-Georg König, Jochen H M Prehn
The transcription factor nuclear factor-κB (NF-κB) regulates neuronal differentiation, plasticity and survival. It is well established that excitatory neurotransmitters such as glutamate control NF-κB activity. Glutamate receptor overactivation is also involved in ischemic- and seizure-induced neuronal injury and neurodegeneration. However, little is known at the single cell-level how NF-κB signaling relates to neuronal survival during excitotoxic injury. We found that silencing of p65/NF-κB delayed N-methyl-d-aspartate (NMDA)-induced excitotoxic injury in hippocampal neurons, suggesting a functional role of p65 in excitotoxicity...
February 23, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28238427/development-of-a-non-radiolabeled-glucosyltransferase-activity-assay-for-c-difficile-toxin-a-and-b-using-ultra-performance-liquid-chromatography
#2
John W Loughney, Catherine Lancaster, Colleen E Price, Van M Hoang, Sha Ha, Richard R Rustandi
Clostridium difficile infection (CDI) is the leading cause of gastroenteritis-associated death in the United States. The major virulent factors of C. difficile are toxin A (TcdA) and toxin B (TcdB). Toxicity is mediated by the glucosyltransferase domains on TcdA and TcdB wherein a glucose is transferred from UDP-glucose to Ras homolog family member A (RhoA) receptor. This modification results in disruption of critical cell signaling events. Vaccination against these toxins is considered the best way to combat the CDI...
January 31, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28237968/nationwide-experience-of-catecholaminergic-polymorphic-ventricular-tachycardia-caused-by-ryr2-mutations
#3
Anders Krogh Broendberg, Jens Cosedis Nielsen, Jesper Bjerre, Lisbeth Noerum Pedersen, Jens Kristensen, Finn Lund Henriksen, Henning Bundgaard, Henrik Kjaerulf Jensen
OBJECTIVE: The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. METHODS: The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives...
February 25, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28237964/vulnerability-to-oxygen-glucose-deprivation-of-primary-neurons-derived-from-tg2576-alzheimer-mice-role-of-intraneuronal-abeta-accumulation-and-astrocytes
#4
Vito Antonio Baldassarro, Alessandra Marchesini, Luciana Giardino, Laura Calzà
Microvascular dysfunction is considered an integral part of Alzheimer disease (AD) pathogenesis, but the possible relationship between amyloid pathology, microvascular dysfunction and cell death is still unclear. In order to investigate the influence of intraneuronal Abeta (Aβ) accumulation on vulnerability to hypoxia, we isolated primary cortical neurons from Tg2576 (carrying the APPSwe mutation) and Wt fetal mice. We first demonstrated that neurons isolated from Tg2576 new-born mice show an increase in VEGFa mRNA expression and a decrease in the expression of the two VEGF receptors, i...
February 24, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28237818/quercetin-inhibits-acid-sensing-ion-channels-through-a-putative-binding-site-in-the-central-vestibular-region
#5
Mohona Mukhopadhyay, Anurag Singh, S Sachchidanand, Amal Kanti Bera
Acid-sensing ion channels (ASICs) are associated with many pathophysiological processes, such as neuronal death during ischemic stroke, epileptic seizure and nociception. However, there is a dearth of ASIC-specific therapeutic blockers. Here we report that quercetin, a plant flavonoid, which is known for its neuroprotective effect, reversibly inhibits homomeric rat ASIC1a, ASIC2a and ASIC3 with an IC50 of about 2 µM. Also, quercetin prevents low pH-induced intracellular calcium rise and cell death in HEK-293 cells, which have endogenous expression of ASIC1a and 2a...
February 22, 2017: Neuroscience
https://www.readbyqxmd.com/read/28237816/mir-146a-promotes-remyelination-in-a-cuprizone-model-of-demyelinating-injury
#6
Jing Zhang, Zheng Gang Zhang, Mei Lu, Xinli Wang, Xia Shang, Stanton B Elias, Michael Chopp
The death of mature oligodendrocytes (OLs) which are the sole myelinating cells of the central nervous system (CNS), leads to demyelination and functional deficits. Currently, there is lack of effective remyelination therapies for patients with demyelinating diseases. MicroRNAs (miRNAs) mediate OL function. We hypothesized that miR-146a, by inactivating interleukin-1 receptor-associated kinase 1 (IRAK1), promotes differentiation of oligodendrocyte progenitor cells (OPCs) and thereby enhances remyelination. To test this hypothesis, a demyelination model induced by a cuprizone (CPZ) diet was employed, in which C57BL/6J mice were fed with a CPZ diet for 5 weeks...
February 22, 2017: Neuroscience
https://www.readbyqxmd.com/read/28237499/mers-cov-spike-nanoparticles-protect-mice-from-mers-cov-infection
#7
Christopher M Coleman, Thiagarajan Venkataraman, Ye V Liu, Gregory M Glenn, Gale E Smith, David C Flyer, Matthew B Frieman
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice...
February 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28236968/regulation-of-embryonic-and-postnatal-development-by-the-csf-1-receptor
#8
Violeta Chitu, E Richard Stanley
Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28236856/could-mucin-16-and-colony-stimulating-factor-2-receptor-beta-possible-graft-versus-host-disease-biomarkers-medical-hypotheses
#9
Milena Monteiro de Souza, Fabiana Martins de Paula, Ricardo Hsieh, Maria Cristina Martins Almeida Macedo, Marcelo Andreetta Corral, Thaís Borguezan Nunes, Fernanda De Paula, Silvia Vanessa Lourenço
Graft versus host disease (GVHD) occurs after bone marrow transplantation and is one of the most important causes of death worldwide. Reviews demonstrated GVHD patients with involvement of various tissues and organs, such as salivary glands. The diagnosis of acute GVHD has been the biopsies and the histopathologic evaluation of tissue from an involved organ. These procedures are invasive. Saliva proteins as possible biomarker for GVHD could facilitate the management and diagnosis accuracy. For support the proposed hypotheses, in this pilot study we collected whole saliva samples from patients with undergoing allogeneic hematopoietic cell transplantation (HCT) and from healthy subjects...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#10
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28230861/ripk3-interactions-with-mlkl-and-camkii-mediate-oligodendrocytes-death-in-the-developing-brain
#11
Yi Qu, Jun Tang, Huiqing Wang, Shiping Li, Fengyan Zhao, Li Zhang, Q Richard Lu, Dezhi Mu
Oligodendrocyte progenitor cells (OPCs) death is a key contributor to cerebral white matter injury (WMI) in the developing brain. A previous study by our group indicated that receptor-interacting proteins (RIPs) are crucial in mediating necroptosis in developing neurons. However, whether this mechanism is involved in OPCs death is unclear. We aimed to explore the mechanisms of RIP-mediated oligodendrocytes (OLs) death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment (OGD/zVAD) in vitro...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230733/ck2-molecular-targeting-tumor-cell-specific-delivery-of-rnai-in-various-models-of-cancer
#12
REVIEW
Janeen H Trembley, Betsy T Kren, Md Joynal Abedin, Rachel I Vogel, Claire M Cannon, Gretchen M Unger, Khalil Ahmed
Protein kinase CK2 demonstrates increased protein expression relative to non-transformed cells in the majority of cancers that have been examined. The elevated levels of CK2 are involved in promoting not only continued proliferation of cancer cells but also their resistance to cell death; thus, CK2 has emerged as a plausible target for cancer therapy. Our focus has been to target CK2 catalytic subunits at the molecular level using RNA interference (RNAi) strategies to achieve their downregulation. The delivery of oligonucleotide therapeutic agents warrants that they are protected and are delivered specifically to cancer cells...
February 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28230361/10-gingerol-a-phytochemical-derivative-from-tongling-white-ginger-inhibits-cervical-cancer-insights-into-the-molecular-mechanism-and-inhibitory-targets
#13
Fang Zhang, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
With an aim to evaluate anti-cancerous activities of 10-gingerol (10-G) against Hela cells, it was purified and identified from Tongling White Ginger by HSCCC, UPLC-TOF-MS/MS and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity and arrested cell cycle in G0/G1-phase. The most cell cycle related genes and proteins expression significantly decreased, followed by slight decrease in few and without affecting cyclin B1 and cyclin E1 (protein)...
February 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28230291/therapeutic-potentials-of-bdnf-trkb-in-breast-cancer-current-status-and-perspectives
#14
Amir Tajbakhsh, Amin Mokhtari-Zaer, Mehdi Rezaee, Fahimeh Afzaljavan, Mehdi Rivandi, Seyed Mahdi Hassanian, Gordon A Ferns, Alireza Pasdar, Amir Avan
Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB and the p75(NTR) death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230214/antioxidant-response-is-a-protective-mechanism-against-nutrient-deprivation-in-c-elegans
#15
Jun Tao, Qin-Yi Wu, Yi-Cheng Ma, Yuan-Li Chen, Cheng-Gang Zou
Animals often experience periods of nutrient deprivation; however, the molecular mechanisms by which animals survive starvation remain largely unknown. In the nematode Caenorhabditis elegans, the nuclear receptor DAF-12 acts as a dietary and environmental sensor to orchestrate diverse aspects of development, metabolism, and reproduction. Recently, we have reported that DAF-12 together with co-repressor DIN-1S is required for starvation tolerance by promoting fat mobilization. In this report, we found that genetic inactivation of the DAF-12 signaling promoted the production of reactive oxygen species (ROS) during starvation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229962/overexpression-of-hsa-mir-939-follows-by-ngfr-down-regulation-and-apoptosis-reduction
#16
Fahimeh Hosseini Aghdaei, Bahram M Soltani, Sadat Dokanehiifard, Seyed Javad Mowla, Masoud Soleimani
Neurotrophin receptors play a crucial role in neuronal survival, differentiation and regeneration. Nerve growth factor receptor (NGFR) or P75(NTR) is a neurotrophin receptor that is involved in many pathological conditions including cancers. Genetic factors that are involved in regulation of neurotrophin receptors are under intense investigation. MiRNAs are novel regulators of signalling pathways that are candidates for regulation of neurotrophin receptors. Computational programs predicted that NGFR gene is a bona fide target for hsa-miR- 939...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28228704/pd-1-and-pd-l1-immune-checkpoint-blockade-to-treat-breast-cancer
#17
REVIEW
Andreas D Hartkopf, Florin-Andrei Taran, Markus Wallwiener, Christina B Walter, Bernhard Krämer, Eva-Maria Grischke, Sara Y Brucker
Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28228590/a-polymorphism-within-the-internal-fusion-loop-of-the-ebola-virus-glycoprotein-modulates-host-cell-entry
#18
Markus Hoffmann, Lisa Crone, Erik Dietzel, Jennifer Paijo, Mariana González-Hernández, Inga Nehlmeier, Ulrich Kalinke, Stephan Becker, Stefan Pöhlmann
The large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two non-human primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228483/new-concepts-and-mechanisms-of-platelet-activation-signaling
#19
REVIEW
Brian Estevez, Xiaoping Du
Upon blood vessel injury, platelets are exposed to adhesive proteins in the vascular wall and soluble agonists, which initiate platelet activation, leading to formation of hemostatic thrombi. Pathological activation of platelets can induce occlusive thrombosis, resulting in ischemic events such as heart attack and stroke, which are leading causes of death globally. Platelet activation requires intracellular signal transduction initiated by platelet receptors for adhesion proteins and soluble agonists. Whereas many platelet activation signaling pathways have been established for many years, significant recent progress reveals much more complex and sophisticated signaling and amplification networks...
March 2017: Physiology
https://www.readbyqxmd.com/read/28228218/-thioridazine-sensitizes-apoptotic-effect-of-trail-in-human-lung-cancer-pc9-cells-through-er-stress-mediated-up-regulation-of-dr5
#20
Juan Li, Yi Wang, Liu Liu, Yuan Yuan, Yangyi Bao
BACKGROUND: Tumor necrosis factor-related apoptosis-inducting ligand (TRAIL) can induce apoptosis of tumor cells, however, various of tumor cells may survive because of resistance to TRAIL-mediated apoptosis. This study is to observe the proliferation inhibition effect of TRAIL sensitized by thioridazine on PC9 cells through endoplasmic reticulum (ER) stress mediated up-regulation of death receptor 5 (DR5) and investigate its mechanism. METHODS: PC9 cells were treated with different concentrations of thioridazine and TRAIL alone or in combination...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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