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https://www.readbyqxmd.com/read/29064427/the-mek-inhibitors-trametinib-and-cobimetinib-induce-a-type-i-interferon-response-in-human-keratinocytes
#1
Daniela Lulli, Maria Luigia Carbone, Saveria Pastore
Mitogen-activated protein kinase kinases (MEK) 1 and 2 have crucial roles in tumorigenesis, cell proliferation, and protection from apoptosis, and their inhibition is therefore an attractive therapeutic strategy in cancer. Orally available and highly selective MEK inhibitors have been developed and assessed in numerous clinical trials, either alone or in combination with cytotoxic chemotherapy and/or other targeted agents. Of note, a complex picture of class-specific adverse effects associates with these drugs, frequently including inflammatory skin rash...
October 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29059831/real-time-gait-analysis-with-accelerometer-based-smart-shoes
#2
R Delgado-Gonzalo, J Hubbard, Ph Renevey, A Lemkaddem, Q Vellinga, D Ashby, J Willardson, M Bertschi
In this paper, we present the evaluation of a new smart shoe capable of performing gait analysis in real time. The system is exclusively based on accelerometers which minimizes the power consumption. The estimated parameters are activity class (rest/walk/run), step cadence, ground contact time, foot impact (zone, strength, and balance), forward distance, and speed. The different parameters have been validated with a customized database of 26 subjects on a treadmill and video data labeled manually. Key measures for running analysis such as the cadence is retrieved with a maximum error of 2%, and the ground contact time with an average error of 3...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29023988/molecular-dynamics-simulation-binding-free-energy-calculation-and-unbinding-pathway-analysis-on-selectivity-difference-between-fkbp51-and-fkbp52-insight-into-the-molecular-mechanism-of-isoform-selectivity
#3
Danfeng Shi, Qifeng Bai, Shuangyan Zhou, Xuewei Liu, Huanxiang Liu, Xiaojun Yao
As co-chaperones of the 90-kDa heat shock protein(HSP90), FK506 binding protein 51 (FKBP51) and FK506 binding protein 52 (FKBP52) modulate the maturation of steroid hormone receptor through their specific FK1 domains (FKBP12-like domain 1). The inhibitors targeting FK1 domains are potential therapies for endocrine-related physiological disorders. However, the structural conservation of the FK1 domains between FKBP51 and FKBP52 make it difficult to obtain satisfactory selectivity in FK506-based drug design. Fortunately, a series of iFit ligands synthesized by Hausch et al exhibited excellent selectivity for FKBP51, providing new opportunity for design selective inhibitors...
October 12, 2017: Proteins
https://www.readbyqxmd.com/read/28806906/age-associated-mrna-expression-changes-in-bovine-endometrial-cells-in-vitro
#4
Nao Tanikawa, Ayaka Ohtsu, Ryouka Kawahara-Miki, Koji Kimura, Shuichi Matsuyama, Hisataka Iwata, Takehito Kuwayama, Koumei Shirasuna
BACKGROUND: Endometrial cells secrete various cytokines and the dysfunction of endometrial cells may directly lead to infertility. Interferon tau (IFNT) secreted by trophoblast cells, a well-known pregnancy recognition signal in ruminants, acts on the uterus to prepare for pregnancy. Aging causes cellular and organ dysfunction, and advanced maternal age is associated with reduced fertility. However, few studies have investigated age-dependent changes in the uterus. METHODS: Using next generation sequencing and real-time PCR, we examined mRNA expression in bovine endometrial cells in vitro obtained from young (mean 45...
August 14, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28768867/mechanism-of-interferon-stimulated-gene-induction-in-hiv-1-infected-macrophages
#5
Najla Nasr, Abdullateef A Alshehri, Thomas K Wright, Maryam Shahid, Bonnie M Heiner, Andrew N Harman, Rachel A Botting, Karla J Helbig, Michael R Beard, Kazuo Suzuki, Anthony D Kelleher, Paul Hertzog, Anthony L Cunningham
Viruses manipulate the complex interferon and interferon-stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells, many of which are antiviral. Here, we examine the mechanism of induction of ISGs and show this occurs in two phases. The first phase was transient (0 to 24 h postinfection [hpi]), induced mainly by extracellular vesicles and one of its component proteins, HSP90α, contained within the HIV inoculum...
October 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28487939/identification-of-novel-genes-associated-with-fracture-healing-in-osteoporosis-induced-by-krm2-overexpression-or-lrp5-deficiency
#6
Feng Gao, Feng Xu, Dankai Wu, Jieping Cheng, Peng Xia
The aim of the present study was to screen potential key genes associated with osteoporotic fracture healing. The microarray data from the Gene Expression Omnibus database accession number GSE51686, were downloaded and used to identify differentially expressed genes (DEGs) in fracture callus tissue samples obtained from the femora of type I collagen (Col1a1)‑kringle containing transmembrane protein 2 (Krm2) mice and low density lipoprotein receptor‑related protein 5‑/‑ (Lrp5‑/‑) transgenic mice of osteoporosis compared with those in wild‑type (WT) mice...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28373872/type-i-interferon-gene-response-is-increased-in-early-and-established-rheumatoid-arthritis-and-correlates-with-autoantibody-production
#7
Julio E Castañeda-Delgado, Yadira Bastián-Hernandez, Noe Macias-Segura, David Santiago-Algarra, Jose D Castillo-Ortiz, Ana L Alemán-Navarro, Pedro Martínez-Tejada, Leonor Enciso-Moreno, Yolanda Garcia-De Lira, Diana Olguín-Calderón, Leendert A Trouw, Cesar Ramos-Remus, Jose A Enciso-Moreno
BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28325014/real-time-monitoring-of-swimming-performance
#8
R Delgado-Gonzalo, A Lemkaddem, Ph Renevey, E Muntane Calvo, M Lemay, K Cox, D Ashby, J Willardson, M Bertschi
This article presents the performance results of a novel algorithm for swimming analysis in real-time within a low-power wrist-worn device. The estimated parameters are: lap count, stroke count, time in lap, total swimming time, pace/speed per lap, total swam distance, and swimming efficiency (SWOLF). In addition, several swimming styles are automatically detected. Results were obtained using a database composed of 13 different swimmers spanning 646 laps and 858.78 min of total swam time. The final precision achieved in lap detection ranges between 99...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28295457/hepatic-ifit3-predicts-interferon-%C3%AE-therapeutic-response-in-patients-of-hepatocellular-carcinoma
#9
COMPARATIVE STUDY
Yingyun Yang, Ye Zhou, Jin Hou, Chunmei Bai, Zhenyang Li, Jia Fan, Irene O L Ng, Weiping Zhou, Huichuan Sun, Qiongzhu Dong, Joyce M F Lee, Chung-Mau Lo, Kwan Man, Yun Yang, Nan Li, Guoshan Ding, Yizhi Yu, Xuetao Cao
Adjuvant interferon-α (IFN-α) therapy is used to control certain types of cancer in clinics. For hepatocellular carcinoma (HCC), IFN-α therapy is effective in only a subgroup of patients; therefore, identifying biomarkers to predict the response to IFN-α therapy is of high significance and clinical utility. As the induced IFN-stimulated gene expression following IFN-α treatment plays pivotal roles in IFN-α effects, we screened IFN-stimulated gene expression in HCC tissues and found that several IFN-stimulated genes were significantly decreased in HCC...
July 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28227572/real-time-monitoring-of-swimming-performance
#10
R Delgado-Gonzalo, A Lemkaddem, Ph Renevey, E Muntane Calvo, M Lemay, K Cox, D Ashby, J Willardson, M Bertschi, R Delgado-Gonzalo, A Lemkaddem, Ph Renevey, E Muntane Calvo, M Lemay, K Cox, D Ashby, J Willardson, M Bertschi, M Lemay, A Lemkaddem, Ph Renevey, D Ashby, M Bertschi, E Muntane Calvo, J Willardson, R Delgado-Gonzalo, K Cox
This article presents the performance results of a novel algorithm for swimming analysis in real-time within a low-power wrist-worn device. The estimated parameters are: lap count, stroke count, time in lap, total swimming time, pace/speed per lap, total swam distance, and swimming efficiency (SWOLF). In addition, several swimming styles are automatically detected. Results were obtained using a database composed of 13 different swimmers spanning 646 laps and 858.78 min of total swam time. The final precision achieved in lap detection ranges between 99...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28210844/elevated-interferon-induced-protein-with-tetratricopeptide-repeats-3-ifit3-is-a-poor-prognostic-marker-in-pancreatic-ductal-adenocarcinoma
#11
Yue Zhao, Annelore Altendorf-Hofmann, Ioannis Pozios, Peter Camaj, Therese Däberitz, Xiaoyan Wang, Hanno Niess, Hendrik Seeliger, Felix Popp, Christopher Betzler, Utz Settmacher, Karl-Walter Jauch, Christiane Bruns, Thomas Knösel
PURPOSE: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. METHODS: The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3...
June 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28070326/effects-of-cranberry-extracts-on-gene-expression-in-thp-1-cells
#12
Daniel B Hannon, Jerry T Thompson, Christina Khoo, Vijaya Juturu, John P Vanden Heuvel
Cranberry contains high levels of nutrients and bioactive molecules that have health-promoting properties. The purpose of the present studies was to determine if cranberry extracts (CEs) contain phytochemicals that exert anti-inflammatory effects. The human monocytic cell line THP-1 was treated with two CEs (CE and 90MX) and subsequently challenged with Lipopolysaccharides (LPS). Tumor necrosis factor α (TNF α) expression was decreased in the CE-treated cells, indicative of an anti-inflammatory effect. Gene expression microarrays identified several immune-related genes that were responsive to CEs including interferon-induced protein with tetratricopeptide repeats 1 and 3 (IFIT 1 and 3), macrophage scavenger receptor 1 (MSR1) and colony-stimulating factor 2 (CSF2)...
January 2017: Food Science & Nutrition
https://www.readbyqxmd.com/read/28031370/binding-of-the-methyl-donor-s-adenosyl-l-methionine-to-middle-east-respiratory-syndrome-coronavirus-2-o-methyltransferase-nsp16-promotes-recruitment-of-the-allosteric-activator-nsp10
#13
Wahiba Aouadi, Alexandre Blanjoie, Jean-Jacques Vasseur, Françoise Debart, Bruno Canard, Etienne Decroly
The Middle East respiratory syndrome coronavirus (MERS-CoV) nonstructural protein 16 (nsp16) is an S-adenosyl-l-methionine (SAM)-dependent 2'-O-methyltransferase (2'-O-MTase) that is thought to methylate the ribose 2'-OH of the first transcribed nucleotide (N1) of viral RNA cap structures. This 2'-O-MTase activity is regulated by nsp10. The 2'-O methylation prevents virus detection by cell innate immunity mechanisms and viral translation inhibition by the interferon-stimulated IFIT-1 protein. To unravel the regulation of nsp10/nsp16 2'-O-MTase activity, we used purified MERS-CoV nsp16 and nsp10...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27905550/deep-sequencing-of-transcriptome-profiling-of-gstm2-knock-down-in-swine-testis-cells
#14
Yuqi Lv, Yi Jin, Yongqiang Zhou, Jianjun Jin, Zhenfa Ma, Zhuqing Ren
Glutathione-S-transferases mu 2 (GSTM2), a kind of important Phase II antioxidant enzyme of eukaryotes, is degraded by nonsense mediated mRNA decay due to a C27T substitution in the fifth exon of pigs. As a reproductive performance-related gene, GSTM2 is involved in embryo implantation, whereas, functional deficiency of GSTM2 induces pre- or post-natal death in piglets potentially. To have some insight into the role of GSTM2 in embryo development, high throughput RNA sequencing is performed using the swine testis cells (ST) with the deletion of GSTM2...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27707917/identification-of-interferon-stimulated-gene-proteins-that-inhibit-human-parainfluenza-virus-type-3
#15
M A G Rabbani, Michael Ribaudo, Ju-Tao Guo, Sailen Barik
A major arm of cellular innate immunity is type I interferon (IFN), represented by IFN-α and IFN-β. Type I IFN transcriptionally induces a large number of cellular genes, collectively known as IFN-stimulated gene (ISG) proteins, which act as antivirals. The IFIT (interferon-induced proteins with tetratricopeptide repeats) family proteins constitute a major subclass of ISG proteins and are characterized by multiple tetratricopeptide repeats (TPRs). In this study, we have interrogated IFIT proteins for the ability to inhibit the growth of human parainfluenza virus type 3 (PIV3), a nonsegmented negative-strand RNA virus of the Paramyxoviridae family and a major cause of respiratory disease in children...
December 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27275413/comprehensive-and-computational-analysis-of-genes-in-human-umbilical-vein-endothelial-cells-responsive-to-x-irradiation
#16
Yukihiro Furusawa, Qing-Li Zhao, Yuichi Hattori, Yoshiaki Tabuchi, Toshiyasu Iwasaki, Takaharu Nomura, Takashi Kondo
Radiation exposure such as A-bomb or radiation therapy is considered a major health-risk factor for cardiovascular disease. In order to understand the molecular mechanisms underlying the inflammatory reaction frequently encountered in the vascular system after exposure to ionizing radiation, we carried out a global scale microarray and computational gene expression analyses on human umbilical endothelial cells (HUVECs) exposed to X-ray (2.5 Gy). The gene ontology analysis revealed that the down-regulated genes were associated with cell cycle regulation, whereas the up-regulated genes were associated with inflammatory responses, in particular, the type 1 interferon response...
June 2016: Genomics Data
https://www.readbyqxmd.com/read/27244557/phylogenetic-sleuthing-reveals-pair-of-paralogous-genes
#17
Jamie E Henzy, Welkin E Johnson
The complex evolutionary history of the IFIT family of antiviral genes has been shaped by continuous interactions between mammalian hosts and their many viruses.
2016: ELife
https://www.readbyqxmd.com/read/27240734/evolution-guided-functional-analyses-reveal-diverse-antiviral-specificities-encoded-by-ifit1-genes-in-mammals
#18
Matthew D Daugherty, Aaron M Schaller, Adam P Geballe, Harmit S Malik
IFIT (interferon-induced with tetratricopeptide repeats) proteins are critical mediators of mammalian innate antiviral immunity. Mouse IFIT1 selectively inhibits viruses that lack 2'O-methylation of their mRNA 5' caps. Surprisingly, human IFIT1 does not share this antiviral specificity. Here, we resolve this discrepancy by demonstrating that human and mouse IFIT1 have evolved distinct functions using a combination of evolutionary, genetic and virological analyses. First, we show that human IFIT1 and mouse IFIT1 (renamed IFIT1B) are not orthologs, but are paralogs that diverged >100 mya...
May 31, 2016: ELife
https://www.readbyqxmd.com/read/27137933/interferon-regulatory-factor-8-irf8-impairs-induction-of-interferon-induced-with-tetratricopeptide-repeat-motif-ifit-gene-family-members
#19
Christine L White, Patricia M Kessler, Benjamin K Dickerman, Keiko Ozato, Ganes C Sen
The chromosomally clustered interferon-induced with tetratricopeptide repeat motif (IFIT) gene family members share structural features at the gene and protein levels. Despite these similarities, different IFIT genes have distinct inducer- and cell type-specific induction patterns. Here, we investigated the mechanism for the observed differential induction of the mouse Ifit1, Ifit2, and Ifit3 genes in B cells and demonstrated that the repressive effect of the transcription factor interferon regulatory factor 8 (IRF8), which is highly expressed in B cells, played an essential role in this regulation...
June 24, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27135915/distinct-expression-of-interferon-induced-protein-with-tetratricopeptide-repeats-ifit-1-2-3-and-other-antiviral-genes-between-subsets-of-dendritic-cells-induced-by-dengue-virus-2-infection
#20
Jingshu Zhang, Daniel Man-Yuen Sze, Benjamin Yat-Ming Yung, Petrus Tang, Wei-June Chen, Kwok-Hung Chan, Polly Hang-Mei Leung
Dengue virus (DENV) infection is an emerging public health hazard threatening inhabitants of the tropics and sub-tropics. Dendritic cells (DCs) are one of the major targets of DENV and the initiators of the innate immune response against the virus. However, current in vitro research on the DENV-DC interaction is hampered by the low availability of ex vivo DCs and donor variation. In the current study, we attempted to develop a novel in vitro DC model using immature DCs derived from the myeloid leukaemia cell line MUTZ-3 (IMDCs) to investigate the DENV-DC interaction...
August 2016: Immunology
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