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https://www.readbyqxmd.com/read/28239983/targeted-deletion-of-gd3-synthase-protects-against-mptp-induced-neurodegeneration
#1
Yada Akkhawattanangkul, Panchanan Maiti, Yi Xue, Dipendra Aryal, William C Wetsel, David Hamilton, Stephen C Fowler, Michael P McDonald
Parkinson's disease is a debilitating neurodegenerative condition for which there is no cure. Converging evidence implicates gangliosides in the pathogenesis of several neurodegenerative diseases, suggesting a potential new class of therapeutic targets. We have shown that interventions that simultaneously increase the neuroprotective GM1 ganglioside and decrease the pro-apoptotic GD3 ganglioside-such as inhibition of GD3 synthase (GD3S) or administration of sialidase-are neuroprotective in vitro and in a number of preclinical models...
February 27, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28239370/capb2-expression-is-associated-with-staphylococcus-aureus-pathogenicity
#2
Dan Li, Yinjuan Guo, Shanshan Wang, Jingnan Lv, Xiuqin Qi, Zengqiang Chen, Lizhong Han, Xueqing Zhang, Liangxing Wang, Fangyou Yu
CapB2 is recognized as a tyrosine kinase and is likely a vital factor in extracellular polysaccharide synthesis in Staphylococcus aureus, but its pathogenicity function and regulatory mechanism remain obscure. Here, we demonstrate that CapB2 enhances bacterial virulence in a murine model. Mice infected with the wild type SA75 strain exhibited significantly larger (P < 0.05) skin lesions from days 4 to 7 of infection than those challenged with the capB2 mutant strain. The effect on virulence was reverted by restoring the capB2 mutation to the wild type...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28239191/the-rise-of-radicals-in-bioinorganic-chemistry
#3
Harry B Gray, Jay R Winkler
Prior to 1950, the consensus was that biological transformations occurred in two-electron steps, thereby avoiding the generation of free radicals. Dramatic advances in spectroscopy, biochemistry, and molecular biology have led to the realization that protein-based radicals participate in a vast array of vital biological mechanisms. Redox processes involving high-potential intermediates formed in reactions with O2 are particularly susceptible to radical formation. Clusters of tyrosine (Tyr) and tryptophan (Trp) residues have been found in many O2-reactive enzymes, raising the possibility that they play an antioxidant protective role...
October 2016: Israel Journal of Chemistry
https://www.readbyqxmd.com/read/28238735/the-caenorhabditis-elegans-matrix-non-peptidase-mnp-1-is-required-for-neuronal-cell-migration-and-interacts-with-the-ror-receptor-tyrosine-kinase-cam-1
#4
Teresa R Craft, Wayne C Forrester
Directed cell migration is critical for metazoan development. During Caenorhabditis elegans development many neuronal, muscle and other cell types migrate. Multiple classes of proteins have been implicated in cell migration including secreted guidance cues, receptors for guidance cues and intracellular proteins that respond to cues to polarize cells and produce the forces that move them. In addition, cell surface and secreted proteases have been identified that may clear the migratory route and process guidance cues...
February 23, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28238714/neuroprotective-effects-of-kukoamine-a-on-neurotoxin-induced-parkinson-s-model-through-apoptosis-inhibition-and-autophagy-enhancement
#5
XiaoLong Hu, Qi Song, Xin Li, DanDan Li, Qiao Zhang, WeiHong Meng, QingChun Zhao
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated Kukoamine A to exhibit strong neuroprotective effects through anti-oxidative stress, anti-inflamation, anti-excitoxicity. In the present study, MPP(+) and MPTP-induced PD models of cell and animal were used to investigate the effects of KuA on PD. Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio and MAPKs family that were induced by MPP(+)...
February 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28238669/ellagic-acid-exerts-protective-effect-in-intrastriatal-6-hydroxydopamine-rat-model-of-parkinson-s-disease-possible-involvement-of-er%C3%AE-nrf2-ho-1-signaling
#6
Tourandokht Baluchnejadmojarad, Nafiseh Rabiee, Sedigheh Zabihnejad, Mehrdad Roghani
Parkinson's disease (PD) is a prevalent movement disorder in the elderly with progressive loss of mesencephalic dopaminergic neurons and incapacitating motor and non-motor complications. Ellagic acid is a natural phenolic compound with potent antioxidant and anti-inflammatory properties. In this study, we investigated its possible neuroprotective effect in 6-hydroxydopamine (6-OHDA) rat model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with ellagic acid at a dose of 50 mg/kg/day for 1 week. Results showed that ellagic acid attenuates apomorphine-induced rotational bias and lowers the latency to initiate and the total time in the narrow beam task and this beneficial effect was partially abrogated following intracerebroventricular microinjection of estrogen receptor β (ERβ) antagonist...
February 23, 2017: Brain Research
https://www.readbyqxmd.com/read/28238445/pentoxifylline-effects-on-capacitation-and-fertility-of-stallion-epididymal-sperm
#7
P N Guasti, G A Monteiro, R R D Maziero, M T Carmo, J A Dell'Aqua, A M Crespilho, E A Rifai, F O Papa
The aims of this study were to determinate whether pentoxifylline (PTX) increases the motion parameters of fresh and frozen-thawed equine epididymal spermatozoa, to evaluate the tyrosine phosphorylation of frozen-thawed epididymal sperm in the presence of PTX and to determine whether the PTX-treatment of stallion epididymal sperm prior to freezing improves the fertility response of mares to a reduced number of spermatozoa per insemination dose. Fifty epididymis were flushed with a skim milk based extender with or without PTX...
February 3, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28238014/positive-minimal-residual-disease-of-flt3-itd-before-hematopoietic-stem-cell-transplantation-resulted-in-a-poor-prognosis-of-an-acute-myeloid-leukemia
#8
Yuka Iwasaki, Rituo Nishiuchi, Michinori Aoe, Takahide Takahashi, Hirokazu Watanabe, Chiho Tokorotani, Kiyoshi Kikkawa, Akira Shimada
Acute myeloid leukemia (AML) patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) often have a poor prognosis, even after hematopoietic stem cell transplantation (HSCT). We report a case of AML with FLT3-ITD identified upon initial diagnosis, who received HSCT at complete remission after 3 consecutive chemotherapies. However, the patient relapsed when the same FLT3-ITD clone emerged, and finally died. Retrospective analysis revealed an allelic ratio of FLT3-ITD/wild type of 1...
February 2017: Acta Medica Okayama
https://www.readbyqxmd.com/read/28238001/structure-based-virtual-screening-of-protein-tyrosine-phosphatase-inhibitors-significance-challenges-and-solutions
#9
REVIEW
Harikrishna Reddy R, Hackyoung Kim, Seungbin Cha, Bongsoo Lee, Young Jun Kim
Phosphorylation is a critical mechanism in biological systems and it is estimated that phosphorylation is indispensable for about 30% of key biological activities such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to diseased conditions. Pathway or biological activity based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers...
February 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28237943/kinome-profiling-identifies-druggable-targets-for-novel-hcmv-antivirals
#10
Kyle C Arend, Erik M Lenarcic, Heather A Vincent, Naim Rashid, Eric Lazear, Ian M MacDonald, Thomas S K Gilbert, Michael P East, Laura E Herring, Gary L Johnson, Lee Graves, Nathaniel J Moorman
Human cytomegalovirus (HCMV) is a significant cause of disease in immunecompromised adults and immune naive newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. There is thus an urgent need for new strategies to treat HCMV infection. Repurposing existing drugs as antivirals is an attractive approach to limit the time and cost of new antiviral drug development. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity, which led us to hypothesize that defining the complement of kinases (the kinome), whose abundance or expression is altered during infection would identify existing kinase inhibitors that could be repurposed as new antivirals...
February 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28237877/osimertinib-induces-autophagy-and-apoptosis-via-reactive-oxygen-species-generation-in-non-small-cell-lung-cancer-cells
#11
Zheng-Hai Tang, Wen-Xiang Cao, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells...
February 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28237781/metabolic-responses-of-the-growing-daphnia-similis-to-chronic-agnps-exposure-as-revealed-by-gc-q-tof-ms-and-lc-q-tof-ms
#12
Bo Zhang, Hui Zhang, Chunlei Du, Qin Xiang Ng, Chaoyang Hu, Yiliang He, Choon Nam Ong
Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. Their fast-growing utilization has increased the occurrence of AgNPs in the environment, posing potential health and ecological risks. In this study, we conducted chronic toxicity tests and investigated the metabolic changes of the growing Daphna similis with exposure to 0, 0.02, and 1 ppb AgNPs, using non-targeted mass spectrometry-based metabolomics. To the best of our knowledge, this study is the first to report the baseline metabolite change of a common aquatic organism Daphnia crustacean through its life-cycle...
February 20, 2017: Water Research
https://www.readbyqxmd.com/read/28237724/the-common-autoimmunity-predisposing-620arg%C3%A2-%C3%A2-trp-variant-of-ptpn22-modulates-macrophage-function-and-morphology
#13
Meihang Li, Hugues Beauchemin, Natalija Popovic, Alan Peterson, Eva d'Hennezel, Ciriaco A Piccirillo, Chao Sun, Constantin Polychronakos
The C1858T single nucleotide polymorphism (SNP) in PTPN22 (protein tyrosine phosphatase nonreceptor 22) leads to the 620 Arg to Trp polymorphism in its encoded human protein LYP. This allelic variant is associated with multiple autoimmune diseases, including type 1 diabetes (T1D), Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the underlying mechanisms are poorly understood. To study how this polymorphism influences the immune system, we generated a mouse strain with a knock-in of the Trp allele, imitating the human disease-associated variant...
February 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28237700/prostaglandin-e1-reduces-the-keratinocyte-toxicity-of-sorafenib-by-maintaining-signal-transducer-and-activator-of-transcription-3-stat3-activity-and-enhancing-the-camp-response-element-binding-protein-creb-activity
#14
Hiroaki Shichiri, Kazuhiro Yamamoto, Maya Tokura, Takahiro Ishida, Atsushi Uda, Toshinori Bito, Chikako Nishigori, Tsutomu Nakagawa, Takeshi Hirano, Ikuko Yano, Midori Hirai
Hand-foot skin reaction (HFSR) is a common side effect of multiple tyrosine kinase inhibitors (mTKIs). HFSR can necessitate dose reductions or interruption of therapy owing to its negative effect on the quality of life. Therefore, effective use of mTKIs requires measures to prevent HFSR. We evaluated the effect of prostaglandin E1 (PGE1) on HFSR, because PGE1 is already used to treat bed sores and skin ulcers and has established angiogenic and antiproliferative effects in keratinocytes. We found that the pathogenesis of sorafenib-induced HFSR is characterized by a decrease in levels of a phosphorylated signal transducer and activator of transcription 3 (STAT3)...
February 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28237688/the-flashlights-on-a-distinct-role-of-protein-kinase-c-%C3%AE-phosphorylation-of-regulatory-and-catalytic-domain-upon-oxidative-stress-in-glioma-cells
#15
Matus Misuth, Jaroslava Joniova, Denis Horvath, Lenka Dzurova, Zuzana Nichtova, Marta Novotova, Pavol Miskovsky, Katarina Stroffekova, Veronika Huntosova
Glioblastoma multiforme are considered to be aggressive high-grade tumors with poor prognosis for patient survival. Photodynamic therapy is one of the adjuvant therapies which has been used for glioblastoma multiforme during last decade. Hypericin, a photosensitizer, can be employed in this treatment. We have studied the effect of hypericin on PKCδ phosphorylation in U87 MG cells before and after light application. Hypericin increased PKCδ phosphorylation at tyrosine 155 in the regulatory domain and serine 645 in the catalytic domain...
February 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28237515/adiporon-an-adiponectin-receptor-agonist-attenuates-pdgf-induced-vsmc-proliferation-through-inhibition-of-mtor-signaling-independent-of-ampk-implications-toward-suppression-of-neointimal-hyperplasia
#16
Arwa Fairaq, Noha M Shawky, Islam Osman, Prahalathan Pichavaram, Lakshman Segar
Hypoadiponectinemia is associated with an increased risk of coronary artery disease. Although adiponectin replenishment mitigates neointimal hyperplasia and atherosclerosis in mouse models, adiponectin therapy has been hampered in a clinical setting due its large molecular size. Recent studies demonstrate that AdipoRon (a small-molecule adiponectin receptor agonist) improves glycemic control in type 2 diabetic mice and attenuates postischemic cardiac injury in adiponectin-deficient mice, in part, through activation of AMP-activated protein kinase (AMPK)...
February 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28237354/-crizotinib-for-ros1-rearranged-non-small-cell-lung-cancer-patients
#17
Charlotte Domblides, Martine Antoine, Armelle Lavole, Jacques Cadranel, Marie Wislez
ROS1 fusions are rare mutations that preferentially concern young and non-smoker women. The ROS1-rearranged protein conserves an intact tyrosine kinase domain, leading to the constitutive activation of the ROS1 tyrosine kinase function and of its downstream pathways, that are known to be involved in tumorigenesis. These molecular abnormalities have shown their oncogenic potential in animals' models and in human, with an early effect on carcinogenesis. Several partners have been identified. Patients with non-small cell lung cancers (NSCLC) harbouring ROS1 alterations can received specific targeted therapies...
February 22, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28237165/treatment-of-choice-for-patients-with-egfr-mutation-positive-non-small-cell-lung-carcinoma-presenting-with-choroidal-metastases-radiotherapy-or-tkis
#18
David Maskell, Konstantinos Geropantas, Michael Kouroupis, Andrew Glenn, Thankamma Ajithkumar
INTRODUCTION: It is not uncommon for patients with non-small cell lung cancer (NSCLC) to develop choroidal metastases (CM). External beam radiotherapy (EBRT) has traditionally been considered the treatment of choice for CM as it offers high response rates and quick relief of symptoms. However, new targeted treatments can offer an effective, alternative treatment strategy for patients harbouring specific genetic abnormalities. CASE STUDY: We present the case of a patient presenting with a symptomatic metastasis to the choroid from an epidermal growth factor receptor (EGFR) mutation-positive NSCLC and exhibiting an excellent clinical and radiological response to the tyrosine kinase inhibitor (TKI) gefitinib...
February 2017: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/28236980/significance-of-immune-checkpoint-proteins-in-egfr-mutant-non-small-cell-lung-cancer
#19
Ross A Soo, Hye Ryun Kim, Bernadette Reyna Asuncion, Zul Fazreen, Mohamed Feroz Mohd Omar, Maria Cynthia Herrera, Joey Sze Yun Lim, Grace Sia, Richie Soong, Byoung-Chul Cho
OBJECTIVES: To characterize the expression of PD-L1, PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Samples from 90 patients with newly diagnosed advanced stage NSCLC harboring EGFR mutations and treated with first line EGFR tyrosine kinase inhibitors (TKI) within 3 months of diagnosis were stained for CTLA-4, PD-L1, PD-1, TIM-3 and CD3 expression by immunohistochemistry...
March 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28236974/vegf-receptor-tyrosine-kinases-key-regulators-of-vascular-function
#20
Alberto Álvarez-Aznar, Lars Muhl, Konstantin Gaengel
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinases are key regulators of vascular development in vertebrates. Their activation is regulated through a family of secreted glycoproteins, the vascular endothelial growth factors (VEGFs). Expression, proteolytic processing, and diffusion range of VEGF proteins need to be tightly regulated, due to their crucial roles in development. While some VEGFs form concentration gradients across developing tissues and act as morphogenes, others function as inhibitors of receptor activation and downstream signaling...
2017: Current Topics in Developmental Biology
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