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https://www.readbyqxmd.com/read/28526925/polyphenolic-extract-attenuates-fatty-acid-induced-steatosis-and-oxidative-stress-in-hepatic-and-endothelial-cells
#1
Laura Vergani, Giulia Vecchione, Francesca Baldini, Elena Grasselli, Adriana Voci, Piero Portincasa, Pier Francesco Ferrari, Bahar Aliakbarian, Alessandro A Casazza, Patrizia Perego
PURPOSE: Phenolic compounds (PC) of virgin olive oil exert several biochemical and pharmacological beneficial effects. Some dietary PC seem to prevent/improve obesity and metabolic-related disorders such as non-alcoholic fatty liver disease (NAFLD). We investigated the possible effects of PC extracted from olive pomace (PEOP) and of the main single molecules present in the extract (tyrosol, apigenin, oleuropein, p-coumaric and caffeic acid) in protecting hepatocytes and endothelial cells against triglyceride accumulation and oxidative stress...
May 19, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28526573/transcriptomic-variation-of-locally-infected-skin-of-epinephelus-coioides-reveals-the-mucosal-immune-mechanism-against-cryptocaryon-irritans
#2
Yazhou Hu, Anxing Li, Yang Xu, Biao Jiang, Geling Lu, Xiaochun Luo
Fish skin is the largest immunologically active mucosal organ, providing first-line defense against external pathogens. However, the skin-associated immune mechanisms of fish are still unclear. Cryptocaryon irritans is an obligate ectoparasitic ciliated protozoan that infects almost all marine fish, and is believed to be an excellent pathogen model to study fish mucosal immunity. In this study, a de novo transcriptome assembly of Epinephelus coioides skin post C. irritans tail-infection was performed for the first time using the Illumina HiSeq™ 2500 system...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28526409/expression-and-purification-of-functional-pdgf-receptor-beta
#3
Qingbin Shang, Liang Zhao, Xiaojing Wang, Meimei Wang, Sen-Fang Sui, Li-Zhi Mi
Platelet Derived Growth Factor receptors (PDGFRs), members of receptor tyrosine kinase superfamily, play essential roles in early hematopoiesis, angiogenesis and organ development. Dysregulation of PDGF receptor signaling under pathological conditions associates with cancers, vascular diseases, and fibrotic diseases. Therefore, they are attractive targets in drug development. Like any other membrane proteins with a single-pass transmembrane domain, the high-resolution structural information of the full-length PDGF receptors is still not resolved...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526339/magnesium-isoglycyrrhizinate-blocks-fructose-induced-hepatic-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-and-lipid-metabolism-disorder
#4
Xiao-Juan Zhao, Yan-Zi Yang, Yan-Jing Zheng, Shan-Chun Wang, Hong-Mei Gu, Ying Pan, Shui-Juan Wang, Hong-Jiang Xu, Ling-Dong Kong
Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels...
May 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28526240/endocrine-actions-of-vitamin-d-in-skin-relevance-for-photocarcinogenesis-of-non-melanoma-skin-cancer-and-beyond
#5
REVIEW
Jörg Reichrath, Roman Saternus, Thomas Vogt
The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH)2D3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)2D3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH)2D3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR)...
May 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28526063/targeting-the-cxcr4-pathway-using-a-novel-anti-cxcr4-igg1-antibody-pf-06747143-in-chronic-lymphocytic-leukemia
#6
Manoj K Kashyap, Carlos I Amaya-Chanaga, Deepak Kumar, Brett Simmons, Nanni Huser, Yin Gu, Max Hallin, Kevin Lindquist, Rolla Yafawi, Michael Y Choi, Ale-Ali Amine, Laura Z Rassenti, Cathy Zhang, Shu-Hui Liu, Tod Smeal, Valeria R Fantin, Thomas J Kipps, Flavia Pernasetti, Januario E Castro
BACKGROUND: The CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28525946/ghrelin-attenuates-vascular-calcification-in-diabetic-patients-with-amputation
#7
Suining Xu, Fei Ye, Lihua Li, Jinchuan Yan, Zhengyang Bao, Zhen Sun, Liangjie Xu, Jie Zhu, Zhongqun Wang
Vascular calcification is established to be a critical factor in diabetes mellitus, which causes cardiovascular and amputation complication of diabetic patients. OPG/RANKL/RANK axis serves as a regulatory role in vascular calcification. Ghrelin, an endogenous ligand of growth hormone secretagogue receptor (GHSR), has been reported to exhibit potent cardiovascular protective effects. However, the role of ghrelin in the regulation of diabetic vascular calcification is still elusive. Here, we reported the role of ghrelin and its relationship with OPG/RANKL/RANK system in patients with diabetic foot amputation...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28525945/the-protective-effect-of-luteolin-on-myocardial-ischemia-reperfusion-i-r-injury-through-tlr4-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-pathway
#8
Xu Zhang, Qianming Du, Yan Yang, Jianing Wang, Shuai Dou, Chao Liu, Junguo Duan
The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30min of left anterior descending (LAD) occlusion followed by 24h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1)Sham, (2)I/R, (3)I/R+Lut(40mg/kg), (4)I/R+Lut(80mg/kg) and (5)I/R+Lut(160mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1)control, (2)hypoxia-reoxygenation(H/R), (3)H/R+Lut(5μM), (4)H/R+Lut(10μM) and (5)H/R+Lut(20μM)...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#9
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#10
Xuelian Zhao, Katie A Howell, Shihua He, Jennifer M Brannan, Anna Z Wec, Edgar Davidson, Hannah L Turner, Chi-I Chiang, Lin Lei, J Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N Turonis, Ana I Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S Spence, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, Kartik Chandran, John M Dye, Xiangguo Qiu, Yuxing Li, M Javad Aman
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525560/activity-dependent-gene-expression-in-the-mammalian-olfactory-epithelium
#11
Qiang Wang, William B Titlow, Declan A McClintock, Arnold J Stromberg, Timothy S McClintock
Activity-dependent processes are important to olfactory sensory neurons (OSNs) in several ways, such as cell survival and the specificity of axonal convergence. The identification of activity-dependent mRNAs has contributed to our understanding of OSN axon convergence, but has revealed surprisingly little about other processes. Published studies of activity-dependent mRNAs in olfactory mucosae overlap poorly, but by combining these agreements with meta-analysis of existing data we identify 443 mRNAs that respond to methods that alter OSN activity...
May 19, 2017: Chemical Senses
https://www.readbyqxmd.com/read/28525281/interaction-of-7-alkoxycoumarins-with-the-aryl-hydrocarbon-receptor
#12
Marco Gargaro, Francesco Epifano, Serena Fiorito, Vito Alessandro Taddeo, Salvatore Genovese, Matteo Pirro, Antonella Turco, Paolo Puccetti, Carsten B Schmidt-Weber, Francesca Fallarino
The aryl hydrocarbon receptor (AhR) is a transcription factor activated by a vast array of natural and synthetic ligands. It plays a pivotal role in numerous physiological and pathological responses, such as cell proliferation and differentiation, induction of xenobiotic metabolizing enzymes, response to environmental toxins, and several others. In this study, we investigated the ability of some natural compounds (oxyprenylated ferulic acid and umbelliferone derivatives) and their semisynthetic analogues (e...
May 19, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28524857/a-defined-metabolic-state-in-pre-b-cells-governs-b-cell-development-and-is-counterbalanced-by-swiprosin-2-efhd1
#13
Merle Stein, Sebastian Dütting, Dimitrios Mougiakakos, Michael Bösl, Kristin Fritsch, Dorothea Reimer, Sophia Urbanczyk, Tobit Steinmetz, Wolfgang Schuh, Aline Bozec, Thomas H Winkler, Hans-Martin Jäck, Dirk Mielenz
B-cell development in the bone marrow comprises proliferative and resting phases in different niches. We asked whether B-cell metabolism relates to these changes. Compared to pro B and small pre B cells, large pre B cells revealed the highest glucose uptake and ROS but not mitochondrial mass, whereas small pre B cells exhibited the lowest mitochondrial membrane potential. Small pre B cells from Rag1(-/-);33.C9 μ heavy chain knock-in mice revealed decreased glycolysis (ECAR) and mitochondrial spare capacity compared to pro B cells from Rag1(-/-) mice...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28524001/brain-derived-neurotrophic-factor-promotes-growth-of-neurons-and-neural-stem-cells-possibly-by-triggering-the-phosphoinositide-3-kinase-akt-glycogen-synthase-kinase-3%C3%AE-%C3%AE-catenin-pathway
#14
Jin-Wei Yang, Zhang Liang, Shi-Kang Deng Deng, Wei Ma, Xian-Bin Wang, Xing-Tong Li, Tong-Tong Wang, Yun-Fei Dai, Jian-Hui Guo, Li-Yan Li
BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a crucial role in promoting survival and differentiation of neurons and neural stem cells (NSCs), but the downstream regulating mechanisms remain poorly understood. OBJECTIVE: We investigated whether BDNF exerts its effect by triggering the phosphoinositide 3-kinase (PI3K), protein kinase B, PKB (AKT), glycogen synthase kinase-3β (GSK-3β) and β-catenin signaling pathway in cultured neurons and NSCs derived from the rat embryonic spinal cord...
May 18, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28523115/discovery-of-fevipiprant-nvp-qaw039-a-potent-and-selective-dp2-receptor-antagonist-for-treatment-of-asthma
#15
David A Sandham, Lucy Barker, Lyndon Brown, Zarin Brown, David Budd, Steven J Charlton, Devnandan Chatterjee, Brian Cox, Gerald Dubois, Nicholas Duggan, Edward Hall, Julia Hatto, Janet Maas, Jodie Manini, Rachael Profit, Darren Riddy, Catherine Ritchie, Bindi Sohal, Duncan Shaw, Rowan Stringer, David A Sykes, Matthew Thomas, Katharine L Turner, Simon J Watson, Ryan West, Elisabeth Willard, Gareth Williams, Jennifer Willis
Further optimization of an initial DP2 receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetic acid (compound 11, NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma.
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28523108/2-aminopyrimidine-derivatives-as-new-selective-fibroblast-growth-factor-receptor-4-fgfr4-inhibitors
#16
Cheng Mo, Zhang Zhang, Christopher P Guise, Xueqiang Li, Jinfeng Luo, Zhengchao Tu, Yong Xu, Adam V Patterson, Jeff B Smaill, Xiaomei Ren, Xiaoyun Lu, Ke Ding
A series of 2-aminopyrimidine derivatives were designed and synthesized as highly selective FGFR4 inhibitors. One of the most promising compounds 2n tightly bound FGFR4 with a Kd value of 3.3 nM and potently inhibited its enzymatic activity with an IC50 value of 2.6 nM, but completely spared FGFR1/2/3. The compound selectively suppressed proliferation of breast cancer cells harboring dysregulated FGFR4 signaling with an IC50 value of 0.38 μM. Furthermore, 2n exhibited extraordinary target specificity in a Kinome-wide screen against 468 kinases, with S(35) and S(10) selectivity scores of 0...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522690/resistance-to-malaria-through-structural-variation-of-red-blood-cell-invasion-receptors
#17
Ellen M Leffler, Gavin Band, George B J Busby, Katja Kivinen, Quang Si Le, Geraldine M Clarke, Kalifa A Bojang, David J Conway, Muminatou Jallow, Fatoumatta Sisay-Joof, Edith C Bougouma, Valentina D Mangano, David Modiano, Sodiomon B Sirima, Eric Achidi, Tobias O Apinjoh, Kevin Marsh, Carolyne M Ndila, Norbert Peshu, Thomas N Williams, Chris Drakeley, Alphaxard Manjurano, Hugh Reyburn, Eleanor Riley, David Kachala, Malcolm Molyneux, Vysaul Nyirongo, Terrie Taylor, Nicole Thornton, Louise Tilley, Shane Grimsley, Eleanor Drury, Jim Stalker, Victoria Cornelius, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Kirk A Rockett, Chris C A Spencer, Dominic P Kwiatkowski
The malaria parasite Plasmodium falciparum invades human red blood cells via interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes, which encode a serologically distinct blood group antigen known as Dantu...
May 18, 2017: Science
https://www.readbyqxmd.com/read/28522562/estrogen-and-cigarette-sidestream-smoke-particulate-matter-exhibit-er%C3%AE-dependent-tumor-promoting-effects-in-lung-adenocarcinoma-cells
#18
Lun-Cheng Kuo, Li-Chuan Cheng, Chia-Huei Lee, Chun-Ju Lin, Pei-Yu Chen, Lih-Ann Li
Estrogen and secondhand smoke are key risk factors for nonsmoking female lung cancer patients, who frequently have lung adenocarcinoma and show tumor ERα expression. We speculated that estrogen and secondhand smoke might cause harmful effects via ERα signaling. Our results showed that 17β-estradiol (E2), the primary form of endogenous estrogen, exacerbated proliferation, migration, and granzyme B resistance of lung adenocarcinoma cells in an ERα-dependent manner. Cigarette sidestream smoke particulate matter (CSSP), the major component of secondhand smoke, could activate ERα activity dose dependently in human lung adenocarcinoma cells...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28522412/athero-inflammatory-nanotherapeutics-ferulic-acid-based-poly-anhydride-ester-nanoparticles-attenuate-foam-cell-formation-by-regulating-macrophage-lipogenesis-and-reactive-oxygen-species-generation
#19
Rebecca A Chmielowski, Dalia S Abdelhamid, Jonathan J Faig, Latrisha K Petersen, Carol R Gardner, Kathryn E Uhrich, Laurie B Joseph, Prabhas V Moghe
Enhanced bioactive anti-oxidant formulations are critical for treatment of inflammatory diseases, such as atherosclerosis. A hallmark of early atherosclerosis is the uptake of oxidized low density lipoprotein (oxLDL) by macrophages, which results in foam cell and plaque formation in the arterial wall. The hypolipidemic, anti-inflammatory, and antioxidative properties of polyphenol compounds make them attractive targets for treatment of atherosclerosis. However, high concentrations of antioxidants can reverse their anti-atheroprotective properties and cause oxidative stress within the artery...
May 15, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28522295/reversal-of-adipose-tissue-loss-by-probucol-in-mice-with-deficiency-of-both-scavenger-receptor-class-b-type-1-and-ldl-receptor-on-high-fat-diet
#20
Xin Guo, Jiawei Liao, Xiaomin Huang, Yuhui Wang, Wei Huang, George Liu
Scavenger receptor class B type 1(SR-B1) and low density lipoprotein receptor (LDLR) play vital roles in cholesterol homeostasis. Previous studies indicated a strong link between cholesterol and adipose tissue (AT). In this study, adult male SR-B1 and LDLR double knockout (DKO) mice were fed with high fat diet (HFD) for 3 months. Interestingly, we found severe loss of AT in DKO mice fed with HFD. To reverse the AT loss in DKO mice, 1% probucol was added in HFD. In DKO mice on HFD, plasma total cholesterol (TC) and free cholesterol (FC) levels were increased 6 and 15 folds respectively compared with wild type (WT) mice...
May 15, 2017: Biochemical and Biophysical Research Communications
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