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https://www.readbyqxmd.com/read/28742217/the-inflammatory-cytokine-interferon-gamma-inhibits-sortilin-1-expression-in-hepatocytes-via-the-jak-stat-pathway
#1
John Pirault, Konstantinos A Polyzos, Marcelo H Petri, Daniel Fj Ketelhuth, Magnus Bäck, Göran K Hansson
Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by regulatory T cells may modulate sortilin-1 expression...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28742068/a-peptide-based-viral-inactivator-inhibits-zika-virus-infection-in-pregnant-mice-and-fetuses
#2
Yufeng Yu, Yong-Qiang Deng, Peng Zou, Qian Wang, Yanyan Dai, Fei Yu, Lanying Du, Na-Na Zhang, Min Tian, Jia-Nan Hao, Yu Meng, Yuan Li, Xiaohui Zhou, Jasper Fuk-Woo Chan, Kwok-Yung Yuen, Cheng-Feng Qin, Shibo Jiang, Lu Lu
Zika virus (ZIKV), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. However, no specific vaccines or antiviral drugs are currently available to prevent or treat ZIKV infection. Here we report that a synthetic peptide derived from the stem region of ZIKV envelope protein, designated Z2, potently inhibits infection of ZIKV and other flaviviruses in vitro. We show that Z2 interacts with ZIKV surface protein and disrupts the integrity of the viral membrane...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28741901/trends-in-hcv-treatment-uptake-efficacy-and-impact-on-liver-fibrosis-in-the-swiss-hiv-cohort-study
#3
Charles Béguelin, Annatina Suter, Enos Bernasconi, Jan Fehr, Helen Kovari, Heiner C Bucher, Marcel Stoeckle, Mathias Cavassini, Mathieu Rougemont, Patrick Schmid, Gilles Wandeler, Andri Rauch
BACKGROUND & AIMS: Hepatitis C virus (HCV) therapies with interferon-free second-generation direct-acting antiviral agents (DAAs) are highly effective and well tolerated. They have the potential to increase treatment eligibility and efficacy in HIV-infected patients. We assessed the impact of DAAs on treatment uptake, efficacy as well as its impact on the burden of liver disease in the Swiss HIV Cohort Study (SHCS). METHODS: We describe clinical and virological characteristics of patients treated with second generation DAAs...
July 25, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28741298/ifnl4-rs368234815-tt-%C3%AE-g-variant-is-associated-with-liver-damage-in-patients-with-non-alcoholic-fatty-liver-disease
#4
Salvatore Petta, Luca Valenti, Antonino Tuttolomondo, Paola Dongiovanni, Rosaria Maria Pipitone, Calogero Cammà, Daniela Cabibi, Vito Di Marco, Anna Ludovica Fracanzani, Sara Badiali, Valerio Nobili, Silvia Fargion, Stefania Grimaudo, Antonio Craxì
BACKGROUND AND AIMS: The IFNL3/4 locus influencing innate immunity regulation has been associated with the severity of hepatitis and fibrosis progression during chronic hepatitis C infection, while contrasting results were reported in NAFLD. In this study, we examined whether rs12979860 and the linked causal rs368234815 variant encoding for the alternative IFNL4 protein variant are associated with liver fibrosis and damage in a large multicenter cohort of patients at risk of NASH. To clarify the mechanism, we also evaluated the impact on interferon-stimulated gene (ISG) hepatic expression in a subset of patients...
July 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28740594/opportunities-for-treatment-of-the-hepatitis-c-virus-infected-patient-with-chronic-kidney-disease
#5
REVIEW
Marco Ladino, Fernando Pedraza, David Roth
The prevalence of hepatitis C virus (HCV) infection amongst patients with chronic kidney disease (CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease...
July 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28740483/a-case-with-spondyloenchondrodysplasia-treated-with-growth-hormone
#6
Takanori Utsumi, Satoshi Okada, Kazushi Izawa, Yoshitaka Honda, Gen Nishimura, Ryuta Nishikomori, Rika Okano, Masao Kobayashi
Spondyloenchondrodysplasia (SPENCD) is an autosomal recessive skeletal dysplasia caused by loss of function mutations in acid phosphatase 5, tartrate resistant (ACP5). Hypomorphic ACP5 mutations impair endochondral bone growth and create an interferon (INF) signature, which lead to distinctive spondylar and metaphyseal dysplasias, and extraskeletal morbidity, such as neurological involvement and immune dysregulation, respectively. We report an affected boy with novel ACP5 mutations, a splice-site mutation (736-2 A>C) and a nonsense mutation (R176X)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28739831/neutrophils-are-central-to-antibody-mediated-protection-against-genital-chlamydia
#7
Elizabeth K Naglak, Sandra G Morrison, Richard P Morrison
Determining the effector populations involved in humoral protection against genital chlamydia infection is crucial to development of an effective chlamydial vaccine. Antibody has been implicated in protection studies in multiple animal models, and we previously showed that the passive transfer of immune serum alone does not confer immunity in the mouse. Using the Chlamydia muridarum model of genital infection, we demonstrate a protective role for both Chlamydia-specific immunoglobulin (Ig) G and polymorphonuclear neutrophils, and show the importance of an antibody/effector cell interaction in mediating humoral immunity...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28739436/efficacy-of-isoniazid-salvage-therapy-for-latent-tuberculosis-infection-in-patients-with-immune-mediated-inflammatory-disorders-a-retrospective-cohort-study-in-taiwan
#8
Shiang-Fen Huang, Ming-Han Chen, Fu-Der Wang, Chang-Youh Tsai, Chang-Phone Fung, Wei-Juin Su
BACKGROUND: Active tuberculosis (TB) in patients with latent tuberculosis infection (LTBI) was associated with use of biological agents for immune-mediated inflammatory disorders (IMIDs). For decreasing active TB, isoniazid prophylaxis therapy was administered before biologic therapy among IMID patients with LTBI. However, for patients who had been received biologics for a long time with unknown status of LTBI or exposure history of active TB, the prevalence of LTBI and efficacy of isoniazid therapy were unclear...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28739427/the-impact-of-genetic-variation-in-il28b-ifnl4-and-hla-genes-on-treatment-responses-against-chronic-hepatitis-c-virus-infection
#9
Fatemeh Sakhaee, Morteza Ghazanfari, Farzam Vaziri, Fatemeh Rahimi Jamnani, Mehdi Davari, Safoora Gharibzadeh, Roohollah Fateh, Farid Abdolrahimi, Shahin Pourazar Dizaji, Abolfazl Fateh, Seyed Davar Siadat
Single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B), interferon lambda 4 (IFNL4) and the human leukocyte antigen (HLA) gene are associated with treatment responses in patients with chronic hepatitis C (CHC) virus infection treated with pegylated interferon-α and ribavirin (pegIFN-α/RBV). We compared the role of IL28B SNPs (rs12979860, rs12980275, and rs8099917), IFNL4 ss469415590 and HLA rs4273729 with treatment outcomes in patients with CHC virus. A total of 520 Iranian patients with CHC infection were enrolled...
July 21, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28739343/inhibition-of-cell-apoptosis-and-amelioration-of-pulmonary-fibrosis-by-thrombomodulin
#10
Kentaro Fujiwara, Tetsu Kobayashi, Hajime Fujimoto, Hiroki Nakahara, Corina N D'Alessandro-Gabazza, Josephine A Hinneh, Yoshinori Takahashi, Taro Yasuma, Kota Nishihama, Masaaki Toda, Masahiro Kajiki, Yoshiyuki Takei, Osamu Taguchi, Esteban C Gabazza
Pulmonary fibrosis is the terminal stage of a group of idiopathic interstitial pneumonias, of which idiopathic pulmonary fibrosis is the most frequent and fatal form. Recent studies have shown that recombinant human thrombomodulin improves exacerbation and clinical outcome of idiopathic pulmonary fibrosis, but the mechanism remains unknown. This study evaluated the mechanistic pathways of the inhibitory activity of recombinant human thrombomodulin in pulmonary fibrosis. Transgenic mice overexpressing human transforming growth factor β1 that develop spontaneously pulmonary fibrosis and wild-type mice treated with bleomycin were used as model of lung fibrosis...
July 21, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28739201/neonatal-detection-of-aicardi-gouti%C3%A3-res-syndrome-by-increased-c26-0-lysophosphatidylcholine-and-interferon-signature-on-newborn-screening-blood-spots
#11
Thais Armangue, Joseph J Orsini, Asako Takanohashi, Francesco Gavazzi, Alex Conant, Nicole Ulrick, Mark A Morrissey, Norah Nahhas, Guy Helman, Heather Gordish-Dressman, Simona Orcesi, Davide Tonduti, Chloe Stutterd, Keith van Haren, Camilo Toro, Alejandro D Iglesias, Marjo S van der Knaap, Raphaela Goldbach Mansky, Anne B Moser, Richard O Jones, Adeline Vanderver
BACKGROUND: Aicardi Goutières Syndrome (AGS) is a heritable interferonopathy associated with systemic autoinflammation causing interferon (IFN) elevation, central nervous system calcifications, leukodystrophy and severe neurologic sequelae. An infant with TREX1 mutations was recently found to have abnormal C26:0 lysophosphatidylcholine (C26:0 Lyso-PC) in a newborn screening platform for X-linked adrenoleukodystrophy, prompting analysis of this analyte in retrospectively collected samples from individuals affected by AGS...
July 20, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28739030/immune-modulatory-micrornas-as-a-novel-mechanism-to-revert-immune-escape-of-tumors
#12
REVIEW
Barbara Seliger
Tumors have developed different strategies to escape immune recognition. This could be due to altered expression of classical and non-classical human leukocyte antigens (HLA), co-inhibitory or co-stimulatory molecules as well as components of the interferon signaling pathway. Furthermore, changes in the tumor microenvironment negatively interfere with anti-tumor immune responses and the frequency and activity of immune effector cells and professional antigen presenting cells (APC), while the number of immune suppressive cells is increased...
July 13, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28738907/rig-i-expression-in-perifascicular-myofibers-is-a-reliable-biomarker-of-dermatomyositis
#13
Xavier Suárez-Calvet, Eduard Gallardo, Iago Pinal-Fernandez, Noemi De Luna, Cinta Lleixà, Jordi Díaz-Manera, Ricardo Rojas-García, Ivan Castellví, M Angeles Martínez, Josep M Grau, Albert Selva-O'Callaghan, Isabel Illa
BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis...
July 24, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28738877/unexpected-complexity-in-the-interference-activity-of-a-cloned-influenza-defective-interfering-rna
#14
Bo Meng, Kirsten Bentley, Anthony C Marriott, Paul D Scott, Nigel J Dimmock, Andrew J Easton
BACKGROUND: Defective interfering (DI) viruses are natural antivirals made by nearly all viruses. They have a highly deleted genome (thus being non-infectious) and interfere with the replication of genetically related infectious viruses. We have produced the first potential therapeutic DI virus for the clinic by cloning an influenza A DI RNA (1/244) which was derived naturally from genome segment 1. This is highly effective in vivo, and has unexpectedly broad-spectrum activity with two different modes of action: inhibiting influenza A viruses through RNA interference, and all other (interferon-sensitive) respiratory viruses through stimulating interferon type I...
July 24, 2017: Virology Journal
https://www.readbyqxmd.com/read/28738820/omega-3-polyunsaturated-fatty-acid-supplementation-attenuates-microglial-induced-inflammation-by-inhibiting-the-hmgb1-tlr4-nf-%C3%AE%C2%BAb-pathway-following-experimental-traumatic-brain-injury
#15
Xiangrong Chen, Shukai Wu, Chunnuan Chen, Baoyuan Xie, Zhongning Fang, Weipeng Hu, Junyan Chen, Huangde Fu, Hefan He
BACKGROUND: Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI...
July 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28738408/cgas-surveillance-of-micronuclei-links-genome-instability-to-innate-immunity
#16
Karen J Mackenzie, Paula Carroll, Carol-Anne Martin, Olga Murina, Adeline Fluteau, Daniel J Simpson, Nelly Olova, Hannah Sutcliffe, Jacqueline K Rainger, Andrea Leitch, Ruby T Osborn, Ann P Wheeler, Marcin Nowotny, Nick Gilbert, Tamir Chandra, Martin A M Reijns, Andrew P Jackson
DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane...
July 24, 2017: Nature
https://www.readbyqxmd.com/read/28738021/commensal-bacteria-ab-use-cd8-t-cells-to-induce-insulin-resistance
#17
REVIEW
Chi Ma, Tim F Greten
Type I interferon-dependent expansion of intrahepatic CD8(+) T cells promotes systemic insulin resistance in obesity.
April 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28738020/resident-memory-t-cells-in-the-skin-mediate-durable-immunity-to-melanoma
#18
Brian T Malik, Katelyn T Byrne, Jennifer L Vella, Peisheng Zhang, Tamer B Shabaneh, Shannon M Steinberg, Aleksey K Molodtsov, Jacob S Bowers, Christina V Angeles, Chrystal M Paulos, Yina H Huang, Mary Jo Turk
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ)...
April 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28738017/distinct-oxysterol-requirements-for-positioning-na%C3%A3-ve-and-activated-dendritic-cells-in-the-spleen
#19
Erick Lu, Eric V Dang, Jeffrey G McDonald, Jason G Cyster
Correct positioning of dendritic cells (DCs) is critical for efficient pathogen encounter and antigen presentation. Epstein-Barr virus-induced gene 2 (EBI2) has been identified as a chemoattractant receptor required for naïve CD4(+)DCIR2(+) DC positioning in response to 7α,25-hydroxycholesterol (7α,25-HC). We now provide evidence that a second EBI2 ligand, 7α,27-HC, is involved in splenic DCIR2(+) DC positioning and homeostasis. Cyp27a1, the enzyme uniquely required for 7α,27-HC synthesis, is expressed by stromal cells in the region of naïve DC localization...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28737923/co-silencing-intestinal-transglutaminase-2-and-interleukin-15-using-gelatin-based-nanoparticles-in-an-in-vitro-model-of-celiac-disease
#20
Husain Attarwala, Valerie Clausen, Prasoon Chaturvedi, Mansoor M Amiji
In this study, we have developed type B gelatin-based nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge and morphology of gelatin nanoparticles were evaluated using Zetasizer instrument and transmission electron microscopy...
July 24, 2017: Molecular Pharmaceutics
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