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https://www.readbyqxmd.com/read/29150961/modulation-of-igg1-immunoeffector-function-by-glycoengineering-of-the-gdp-fucose-biosynthesis-pathway
#1
Ronan M Kelly, Ronald L Kowle, Zhirui Lian, Beth A Strifler, Derrick R Witcher, Bhavin S Parekh, Tongtong Wang, Christopher C Frye
Cross-linking of the Fcγ receptors expressed on the surface of hematopoietic cells by IgG immune complexes triggers the activation of key immune effector mechanisms, including antibody-dependent cell mediated cytotoxicity (ADCC). A conserved N-glycan positioned at the N-terminal region of the IgG CH 2 domain is critical in maintaining the quaternary structure of the molecule for Fcγ receptor engagement. The removal of a single core fucose residue from the N-glycan results in a considerable increase in affinity for FcγRIIIa leading to an enhanced receptor-mediated immunoeffector function...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150958/inhibition-of-mir-200b-mir-429-contributes-to-neuropathic-pain-development-through-targeting-zinc-finger-e-box-binding-protein-1
#2
Xue-Tao Yan, Ying Zhao, Xiao-Li Cheng, Xiang-Hu He, Yu Wang, Wen-Zhong Zheng, Hu Chen, Yan-Lin Wang
Many studies have reported that microRNAs participate in neuropathic pain development. Previously, miR-200b and miR-429 are reported to be involved in various diseases. In our current study, we focused on their roles in neuropathic pain and we found that miR-200b and miR-429 were significantly decreased in chronic constriction injury (CCI) rat spinal cords and isolated microglials. miR-200b and miR-429 overexpression were able to relieve neuropathic pain through modulating PWT and PWL in CCI rats. Meanwhile, we observed that both miR-200b and miR-429 upregulation could repress neuroinflammation via inhibiting inflammatory cytokines such as IL-6, IL-1β and TNF-α in CCI rats...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150931/microrna-497-accelerates-apoptosis-while-inhibiting-proliferation-migration-and-invasion-through-negative-regulation-of-the-mapk-erk-signaling-pathway-via-raf-1
#3
Ling Tao, Xia Li, Na-Na Han, Qi Zhou, Zhi-Le Liu
The aim of this study is to explore the various modes of action miR-497 has on human cervical cancer (CC) cell behavior. We also speculate that miR-497 achieves its anti-tumor role by governing RAF-1 via MAPK/ERK signaling pathway. CC tissues with corresponding adjacent normal tissues were collected from 168 CC patients. RAF-1-positive cells were identified by means of immunohistochemistry in tissues. A series of inhibitors, mimics and siRNA against RAF-1 were introduced to validate regulatory mechanisms for miR-497 and RAF-1...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150880/a-slowly-developed-severe-cutaneous-adverse-reaction-to-idelalisib
#4
L Huilaja, O Lindgren, M Soronen, T Siitonen, K Tasanen
Intracellular signal mediator phosphatidylinositol-3-kinase (PIK3K) -δ, an isoform of PIK3K, is expressed in hematopoietic cells especially in lymphoid lineage 1. Idelalisib is a novel PIK3K-δ targeted kinase inhibitor which is approved for relapsed follicular B-cell non-Hodgkin lymphoma as a monotherapy and in combination with rituximab, an anti-CD20 antibody, for relapsed chronic lymphocytic leukemia (CLL) 2. Only one case describing the clinical features of severe cutaneous adverse reaction (SCAR) of idelalisib in detail has been previously published 3...
November 17, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29150876/toxicological-characterization-of-zno-nanoparticles-in-malignant-and-non-malignant-cells
#5
Helena Moratin, Agmal Scherzad, Thomas Gehrke, Pascal Ickrath, Katrin Radeloff, Norbert Kleinsasser, Stephan Hackenberg
The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells...
November 18, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29150847/chronic-sun-exposure-is-associated-with-distinct-histone-acetylation-changes-in-human-skin
#6
S Ding, J Chen, Q Zeng, J Lu, L Tan, A Guo, J Kang, S Yang, Y Xiang, C Zuo, J Huang
BACKGROUND: Photoaging is attributed to continuous sunlight or artificial UV exposure and manifests the clinical and histological changes of skin. Epigenetic changes have been found to be involved in the pathogenesis of photoaging. However, the underlying mechanisms are unclear. OBJECTIVES: To analyse histone modification patterns in sun-exposed and non-exposed skins, and identify the abnormally histone modified-genes related to photoaging. METHODS: Skin biopsies were collected both from the outer forearm (sun-exposed area) and the buttock (sun-protected area) in 20 healthy middle-aged female volunteers...
November 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29150834/il-22-neutralizing-autoantibodies-impair-fungal-clearance-in-murine-oropharyngeal-candidiasis-model
#7
Rudolf Bichele, Jaanika Kärner, Kai Truusalu, Imbi Smidt, Reet Mändar, Heather R Conti, Sarah L Gaffen, Pärt Peterson, Martti Laan, Kai Kisand
Protection against mucocutaneous candidiasis depends on the T helper (Th)17 pathway, as gene defects affecting its integrity result in inability to clear Candida albicans infection on body surfaces. Moreover, autoantibodies neutralizing Th17 cytokines have been related to chronic candidiasis in a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene. However, the direct pathogenicity of these autoantibodies has not yet been addressed...
November 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29150812/factors-influencing-platelet-transfusion-refractoriness-in-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#8
Pilar Solves, Jaime Sanz, Carmen Freiria, Marta Santiago, Ana Villalba, Inés Gómez, Pau Montesinos, Juan Montoro, Jose Luis Piñana, José Ignacio Lorenzo, Nieves Puig, Guillermo F Sanz, Miguel Ángel Sanz, Nelly Carpio
Hematopoietic stem cell transplantation has been considered a risk factor for development of platelet transfusion refractoriness. The objective of this study was to assess the platelet transfusion refractoriness rate in patients undergoing allogeneic hematopoietic stem cell transplantation from different sources. We retrospectively reviewed the charts and transfusion records of patients who underwent allogeneic stem cell transplantation at our institution between 2013 and 2015. The evaluation of post-transfusion platelet count was assessed for each transfusion given, from day of progenitor infusion to day 30 after transplantation...
November 17, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29150769/changes-in-expression-of-the-membrane-receptors-cd14-mhc-ii-sr-a-and-tlr4-in-tissue-specific-monocytes-macrophages-following-porphyromonas-gingivalis-lps-stimulation
#9
Chunfang Wu, Chongwu Liu, Kai Luo, Yanfen Li, Jun Jiang, Fuhua Yan
The aim of the study was to provide a theoretical foundation for understanding the relationship between periodontal diseases and systemic diseases by examining the inflammatory effect of Porphyromonas gingivalis lipopolysaccharide (LPS) on monocytes/macrophages isolated from tissues distinct from the oral cavity in normal and hyperlipidemic New Zealand white rabbits. Macrophages were isolated from four separate tissues (mononuclear cells from blood, alveolar macrophages, peritoneal macrophages, and Kupffer cells) from both normal and hyperlipidemic New Zealand white rabbits...
November 18, 2017: Inflammation
https://www.readbyqxmd.com/read/29150708/production-of-arabitol-from-enzymatic-hydrolysate-of-soybean-flour-by-debaryomyces-hansenii-fermentation
#10
Abdullah A Loman, S M M Islam, Lu-Kwang Ju
Arabitol is a low-calorie sugar alcohol with anti-cariogenic properties. Enzymatic hydrolysate of soybean flour is a new renewable biorefinery feedstock containing hexose, pentose, and organic nitrogen sources. Arabitol production by Debaryomyces hansenii using soybean flour hydrolysate was investigated. Effects of medium composition, operating conditions, and culture stage (growing or stationary phase) were studied. Production was also compared at different culture volumes to understand the effect of dissolved oxygen concentration (DO)...
November 17, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29150670/ultrahigh-field-mr-imaging-of-a-subconjunctival-anti-glaucoma-drug-delivery-system-in-a-rabbit-model
#11
Franziska Kopp, Thomas Eickner, Stefan Polei, Karen Falke, Martin Witt, Niels Grabow, Oliver Stachs, Rudolf F Guthoff, Tobias Lindner
Local drug delivery systems (DDS) have become a favourable approach for the treatment of numerous diseases. Biomedical imaging techniques such as ultrahigh field magnetic resonance imaging (UHF-MRI) offer unique insight into DDS biodegradation in vivo. We describe the establishment of a 7 Tesla MRI routine for longitudinal in vivo examinations of a subconjunctival DDS for the treatment of glaucoma in a rabbit model. In initial in vitro examinations the T2-relaxation times of the polymeric DDS components were assessed...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150641/repurposing-of-the-anti-malaria-drug-chloroquine-for-zika-virus-treatment-and-prophylaxis
#12
Sergey A Shiryaev, Pinar Mesci, Antonella Pinto, Isabella Fernandes, Nicholas Sheets, Sujan Shresta, Chen Farhy, Chun-Teng Huang, Alex Y Strongin, Alysson R Muotri, Alexey V Terskikh
One of the major challenges of the current Zika virus (ZIKV) epidemic is to prevent congenital foetal abnormalities, including microcephaly, following ZIKV infection of pregnant women. Given the urgent need for ZIKV prophylaxis and treatment, repurposing of approved drugs appears to be a viable and immediate solution. We demonstrate that the common anti-malaria drug chloroquine (CQ) extends the lifespan of ZIKV-infected interferon signalling-deficient AG129 mice. However, the severity of ZIKV infection in these mice precludes the study of foetal (vertical) viral transmission...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150589/change-in-hydration-indices-associated-with-an-increase-in-total-water-intake-of-more-than-0-5%C3%A2-l-day-sustained-over-4%C3%A2-weeks-in-healthy-young-men-with-initial-total-water-intake-below-2%C3%A2-l-day
#13
Jodi D Stookey, Janice Hamer, David W Killilea
This secondary data analysis addressed gaps in knowledge about effects of chronic water intake. Longitudinal data from the Adapt Study were used to describe effects of prescribing a sustained increase in water intake relative to baseline, for 4 weeks, on multiple indices of total body water (TBW) flux, regulation, distribution, and volume in five healthy, free-living, young men, with mean total water intake initially below 2 L/day. Indices were measured weekly. Within-person fixed effect models tested for significant changes in indices over time and associations between changes in indices...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29150563/nfat5-regulated-macrophage-polarization-supports-the-proinflammatory-function-of-macrophages-and-t-lymphocytes
#14
Mónica Tellechea, Maria Buxadé, Sonia Tejedor, Jose Aramburu, Cristina López-Rodríguez
Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150444/toll-like-receptor-4-induced-ryanodine-receptor-2-oxidation-and-sarcoplasmic-reticulum-ca2-leakage-promote-cardiac-contractile-dysfunction-in-sepsis
#15
Jie Yang, Rui Zhang, Xin Jiang, Jingzhang Lv, Ying Li, Hongyu Ye, Wenjuan Liu, Gang Wang, Cuicui Zhang, Na Zheng, Ming Dong, Yan Wang, Peiya Chen, Kumar Santosh, Yong Jiang, Jie Liu
Studies suggest the potential role of sarcoplasmic reticulum (SR) Ca2+ leak in cardiac contractile dysfunction in sepsis. However, direct supporting evidence is lacking, and the mechanisms underlying this SR leak are poorly understood. Here, we investigated the changes in cardiac Ca2+ handling and contraction in LPS-treated rat cardiomyocytes and a mouse model of polymicrobial sepsis produced by cecal ligation and puncture (CLP). LPS decreased the systolic Ca2+ transient and myocyte contraction, as well as SR Ca2+ content...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29150430/interferon-%C3%A1%C2%B5-2-signaling-in-melanocytes-and-melanoma-cells-regulates-expression-of-ctla-4
#16
Xuan Mo, Hanghang Zhang, Sarah Preston, Kayla Martin, Bo Zhou, Nish Vadalia, Ana M Gamero, Jonathan Soboloff, Italo Tempera, M Raza Zaidi
CTLA-4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA-4 immunotherapy is highly effective at reactivating T cell responses against melanoma, which is postulated to be due to targeting CTLA-4 on T cells. Here we report that CTLA-4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-gamma (IFNG) signaling activated the expression of the human CTLA-4 gene in a melanocyte and melanoma cell-specific manner...
November 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29150396/identification-of-pyruvate-dehydrogenase-kinase-1-inhibitors-with-anti-osteosarcoma-activity
#17
Aiping Fang, Huiqiang Luo, Liping Liu, Haibo Fan, Yaying Zhou, Yuqin Yao, Yue Zhang
Overexpression of pyruvate dehydrogenase kinases (PDKs), especially PDK1 has been observed in a variety of cancers. Thus, targeting PDK1 offers an attractive opportunity for the development of cancer therapies. In this letter, we reported the identification of two novel PDK1 inhibitors as anti-osteosarcoma agents. We found that TM-1 and TM-2 inhibited PDK1 with the IC50 values of 2.97 and 3.41 μM, respectively. Furthermore, TM-1 and TM-2 dose-dependently reduced phosphorylation of pyruvate dehydrogenase complex in MG-63 osteosarcoma cells...
October 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29150333/design-synthesis-and-evaluation-of-novel-dihydrostilbene-derivatives-as-potential-anti-melanogenic-skin-protecting-agents
#18
Yu Zhu, Wen-Hui Pan, Chuen Fai Ku, Hong-Jie Zhang, Siu Wai Tsang
The stems of Dendrobium orchids (Orchidaceae), also known as Shi Hu, have been used for medicinal purposes for centuries in oriental countries. In fact, the health benefits of Shi Hu have been evidenced by its modern pharmacological actions on conquering oxidative stress in pathological conditions. From the extracts of two commonly used Dendrobium species, we obtained discernible amounts of stilbenoids, explicitly trans-resveratrol (1) and dihydro-resveratrol (2), which are prototypical antioxidants. When applied to cultured melanocytes, these stilbenoids, dihydro-resveratrol (2) in particular, significantly reduced melanin formation via inhibiting tyrosinase activity and expression of tyrosinase-related proteins...
October 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29150331/anti-amyloidogenic-and-anti-apoptotic-effect-of-%C3%AE-bisabolol-against-a%C3%AE-induced-neurotoxicity-in-pc12-cells
#19
Balakrishnan Shanmuganathan, Venkatesan Suryanarayanan, Sethuraman Sathya, Muralidharan Narenkumar, Sanjeev Kumar Singh, Kandasamy Ruckmani, Kasi Pandima Devi
Alzheimer's disease (AD) is a life-threatening neurodegenerative disorder leading to dementia, with a progressive decline in memory and other thinking skills of elderly populace. Of the multiple etiological factors of AD, the accumulation of senile plaques (SPs) particularly as Aβ oligomers correlates with the relentlessness cognitive impairment in AD patients and play a vital role in AD pathology. Since natural essential oil constituents have successfully served as a source of drugs for AD treatment, the present study aims at the in vitro and in silico investigation of anti-amyloidogenic potential and anti-apoptotic property of the α-bisabolol against Aβ25-35 induced neurotoxicity in PC12 cells...
October 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29150330/the-structural-requirements-of-histone-deacetylase-inhibitors-c4-modified-saha-analogs-display-dual-hdac6-hdac8-selectivity
#20
Ahmed T Negmeldin, Joseph R Knoff, Mary Kay H Pflum
Histone deacetylase (HDAC) enzymes govern the post-translational acetylation state of lysine residues on protein substrates, leading to regulatory changes in cell function. Due to their role in cancers, HDAC proteins have emerged as promising targets for cancer treatment. Four HDAC inhibitors have been approved as anti-cancer therapeutics, including SAHA (Suberoylanilide hydroxamic acid, Vorinostat, Zolinza). SAHA is a nonselective HDAC inhibitor that targets most of the eleven HDAC isoforms. The nonselectivity of SAHA might account for its clinical side effects, but certainly limits its use as a chemical tool to study cancer-related HDAC cell biology...
October 31, 2017: European Journal of Medicinal Chemistry
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