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Yuhan Zhao, Lihua Wu, Xuetian Yue, Cen Zhang, Jianming Wang, Jun Li, Xiaohui Sun, Yiming Zhu, Zhaohui Feng, Wenwei Hu
Tumor suppressor p53 prevents early death due to cancer development. However, the role of p53 in aging process and longevity has not been well-established. In humans, single nucleotide polymorphism (SNP) with either arginine (R72) or proline (P72) at codon 72 influences p53 activity; the P72 allele has a weaker p53 activity and function in tumor suppression. Here, employing a mouse model with knock-in of human TP53 gene carrying codon 72 SNP, we found that despite increased cancer risk, P72 mice that escape tumor development display a longer lifespan than R72 mice...
March 20, 2018: ELife
Qiaoxian Huang, Shengke Li, Yuan-Fu Ding, Hang Yin, Lian-Hui Wang, Ruibing Wang
Due to its outstanding capability to facilitate DNA condensation, transportation and endosomal escape, polyethylenimine (PEI) has been frequently studied for gene delivery. However, its molecular weight (M.W.) dependent transfection efficiency and cytotoxicity has severely limited its clinical application. To resolve this dilemma, a supramolecular strategy was developed for the first time, in which PEI with large M.W. (branched, 25 kDa) that has a satisfactory transfection efficiency, yet high non-specific cytotoxicity for gene delivery was wrapped with macrocyclic cucurbit[7]uril (CB[7])...
March 20, 2018: Biomaterials Science
Jeffrey R Powell
Although numerous viruses are transmitted by mosquitoes, four have caused the most human suffering over the centuries and continuing today. These are the viruses causing yellow fever, dengue, chikungunya, and Zika fevers. Africa is clearly the ancestral home of yellow fever, chikungunya, and Zika viruses and likely the dengue virus. Several species of mosquitoes, primarily in the genus Aedes , have been transmitting these viruses and their direct ancestors among African primates for millennia allowing for coadaptation among viruses, mosquitoes, and primates...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Y Dessaux, D Faure
Agrobacterium populations live in different habitats (bare soil, rhizosphere, host plants), and hence face different environmental constraints. They have evolved the capacity to exploit diverse resources and to escape plant defense and competition from other microbiota. By modifying the genome of their host, Agrobacterium populations exhibit the remarkable ability to construct and exploit the ecological niche of the plant tumors that they incite. This niche is characterized by the accumulation of specific, low molecular weight compounds termed opines that play a critical role in Agrobacterium 's lifestyle...
March 20, 2018: Current Topics in Microbiology and Immunology
M Di Giulio, V Di Valerio, D Bosco, E Marsich, A Cataldi, L Cellini, S Sancilio
The molecular mechanisms leading to Streptococcus mitis capability of entering oral cells were investigated in a co-culture of S. mitis and Human Gingival Fibroblasts (HGFs) in the presence of saliva. An innovative colloidal solution based on silver nanoparticles (Chitlac-nAg), a promising device for daily oral care, was added to the experimental system in order to study the effects of silver on the bacterial overgrowth and ability to enter non-phagocytic eukaryotic cells. The entry of bacteria into the eukaryotic cells is mediated by a signalling pathway involving FAK, integrin β1, and the two cytoskeleton proteins vinculin and F-actin, and down-regulated by the presence of saliva both at 3 and 48 h of culture, whereas Chitlac-n Ag exposure seems to influence, by incrementing it, the number of bacteria entering the fibroblasts only at 48 h...
March 19, 2018: Journal of Materials Science. Materials in Medicine
Désirée van der Heijde, Atul Deodhar, Oliver FitzGerald, Roy Fleischmann, Dafna Gladman, Alice B Gottlieb, Bengt Hoepken, Lars Bauer, Oscar Irvin-Sellers, Majed Khraishi, Luke Peterson, Anthony Turkiewicz, Jürgen Wollenhaupt, Philip J Mease
Objective: To report the efficacy, patient-reported, radiographic and safety outcomes of 4 years' certolizumab pegol (CZP) treatment in patients with psoriatic arthritis (PsA). Methods: RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to Week 24, dose-blind to Week 48 and open-label (OL) to Week 216. Patients were randomised 1:1:1 to either placebo or CZP 200 mg every 2 weeks (Q2W) or 400 mg every 4 weeks (Q4W) (following 400 mg at Weeks 0/2/4)...
2018: RMD Open
Hongyoon Choi, Kwon Joong Na
Although metabolic modulation in the tumor microenvironment (TME) is one of the key mechanisms of cancer immune escape, there is a lack of understanding of the comprehensive immune landscape of the TME and its association with tumor metabolism based on clinical evidence. We aimed to investigate the relationship between the immune landscape in the TME and tumor glucose metabolism in lung adenocarcinoma. Methods: Using RNA sequencing and image data, we developed a transcriptome-based tumor metabolism estimation model...
2018: Theranostics
Jiao Ji, Yan Yu, Zhi-Ling Li, Ming-Yuan Chen, Rong Deng, Xiang Huang, Guang-Feng Wang, Meng-Xia Zhang, Qi Yang, Senthilkumar Ravichandran, Gong-Kan Feng, Xue-Lian Xu, Chen-Lu Yang, Miao-Zhen Qiu, Lin Jiao, Dajun Yang, Xiao-Feng Zhu
Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties...
2018: Theranostics
Qingcui Li, Chengliang Dai, Rui Xue, Peigang Wang, Lin Chen, Yijie Han, Ulrike Erben, Zhihai Qin
Myeloid-derived suppressor cells (MDSCs) often expand during cancer or chronic inflammation and dampen immune responses. However, mechanisms underlying their capacity to escape intrinsic apoptosis in the inflammatory environment are still largely unknown. In this study, we investigated this in mouse tumor models with MDSC accumulation. Spontaneous rejection of tumors implanted into mice deficient for the small Ca2+ -binding protein S100A4 (S100A4-/- ) was accompanied by low numbers of peripheral MDSCs. This was independent of S100A4 expression on tumor cells...
2018: Frontiers in Immunology
Xiaoyong Chen, Shasha Liu, Mohsan Ullah Goraya, Mohamed Maarouf, Shile Huang, Ji-Long Chen
Influenza A viruses (IAVs) are contagious pathogens responsible for severe respiratory infection in humans and animals worldwide. Upon detection of IAV infection, host immune system aims to defend against and clear the viral infection. Innate immune system is comprised of physical barriers (mucus and collectins), various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, which provide first line of defense against IAV infection. The adaptive immunity is mediated by B cells and T cells, characterized with antigen-specific memory cells, capturing and neutralizing the pathogen...
2018: Frontiers in Immunology
Zheng Liu, Maro J Kariya, Christopher D Chute, Amy K Pribadi, Sarah G Leinwand, Ada Tong, Kevin P Curran, Neelanjan Bose, Frank C Schroeder, Jagan Srinivasan, Sreekanth H Chalasani
Animals respond to predators by altering their behavior and physiological states, but the underlying signaling mechanisms are poorly understood. Using the interactions between Caenorhabditis elegans and its predator, Pristionchus pacificus, we show that neuronal perception by C. elegans of a predator-specific molecular signature induces instantaneous escape behavior and a prolonged reduction in oviposition. Chemical analysis revealed this predator-specific signature to consist of a class of sulfolipids, produced by a biochemical pathway required for developing predacious behavior and specifically induced by starvation...
March 19, 2018: Nature Communications
Brittany A Baker, Debra L Hickman
Selection of an appropriate method of euthanasia involves balancing the wellbeing of the animal during the procedure with the intended use of the animal after death and the physical and psychologic safety of the observer or operator. The recommended practices for anesthesia as compared with euthanasia are very disparate, despite the fact that all chemical methods of euthanasia are anesthetic overdoses. To explain this disparity, this study sought to determine whether perception bias is inherent in the discussion of euthanasia compared with anesthesia...
March 1, 2018: Journal of the American Association for Laboratory Animal Science: JAALAS
Ferdinand Roesch, Molly OhAinle, Michael Emerman
The InterFeron Induced TransMembrane (IFITM) proteins are interferon stimulated genes that restrict many viruses, including HIV-1. SAMHD1 is another restriction factor blocking replication of HIV-1 and other viruses. Some lentiviruses evolved Vpx/Vpr proteins to degrade SAMHD1. However, this viral antagonism can be perturbed by host mechanisms: a recent study showed that in interferon (IFN) treated THP1 cells, Vpx is unable to degrade SAMHD1. In the present work, we designed an Interferon Stimulated Genes (ISGs)-targeted CRISPR knockout screen in order to identify ISGs regulating this phenotype...
March 20, 2018: Retrovirology
Steven Koprowski, Michael J VanLue, Michael E McCormick
Stress velopharyngeal incompetence (VPI) is a challenging clinical entity that can be managed by a variety of surgical and nonsurgical approaches. We describe the case of a clarinetist who presented with nasal air escape while playing. She had successful improvement in her symptoms after targeted injection of a hyaluronic acid compound to her posterior pharyngeal wall. Our objective is to describe the safety and efficacy of this technique, to emphasize the multidisciplinary management of patients with stress VPI, and to review the importance of both nasopharyngoscopy and videofluoroscopy in their evaluation...
April 2018: Cleft Palate-craniofacial Journal
P Leon Brown, Panos Zanos, Leiming Wang, Greg I Elmer, Todd D Gould, Paul D Shepard
Background: The volatile anesthetic isoflurane may exert a rapid and long-lasting antidepressant effect in patients with medication-resistant depression. The mechanism underlying the putative therapeutic actions of the anesthetic have been attributed to its ability to elicit cortical burst suppression, a distinct EEG pattern with features resembling the characteristic changes that occur following electroconvulsive therapy. It is currently unknown whether the antidepressant actions of isoflurane are shared by anesthetics that do not elicit cortical burst suppression...
March 15, 2018: International Journal of Neuropsychopharmacology
Brian E Powers, Nicholas A Santiago, Barbara J Strupp
The Ts65Dn mouse model of Down syndrome recapitulates the hallmark areas of dysfunction that characterize the human disorder, including impaired performance in tasks designed to tap hippocampus-dependent learning and memory. Unfortunately, performance in the water maze tasks most commonly used for this purpose can be affected by behavioral and/or physiological abnormalities characteristic of Ts65Dn mice (e.g., thigmotaxis, susceptibility to hypothermia, stress reactivity), which complicates interpretation of impaired performance...
February 2018: Behavioral Neuroscience
Jing Huang, Peng Guo, Marsha A Moses
The acquisition of the angiogenic phenotype is an essential component of the escape from tumor dormancy. Although several classic in vitro assays (e.g., proliferation, migration, and others) and in vivo models have been developed to investigate and characterize angiogenic and non-angiogenic cell phenotypes, these methods are time and labor intensive, and often require expensive reagents and instruments, as well as significant expertise. In a recent study, we used a novel quantitative phase imaging (QPI) technique to conduct time-lapse and labeling-free characterizations of angiogenic and non-angiogenic human osteosarcoma KHOS cells...
February 16, 2018: Journal of Visualized Experiments: JoVE
Basma R Damiri, Hisham N Sandouka, Eiad H Janini, Omar N Yaish
BACKGROUND: Substance use has been an increasing problem in the occupied Palestinian territory for decades. The aim of this study was to describe the practice, knowledge, and attitudes associated with substance use by university students in the occupied Palestinian territory. METHODS: This cross-sectional study was done in 2015. Male and female students from four main public universities in the West Bank were recruited to fill out a self-administered questionnaire...
February 21, 2018: Lancet
Scott Ledger, Annett Howe, Stuart Turville, Anupriya Aggarwal, Borislav Savkovic, Andrew Ong, Orit Wolstein, Maureen Boyd, Michelle Millington, Paul R Gorry, John M Murray, Geoff Symonds
The gene therapeutic Cal-1 comprises the anti-HIV agents: sh5, a short hairpin RNA to CCR5 that down-regulates CCR5 expression; and maC46 (C46), a peptide that inhibits viral fusion with the cell membrane. These constructs were assessed for inhibition of viral replication and selective cell expansion in a number of settings. METHODS: HIV replication, selective outgrowth and cell surface viral binding were analysed with a single cycle infection assay of 6 pseudotyped HIV strains and a static and longitudinal passaging of MOLT4/CCR5 cells with HIV...
February 10, 2018: Journal of Gene Medicine
Yu-Ru Guo, Hsiu-Chuan Lee, Yun-Chun Lo, Shao-Chuan Yu, Shih-Yi Huang
Nutritional deficit of n-3 polyunsaturated fatty acids (PUFAs) is closely related to cognitive impairment and depression in later life. Cognitive impairment and depression lead to comorbidities, such as metabolic syndrome, in elderly people. The aim of this study is to evaluate the effects of dietary n-3 PUFAs on cognition and depressive-like behavior in an accelerated senescence rat model with prediabetic status. Rats were cotreated with d-gal and sucrose solution for 7 months and then fed fish-oil- or flaxseed-oil-rich diets for 3 months...
March 19, 2018: Food & Function
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