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https://www.readbyqxmd.com/read/29673125/major-pathologic-response-and-rad51-predict-survival-in-lung-cancer-patients-receiving-neoadjuvant-chemotherapy
#1
Apar Pataer, Ruping Shao, Arlene M Correa, Carmen Behrens, Jack A Roth, Ara A Vaporciyan, Ignacio I Wistuba, Stephen G Swisher
In a previous study, we determined that major pathologic response (MPR) as indicated by the percentage of residual viable tumor cells predicted overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. In this study, we assessed whether two genes and five protein biomarkers could predict MPR and OS in 98 patients with NSCLC receiving neoadjuvant chemotherapy. We collected formalin-fixed, paraffin-embedded specimens of resected NSCLC tumors from 98 patients treated with neoadjuvant chemotherapy...
April 19, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29672716/mir-122-does-not-impact-recognition-of-the-hcv-genome-by-innate-sensors-of-rna-but-rather-protects-the-5-end-from-the-cellular-pyrophosphatases-dom3z-and-dusp11
#2
Yalena Amador-Cañizares, Annie Bernier, Joyce A Wilson, Selena M Sagan
Hepatitis C virus (HCV) recruits two molecules of the liver-specific microRNA-122 (miR-122) to the 5' end of its genome. This interaction promotes viral RNA accumulation, but the precise mechanism(s) remain incompletely understood. Previous studies suggest that miR-122 is able to protect the HCV genome from 5' exonucleases (Xrn1/2), but this protection is not sufficient to account for the effect of miR-122 on HCV RNA accumulation. Thus, we investigated whether miR-122 was also able to protect the viral genome from innate sensors of RNA or cellular pyrophosphatases...
April 17, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29658572/pkr-inhibition-mediates-endotoxin-tolerance-in-macrophages-through-inactivation-of-pi3k-akt-signaling
#3
Hailin Xu, Juan Chen, Xiang Si, Minying Chen, Fei Pei, Chunfang Qiu, Jianfeng Wu, Xiangdong Guan
Following long‑term exposure to endotoxins, macrophages enter an immunosuppressive state that renders them unable respond to subsequent exposures to endotoxin, a phenomenon that is termed 'endotoxin tolerance'. Endotoxin tolerance increases the risks of secondary infection and mortality in patients with sepsis. In endotoxin‑tolerant macrophages, the mixed variation of gene transcription is referred to as macrophage reprogramming. The mechanisms underlying macrophage reprogramming remain unclear at present...
April 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29658464/-modulation-by-sumo-of-pkr-activation-and-stability
#4
Faten El Asmi, Ghizlane Maarifi, Mohamed Ali Maroui, Laurent Dianoux, Mounira K Chelbi-Alix
No abstract text is available yet for this article.
April 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29625900/adar1-and-pkr-interferon-stimulated-genes-with-clashing-effects-on-hiv-1-replication
#5
REVIEW
Roman Radetskyy, Aïcha Daher, Anne Gatignol
The induction of hundreds of Interferon Stimulated Genes (ISGs) subsequent to virus infection generates an antiviral state that functions to restrict virus growth at multiple steps of their replication cycles. In the context of Human Immunodeficiency Virus-1 (HIV-1), ISGs also possess antiviral functions, but some ISGs show proapoptotic or proviral activity. One of the most studied ISGs, the RNA activated Protein Kinase (PKR), shuts down the viral protein synthesis upon activation. HIV-1 has evolved to evade its inhibition by PKR through viral and cellular mechanisms...
March 26, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29625403/inhibition-of-vaccinia-virus-replication-by-nitazoxanide
#6
Sarah E Hickson, Daciana Margineantu, David M Hockenbery, Julian A Simon, Adam P Geballe
Nitazoxanide (NTZ) is an FDA-approved anti-protozoal drug that inhibits several bacteria and viruses as well. However, its effect on poxviruses is unknown. Therefore, we investigated the impact of NTZ on vaccinia virus (VACV). We found that NTZ inhibits VACV production with an EC50 of ~2 μM, a potency comparable to that reported for several other viruses. The inhibitory block occurs early during the viral life cycle, prior to viral DNA replication. The mechanism of viral inhibition is likely not due to activation of intracellular innate immune pathways, such as protein kinase R (PKR) or interferon signaling, contrary to what has been suggested to mediate the effects of NTZ against some other viruses...
April 3, 2018: Virology
https://www.readbyqxmd.com/read/29621736/antiviral-activity-of-porcine-interferon-delta-8-against-foot-and-mouth-disease-virus-in-vitro
#7
Shi-Fang Li, Jun-Jun Shao, Fu-Rong Zhao, Mei-Jiao Gong, Yin-Li Xie, Hui-Yun Chang, Yong-Guang Zhang
Foot-and-mouth disease (FMD) is one of the most devastating diseases affecting livestock. Since vaccines fail to provide protection until seven days post-vaccination, the application of anti-viral molecules is imperative for suppressing the spread of FMDV prior to development of an adaptive immune response. Interferons (IFNs) are effective for the host to fight FMDV infections; however, a novel type I IFNs, interferon delta (IFN-δ), has not been investigated for their antiviral effects against this virus. Thus, this study investigated FMDV infection, upon pre- and post-treatment with PoIFN-δ8...
April 2, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29602068/ectromelia-virus-lacking-the-e3l-ortholog-is-replication-defective-and-nonpathogenic-but-does-induce-protective-immunity-in-a-mouse-strain-susceptible-to-lethal-mousepox
#8
Tiffany R Frey, Katherine S Forsyth, Maura M Sheehan, Brian C De Haven, Julia G Pevarnik, Erin S Hand, Marie C Pizzorno, Laurence C Eisenlohr, Adam R Hersperger
All known orthopoxviruses, including ectromelia virus (ECTV), contain a gene in the E3L family. The protein product of this gene, E3, is a double-stranded RNA-binding protein. It can impact host range and is used by orthopoxviruses to combat cellular defense pathways, such as PKR and RNase L. In this work, we constructed an ECTV mutant with a targeted disruption of the E3L open reading frame (ECTVΔE3L). Infection with this virus resulted in an abortive replication cycle in all cell lines tested. We detected limited transcription of late genes but no significant translation of these mRNAs...
March 27, 2018: Virology
https://www.readbyqxmd.com/read/29601799/the-three-branches-of-the-unfolded-protein-response-exhibit-differential-significance-in-breast-cancer-growth-and-stemness
#9
Chuang Li, Qianqian Fan, Hongyang Quan, Meng Nie, Yunping Luo, Lin Wang
The unfolded protein response (UPR) is widely activated in cancers. The mammalian UPR encompasses three signaling branches, namely inositol-requiring enzyme-1α (IRE1α), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6α (ATF6α). The functional significance of each branch in tumorigenesis is incompletely understood, especially in cancer stem cells (CSCs). Here, we report that inhibition and silencing of the three UPR sensors has differential effects on breast cancer growth and the CSC population...
March 27, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29563296/new-threats-of-h7n9-influenza-virus-the-spread-and-evolution-of-highly-and-low-pathogenic-variants-with-high-genomic-diversity-in-wave-five
#10
Chuansong Quan, Weifeng Shi, Yang Yang, Yongchun Yang, Xiaoqing Liu, Wen Xu, Hong Li, Juan Li, Qianli Wang, Zhou Tong, Gary Wong, Cheng Zhang, Sufang Ma, Zhenghai Ma, Guanghua Fu, Zewu Zhang, Yu Huang, Houhui Song, Liuqing Yang, William J Liu, Yingxia Liu, Wenjun Liu, George F Gao, Yuhai Bi
H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in Wave Five; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny and genetic evolution of 240 H7N9 viruses in Wave Five, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis displayed the newly-emerging highly pathogenic (HP) and low pathogenic (LP) H7N9 viruses were co-circulating, causing human and poultry infections across China...
March 21, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29562775/restoring-in-vivo-like-membrane-lipidomics-promotes-exosome-trophic-behavior-from-human-placental-mesenchymal-stromal-stem-cells
#11
Claudia Cavallini, Chiara Zannini, Elena Olivi, Riccardo Tassinari, Valentina Taglioli, Martina Rossi, Paola Poggi, Alexandros Chatgilialoglu, Giuliana Simonazzi, Francesco Alviano, Laura Bonsi, Carlo Ventura
Human mesenchymal stem cells (hMSCs) are an effective tool in regenerative medicine notably for their intrinsic plentiful paracrine activity rather than differentiating properties. The hMSC secretome includes a wide spectrum of regulatory and trophic factors, encompassing several naked molecules as well as different kinds of extracellular vesicles (EVs). Among EVs, exosomes represent an intriguing population, able to shuttle proteins, transcription factors, and genetic materials, with a relevant role in cell-to-cell communication, modulating biological responses in recipient cells...
January 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29561199/dietary-supplement-use-among-students-of-pharmacy-colleges-in-the-city-of-karachi-pakistan-prevalence-opinions-and-attitudes
#12
Atta Abbas Naqvi, Rizwan Ahmad, Fatima Zehra, Raafia Yousuf, Bharti Kachela, Muhammad Nehal Nadir
This study was conducted among pharmacy students in Karachi, Pakistan, to document prevalence, opinions and their attitudes toward dietary supplement (DS) use. A cross-sectional study was conducted for a period of four months. The study used a specially formulated dietary supplement questionnaire (DSQ). The prevalence of DS use was reported at 48.2%: 51% in males and 47.3% in females. Physician recommendation was cited by majority of students as reason for DS use (n = 153, 25%). Most of the students used multivitamins (n = 315, 51...
March 21, 2018: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/29541018/perk-pathway-activation-promotes-intracerebral-hemorrhage-induced-secondary-brain-injury-by-inducing-neuronal-apoptosis-both-in-vivo-and-in-vitro
#13
Chengjie Meng, Juyi Zhang, Baoqi Dang, Haiying Li, Haitao Shen, Xiang Li, Zhong Wang
The protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) signaling pathway was reported to exert an important role in neuronal apoptosis. The present study was designed to investigate the roles of the PERK signaling pathway in the secondary brain injury (SBI) induced by intracerebral hemorrhage (ICH) and its potential mechanisms. Sprague-Dawley rats were used to establish ICH models by injecting autologous blood (100 μl), and cultured primary rat cortical neurons were exposed to oxyhemoglobin (10 μM) to mimic ICH in vitro ...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29540678/inhibition-of-sec61-dependent-translocation-by-mycolactone-uncouples-the-integrated-stress-response-from-er-stress-driving-cytotoxicity-via-translational-activation-of-atf4
#14
Joy Ogbechi, Belinda S Hall, Thomas Sbarrato, Jack Taunton, Anne E Willis, Ronald C Wek, Rachel E Simmonds
Mycolactone is the exotoxin virulence factor of Mycobacterium ulcerans that causes the neglected tropical disease Buruli ulcer. We recently showed it to be a broad spectrum inhibitor of Sec61-dependent co-translational translocation of proteins into the endoplasmic reticulum (ER). An outstanding question is the molecular pathway linking this to its known cytotoxicity. We have now used translational profiling to better understand the reprogramming that occurs in cells exposed to mycolactone. Gene ontology identified enrichment in genes involved in cellular response to stress, and apoptosis signalling among those showing enhanced translation...
March 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29540594/exacerbated-apoptosis-of-cells-infected-with-infectious-bursal-disease-virus-ibdv-upon-exposure-to-interferon-alpha-ifn-%C3%AE
#15
Liliana L Cubas-Gaona, Elisabet Diaz-Beneitez, Marina Ciscar, José F Rodríguez, Dolores Rodríguez
Infectious bursal disease virus (IBDV) belongs to the Birnaviridae family and is the etiological agent of a highly contagious and immunosuppressive disease (IBD) that affects domestic chickens ( Gallus gallus ). IBD or Gumboro disease leads to high morbidity and mortality of infected animals, and is responsible for major economic losses to the poultry industry world-wide. IBD is characterized by a massive loss of IgM-bearing B lymphocytes and the destruction of the bursa of Fabricius. The molecular bases of the IBDV pathogenicity are still poorly understood, nonetheless, an exacerbated cytokine immune response and B cell depletion due to apoptosis are considered main factors contributing to the severity of the disease...
March 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29537336/the-prokineticins-neuromodulators-and-mediators-of-inflammation-and-myeloid-cell-dependent-angiogenesis
#16
Lucia Negri, Napoleone Ferrara
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility...
April 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29530722/mutation-of-adjacent-cysteine-residues-in-the-nss-protein-of-rift-valley-fever-virus-results-in-loss-of-virulence-in-mice
#17
Gaby E R Monteiro, Petrus Jansen Van Vanuren, Paul J Wichgers Schreur, Lieza Odendaal, Sarah J Clift, Jeroen Kortekaas, Janusz T Paweska
The NSs protein encoded by the S segment of Rift Valley fever virus (RVFV) is the major virulence factor, counteracting the host innate antiviral defence. It contains five highly conserved cysteine residues at positions 39, 40, 149, 178 and 194, which are thought to stabilize the tertiary and quaternary structure of the protein. Here, we report significant differences between clinical, virological, histopathological and host gene responses in BALB/c mice infected with wild-type RVFV (wtRVFV) or a genetic mutant having a double cysteine-to-serine substitution at residues 39 and 40 of the NSs protein (RVFV-C39S/C40S)...
March 9, 2018: Virus Research
https://www.readbyqxmd.com/read/29518158/inclusion-bodies-of-human-parainfluenza-virus-type-3-inhibit-antiviral-stress-granule-formation-by-shielding-viral-rnas
#18
Zhulong Hu, Yuang Wang, Qiaopeng Tang, Xiaodan Yang, Yali Qin, Mingzhou Chen
Viral invasion triggers the activation of the host antiviral response. Besides the innate immune response, stress granules (SGs) also act as an additional defense response to combat viral replication. However, many viruses have evolved various strategies to suppress SG formation to facilitate their own replication. Here, we show that viral mRNAs derived from human parainfluenza virus type 3 (HPIV3) infection induce SG formation in an eIF2α phosphorylation- and PKR-dependent manner in which viral mRNAs are sequestered and viral replication is inhibited independent of the interferon signaling pathway...
March 8, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29512253/palladium-catalyzed-enantioselective-c-h-olefination-of-diaryl-sulfoxides-via-parallel-kinetic-resolution-and-desymmetrization
#19
Yu-Chao Zhu, Yan Li, Bo-Chao Zhang, Feng-Xu Zhang, Yi-Nuo Yang, Xi-Sheng Wang
The first example of Pd(II)-catalyzed enantioselective C-H olefination with non-chiral or racemic sulfoxides as directing group has been developed. A variety of chiral diaryl sulfoxides with high enantioselectivity (up to >99%) have been synthesized through both desymmetrization and parallel kinetic resolution (PKR). This is the first report of transition-metal-catalyzed enantioselective C(sp2)-H functionalization via PKR, and it represents a novel strategy to construct sulfur-chiral center.
March 7, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29510614/expression-of-immunoproteasome-subunit-lmp7-in-breast-cancer-and-its-association-with-immune-related-markers
#20
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Purpose: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. Materials and Methods: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts...
February 26, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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