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https://www.readbyqxmd.com/read/28432927/type-2-bvdv-n-pro-suppresses-ifn-1-pathway-signaling-in-bovine-cells-and-augments-brsv-replication
#1
Abdulrahman A Alkheraif, Christina L Topliff, Jay Reddy, Chandirasegaran Massilamany, Ruben O Donis, Gregor Meyers, Kent M Eskridge, Clayton L Kelling
Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional N(pro) mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28426973/non-linear-enhancement-of-mrna-delivery-efficiencies-by-influenza-a-derived-ns1-protein-engendering-host-gene-inhibition-property
#2
Kyle K L Phua, Yi Liu, Shun Hui Sim
Nucleic acid induced immunogenicity remains a significant impediment in biomedical therapeutics because the innate immune system is a complex network overlaid with functional redundancies. Herein we report that non-structural protein 1 (NS1), an immune evasion protein derived from influenza A virus, when co-delivered in mRNA format is a potent mRNA transfection enhancer without toxicity. Transfection enhancement is mediated by NS1's effector domain through inhibition of IRF3 and PKR, activators of early anti-viral responses as well as CPSF30, a non immunostimulating protein...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28410401/ripk3-interacts-with-mavs-to-regulate-type-i-ifn-mediated-immunity-to-influenza-a-virus-infection
#3
Jeffrey Downey, Erwan Pernet, François Coulombe, Benoit Allard, Isabelle Meunier, Joanna Jaworska, Salman Qureshi, Donald C Vinh, James G Martin, Philippe Joubert, Maziar Divangahi
The type I interferon pathway plays a critical role in both host defense and tolerance against viral infection and thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be involved in anti-viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus (IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/- mice are highly susceptible to IAV infection, exhibiting elevated pulmonary viral load and heightened morbidity and mortality...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28389754/roles-of-grp78-in-female-mammalian-reproduction
#4
Cheng Zhang
The glucose-regulated protein (GRP78) also referred to as immunoglobulin heavy chain binding protein (Bip) is one of the best characterized endoplasmic reticulum (ER) chaperone proteins, which belongs to the heat-shock protein (HSP) family. GRP78 as a central regulator of ER stress (ERS) plays many important roles in cell survival and apoptosis through controlling the activation of transmembrane ERS sensors: PKR-like ER-associated kinase (PERK), inositol requiring kinase 1 (IRE1), and activating transcription factor 6 (ATF6)...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28389244/colostrum-oxytocin-modulates-cellular-stress-response-inflammation-and-autophagy-markers-in-newborn-rat-gut-villi
#5
Benjamin Y Klein, Hadassah Tamir, Robert J Ludwig, Sara B Glickstein, Martha G Welch
Little is known about the role of oxytocin (OT) in colostrum during early gut colonization. We previously showed that transient OT receptor (OTR) expression on newborn rat enterocytes coincides with the milk-suckling period, and that OT activates endoplasmic reticulum stress sensors in cultured enterocytes. Here, we explored whether colostrum-OT attenuates stress in newborn villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase)...
April 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28374749/pkr-activation-and-eif2%C3%AE-phosphorylation-mediate-human-globin-mrna-splicing-at-spliceosome-assembly
#6
Lena Ilan, Farhat Osman, Lise Sarah Namer, Einav Eliahu, Smadar Cohen-Chalamish, Yitzhak Ben-Asouli, Yona Banai, Raymond Kaempfer
Short elements in mammalian mRNA can control gene expression by activating the RNA-dependent protein kinase PKR that attenuates translation by phosphorylating cytoplasmic eukaryotic initiation factor 2α (eIF2α). We demonstrate a novel, positive role for PKR activation and eIF2α phosphorylation in human globin mRNA splicing. PKR localizes in splicing complexes and associates with splicing factor SC35. Splicing and early-stage spliceosome assembly on β-globin pre-mRNA depend strictly on activation of PKR by a codon-containing RNA fragment within exon 1 and on phosphorylation of nuclear eIF2α on Serine 51...
April 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28371616/salvianolic-acid-a-protects-retinal-pigment-epithelium-from-ox-ldl-induced-inflammation-in-an-age-related-macular-degeneration-model
#7
Ke Mao, Wanting Shu, Qinghua Qiu, Qing Gu, Xingwei Wu
BACKGROUND: Salvianolic acid A (Sal A), an active monomer of Salvia miltiorrhiza, is a phenolic carboxylic acid derivative. The present study was performed to investigate the underlying mechanism of the anti-inflammation effect of Sal A, especially focusing on mTOR-KEAP1-Nrf2 and P2X7R-PKR-NLRP3 signaling pathways. METHODS: SD mice were divided into four groups: PBS, oxidized-low density lipoprotein (ox-LDL, 3 mg/kg), and ox-LDL (3 mg/kg) + Sal A (5 mg/kg) and + Sal A (10 mg/ml) groups...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28362919/activation-of-nuclear-factor-kappa-b-in-endothelial-cells-of-chronic-subdural-hematoma-outer-membranes
#8
Koji Osuka, Yasuo Watanabe, Nobuteru Usuda, Masahiro Aoyama, Reo Kawaguchi, Mikinobu Takeuchi, Masakazu Takayasu
BACKGROUND: Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Nuclear factor-kappa B (NF-κB) induces the production of inflammatory cytokines and adhesion molecules, which play an essential role in angiogenesis and inflammation. Recently, the double-stranded RNA-activated protein kinase (PKR) was shown to directly interact with NF-κB subunits to influence its transcriptional activity. OBJECTIVE: To examine the expression of NF-κB signaling pathway components and PKR in CSDH outer membranes...
April 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28357896/a-novel-thermally-stable-heteropolysaccharide-based-bioflocculant-from-hydrocarbonoclastic-strain-kocuria-rosea-bu22s-and-its-application-in-dye-removal
#9
Habib Chouchane, Mouna Mahjoubi, Besma Ettoumi, Mohamed Neifar, Ameur Cherif
A new bioflocculant named pKr produced by hydrocarbonoclastic strain Kocuria rosea BU22S (KC152976) was investigated. Gas chromatography-flame ionization detector (GC-FID) analysis confirmed the high potential of the strain BU22S in the degradation of n-alkanes. Plackett-Burman experimental design and response surface methodology were carried out to optimize pKr production. Glucose, peptone and incubation time were found to be the most significant factors affecting bioflocculant production. Maximum pKr production was about 4...
April 20, 2017: Environmental Technology
https://www.readbyqxmd.com/read/28347954/interaction-of-irf9-and-stat2-synergistically-up-regulates-ifn-and-pkr-transcription-in-ctenopharyngodon-idella
#10
REVIEW
Zhen Wu, Liqiang Wang, Xiaowen Xu, Gang Lin, Huiling Mao, Xiaoqin Ran, Tao Zhang, Keyi Huang, Haizhou Wang, Qingli Huang, Qun Xu, Chengyu Hu
IRF9 is a key factor in the JAK-STAT pathway. Under the stimulation of type I IFN, IRF9 interacts with STAT1 and STAT2 to form the IFN-I-stimulated gene factor 3 (ISGF3) which activates the transcription of ISG. However, many studies also showed that the dimmer IRF9/STAT2 rather than the tripolymer IRF9/STAT1/STAT2 acts as the ISGF3 in cells in response to IFN signals. In the present study, the full-length cDNA sequence of IRF9 (termed CiIRF9, KT601055) and STAT2 (term CiSTAT2, KT781914) from grass carp were cloned and identified...
March 24, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28341446/pkr-induces-the-expression-of-nlrp3-by-regulating-the-nf-%C3%AE%C2%BAb-pathway-in-porphyromonas-gingivalis-infected-osteoblasts
#11
Kaya Yoshida, Hirohiko Okamura, Yuka Hiroshima, Kaori Abe, Jun-Ichi Kido, Yasuo Shinohara, Kazumi Ozaki
The double-stranded RNA-dependent kinase (PKR), which is activated by double stranded RNA, induces inflammation by regulating NF-κB signaling. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome also modulates inflammation in response to infection. Porphyromonas gingivalis (P.gingivalis) is an oral bacterium which is implicated in the pathogenesis of periodontal diseases. We previously reported that PKR is a key modulator of bone metabolism and inflammation in the periodontal tissue. PKR was also reported to induce inflammation in response to microbes by regulating the NLRP3 inflammasome, suggesting that PKR could affect inflammation along with NLRP3 in periodontal diseases...
March 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28337142/icariside-ii-effectively-reduces-spatial-learning-and-memory-impairments-in-alzheimer-s-disease-model-mice-targeting-beta-amyloid-production
#12
Lingli Yan, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Fei Li, Jingshan Shi, Qihai Gong
Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer's disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28334970/expenditure-tracking-and-review-of-reproductive-maternal-newborn-and-child-health-policy-in-pakistan
#13
Muhammad Ashar Malik, Abdul Sattar Nahyoun, Arjumand Rizvi, Zaid Ahmad Bhatti, Zulfiqar Ahmad Bhutta
Since 2001 substantial resources have been allocated to the reproductive, maternal, newborn and child health sector (RMNCH) in Pakistan. Many new programmes have been started and coverage of some existing programmes has been extended to un-served and rural areas. Despite these efforts the Millennium Development Goals (MDGs) 4 and 5 were not achieved (2000-15). Maternal Mortality Ratio was reduced to 170 per 100 000 live births (target 100) by 2013 at an annual reduction rate of 3.6% (1990-2013). Against the target of 46 per 1000 live births, the Under Five Mortality Rate was reduced to 81 per 1000 live births by 2015 at an annual reduction rate of 2...
March 15, 2017: Health Policy and Planning
https://www.readbyqxmd.com/read/28324201/potential-roles-of-mitochondria-associated-er-membranes-mams-in-traumatic-brain-injury
#14
REVIEW
Dongdong Sun, Xin Chen, Gang Gu, Jianhao Wang, Jianning Zhang
The endoplasmic reticulum (ER) and mitochondria have both been shown to be critical in cellular homeostasis. The functions of the ER and mitochondria are independent but interrelated. These two organelles could form physical interactions, known as MAMs, to regulate physiological functions between ER and mitochondria to maintain Ca(2+), lipid, and metabolite exchange. Several proteins are located in MAMs, including RNA-dependent protein kinase (PKR)-like ER kinase, inositol 1,4,5-trisphosphate receptors, phosphofurin acidic cluster sorting protein-2 and sigma-1 receptor to ensure regulation...
March 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28322789/high-glucose-impairs-insulin-signaling-via-activation-of-pkr-pathway-in-l6-muscle-cells
#15
Mary Priyanka Udumula, Mangali Suresh Babu, Audesh Bhat, Indu Dhar, Dharmarajan Sriram, Arti Dhar
Double stranded RNA (dsRNA) activated protein kinase R (PKR), a ubiquitously expressed serine/threonine kinase is a key inducer of inflammation, insulin resistance and glucose homeostasis in obesity. Recent studies have demonstrated that PKR can respond to metabolic stress in mice as well as in humans. However the underlying molecular mechanism is not fully understood. The aim of the present study was to examine the effect of high glucose on cultured rat L6 muscle cells and to investigate whether inhibition of PKR could prevent any deleterious effects of high glucose in these cells...
May 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300830/smad7-knockdown-activates-protein-kinase-rna-associated-eif2%C3%AE-pathway-leading-to-colon-cancer-cell-death
#16
Veronica De Simone, Gerolamo Bevivino, Silvia Sedda, Roberta Izzo, Federica Laudisi, Vincenzo Dinallo, Eleonora Franzè, Alfredo Colantoni, Angela Ortenzi, Silvia Salvatori, Piero Rossi, Giuseppe S Sica, Massimo C Fantini, Carmine Stolfi, Giovanni Monteleone
Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. These findings occur in CRC cells unresponsive to TGF-β1, thus suggesting the existence of a Smad7-mediated TGF-β1-independent mechanism that controls CRC cell behavior. Here we show that Smad7 inhibition with a specific Smad7 antisense oligonucleotide upregulates eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, a transcription factor involved in the regulation of cell cycle arrest and induction of cell death, and induces activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homology protein (CHOP), two downstream targets of eIF2α...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28298621/silencing-nc886-a-non-coding-rna-induces-apoptosis-of-human-endometrial-cancer-cells-1a-in-vitro
#17
Zhuoying Hu, Hongyu Zhang, Liangdan Tang, Meng Lou, Yanqing Geng
BACKGROUND The role that nc886, a non-coding microRNA, plays in human endometrial cancer is unknown. The present study aimed to describe the functional role of nc886 in human endometrial cancer-1A (HEC-1A) cell line, which may provide another target for human endometrial cancer treatment. MATERIAL AND METHODS The expression levels of nv886 in normal human endometrial tissue and the early phase and late phase of human endometrial cancer tissues were determined and compared by fluorescence in situ hybridization (FISH)...
March 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28267207/listeria-monocytogenes-induces-an-interferon-enhanced-activation-of-the-integrated-stress-response-that-is-detrimental-for-resolution-of-infection-in-mice
#18
Carolina Valderrama, Amy Clark, Fumihiko Urano, Emil R Unanue, Javier A Carrero
Type I interferons (IFNs) induce a detrimental response during Listeria monocytogenes (L. monocytogenes) infection. We were interested in identifying mechanisms linking IFN signaling to negative host responses against L. monocytogenes infection. Herein, we found that infection of myeloid cells with L. monocytogenes led to a coordinated induction of type I IFNs and activation of the integrated stress response (ISR). Infected cells did not induce Xbp1 splicing or BiP upregulation, indicating that the unfolded protein response was not triggered...
March 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28266737/epidermal-keratinocytes-sense-dsrna-via-the-nlrp3-inflammasome-mediating-interleukin-il-1%C3%AE-and-il-18-release
#19
Xiuju Dai, Mikiko Tohyama, Masamoto Murakami, Koji Sayama
Skin epidermis, in addition to its barrier function, is able to actively sense harmful pathogens using pattern recognition receptors. In immune cells, the nucleotide-binding oligomerization domain, leucine-rich repeat, pyrin domain containing 3 (NLRP3) inflammasome can mediate innate immunity against viral infection via a mechanism involving viral dsRNA recognition. Epidermal keratinocytes express NLRP3 inflammasome, which can sense contact sensitizers and mite allergens, leading to pro-interleukin (IL)-1β and pro-IL-18 cleavage into their active forms...
March 7, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28266275/molecular-basis-of-human-diseases-and-targeted-therapy-based-on-small-molecule-inhibitors-of-er-stress-induced-signaling-pathways
#20
W Rozpędek, A Nowak, D Pytel, J Alan Diehl, I Majsterek
The Endoplasmic Reticulum (ER) provides a conserved protein quality control system and plays a fundamental role in cell growth and homeostasis. Disturbances in the ER homeostasis may originate especially from hypoxia, glucose deficiency, presence of mutant proteins, that directly impair protein folding capacity and after deposition of unfolded and misfolded proteins within ER lumen trigger ER stress conditions. That subsequently activates the Unfolded Protein Response (UPR) branches, which has a dual pro-adaptive or pro-apoptotic role dependently on severity and time of duration of ER stress conditions...
March 6, 2017: Current Molecular Medicine
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