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https://www.readbyqxmd.com/read/29454302/aerobic-exercise-inhibits-obesity-induced-respiratory-phenotype
#1
Jefferson Comin Jonco Aquino-Junior, BreAnne MacKenzie, Ana Roberta Almeida-Oliveira, Ana Carolina Martins, Manoel Carneiro Oliveira-Junior, Auriléa Aparecida Britto, Fernanda Magalhaes Arantes-Costa, Nilsa Regina Damaceno-Rodrigues, Elia Garcia Caldini, Ana Paula Ligeiro de Oliveira, Dioze Guadagnini, Luiz Osorio Leiria, Djalma Rabelo Ricardo, Mario Jose Abdalla Saad, Rodolfo Paula Vieira
PURPOSE: Obesity results in decreased lung function and increased inflammation. Moderate aerobic exercise (AE) reduced lung inflammation and remodeling in a variety of respiratory disease models. Therefore, this study investigated whether AE can attenuate a diet-induced obesity respiratory phenotype; including airway hyper-responsiveness (AHR), remodeling and inflammation. METHODS: Sixty C57Bl/6 male mice were distributed into four groups: control lean (CL), exercise lean (EL), obese (O) and obese exercise (OE) groups (2 sets of 7 and 8 mice per group; n = 15)...
February 14, 2018: Cytokine
https://www.readbyqxmd.com/read/29454091/anlotinib-inhibits-angiogenesis-via-suppressing-the-activation-of-vegfr2-pdgfr%C3%AE-and-fgfr1
#2
Binyan Lin, Xiuming Song, Dawei Yang, Dongsheng Bai, Yuyuan Yao, Na Lu
Tumor cells recruit vascular endothelial cells and circulating endothelial progenitor cells to form new vessels to support their own growth and metastasis. VEGF, PDGF-BB and FGF-2 are three major pro-angiogenic factors and applied to promote angiogenesis. In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing assay, chamber directional migration assay and tube formation assay indicated that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation of capillary-like tubes in endothelial cells...
February 14, 2018: Gene
https://www.readbyqxmd.com/read/29454064/rna-based-micelles-a-novel-platform-for-chemotherapeutic-drug-loading-and-delivery
#3
Yi Shu, Hongran Yin, Mehdi Rajabi, Hui Li, Mario Vieweger, Sijin Guo, Dan Shu, Peixuan Guo
RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures for biotechnological and biomedical applications. In addition to current self-assembly strategies utilizing base pairing, motif piling and tertiary interactions, we reported for the first time to build RNA based micellar nanoconstruct with a cholesterol molecule conjugated onto one helical end of a branched pRNA three-way junction (3WJ) motif. The resulting amphiphilic RNA micelles consist of a hydrophilic RNA head and a covalently linked hydrophobic lipid tail that can spontaneously assemble in aqueous solution via hydrophobic interaction...
February 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29454023/interaction-between-hypothermia-and-delayed-mesenchymal-stem-cell-therapy-in-neonatal-hypoxic-ischemic-brain-injury
#4
Josephine Herz, Christian Köster, Barbara S Reinboth, Mark Dzietko, Wiebke Hansen, Hemmen Sabir, Cindy van Velthoven, Ivo Bendix, Ursula Felderhoff-Müser
Acute hypothermia treatment (HT) is the only clinically established intervention following neonatal hypoxic-ischemic brain injury. However, almost half of all cooled infants still die or suffer from long-lasting neurological impairments. Regenerative therapies, such as mesenchymal stem cells (MSC) appear promising as adjuvant therapy. In the present study, we hypothesized that HT combined with delayed MSC therapy results in augmented protection, improving long-term neurological outcome. Postnatal day 9 (P9) C57BL/6 mice were exposed to hypoxia-ischemia followed by 4 hours HT...
February 14, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29454008/temozolomide-affects-extracellular-vesicles-released-by-glioblastoma-cells
#5
Gwennan André-Grégoire, Nicolas Bidère, Julie Gavard
Glioblastoma multiforme (GBM) is the most aggressive primary tumour within the brain as well as the most common and lethal cerebral cancer, mainly because of treatment failure. Indeed, tumour recurrence is inevitable and fatal in a short period of time. Glioblastoma stem-like cells (GSCs) are thought to participate in tumour initiation, expansion, resistance to treatments, including to the alkylating chemotherapeutic agent temozolomide, and relapse. Here, we assessed whether extracellular vesicles (EVs) released by GSCs could disseminate factors involved in resistance mechanisms...
February 14, 2018: Biochimie
https://www.readbyqxmd.com/read/29453986/sterol-o-acyltransferase-1-deficiency-improves-defective-insulin-signaling-in-the-brains-of-mice-fed-a-high-fat-diet
#6
Ning Xu, Hao Meng, Tian-Yi Liu, Ying-Li Feng, Yuan Qi, Dong-Huan Zhang, Hong-Lei Wang
Insulin resistance induced by a high-fat diet (HFD) is related to metabolic diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore the role of SOAT1 in the hypothalamus. The results show that the WT mice exhibited a significant increase in body weight as well as hepatic histologic changes; they also had a lower glucose and insulin tolerance than the WT mice fed a normal diet...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453856/defective-rna-sensing-by-rig-i-in-severe-influenza-virus-infection
#7
Sofie Eg Jørgensen, Mette Christiansen, Laura Barrett Ryø, Hans Henrik Gad, Jakob Gjedsted, Peter Staeheli, Jacob Giehm Mikkelsen, Merete Storgaard, Rune Hartmann, Trine Hyrup Mogensen
Influenza virus infection causes worldwide seasonal epidemics. Although influenza usually is a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in antiviral responses during influenza. However, IFN regulatory factor (IRF)7 deficiency is so far the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 Swine Flu pandemic...
February 17, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29453815/the-use-of-chitosan-porous-3d-scaffolds-embedded-with-resolvin-d1-to-improve-in-vivo-bone-healing
#8
Daniela P Vasconcelos, Madalena Costa, Nuno Neves, José H Teixeira, Daniel M Vasconcelos, Susana G Santos, Artur P Águas, Mário A Barbosa, Judite N Barbosa
The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch+RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed...
February 17, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29453795/inflammatory-and-degenerative-phases-resulting-from-anterior-cruciate-rupture-in-a-non-invasive-murine-model-of-post-traumatic-osteoarthritis
#9
Sophie Jane Gilbert, Cleo Selina Bonnet, Paulina Stadnik, Victor Colin Duance, Deborah JaneMason, Emma Jane Blain
Joint injury is the predominant risk factor for post-traumatic osteoarthritis development (PTOA). Several non-invasive mouse models mimicking human PTOA investigate molecular mechanisms of disease development; none have characterised the inflammatory response to this acute traumatic injury. Our aim was to characterise the early inflammatory phase and later degenerative component in our in vivo non-invasive murine model of PTOA induced by anterior cruciate ligament (ACL) rupture. Right knees of 12-week-old C57Bl6 mice were placed in flexion at a 30° offset position and subjected to a single compressive load (12N, 1...
February 17, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29453720/cytotoxic-effect-of-chlorpyrifos-is-associated-with-activation-of-nrf-2-ho-1-system-and-inflammatory-response-in-tongue-of-male-wistar-rats
#10
Norhan M El-Sayed, Amal A M Ahmed, Manar A A Selim
Repeated administration of chlorpyrifos (CPF), an organophosphate pesticide, can increase the risk of oral cytotoxicity. The current study was designed to assess the mechanism by which CPF mediates its cytotoxic effect on lingual mucosa of rats. Twenty-four male Wistar rats were used in the present study and divided into three groups: group I: healthy rats (negative control), group II: rats treated with CPF 1/40 LD50 (3.375 mg/kg, orally/daily) for 28 days, group III: rats treated with CPF 1/10 LD50 (13.5 mg/kg, orally/daily) for 28 days...
February 16, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29453608/chemopreventive-action-of-imatinib-a-tyrosine-kinase-inhibitor-in-the-regulation-of-angiogenesis-and-apoptosis-in-rat-model-of-lung-cancer
#11
Kulvinder Kumar, Preety Ghanghas, S N Sanyal
The present study explored the events of angiogenesis and apoptosis in 7,12-dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat and its chemoprevention with Imatinib, a receptor tyrosine kinase inhibitor. Further, it includes lipopolysaccharide (LPS) mediating inflammation along with DMBA for the promotion of lung carcinogenesis. The animals received a single intratracheal instillation of DMBA (20 mg/kg body weight) in olive oil and LPS (0.6 mg/kg body weight) to induce tumors in 16 weeks. Besides morphology and histology of the lung tissues, RT-PCR, western blots, and immunofluorescence were performed for the expression of apoptotic and angiogenic proteins...
February 16, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29453541/detection-of-dna-damage-induced-by-cerium-dioxide-nanoparticles-from-models-to-molecular-mechanism-activated
#12
Tiago Alves Jorge de Souza, Thiago Lopes Rocha, Leonardo Pereira Franchi
This chapter will present an original effort to summarize the relevant data about the cyto-genotoxicity induced by cerium dioxide nanoparticles (nanoceria) in physiologically (in vivo and in vitro) relevant models. In this way, this chapter should be extremely useful to everyone who wants to plan their research and publishing their results. Massive application of nanoceria at different fields is increasing year after year, and it is urgent to address and discuss their use and its safety-related issues. Specifically, the nanoceria are being designed for nanomedicine, cosmetics, polishing materials and additives for automotive fuels...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29453346/anti-inflammatory-effect-of-tauroursodeoxycholic-acid-in-raw-264-7-macrophages-bone-marrow-derived-macrophages-bv2-microglial-cells-and-spinal-cord-injury
#13
Seong Jun Kim, Wan-Kyu Ko, Min-Jae Jo, Yoshie Arai, Hyemin Choi, Hemant Kumar, In-Bo Han, Seil Sohn
This study aimed to investigate the anti-inflammatory effects of tauroursodeoxycholic acid (TUDCA) after spinal cord injury (SCI) in rats. We induced an inflammatory process in RAW 264.7 macrophages, BV2 microglial cells, and bone marrow-derived macrophages (BMM) using lipopolysaccharide (LPS). The anti-inflammatory effects of TUDCA on LPS-stimulated RAW 264.7 macrophages, BV2 microglial cells, and BMMs were analyzed using nitric oxide (NO) assays, quantitative real-time polymerase chain reactions (qRT-PCR), and enzyme-linked immunosorbent assays (ELISA)...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#14
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453319/leptin-signaling-mediates-obesity-associated-csc-enrichment-and-emt-in-preclinical-tnbc-models
#15
Laura W Bowers, Emily L Rossi, Shannon B McDonell, Steven S Doerstling, Subreen A Khatib, Claire G Lineberger, Jody E Albright, Xiaohu Tang, Linda A deGraffenried, Stephen D Hursting
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n=15/group)...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453315/autophagic-flux-is-regulated-by-interaction-between-the-c-terminal-domain-of-patched1-and-atg101
#16
Lucy X Chen, Cintli C Morales-Alcala, Natalia A Riobo-Del Galdo
The Hedgehog (Hh) receptor Patched1 (PTCH1) is a well-known tumor suppressor that in its active form represses Smoothened (SMO) activity, inhibits proliferation, and induces apoptosis. The cytoplasmic C-terminal domain (CTD) regulates PTCH1 turnover and nucleates a pro-apoptotic complex. In this study, it was mechanistically determined that Autophagy Related 10 (ATG101), essential for mammalian autophagy, physically interacts with the CTD of PTCH1 and connects it to the ULK complex, which stimulates the autophagy machinery in response to changes in nutrient availability...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453250/retinal-chitosan-conjugates-effectively-deliver-active-chromophores-to-retinal-photoreceptor-cells-in-blind-mice-and-dogs
#17
Songqi Gao, Shirin Kahremany, Jianye Zhang, Beata Jastrzebska, Janice Querubin, Simon M Petersen-Jones, Krzysztof Palczewski
The retinoid (visual) cycle consists of a series of biochemical reactions needed to regenerate the visual chromophore, 11-cis-retinal and sustain vision. Genetic or environmental factors affecting chromophore production can lead to blindness. Using animal models that mimic human retinal diseases, we previously demonstrated that mechanism-based pharmacological interventions can maintain vision in otherwise incurable genetic diseases of the retina. Here, we report that after 9-cis-retinal administration to lecithin:retinol acyltransferase-deficient (Lrat-/-) mice, the drug was rapidly absorbed and then cleared within 1-2 h...
February 16, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29453229/crystal-structure-of-plant-legumain-reveals-a-unique-two-chain-state-with-ph-dependent-activity-regulation
#18
Florian B Zauner, Elfriede Dall, Christof Regl, Luigi Grassi, Chrisitian G Huber, Chiara Cabrele, Hans Brandstetter
The vacuolar cysteine protease legumain can cleave and selectively rebuild peptide bonds, thereby vastly expanding the sequential repertoire of biomolecules. In this context, plant legumains have recently at-tracted particular interest. Furthermore, legumains have important roles in many physiological pro-cesses, including programmed cell death. Their efficient peptide bond ligase activity has gained tremen-dous interest in the design of cyclic peptides for drug design. However, the mechanistic understanding of these dual activities is incomplete and partly conflicting...
February 16, 2018: Plant Cell
https://www.readbyqxmd.com/read/29453135/dual-inhibitors-of-the-pro-survival-proteins-bcl-2-and-mcl-1-derived-from-natural-compound-meiogynin-a
#19
Alma Abou Samra, Aude Robert, Crystal Gov, Loëtitia Favre, Laure Eloy, Eric Jacquet, Jérôme Bignon, Joëlle Wiels, Sandy Desrat, Fanny Roussi
Thirty analogues of natural meiogynin A, a pan-Bcl-2 inhibitor, were prepared in order to elaborate cytotoxic compounds on specific cancer cells overexpressing one or more proteins of the Bcl-2 family. The interaction of all the new analogues with Bcl-xL, Mcl-1 and Bcl-2 proteins was first evaluated by fluorescence polarization assay (FPA) and showed that modulation of the lateral chain has a dramatic impact as subtle changes significantly modify the activity on the target proteins. The acetoxymethyl prodrugs of the two most active compounds were then elaborated to determine their cytotoxicity on B cell lines...
February 5, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29453076/development-of-novel-synthesized-phthalazinone-based-parp-1-inhibitors-with-apoptosis-inducing-mechanism-in-lung-cancer
#20
Hadia Almahli, Elie Hadchity, Maiy Y Jaballah, Racha Daher, Hazem A Ghabbour, Maha M Kabil, Nasser S Al-Shakliah, Wagdy M Eldehna
Herein we report the synthesis of two series of 4-phenylphthalazin-1-ones 11a-i and 4- benzylphthalazin-1-ones 16a-h as anti-lung adenocarcinoma agents with potential inhibitory activity against PARP-1. All the newly synthesized phthalazinones were evaluated for their anti-proliferative activity against A549 lung carcinoma cell line. Phthalazinones 11c-i and 16b, c showed significant cytotoxic activity against A549 cells at different concentrations (0.1, 1 and 10 μM) for two time intervals (24 h and 48 h)...
February 7, 2018: Bioorganic Chemistry
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