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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
#1
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
#2
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
#3
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
#4
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
#5
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...
March 17, 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
#6
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
#7
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
#8
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
#9
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
#10
I Majsterek, J Alan Diehl, D Pytel, A Nowak, W Rozpędek
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
https://www.readbyqxmd.com/read/28263879/ctenopharyngodon-idella-irf2-and-atf4-down-regulate-the-transcriptional-level-of-prkra
#11
Keyi Huang, Guoqin Qi, Zhicheng Sun, Xiancheng Liu, Xiaowen Xu, Haizhou Wang, Zhen Wu, Yiqi Wan, Chengyu Hu
PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A) is a protective protein which regulates the adaptation of cells to ER stress and virus-stimulated signaling pathways by activating PKR. In the present study, a grass carp (Ctenopharyngodon idella) PRKRA full-length cDNA (named CiPRKRA, KT891991) was cloned and identified. The full-length cDNA is comprised of a 5' UTR (36 bp), a 3' UTR (350 bp) and the longest ORF (882 bp) encoding a polypeptide of 293 amino acids. The deduced amino acid sequence of CiPRKRA contains three typical dsRNA binding motifs (dsRBM)...
March 2, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28250123/influenza-a-virus-virulence-depends-on-two-amino-acids-in-the-n-terminal-domain-of-its-ns1-protein-facilitating-inhibition-of-pkr
#12
Kristina L Schierhorn, Fabian Jolmes, Julia Bespalowa, Sandra Saenger, Christin Peteranderl, Julia Dzieciolowski, Matthias Budt, Stephan Pleschka, Andreas Herrmann, Susanne Herold, Thorsten Wolff
The RNA-dependent protein kinase (PKR) has broad antiviral activity inducing translational shut-down of viral and cellular genes and is therefore targeted by various viral proteins to facilitate pathogen propagation. The pleiotropic NS1 protein of influenza A virus acts as silencer of PKR activation and ascertains high level viral replication and virulence. However, the exact way of this inhibition remains controversial. To elucidate the structural requirements within the NS1 protein for PKR inhibition, we generated a set of mutant viruses identifying highly conserved arginine residues 35 and 46 within the NS1 N-terminus as being most critical not only for binding to and blocking activation of PKR, but also for efficient virus propagation...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228218/-thioridazine-sensitizes-apoptotic-effect-of-trail-in-human-lung-cancer-pc9-cells-through-er-stress-mediated-up-regulation-of-dr5
#13
Juan Li, Yi Wang, Liu Liu, Yuan Yuan, Yangyi Bao
BACKGROUND: Tumor necrosis factor-related apoptosis-inducting ligand (TRAIL) can induce apoptosis of tumor cells, however, various of tumor cells may survive because of resistance to TRAIL-mediated apoptosis. This study is to observe the proliferation inhibition effect of TRAIL sensitized by thioridazine on PC9 cells through endoplasmic reticulum (ER) stress mediated up-regulation of death receptor 5 (DR5) and investigate its mechanism. METHODS: PC9 cells were treated with different concentrations of thioridazine and TRAIL alone or in combination...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28218858/formal-synthesis-of-%C3%A2-aplykurodinone-1-through-a-hetero-pauson-khand-cycloaddition-approach
#14
Cheng Tao, Jing Zhang, Xiaoming Chen, Huifei Wang, Yun Li, Bin Cheng, Hongbin Zhai
The tricyclic intermediate 2 has been synthesized in eight steps from known compound 6 in 20% overall yield. As such, this constitutes a highly efficient formal synthesis of (±)-aplykurodinone-1. This synthesis features a unique, one-pot, intramolecular hetero-Pauson-Khand reaction (h-PKR)/desilylation sequence to expeditiously construct the tricyclic framework, providing valuable insights for expanding the scope and boundaries of h-PKR.
February 20, 2017: Organic Letters
https://www.readbyqxmd.com/read/28215278/nucleic-acid-immunity
#15
G Hartmann
Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28202752/human-herpesvirus-6a-hhv-6a-exhibits-restrictive-propagation-with-limited-activation-of-pkr-eif2%C3%AE-stress-pathway
#16
Eyal Sharon, Niza Frenkel
The eIF2α protein plays a critical role in the regulation of translation. The production of dsRNA during viral replication can activate protein kinase R (PKR) which phosphorylates the eIF2α, leading to inhibition of the initial step of translation. Many viruses have evolved gene products targeting PKR-eIF2a pathway, indicating its importance in antiviral defense. In the present study we focus on alternations of PKR-eIF2a pathway along HHV-6A infection while monitoring viral gene expression and infectious viral yields...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28186978/combination-antiretroviral-therapy-cart-restores-hiv-1-infection-mediated-impairment-of-jak-stat-signaling-pathway
#17
Man-Qing Liu, Min Zhao, Wen-Hua Kong, Li Tang, Fang Wang, Ze-Rong Zhu, Xia Wang, Hong-Yan Qiu, Dun-Jin Zhou, Xu Wang, Wen-Zhe Ho, Wang Zhou
JAK-STAT signaling pathway has a crucial role in host innate immunity against viral infections, including HIV-1. We therefore examined the impact of HIV-1 infection and combination antiretroviral therapy (cART) on JAK-STAT signaling pathway. Compared to age-matched healthy donors (n = 18), HIV-1-infected subjects (n = 18) prior to cART had significantly lower expression of toll-like receptors (TLR-1/4/6/7/8/9), the IFN regulatory factors (IRF-3/7/9), and the antiviral factors (OAS-1, MxA, A3G, PKR, and Tetherin)...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28167698/adar1-and-pact-contribute-to-efficient-translation-of-transcripts-containing-hiv-1-trans-activating-response-tar-element
#18
Evelyn Chukwurah, Indhira Handy, Rekha C Patel
Human immunodeficiency virus type 1 (HIV-1) has evolved various measures to counter the host cell's innate antiviral response during the course of infection. Interferon (IFN)-stimulated gene products are produced following HIV-1 infection to limit viral replication, but viral proteins and RNAs counteract their effect. One such mechanism is specifically directed against the IFN-induced Protein Kinase R (PKR), which is centrally important to the cellular antiviral response. In the presence of viral RNAs, PKR is activated and phosphorylates the translation initiation factor, eIF2α...
February 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28158275/early-endonuclease-mediated-evasion-of-rna-sensing-ensures-efficient-coronavirus-replication
#19
Eveline Kindler, Cristina Gil-Cruz, Julia Spanier, Yize Li, Jochen Wilhelm, Huib H Rabouw, Roland Züst, Mihyun Hwang, Philip V'kovski, Hanspeter Stalder, Sabrina Marti, Matthias Habjan, Luisa Cervantes-Barragan, Ruth Elliot, Nadja Karl, Christina Gaughan, Frank J M van Kuppeveld, Robert H Silverman, Markus Keller, Burkhard Ludewig, Cornelia C Bergmann, John Ziebuhr, Susan R Weiss, Ulrich Kalinke, Volker Thiel
Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28157174/myxoma%C3%A2-virus%C3%A2-dsrna%C3%A2-binding%C3%A2-protein%C3%A2-m029%C3%A2-inhibits%C3%A2-the%C3%A2-type%C3%A2-i%C3%A2-ifn-induced%C3%A2-antiviral%C3%A2-state%C3%A2-in%C3%A2-a%C3%A2-highly%C3%A2-species-specific%C3%A2-fashion
#20
Masmudur M Rahman, Grant McFadden
Myxoma virus (MYXV) is Leporipoxvirus that possesses a specific rabbit-restricted host tropism but exhibits a much broader  cellular host range in cultured cells. MYXV is able to efficiently  block all aspects of the type I interferon (IFN)-induced  antiviral  state  in rabbit cells, partially in  human  cells  and  very  poorly  in  mouse  cells.  The mechanism(s) of this species-specific inhibition of  type I IFN-induced antiviral state is not well understood...
February 2, 2017: Viruses
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