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https://www.readbyqxmd.com/read/30121880/pharmacological-evaluation-of-tak-828f-a-novel-orally-available-ror%C3%AE-t-inverse-agonist-on-murine-colitis-model
#1
Keiko Igaki, Yoshiki Nakamura, Yusaku Komoike, Keiko Uga, Akira Shibata, Yoshimasa Ishimura, Masashi Yamasaki, Yasuhiro Tsukimi, Noboru Tsuchimori
IL-17-producing Th17 cells and IFN-γ and IL-17 double-producing Th1/17 cells have been identified as the pathogenic cells in inflammatory bowel disease (IBD). Retinoic acid-related orphan receptor γt (RORγt) is a master regulator for the differentiation and activation of Th17 and Th1/17 cells. We discovered a novel orally available TAK-828F, a strong and selective RORγt inverse agonist. To assess the potential of RORγt blockade in the therapy for IBD, the efficacy of TAK-828F in activated T cell transfer mouse colitis model was investigated...
August 18, 2018: Inflammation
https://www.readbyqxmd.com/read/30120933/dsrna-sensing-induces-loss-of-cell-identity
#2
Rongying Zhou, Gaofeng Wang, Dongwon Kim, Sooah Kim, Nasif Islam, Ruosi Chen, Zixiao Wang, Ang Li, Edward F McCarthy, Li Li, Zhiqi Hu, Luis A Garza
How cell and tissue identity persist despite constant cell turnover is an important biologic question with cell therapy implications. While many mechanisms exist, we investigated the controls for site-specific gene expression in skin given its diverse structures and functions. For example, the transcriptome of in vivo palmoplantar (i.e. volar) epidermis is globally unique including Keratin 9 (KRT9). While volar fibroblasts have the capacity to induce KRT9 in non-volar keratinocytes, we demonstrate here that volar keratinocytes continue to express KRT9 in vitro solo-cultures...
August 15, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30120041/a-radiomics-approach-to-assess-tumour-infiltrating-cd8-cells-and-response-to-anti-pd-1-or-anti-pd-l1-immunotherapy-an-imaging-biomarker-retrospective-multicohort-study
#3
Roger Sun, Elaine Johanna Limkin, Maria Vakalopoulou, Laurent Dercle, Stéphane Champiat, Shan Rong Han, Loïc Verlingue, David Brandao, Andrea Lancia, Samy Ammari, Antoine Hollebecque, Jean-Yves Scoazec, Aurélien Marabelle, Christophe Massard, Jean-Charles Soria, Charlotte Robert, Nikos Paragios, Eric Deutsch, Charles Ferté
BACKGROUND: Because responses of patients with cancer to immunotherapy can vary in success, innovative predictors of response to treatment are urgently needed to improve treatment outcomes. We aimed to develop and independently validate a radiomics-based biomarker of tumour-infiltrating CD8 cells in patients included in phase 1 trials of anti-programmed cell death protein (PD)-1 or anti-programmed cell death ligand 1 (PD-L1) monotherapy. We also aimed to evaluate the association between the biomarker, and tumour immune phenotype and clinical outcomes of these patients...
August 14, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/30119681/the-expression-signature-of-very-long-non-coding-rna-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome
#4
Chin-An Yang, Sandra Bauer, Yu-Chen Ho, Franziska Sotzny, Jan-Gowth Chang, Carmen Scheibenbogen
BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease with huge social-economic impact. It has been suggested that immune dysregulation, nitrooxidative stress, and metabolic impairment might contribute to disease pathogenesis. However, the etiology of ME/CFS remains largely unclear, and diagnostic/prognostic disease markers are lacking. Several long noncoding RNAs (lncRNA, > 200 bp) have been reported to play roles in immunological diseases or in stress responses...
August 17, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/30119635/il-33-facilitates-proliferation-of-colorectal-cancer-dependent-on-cox2-pge-2
#5
Yongkui Li, Jie Shi, Shanshan Qi, Jian Zhang, Dong Peng, Zhenzhen Chen, Guobin Wang, Zheng Wang, Lin Wang
BACKGROUND: Interleukin-33 (IL-33) participates in various types of diseases including cancers. Previous studies of this cytokine in cancers mainly focused on its regulation on immune responses by which IL-33 modulated cancer progression. The IL-33 triggered signals in cancer cells remain unclear. METHODS: We analyzed IL-33 gene expression in human colorectal cancer (CRC) tissues and carried out gene enrichment analysis with TCGA Data Portal. We studied CRC proliferation in vivo by inoculating MC38 tumors in IL-33 transgenic mice...
August 17, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/30117304/molecular-profiles-of-tumor-contrast-enhancement-a-radiogenomic-analysis-in-anaplastic-gliomas
#6
Xing Liu, Yiming Li, Zhiyan Sun, Shaowu Li, Kai Wang, Xing Fan, Yuqing Liu, Lei Wang, Yinyan Wang, Tao Jiang
The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is conventionally regarded as an indicator for tumor malignancy. However, the biological behaviors and molecular mechanism of enhanced tumor are not well illustrated. The aim of this study was to investigate the molecular profiles associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1-weighted MR imaging. In this retrospective database study, RNA sequencing and MR imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the Chinese Glioma Genome Atlas (CGGA) were collected...
August 16, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/30115913/transcriptomic-signatures-of-schizophrenia-revealed-by-dopamine-perturbation-in-an-ex-vivo-model
#7
Jubao Duan, Harald H H Göring, Alan R Sanders, Winton Moy, Jessica Freda, Eugene I Drigalenko, Mark Kos, Deli He, Pablo V Gejman
The dopaminergic hypothesis of schizophrenia (SZ) postulates that dopaminergic over activity causes psychosis, a central feature of SZ, based on the observation that blocking dopamine (DA) improves psychotic symptoms. DA is known to have both receptor- and non-receptor-mediated effects, including oxidative mechanisms that lead to apoptosis. The role of DA-mediated oxidative processes in SZ has been little studied. Here, we have used a cell perturbation approach and measured transcriptomic profiles by RNAseq to study the effect of DA exposure on transcription in B-cell transformed lymphoblastoid cell lines (LCLs) from 514 SZ cases and 690 controls...
August 16, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/30115651/a-systemic-inflammatory-signature-reflecting-crosstalk-between-innate-and-adaptive-immunity-is-associated-with-incident-polyneuropathy-kora-f4-ff4-study
#8
Christian Herder, Julia M Kannenberg, Maren Carstensen-Kirberg, Alexander Strom, Gidon J Bönhof, Wolfgang Rathmann, Cornelia Huth, Wolfgang Koenig, Margit Heier, Jan Krumsiek, Annette Peters, Christa Meisinger, Michael Roden, Barbara Thorand, Dan Ziegler
Prospective analyses on biomarkers of inflammation and distal sensorimotor polyneuropathy (DSPN) are scarce and limited to innate immunity. Therefore, we aimed to assess associations between biomarkers reflecting multiple aspects of immune activation and DSPN. The study was based on 127 cases with incident DSPN and 386 non-cases from the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort (follow-up 6.5 years). Serum levels of biomarkers of inflammation were measured using proximity extension assay technology...
August 16, 2018: Diabetes
https://www.readbyqxmd.com/read/30115097/chromosome-scale-comparative-sequence-analysis-unravels-molecular-mechanisms-of-genome-dynamics-between-two-wheat-cultivars
#9
Anupriya Kaur Thind, Thomas Wicker, Thomas Müller, Patrick M Ackermann, Burkhard Steuernagel, Brande B H Wulff, Manuel Spannagl, Sven O Twardziok, Marius Felder, Thomas Lux, Klaus F X Mayer, Beat Keller, Simon G Krattinger
BACKGROUND: Recent improvements in DNA sequencing and genome scaffolding have paved the way to generate high-quality de novo assemblies of pseudomolecules representing complete chromosomes of wheat and its wild relatives. These assemblies form the basis to compare the dynamics of wheat genomes on a megabase scale. RESULTS: Here, we provide a comparative sequence analysis of the 700-megabase chromosome 2D between two bread wheat genotypes-the old landrace Chinese Spring and the elite Swiss spring wheat line 'CH Campala Lr22a'...
August 17, 2018: Genome Biology
https://www.readbyqxmd.com/read/30114214/genomic-signatures-of-adaptive-introgression-and-environmental-adaptation-in-the-sheko-cattle-of-southwest-ethiopia
#10
Hussain Bahbahani, Arwa Afana, David Wragg
Although classified as an African taurine breed, the genomes of Sheko cattle are an admixture of Asian zebu and African taurine ancestries. They populate the humid Bench Maji zone in Sheko and Bench districts in the south-western part of Ethiopia and are considered as a trypanotolerant breed with high potential for dairy production. Here, we investigate the genome of Sheko cattle for candidate signatures of adaptive introgression and positive selection using medium density genome-wide SNP data. Following locus-ancestry deviation analysis, 15 and 72 genome regions show substantial excess and deficiency in Asian zebu ancestry, respectively...
2018: PloS One
https://www.readbyqxmd.com/read/30113252/lack-of-short-chain-fatty-acids-and-overgrowth-of-opportunistic-pathogens-define-dysbiosis-of-neuromyelitis-optica-spectrum-disorders-a-chinese-pilot-study
#11
Junli Gong, Wei Qiu, Qin Zeng, Xiyuan Liu, Xiaobo Sun, Huijuan Li, Yu Yang, Aimin Wu, Jian Bao, Yuge Wang, Yaqing Shu, Xueqiang Hu, Joseph A Bellanti, Song Guo Zheng, Yongjun Lu, Zhengqi Lu
BACKGROUND: Intestinal microbiota is an important environmental factor in the initiation and progression of autoimmune diseases. However, investigations on the gut microbiome in neuromyelitis optica spectrum disorders (NMOSD) are relatively insufficient, especially for that of the Asia population. OBJECTIVES: To evaluate whether or not the intestinal microbiota of NMOSD patients had specific microbial signatures. METHODS: Next-generation sequencing and gas chromatography were employed to compare the fecal microbial composition and short-chain fatty acids (SCFAs) spectrum between patients with NMOSD ( n = 84) and healthy controls ( n = 54)...
August 16, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/30111606/balancing-selection-and-introgression-of-newt-immune-response-genes
#12
Anna Fijarczyk, Katarzyna Dudek, Marta Niedzicka, Wiesław Babik
The importance of interspecific introgression as a source of adaptive variation is increasingly recognized. Theory predicts that beneficial genetic variants cross species boundaries easily even when interspecific hybridization is rare and gene flow is strongly constrained throughout the genome. However, it remains unclear whether certain classes of genes are particularly prone to adaptive introgression. Genes affected by balancing selection (BS) may constitute such a class, because forms of BS that favour novel, initially rare alleles, should facilitate introgression...
August 15, 2018: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/30111332/comprehensive-gene-expression-profiling-identifies-distinct-and-overlapping-transcriptional-profiles-in-non-specific-interstitial-pneumonia-and-idiopathic-pulmonary-fibrosis
#13
Matthew J Cecchini, Karishma Hosein, Christopher J Howlett, Mariamma Joseph, Marco Mura
BACKGROUND: The clinical-radiographic distinction between idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) is challenging. We sought to investigate the gene expression profiles of IPF and NSIP vs. normal controls. METHODS: Gene expression from explanted lungs of patients with IPF (n = 22), NSIP (n = 10) and from normal controls (n = 11) was assessed. Microarray analysis included Significance Analysis of Microarray (SAM), Ingenuity Pathway, Gene-Set Enrichment and unsupervised hierarchical clustering analyses...
August 15, 2018: Respiratory Research
https://www.readbyqxmd.com/read/30108162/molecular-predictors-of-prevention-of-recurrence-in-hcc-with-sorafenib-as-adjuvant-treatment-and-prognostic-factors-in-the-phase-3-storm-trial
#14
Roser Pinyol, Robert Montal, Laia Bassaganyas, Daniela Sia, Tadatoshi Takayama, Gar-Yang Chau, Vincenzo Mazzaferro, Sasan Roayaie, Han Chu Lee, Norihiro Kokudo, Zhongyang Zhang, Sara Torrecilla, Agrin Moeini, Leonardo Rodriguez-Carunchio, Edward Gane, Chris Verslype, Adina Emilia Croitoru, Umberto Cillo, Manuel de la Mata, Luigi Lupo, Simone Strasser, Joong-Won Park, Jordi Camps, Manel Solé, Swan N Thung, Augusto Villanueva, Carol Pena, Gerold Meinhardt, Jordi Bruix, Josep M Llovet
OBJECTIVE: Sorafenib is the standard systemic therapy for advanced hepatocellular carcinoma (HCC). Survival benefits of resection/local ablation for early HCC are compromised by 70% 5-year recurrence rates. The phase 3 STORM trial comparing sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint of improving recurrence-free survival (RFS). The biomarker companion study BIOSTORM aims to define (A) predictors of recurrence prevention with sorafenib and (B) prognostic factors with B level of evidence...
August 14, 2018: Gut
https://www.readbyqxmd.com/read/30106935/ultrasound-modulated-optical-tomography-in-scattering-media-flux-filtering-based-on-persistent-spectral-hole-burning-in-the-optical-diagnosis-window
#15
Caroline Venet, Maïmouna Bocoum, Jean-Baptiste Laudereau, Thierry Chaneliere, François Ramaz, Anne Louchet-Chauvet
Ultrasound-modulated optical tomography (UOT) is a powerful imaging technique to discriminate healthy from unhealthy biological tissues based on their optical signature. Among the numerous detection techniques developed for acousto-optic imaging, only those based on spectral filtering are intrinsically immune to speckle decorrelation. This Letter reports on UOT imaging based on spectral hole burning in Tm:YAG crystal under a moderate magnetic field (200G) with a well-defined orientation. The deep and long-lasting holes translate into a more efficient UOT imaging with a higher contrast and faster imaging frame rate...
August 15, 2018: Optics Letters
https://www.readbyqxmd.com/read/30105007/systems-biology-reveals-relevant-gaps-in-fc-%C3%AE-r-expression-impaired-regulatory-cytokine-microenvironment-interfaced-with-anti-trypanosoma-cruzi-igg-reactivity-in-cardiac-chagas-disease-patients
#16
Juliana de A S Gomes, Fernanda F de Araújo, Daniele M Vitelli-Avelar, Renato Sathler-Avelar, Paula S Lage, Ana P B Wendling, Isabela N P C do Vale, João C P Dias, Silvana M Elói-Santos, Andréa Teixeira-Carvalho, Olindo A Martins-Filho
The systems biology approach has become an innovative tool when it comes to shedding light on the complex immune response underlying the development/maintenance of distinct clinical forms of Chagas disease. The goal of this study was to describe an integrative overview of Fc-γR expression, cytokine microenvironment and anti- Trypanosoma cruzi IgG interface in indeterminate-(IND) and cardiac-(CARD) patients. Data demonstrated that IND displayed an overall higher Fcγ-R expression (CD16; CD32; CD64) on neutrophils-(NEU), along with (CD16; CD64) on monocytes-(MON) as compared to CARD...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30104673/pan-cancer-deconvolution-of-tumour-composition-using-dna-methylation
#17
Ankur Chakravarthy, Andrew Furness, Kroopa Joshi, Ehsan Ghorani, Kirsty Ford, Matthew J Ward, Emma V King, Matt Lechner, Teresa Marafioti, Sergio A Quezada, Gareth J Thomas, Andrew Feber, Tim R Fenton
The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: 'immune hot' and 'immune cold', which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity and oncogenic driver events...
August 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/30104497/new-development-of-biomarkers-for-gastrointestinal-cancers-from-neoplastic-cells-to-tumor-microenvironment
#18
REVIEW
Jiajia Zhang, Shafat Quadri, Christopher L Wolfgang, Lei Zheng
Biomarkers refer to a plethora of biological characteristics that can be quantified to facilitate cancer diagnosis, forecast the prognosis of disease, and predict a response to treatment. The identification of objective biomarkers is among the most crucial steps in the realization of individualized cancer care. Several tumor biomarkers for gastrointestinal malignancies have been applied in the clinical setting to help differentiate between cancer and other conditions, facilitate patient selection for targeted therapies, and to monitor treatment response and recurrence...
August 13, 2018: Biomedicines
https://www.readbyqxmd.com/read/30104241/paclitaxel-reduces-tumor-growth-by-reprogramming-tumor-associated-macrophages-to-an-m1-profile-in-a-tlr4-dependent-manner
#19
Carlos W Wanderley, David F Colon, Joao Paulo Mesquita Luiz, Francisco F Oliveira, Paula R Viacava, Caio A Leite, Janaina A Pereira, Camila M Silva, Cassia R Silva, Rangel L Silva, Cesar A Speck-Hernandez, Jose M Mota, Jose C Alves-Filho, Roberto C Lima-Júnior, Thiago M Cunha, Fernando Q Cunha
Paclitaxel (PCX) is an antineoplastic agent widely used to treat several solid tumor types. The primary mechanism of action of PCX is based on microtubule stabilization inducing cell cycle arrest. Here, we use several tumor models to show that PCX not only induces tumor cell cycle arrest, but also promotes antitumor immunity. In vitro, PCX reprogrammed M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. PCX also modulated the tumor-associated macrophages (TAMs) profile in mouse models of breast and melanoma tumors; gene expression analysis showed that PCX altered the M2-like signature of TAMs toward an M1-like profile...
August 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/30103384/targeting-the-microenvironment-in-high-grade-serous-ovarian-cancer
#20
REVIEW
Nkechiyere G Nwani, Livia E Sima, Wilberto Nieves-Neira, Daniela Matei
Cancer⁻stroma interactions play a key role in cancer progression and response to standard chemotherapy. Here, we provide a summary of the mechanisms by which the major cellular components of the ovarian cancer (OC) tumor microenvironment (TME) including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This profile is correlated with clinical outcomes and can be a target for therapy...
August 10, 2018: Cancers
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