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https://www.readbyqxmd.com/read/29346834/twelve-week-ravidasvir-plus-ritonavir-boosted-danoprevir-and-ribavirin-for-non-cirrhotic-hcv-genotype-1-patients-a-phase-2-study
#1
Jia-Horng Kao, Min-Lung Yu, Chi-Yi Chen, Cheng-Yuan Peng, Ming-Yao Chen, Huoling Tang, Qiaoqiao Chen, Jinzi J Wu
BACKGROUND AND AIM: The need for all-oral HCV treatments with higher response rates, improved tolerability and lower pill burden compared to interferon-inclusive regimen has led to the development of new direct-acting antiviral agents (DAAs). Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVERST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis...
January 18, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29346778/diverse-brain-myeloid-expression-profiles-reveal-distinct-microglial-activation-states-and-aspects-of-alzheimer-s-disease-not-evident-in-mouse-models
#2
Brad A Friedman, Karpagam Srinivasan, Gai Ayalon, William J Meilandt, Han Lin, Melanie A Huntley, Yi Cao, Seung-Hye Lee, Patrick C G Haddick, Hai Ngu, Zora Modrusan, Jessica L Larson, Joshua S Kaminker, Marcel P van der Brug, David V Hansen
Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346611/combined-roles-of-atp-and-small-hairpin-rna-in-the-activation-of-rig-i-revealed-by-solution-based-analysis
#3
Neelam Shah, Simone A Beckham, Jacqueline A Wilce, Matthew C J Wilce
RIG-I (retinoic acid inducible gene-I) is a cytosolic innate immune protein that senses viral dsRNA with a 5'-triphosphate overhang. Upon interaction with dsRNA a de-repression of the RIG-I CARD domains takes place that ultimately leads to the production of type I interferons and pro-inflammatory cytokines. Here we investigate the RIG-I conformational rearrangement upon interaction with an activating 5'-triphosphate-10-base pair dsRNA hairpin loop (10bp) compared with a less active 5'-triphosphate-8-base pair dsRNA hairpin loop (8bp)...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346347/cd103-cd11b-mucosal-classical-dendritic-cells-initiate-long-term-switched-antibody-responses-to-flagellin
#4
A Flores-Langarica, K Müller Luda, E K Persson, C N Cook, S Bobat, J L Marshall, M W Dahlgren, K Hägerbrand, K M Toellner, M D Goodall, D R Withers, I R Henderson, B Johansson Lindbom, A F Cunningham, W W Agace
Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b- (SP) are not required for these responses...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346345/the-cytosolic-sensor-sting-is-required-for-intestinal-homeostasis-and-control-of-inflammation
#5
M C C Canesso, L Lemos, T C Neves, F M Marim, T B R Castro, É S Veloso, C P Queiroz, J Ahn, H C Santiago, F S Martins, J Alves-Silva, E Ferreira, D C Cara, A T Vieira, G N Barber, S C Oliveira, A M C Faria
STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346274/irf4-mediates-the-oncogenic-effects-of-stat3-in-anaplastic-large-cell-lymphomas
#6
Cecilia Bandini, Aldi Pupuleku, Elisa Spaccarotella, Elisa Pellegrino, Rui Wang, Nicoletta Vitale, Carlotta Duval, Daniela Cantarella, Andrea Rinaldi, Paolo Provero, Ferdinando Di Cunto, Enzo Medico, Francesco Bertoni, Giorgio Inghirami, Roberto Piva
Systemic anaplastic large cell lymphomas (ALCL) are a category of T-cell non-Hodgkin's lymphomas which can be divided into anaplastic lymphoma kinase (ALK) positive and ALK negative subgroups, based on ALK gene rearrangements. Among several pathways aberrantly activated in ALCL, the constitutive activation of signal transducer and activator of transcription 3 (STAT3) is shared by all ALK positive ALCL and has been detected in a subgroup of ALK negative ALCL. To discover essential mediators of STAT3 oncogenic activity that may represent feasible targets for ALCL therapies, we combined gene expression profiling analysis and RNA interference functional approaches...
January 18, 2018: Cancers
https://www.readbyqxmd.com/read/29346269/identification-of-secreted-proteins-involved-in-nonspecific-dsrna-mediated-lutzomyia-longipalpis-ll5-cell-antiviral-response
#7
Andrea Martins-da-Silva, Erich Loza Telleria, Michel Batista, Fabricio Klerynton Marchini, Yara Maria Traub-Csekö, Antonio Jorge Tempone
Hematophagous insects transmit infectious diseases. Sand flies are vectors of leishmaniasis, but can also transmit viruses. We have been studying immune responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. We identified a non-specific antiviral response in L. longipalpis LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs). This response is reminiscent of interferon response in mammals. We are investigating putative effectors for this antiviral response...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29345964/immune-response-to-dengue-and-zika
#8
Annie Elong Ngono, Sujan Shresta
Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection...
January 18, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29345798/clinical-impact-of-pharmacokinetic-interactions-between-the-hcv-protease-inhibitor-simeprevir-and-frequently-used-concomitant-medications
#9
Fiona Marra, Christoph Höner Zu Siederdissen, Saye Khoo, David Back, Michael Schlag, Sivi Ouwerkerk-Mahadevan, Ceyhun Bicer, Isabelle Lonjon-Domanec, Wolfgang Jessner, Maria Beumont-Mauviel, Ronald Kalmeijer, Markus Cornberg
AIMS: Direct-acting antivirals (DAAs) for the treatment of hepatitis C (HCV) can be associated with drug-drug interactions (DDIs) with concomitant medications. The practical clinical implications of such DDIs are poorly understood. We assessed the clinical impact of possible pharmacokinetic (PK) interactions between simeprevir and frequently prescribed concomitant medications. METHODS: This post-hoc analysis pooled data from 9 studies which evaluated simeprevir (SMV)-based interferon-free HCV treatment...
January 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29345577/probiotics-and-paraprobiotics-in-viral-infection-clinical-application-and-effects-on-the-innate-and-acquired-immune-systems
#10
Osamu Kanauchi, Akira Andoh, Sazaly AbuBakar, Naoki Yamamoto
Recently, the risk of viral infection has dramatically increased owing to changes in human ecology such as global warming and an increased geographical movement of people and goods. However, the efficacy of vaccines and remedies for infectious diseases is limited by the high mutation rates of viruses, especially, RNA viruses. Here, we comprehensively review the effectiveness of several probiotics and paraprobiotics (sterilized probiotics) for the prevention or treatment of virally-induced infectious diseases...
January 16, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29345407/hepatitis-c-eradication-with-daa-and-risk-of-liver-cancer-recurrence-the-debate-unrests
#11
Massimo Colombo, Vincenzo Boccaccio
The advent of user friendly and highly successful oral regimens based on direct antiviral agents (DAA), has made a cure of hepatitis C possible in more than 95% of treated patients, including those who were considered difficult to cure with interferon, a vast category including patients with advanced liver disease and those who had a hepatocellular carcinoma (HCC) successfully eradicated by resection or local ablation1 . Despite low rates of treatment uptake and response to therapy with interferon, such hard to treat patients were able to gain significant health benefits, like halting of progression towards liver failure and prevention of second primary tumours, once replication of the hepatitis C virus (HCV) was permanently shut down2,3 ...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345350/activation-of-the-sympathetic-nervous-system-modulates-neutrophil-function
#12
Alyce J Nicholls, Shu Wen Wen, Pam Hall, Michael J Hickey, Connie H Y Wong
Emerging evidence has revealed that noradrenaline (NA), the main neurotransmitter of the sympathetic nervous system (SNS), regulates a variety of immune functions via binding to adrenergic receptors present on immune cells. In this study, we examined the role of NA in the regulation of neutrophil functions. Neutrophils were isolated from the bone marrow of naïve mice and treated with NA at various concentrations to assess the effect on various neutrophil functions. Additionally, we performed cremaster intravital microscopy to examine neutrophil-endothelial cell interactions following NA superfusion in vivo...
December 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345347/interferons-and-beyond-induction-of-antiretroviral-restriction-factors
#13
REVIEW
Dominik Hotter, Frank Kirchhoff
Antiviral restriction factors are structurally and functionally diverse cellular proteins that play a key role in the first line of defense against viral pathogens. Although many cell types constitutively express restriction factors at low levels, their induction in response to viral exposure and replication is often required for potent control and repulse of the invading pathogens. It is well established that type I IFNs efficiently induce antiviral restriction factors. Accumulating evidence suggests that other types of IFN, as well as specific cytokines, such as IL-27, and other activators of the cell are also capable of enhancing the expression of restriction factors and hence to establish an antiviral cellular state...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345061/monocyte-subsets-exhibit-transcriptional-plasticity-and-a-shared-response-to-interferon-in-siv-infected-rhesus-macaques
#14
Brian T Nowlin, John Wang, Jamie L Schafer, Patrick Autissier, Tricia H Burdo, Kenneth C Williams
The progression to AIDS is influenced by changes in the biology of heterogeneous monocyte subsets. Classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes may represent progressive stages of monocyte maturation or disparate myeloid lineages with different turnover rates and function. To investigate the relationship between monocyte subsets and the response to SIV infection, we performed microarray analysis of monocyte subsets in rhesus macaques at three time points: prior to SIV infection, 26 days postinfection, and necropsy with AIDS...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344664/crucial-role-of-ox40-ox40l-signaling-in-a-murine-model-of-asthma
#15
Wei Lei, Daxiong Zeng, Gaoqin Liu, Yehan Zhu, Jiajia Wang, Hongya Wu, Junhong Jiang, Jianan Huang
The aim of the present study was to explore the roles of OX40/OX40 ligand (OX40L) signaling and OX40+ T cells in ovalbumin (OVA)‑induced mouse asthma model. Asthma was induced by OVA exposure and subsequent co‑treatment with OX40L protein, neutralizing anti‑OX40L blocking antibody, OX40+ T cells or PBS. The protein expression levels of interleukin (IL)‑4, IL‑6, IL‑13, IL‑17, tumor necrosis factor (TNF)‑α and interferon (IFN)‑γ in bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific ELISA...
January 18, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344662/dengue-virus-1-ns5-genetic-variant-associated-with-a-severe-clinical-infection-possible-reduction-of-the-innate-immune-response-by-inhibition-of-interferon-type-1-and-the-janus-kinase-signal-transducer-and-activator-of-transcription-signaling-pathway
#16
Iván Delgado-Enciso, Uriel A López-Lemus, Jose A Valcarcel-Gamiño, Iram P Rodriguez-Sanchez, Salvador Valle-Reyes, Margarita L Martinez-Fierro, Valery Melnikov, José Guzmán-Esquivel, Felipe Vaca-Paniagua, Laura L Valdez-Velazquez, Luz M Baltazar-Rodriguez, Alejandro D Soriano-Hernandez, Brenda Paz-Michel, Francisco Espinoza-Gómez
Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pathogens affecting humans. Genetic variations in viruses are likely to be a condition for more effective evasion of the immune system and resulting in severe clinical consequences. The DENV‑1 NS5 gene was sequenced to establish whether during an epidemic burst there were genetic variations of the virus and whether any variant was associated (through a case‑control design) with severe clinical behavior. A total of 31 patients positive for DENV‑1 were enrolled...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344558/therapeutic-potential-of-bleomycin-plus-suicide-or-interferon-%C3%AE-gene-transfer-combination-for-spontaneous-feline-and-canine-melanoma
#17
Lucrecia Agnetti, Chiara Fondello, Marcela S Villaverde, Gerardo C Glikin, Liliana M E Finocchiaro
We originated and characterized melanoma cell lines derived from tumors of two feline and two canine veterinary patients. These lines reestablished the morphology, physiology and cell heterogeneity of their respective parental tumors. We evaluated the cytotoxicity of bleomycin (BLM) alone, or combined with interferon-β (IFN-β) or HSVtk/GCV suicide gene (SG) lipofection on these cells. Although the four animals presented stage III disease (WHO system), SG treated feline tumors displayed stable disease in vivo, while the canine ones exhibited partial response...
November 2017: Oncoscience
https://www.readbyqxmd.com/read/29344268/interferon-%C3%AE-and-colorectal-cancer-an-up-to-date
#18
REVIEW
Christoforos Kosmidis, Konstantinos Sapalidis, Triantafyllia Koletsa, Maria Kosmidou, Christoforos Efthimiadis, George Anthimidis, Nikolaos Varsamis, Nikolaos Michalopoulos, Charilaos Koulouris, Stefanos Atmatzidis, Lazaros Liavas, Titika-Marina Strati, Georgios Koimtzis, Alexandros Tsakalidis, Stylianos Mantalovas, Katerina Zarampouka, Maria Florou, Dimitrios E Giannakidis, Eleni Georgakoudi, Sofia Baka, Paul Zarogoulidis, Yan-Gao Man, Isaac Kesisoglou
Colorectal cancer still remains the third cause of cancer death among cancer patients. Early diagnosis is crucial and they can be either endoscopic or with blood biomarkers. Endoscopic methods consist of gastroscopy and colonoscopy, however; in recent years, endoscopic ultrasound is being used. The microenvironment is very important for the successful delivery of the treatment. Several proteins and hormones play a crucial role in the efficiency of the treatment. In the current mini review we will focus on interferon-γ...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344209/the-effect-of-royal-jelly-on-the-growth-of-breast-cancer-in-mice
#19
Shuang Zhang, Qiqi Shao, Haiyang Geng, Songkun Su
Due to various pharmacological properties, including antioxidative, anti-inflammatory and antibiotic properties, royal jelly (RJ) has been widely consumed in daily diets in numerous countries. In the present study, the effect of RJ on 4T1-bearing mice was investigated. The study was performed by feeding 4T1-bearing mice with RJ using either the prophylactic-therapeutic (PTRJ) or therapeutic (TRJ) method. The experimental results for the PTRJ group demonstrated that the weight of tumor was significantly reduced (RJ 0...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343810/mitochondrial-dna-damage-and-subsequent-activation-of-z-dna-binding-protein-1-links-oxidative-stress-to-inflammation-in-epithelial-cells
#20
Bartosz Szczesny, Michela Marcatti, Akbar Ahmad, Mauro Montalbano, Attila Brunyánszki, Sofia-Iris Bibli, Andreas Papapetropoulos, Csaba Szabo
This report identifies mitochondrial DNA (mtDNA) as a target and active mediator that links low-level oxidative stress to inflammatory response in pulmonary epithelial cells. Extrusion of mtDNA into the bronchoalveolar lavage fluid occurs as an early event in mice subjected to cigarette smoke injury, concomitantly with the depletion of mtDNA in the lung tissue. In cultured lung epithelial cells, prolonged, low-level oxidative stress damages the mtDNA, without any detectable damage to the nuclear DNA. In turn, cellular depletion of the mtDNA occurs, together with a transient remodeling of cellular bioenergetics and morphology - all without any detectable impairment in overall cell viability...
January 17, 2018: Scientific Reports
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