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https://www.readbyqxmd.com/read/28445620/smad4-inhibits-vegf-a-and-vegf-c-expressions-via-enhancing-smad3-phosphorylation-in-colon-cancer
#1
Xuemei Li, Xinlei Li, Xiaohong Lv, Jianbing Xiao, Baoquan Liu, Yafang Zhang
Smad4 is a critical factor in the TGF-β pathway and is involved in tumor progression and metastasis, but the role of Smad4 in colon cancer cells is unclear. The aim of this study is to explore the effect and the underlying mechanism of Smad4 on the growth, migration and apoptosis of colon cancer cells as well as vascular endothelial growth factor (VEGF)-A and VEGF-C secreted by these cells. In this study, we showed that Smad4, VEGF-A and VEGF-C are independent prognostic factors of colon cancer, and Smad4 expression was negatively correlated with VEGF-A and -C in samples...
April 26, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28445592/polo-like-kinase-1-is-a-proviral-host-factor-for-hepatitis-b-virus-replication
#2
Ahmed M Diab, Adrien Foca, Floriane Fusil, Thomas Lahlali, Pascal Jalaguier, Fouzia Amirache, Lia N'Guyen, Nathalie Isorce, François-Loïc Cosset, Fabien Zoulim, Ourania M Andrisani, David Durantel
Chronic Hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for CHB and HCC are perfectible. Herein, we identified cellular Serine/Threonine Polo-like-kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy. To this end, we employed physiologically relevant HBV infection models of Primary Human Hepatocytes (PHH) and differentiated HepaRG cells, in conjunction with pharmacologic PLK1 inhibitors, siRNA-mediated knockdown, and overexpression of constitutively active PLK1 (PLK1(CA) )...
April 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#3
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28445362/effect-of-human-fat-graft-on-breast-cancer-metastasis-in-a-murine-model
#4
Roberto Moltó-García, Virina González-Alonso, María Eloísa Villaverde-Doménech, Edurne Novella-Maestre
BACKGROUND: Isolated adipose stem cells have been reported to encourage migration and early metastasis of breast cancer. Mimicking a surgical situation, the authors developed a human breast cancer model to evaluate in vivo whether human adipose tissue promotes tumor growth and invasion. METHODS: Human adipose tissue was obtained from four patients. The MDA-MB-468 cell line was cultured with a lentiviral vector encoding a puromycin resistance gene and mCherry fluorescent protein...
May 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28442754/vector-competence-and-transovarial-transmission-of-two-aedes-aegypti-strains-to-zika-virus
#5
Chun-Xiao Li, Xiao-Xia Guo, Yong-Qiang Deng, Dan Xing, Ai-Juan Sun, Qin-Mei Liu, Qun Wu, Yan-de Dong, Ying-Mei Zhang, Heng-Duan Zhang, Wu-Chun Cao, Cheng-Feng Qin, Tong-Yan Zhao
Zika virus (ZIKV) has become a serious threat to global health since the outbreak in Brazil in 2015. Additional Chinese cases have continuously been reported since the first case of laboratory-confirmed ZIKV infection in China on 6 February 2016. Aedes aegypti is the most important vector for ZIKV. This study shows that two strains from China exhibit high levels of midgut infection and highly disseminated infection of salivary glands and ovaries. Both strains can transmit ZIKV to infant mice bitten by infectious mosquitoes...
April 26, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28442624/unphosphorylated-isgf3-drives-constitutive-expression-of-interferon-stimulated-genes-to-protect-against-viral-infections
#6
Wenshi Wang, Yuebang Yin, Lei Xu, Junhong Su, Fen Huang, Yijin Wang, Patrick P C Boor, Kan Chen, Wenhui Wang, Wanlu Cao, Xinying Zhou, Pengyu Liu, Luc J W van der Laan, Jaap Kwekkeboom, Maikel P Peppelenbosch, Qiuwei Pan
Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28442607/n-methyl-d-aspartate-nmda-receptor-blockade-prevents-neuronal-death-induced-by-zika-virus-infection
#7
Vivian V Costa, Juliana L Del Sarto, Rebeca F Rocha, Flavia R Silva, Juliana G Doria, Isabella G Olmo, Rafael E Marques, Celso M Queiroz-Junior, Giselle Foureaux, Julia Maria S Araújo, Allysson Cramer, Ana Luíza C V Real, Lucas S Ribeiro, Silvia I Sardi, Anderson J Ferreira, Fabiana S Machado, Antônio C de Oliveira, Antônio L Teixeira, Helder I Nakaya, Danielle G Souza, Fabiola M Ribeiro, Mauro M Teixeira
Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442605/the-toll-like-receptor-4-antagonist-eritoran-protects-mice-from-lethal-filovirus-challenge
#8
Patrick Younan, Palaniappan Ramanathan, Jessica Graber, Fabian Gusovsky, Alexander Bukreyev
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa, which has seen intermittent reemergence since it was officially declared over in February of 2016, has demonstrated the need for the rapid development of therapeutic intervention strategies. Indirect evidence has suggested that the EBOV infection shares several commonalities associated with the onset of bacterial sepsis, including the development of a "cytokine storm." Eritoran, a Toll-like receptor 4 (TLR4) antagonist, was previously shown to result in protection of mice against lethal influenza virus infection...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442482/a-bag3-coding-variant-in-mice-determines-susceptibility-to-ischemic-limb-muscle-myopathy-by-directing-autophagy
#9
Joseph M McClung, Timothy J McCord, Terence E Ryan, Cameron A Schmidt, Thomas D Green, Kevin W Southerland, Jessica L Reinardy, Sarah B Mueller, Talaignair N Venkatraman, Christopher D Lascola, Sehoon Keum, Douglas A Marchuk, Espen E Spangenburg, Ayotunde O Dokun, Brian H Annex, Christopher D Kontos
Background -Critical limb ischemia (CLI) is a manifestation of peripheral artery disease (PAD) that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered two overlapping quantitative trait loci (QTL) in mice, Lsq-1 and Civq-1, that affected limb muscle survival and stroke volume following femoral artery or middle cerebral artery ligation, respectively. Here we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hindlimb ischemia (HLI)...
April 25, 2017: Circulation
https://www.readbyqxmd.com/read/28442428/rapamycin-modulation-of-p70-s6-kinase-signaling-inhibits-rift-valley-fever-virus-pathogenesis
#10
Todd M Bell, Virginia Espina, Svetlana Senina, Caitlin Woodson, Ashwini Brahms, Brian Carey, Shih-Chao Lin, Lindsay Lundberg, Chelsea Pinkham, Alan Baer, Claudius Mueller, Elizabeth A Chlipala, Faye Sharman, Cynthia de la Fuente, Lance Liotta, Kylene Kehn-Hall
Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA)...
April 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#11
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28439019/type-i-interferons-induced-by-endogenous-or-exogenous-viral-infections-promote-metastasis-and-relapse-of-leishmaniasis
#12
Matteo Rossi, Patrik Castiglioni, Mary-Anne Hartley, Remzi Onur Eren, Florence Prével, Chantal Desponds, Daniel T Utzschneider, Dietmar Zehn, Maria G Cusi, F Matthew Kuhlmann, Stephen M Beverley, Catherine Ronet, Nicolas Fasel
The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis (LgyLRV1(-) ) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing (LgyLRV1(+) ) infection phenotype...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438967/immune-induced-fever-is-dependent-on-local-but-not-generalized-prostaglandin-e2-synthesis-in-the-brain
#13
Anna Eskilsson, Takashi Matsuwaki, Kiseko Shionoya, Elahe Mirrasekhian, Joanna Zajdel, Markus Schwaninger, David Engblom, Anders Blomqvist
Fever occurs upon binding of prostaglandin E2 (PGE2) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE2 has not been clearly determined. Here, using mice of both sexes, we examined the role of local vs generalized PGE2 production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreER(T2) under the Slco1c1 promoter, PGE2 levels in the cerebrospinal fluid were only weakly related to the magnitude of the febrile response, whereas the PGE2 synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever...
April 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28438857/reduced-competitive-repopulation-capacity-of-multipotential-hematopoietic-stem-cells-in-the-bone-marrow-of-friend-virus-infected-fv2-resistant-mice
#14
Michael W Epperly, Xichen Zhang, Renee Fisher, Wen Hou, Darcy Franicola, Donna Shields, Michael Quickel, Pamela Hankey-Giblin, Hong Wang, Joel S Greenberger
BACKGROUND/AIM: The polycythemia form of Friend leukemia virus (FVP) causes splenomegaly and lethal erythroleukemia in Fv-2(s)-susceptible mouse strains. We sought to determine whether the hematopoietic stem cell (HSC) pool was expanded in Fv-2(r)-resistant mice. MATERIALS AND METHODS: The 120-day bone marrow transplantation competitive repopulation assay was used to determine whether FVP-infected Fv-2(r) C57BL/6 mice demonstrated expansion of the HSC pool compared to the pool of committed hematopoietic progenitor cells in the same marrow assayed in vitro...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28437636/chimeric-flock-house-virus-protein-a-with-endoplasmic-reticulum-targeting-domain-enhances-viral-replication-and-virus-like-particle-trans-encapsidation-in-plants
#15
Yiyang Zhou, Christopher M Kearney
Flock House virus (FHV) RNA can be trans-encapsidated, entirely in planta, by tobacco mosaic virus coat protein to form virus-like particles (VLPs). Vaccination with these VLPs leads to strong antigen expression in mice and immune-activation. We hypothesize that creating an additional cellular site for replication and/or trans-encapsidation might significantly improve the final output of trans-encapsidated product. FHV protein A was engineered to target the endoplasmic reticulum (ER) via a heterologous tobacco etch virus ER-targeting domain, and was expressed in cis or in trans relative to the replicating FHV RNA1...
April 21, 2017: Virology
https://www.readbyqxmd.com/read/28436958/local-clearance-of-senescent-cells-attenuates-the-development-of-post-traumatic-osteoarthritis-and-creates-a-pro-regenerative-environment
#16
Ok Hee Jeon, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod, Alain P Vasserot, Jae Wook Chung, Do Hun Kim, Yan Poon, Nathaniel David, Darren J Baker, Jan M van Deursen, Judith Campisi, Jennifer H Elisseeff
Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery, yet their role in disease pathogenesis is unknown...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28436740/major-immunodominant-region-of-hepatitis-b-virus-core-antigen-as-a-delivery-vector-to-improve-the-immunogenicity-of-the-fusion-antigen-rop2-sag1-multiepitope-from-toxoplasma-gondii-in-mice
#17
Wenhuan Wang, Fangfang Feng, Jinhui Lv, Zixin Xie, Jun Chen, Lifang Zhang, Wenshu Li
To prepare the dominant multiepitope fusion antigen ROP2-SAG1 (RSmultiepitope) from Toxoplasma gondii in a prokaryotic system, the major immunodominant region (MIR) of the human hepatitis B virus core antigen (HBcAg(MIR)) was used as a delivery vector. The gene encoding the RSmultiepitope was inserted into HBcAg(MIR), and rHBcAg(MIR)-RSmultiepitope was prepared, purified, and administered to BALB/c mice through intradermal injection. An indirect enzyme-linked immunosorbent assay analysis based on a multiepitope peptide facilitated the specific differentiation of sera obtained from mice immunized with the rHBcAg(MIR)-RSmultiepitope protein, and high titers (greater than 1:6,400) of specific anti-RSmultiepitope antibodies were obtained...
April 24, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28436459/identification-of-pro-inflammatory-cd205-macrophages-in-livers-of-hepatitis-b-virus-transgenic-mice-and-patients-with-chronic-hepatitis-b
#18
Liang Yong, Minmin Li, Yimin Gao, Yanru Deng, Wenbin Liu, Dake Huang, Cuiping Ren, Miao Liu, Jijia Shen, Xin Hou
Hepatic macrophages play a central role in disease pathogenesis during hepatitis B virus (HBV) infection. Our previous study found that CD205(+) macrophages in the liver of hepatitis B surface antigen transgenic (HBs-Tg) mice increased significantly compared with those in wild-type mice, and these increased CD205(+) macrophages were involved in CpG-oligodeoxynucleotide-induced liver injury in HBs-Tg mice. Here, we analysed the phenotype and function of CD205(+) macrophages derived from the liver of HBs-Tg mice and patients with chronic hepatitis B (CHB)...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435679/targeting-the-pro-inflammatory-factor-ccl2-mcp-1-with-bindarit-for-influenza-a-h7n9-treatment
#19
Stefan Wolf, Scott Johnson, Olivia Perwitasari, Suresh Mahalingam, Ralph A Tripp
Influenza A viruses are important human and animal pathogens. Seasonal influenza viruses cause infections every year, and occasionally zoonotic viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. Three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus were reported in 2013, and there have been several cases reported across South East Asia, and recently in North America. Most patients experience severe respiratory illness, with mortality rates approaching 40%...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28434866/lentiviral-vectors-with-cellular-promoters-correct-anemia-and-lethal-bone-marrow-failure-in-a-mouse-model-for-diamond-blackfan-anemia
#20
Shubhranshu Debnath, Pekka Jaako, Kavitha Siva, Michael Rothe, Jun Chen, Maria Dahl, H Bobby Gaspar, Johan Flygare, Axel Schambach, Stefan Karlsson
Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with Diamond-Blackfan anemia have mutations in a gene encoding ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral vector with the spleen focus-forming virus promoter, we demonstrated that the Diamond-Blackfan anemia phenotype can be successfully treated in Rps19-deficient mice. In our present study, we assessed the efficacy of a clinically relevant promoter, the human elongation factor 1α short promoter, with or without the locus control region of the β-globin gene for treatment of RPS19-deficient Diamond-Blackfan anemia...
April 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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