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https://www.readbyqxmd.com/read/29777901/interrogation-of-ethnomedicinal-plants-for-synthetic-lethality-effects-in-combination-with-deficiency-in-the-dna-repair-endonuclease-rad1-using-a-yeast-cell-based-assay
#1
Hsu Mon Aung, Chananya Huangteerakul, Wittaya Panvongsa, Amornrat N Jensen, Arthit Chairoungdua, Suchada Sukrong, Laran T Jensen
ETHNOPHARMACOLOGICAL RELEVANCE: Plant materials used in this study were selected based on the ethnobotanical literature. Plants have either been utilized by Thai practitioners as alternative treatments for cancer or identified to exhibit anti-cancer properties. AIM OF THE STUDY: To screen ethnomedicinal plants using a yeast cell-based assay for synthetic lethal interactions with cells deleted for RAD1, the yeast homologue of human ERCC4 (XPF) MATERIALS AND METHODS: Ethanolic extracts from thirty-two species of medicinal plants utilized in Thai traditional medicine were screened for synthetic lethal/sick interactions using a yeast cell-based assay...
May 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29777684/repositioning-of-anti-cancer-drug-candidate-azd7762-to-an-anti-allergic-drug-suppressing-ige-mediated-mast-cells-and-allergic-responses-via-the-inhibition-of-lyn-and-fyn
#2
Young Hwan Park, Do Kyun Kim, Hyun Woo Kim, Hyuk Soon Kim, Dajeong Lee, Min Bum Lee, Keun Young Min, Jimo Koo, Su Jeong Kim, Changhee Kang, Young Mi Kim, Hyung Sik Kim, Wahn Soo Choi
Mast cells are critical effector cells in IgE-mediated allergic responses. The aim of this study was to investigate the anti-allergic effects of 3-[(aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-thiophenecarboxamide (AZD7762) in vitro and in vivo. AZD7762 inhibited the antigen-stimulated degranulation from RBL-2H3 (IC50 , ∼ 27.9 nM) and BMMCs (IC50 , ∼ 99.3 nM) in a dose-dependent manner. AZD7762 also inhibited the production of TNF-α and IL-4. As the mechanism of its action, AZD7762 inhibited the activation of Syk and its downstream signaling proteins, such as Linker of activated T cells (LAT), phospholipase (PL) Cγ1, Akt, and mitogen-activated protein (MAP) kinases (Erk1 / 2, p38, and JNK) in mast cells...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29777666/analysis-of-cross-resistance-to-vip3-proteins-in-eight-insect-colonies-from-four-insect-species-selected-for-resistance-to-bacillus-thuringiensis-insecticidal-proteins
#3
Joaquín Gomis-Cebolla, Yuequin Wang, Yudong Quan, Kanglai He, Tom Walsh, Bill James, Sharon Downes, Wendy Kain, Ping Wang, Kathy Leonard, Tom Morgan, Brenda Oppert, Juan Ferré
Bacillus thuringiensis Vip3 proteins are synthesized and secreted during the vegetative growth phase. They are activated by gut proteases, recognize and bind to midgut receptors, form pores and lyse cells. We tested the susceptibility to Vip3Aa and Vip3Ca of Cry1A-, Cry2A-, Dipel- and Vip3-resistant insect colonies from different species to determine whether resistance to other insecticidal proteins confers cross-resistance to Vip3 proteins. As expected, the colonies resistant to Cry1A proteins, Dipel (Helicoverpa armigera, Trichoplusia ni, Ostrinia furnacalis and Plodia interpunctella) or Cry2Ab (H...
May 16, 2018: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/29777224/progression-of-whole-blood-transcriptional-signatures-from-interferon-induced-to-neutrophil-associated-patterns-in-severe-influenza
#4
Jake Dunning, Simon Blankley, Long T Hoang, Mike Cox, Christine M Graham, Philip L James, Chloe I Bloom, Damien Chaussabel, Jacques Banchereau, Stephen J Brett, Miriam F Moffatt, Anne O'Garra, Peter J M Openshaw
Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777223/card9-s12n-facilitates-the-production-of-il-5-by-alveolar-macrophages-for-the-induction-of-type-2-immune-responses
#5
Xia Xu, Jin-Fu Xu, Guoxing Zheng, Hai-Wen Lu, Jie-Lin Duan, Wei Rui, Jian-Hong Guan, Li-Qing Cheng, Dan-Dan Yang, Ming-Chao Wang, Quan-Zhen Lv, Jian-Xiong Li, Xueqiang Zhao, Chun-Xia Chen, Peng Shi, Xin-Ming Jia, Xin Lin
The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH 1 and TH 17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N ), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777158/mesenchymal-stem-cells-and-t-cells-in-the-formation-of-tertiary-lymphoid-structures-in-lupus-nephritis
#6
S Esmaeil Dorraji, Aud-Malin K Hovd, Premasany Kanapathippillai, Gunnstein Bakland, Gro Østli Eilertsen, Stine L Figenschau, Kristin A Fenton
Tertiary lymphoid structures (TLS) develop in the kidneys of lupus-prone mice and systemic lupus erythematosus (SLE) patients with lupus nephritis (LN). Here we investigated the presence of mesenchymal stem cells (MSCs) in the development of TLS in murine LN, as well as the role of human MSCs as lymphoid tissue organizer (LTo) cells on the activation of CD4+ T cells from three groups of donors including Healthy, SLE and LN patients. Mesenchymal stem like cells were detected within the pelvic wall and TLS in kidneys of lupus-prone mice...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777027/t-cell-proliferation-and-colitis-are-initiated-by-defined-intestinal-microbes
#7
Pailin Chiaranunt, Justin T Tometich, Junyi Ji, Timothy W Hand
Inflammatory bowel disease has been associated with the dysregulation of T cells specific to Ags derived from the intestinal microbiota. How microbiota-specific T cells are regulated is not completely clear but is believed to be mediated by a combination of IgA, regulatory T cells, and type 3 innate lymphoid cells. To test the role of these regulatory components on microbiota-specific T cells, we bred CBir1 TCR transgenic (CBir1Tg) mice (specific to flagellin from common intestinal bacteria) onto a lymphopenic Rag1-/- background...
May 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29776755/neutral-ph-and-low-glucose-degradation-product-dialysis-fluids-induce-major-early-alterations-of-the-peritoneal-membrane-in-children-on-peritoneal-dialysis
#8
Betti Schaefer, Maria Bartosova, Stephan Macher-Goeppinger, Peter Sallay, Peter Vörös, Bruno Ranchin, Karel Vondrak, Gema Ariceta, Ariane Zaloszyc, Aysun K Bayazit, Uwe Querfeld, Rimante Cerkauskiene, Sara Testa, Christina Taylan, Johan VandeWalle, YokChin Yap, Rafael T Krmar, Rainer Büscher, Anne K Mühlig, Dorota Drozdz, Salim Caliskan, Felix Lasitschka, Sahar Fathallah-Shaykh, Enrico Verrina, Günter Klaus, Klaus Arbeiter, Raj Bhayadia, Anette Melk, Philipp Romero, Bradley A Warady, Franz Schaefer, Akos Ujszaszi, Claus Peter Schmitt
The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products...
May 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29776611/nasal-delivery-of-chitosan-alginate-nanoparticle-encapsulated-bee-apis-mellifera-venom-promotes-antibody-production-and-viral-clearance-during-porcine-reproductive-and-respiratory-syndrome-virus-infection-by-modulating-t-cell-related-responses
#9
Jina Lee, Yun-Mi Kim, Ju-Heon Kim, Cheong-Weon Cho, Jong-Woon Jeon, Jin-Kyu Park, Sang-Ho Lee, Bock-Gie Jung, Bong-Joo Lee
In this study, we administered specially developed chitosan/alginate nanoparticle encapsulated BV (CH/AL-BV) which has slow-releasing properties and mucosal adhesiveness to pig via nasal route and evaluate whether it can facilitate systemic immune response and improve clearance of porcine reproductive and respiratory syndrome virus (PRRSV). The CH/AL-BV-administered group with PRRSV vaccination showed significantly enhanced Th1-related responses including a high population of CD4+ T lymphocyte and cytokine mRNA levels including interferon-gamma (IFN-γ) and interleukin (IL)-12 and increased PRRSV-specific IgG levels...
June 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29776597/the-role-of-fdg-pet-in-detecting-rejection-after-liver-transplantation
#10
Ashley M Watson, Neal Bhutiani, Prejesh Philips, Eric G Davis, Mary Eng, Robert M Cannon, Christopher M Jones
BACKGROUND: The activation and increased metabolic activity of T cells in acute cellular rejection could allow fluoro-2-deoxyglucose positron emission tomography to be utilized for detection of acute cellular rejection. The objective of this study was to evaluate the effectiveness of fluoro-2-deoxyglucose positron emission tomography in detecting acute cellular rejection in the clinical setting. METHODS: Fluoro-2-deoxyglucose positron emission tomography studies were performed on 88 orthotopic liver transplant patients at 7 and 17 days postoperatively (first positron emission tomography and second positron emission tomography, respectively)...
May 15, 2018: Surgery
https://www.readbyqxmd.com/read/29776451/myeloid-specific-tak1-deletion-results-in-reduced-brain-monocyte-infiltration-and-improved-outcomes-after-stroke
#11
Anjali Chauhan, Jacob Hudobenko, Abdullah Al Mamun, Edward C Koellhoffer, Anthony Patrizz, Rodney M Ritzel, Bhanu P Ganesh, Louise D McCullough
BACKGROUND: Activation of transforming growth factor-β-activated kinase 1 (TAK1) occurs after stroke and leads to an exacerbation of brain injury. TAK1 is involved in innate and adaptive immune responses, but it has divergent inflammatory effects that are dependent on the cell type in which it is activated. There is a robust infiltration of myeloid cells after stroke; however, the contribution of myeloid TAK1 to cerebral ischemia is currently unknown. We hypothesized that myeloid-specific deletion of TAK1 would protect against ischemic brain injury...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#12
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29776374/the-toxoplasma-gondii-me-49-strain-upregulates-levels-of-a20-that-inhibit-nf-%C3%AE%C2%BAb-activation-and-promotes-apoptosis-in-human-leukaemia-t-cell-lines
#13
Qian Chen, Min-Hui Pang, Xiao-Hong Ye, Guang Yang, Chen Lin
BACKGROUND: Acute T-lymphocyte leukaemia is a form of haematological malignancy with abnormal activation of NF-κB pathway, which results in high expression of A20 and ABIN1, which constitute a negative feedback mechanism for the regulation of NF-κB activation. Clinical studies have found that acute T-lymphocyte leukaemia patients are susceptible to Toxoplasma gondii infection; however, the effect of T. gondii on the proliferation and apoptosis of human leukaemia T-cells remains unclear...
May 18, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29776088/how-nonuniform-contact-profiles-of-t-cell-receptors-modulate-thymic-selection-outcomes
#14
Hanrong Chen, Arup K Chakraborty, Mehran Kardar
T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775592/dietary-and-microbial-oxazoles-induce-intestinal-inflammation-by-modulating-aryl-hydrocarbon-receptor-responses
#15
Shankar S Iyer, Thomas Gensollen, Amit Gandhi, Sungwhan F Oh, Joana F Neves, Frederic Collin, Richard Lavin, Carme Serra, Jonathan Glickman, Punyanganie S A de Silva, R Balfour Sartor, Gurdyal Besra, Russell Hauser, Anthony Maxwell, Amadeu Llebaria, Richard S Blumberg
Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs)...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29775473/na-k-atpase-signaling-mediates-mir-29b-3p-regulation-and-cardiac-fibrosis-formation-in-mice-with-chronic-kidney-disease
#16
Christopher A Drummond, Xiaoming Fan, Steven T Haller, David J Kennedy, Jiang Liu, Jiang Tian
The Na/K-ATPase is an important membrane ion transporter and a signaling receptor that is essential for maintaining normal cell function. The current study examined the role of Na/K-ATPase signaling in regulating miR-29b-3p, an anti-fibrotic microRNA, in a mouse chronic kidney disease (CKD) model (5/6th partial nephrectomy or PNx). The results showed that CKD induced significant reduction of miR-29b-3p expression in the heart tissue by activation of Src and NFκB signaling in these animals. To demonstrate the role of Na/K-ATPase signaling, we also performed the PNx surgery on Na/K-ATPase α1 heterozygous (α1+/-) mice, which expresses ~40% less Na/K-ATPase α1 compared to their wild type littermates (WT) and exhibits deficiency in Na/K-ATPase signaling...
2018: PloS One
https://www.readbyqxmd.com/read/29775453/ts-hsp70-induces-protective-immunity-against-trichinella-spiralis-infection-in-mouse-by-activating-dendritic-cells-through-tlr2-and-tlr4
#17
Rui Zhang, Qing Sun, Yi Chen, Ximeng Sun, Yuan Gu, Zhang Zhao, Yuli Cheng, Limei Zhao, Jingjing Huang, Bin Zhan, Xinping Zhu
BACKGROUND: Trichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways. METHODS AND FINDINGS: After blocking with anti-TLR2 and TLR4 antibodies, the binding of Ts-Hsp70 to DCs was significantly reduced...
May 18, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#18
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29775416/downregulation-of-the-%C3%AE-1-and-%C3%AE-1-subunit-of-sgc-in-arterial-smooth-muscle-cells-of-opscc-is-hpv-independent
#19
Y Korkmaz, H C Roggendorf, O G Siefer, J Seehawer, T Imhof, M Plomann, W Bloch, A Friebe, C U Huebbers
The nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC) is a heterodimeric enzyme with an α and β subunit. NO binds to heme of the β1 -subunit of sGC, activates the enzyme in the reduced heme iron state in vascular smooth muscle cells (VSMCs), and generates cGMP-inducing vasodilatation and suppression of VSMC proliferation. In the complex tumor milieu with higher levels of reactive oxygen species (ROS), sGC heme iron may become oxidized and insensitive to NO. To change sGC from an NO-insensitive to NO-sensitive state or NO-independent manner, protein expression of sGC in VSMC is required...
May 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29775310/fragment-based-discovery-of-a-potent-orally-bioavailable-inhibitor-which-modulates-the-phosphorylation-and-catalytic-activity-of-erk1-2
#20
Tom D Heightman, Valerio Berdini, Hannah Braithwaite, Ildiko Maria Buck, Megan Cassidy, Juan Castro, Aurelie Courtin, James E H Day, Charlotte East, Lynsey Fazal, Brent Graham, Charlotte M Griffiths-Jones, John F Lyons, Vanessa Martins, Sandra Muench, Joanne M Munck, David Norton, Marc O'Reilly, Nick Palmer, Puja Pathuri, Michael Reader, David C Rees, Sharna J Rich, Caroline Richardson, Harpreet Saini, Neil T Thompson, Nicola G Wallis, Hugh Walton, Nicola E Wilsher, Alison J-A Woolford, Michael Cooke, David Cousin, Stuart Onions, Jonathan Shannon, John Watts, Christopher W Murray
Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signalling through ERK1/2. Here we describe the fragment based generation of ERK1/2 inhibitors which block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity...
May 18, 2018: Journal of Medicinal Chemistry
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