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Sameera Nallanthighal, Ramune Reliene
Owing to new and unique properties, engineered nanoparticles (NPs) likely pose different risks than their constituent chemicals and these risks need to be understood. In particular, it is important to assess genotoxicity, since genotoxicity is a precursor to carcinogenicity. Here we describe a battery of tests for the assessment of genotoxicity of NPs in vivo in mice. Mice can be exposed to NPs for various exposure durations and by any route of exposure, provided NPs are absorbed into the systemic blood circulation...
2019: Methods in Molecular Biology
Rong Wan, Yiqun Mo, Ruirui Tong, Meiqin Gao, Qunwei Zhang
DNA double-strand breaks (DSBs), one of the most severe lesions of DNA damage triggered by various genotoxic insults, can lead to chromosome change, genomic instability, and even tumorigenesis if not repaired efficiently. In response to DNA damage, histone H2AX molecules are rapidly phosphorylated at serine 139 near the site of DNA DSBs and form γ-H2AX foci. As an early important cellular event linked to DNA damage and repair, γ-H2AX is a highly sensitive biomarker for "monitoring" DNA damage and consequently is a useful tool in genetic toxicology screen...
2019: Methods in Molecular Biology
Maria Dusinska, Espen Mariussen, Elise Rundén-Pran, Alexandra Misci Hudecova, Elisabeth Elje, Alena Kazimirova, Naouale El Yamani, Nils Dommershausen, Julian Tharmann, Dagmar Fieblinger, Frank Herzberg, Andreas Luch, Andrea Haase
Genotoxicity is associated with serious health effects and includes different types of DNA lesions, gene mutations, structural chromosome aberrations involving breakage and/or rearrangements of chromosomes (referred to as clastogenicity) and numerical chromosome aberrations (referred to as aneuploidy). Assessing the potential genotoxic properties of chemicals, including nanomaterials (NMs), is a key element in regulatory safety assessment. State-of-the-art genotoxicity testing includes a battery of assays covering gene mutations, structural and numerical chromosome aberrations...
2019: Methods in Molecular Biology
Dustin T Savage, J Zach Hilt, Thomas D Dziubla
As a consequence of their increase in annual production and widespread distribution in the environment, nanoparticles potentially pose a significant public health risk. The sought-after catalytic activity granted by their physiochemical properties doubles as a hazard to physiological processes following exposure through inhalation, oral, transdermal, subcutaneous, and intravenous uptake. Upon uptake into the body, their size, morphology, surface charge, coating, and chemical composition augment the response of biological systems to the materials and enhance their toxicity...
2019: Methods in Molecular Biology
Zubir S Rentiya, Matthew Wells, Junun Bae, Kuan-Jen Chen, An-Ning Chao, Nicholas Turgeon, Syed M Shah, Mostafa Hanout
Interferons are cytokines that regulate the host's response to viral infection, particularly in the setting of the immunologic response to the hepatitis C virus (HCV). While the virus has the ability to evade the host's innate and specific immunity, exogenous interferon-α with combined ribavirin, treatments have been found to achieve a significant sustained viral response in subgroups of patients with chronic HCV. One of the major side effects of interferon-α is an ocular retinopathy characterized by flame-shaped hemorrhages and cotton wool spots visualized on funduscopic examination...
December 13, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
Soroush Nasri, Bostjan Humara, Ahmad Anjomshoaa, Nourodin Moradi, Naghmeh Gholipour, Sakineh Mashjoor, Peng Zhang
Diffuse gastric cancer (DGC) is one of the two primary types of stomach cancer. Carriers of germline mutations in the gene encoding E-cadherin are predisposed to DGC. The primary aim of the present study was to determine if genomic instability is an early event in DGC and how it may lead to disease progression. Chromosomal aberrations in early intramucosal hereditary diffuse gastric cancer (eHDGC) were assessed using array comparative genomic hybridization (array CGH). Notably, no aneuploidy or other large-scale chromosomal rearrangements were detected...
December 13, 2018: Pathology Oncology Research: POR
Shenglan Li, Liuqing Yang, Jinglei Li, Tingting Chen, Ming Ye
The purpose of this study was to examine the protective effects of intracellular homogeneous melanin produced by Lachnum YM156 (LIM) against ultraviolet B (UVB) induced damage in mice. The possible structural formula of the LIM was concluded based on elemental analysis, ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and mass spectrometry (MS). The LIM was modified by arginine to improve its water solubility and biological activities...
December 14, 2018: Applied Biochemistry and Biotechnology
Sayaka Ishigaki, Naro Ohashi, Shinsuke Isobe, Naoko Tsuji, Takamasa Iwakura, Masafumi Ono, Yukitoshi Sakao, Takayuki Tsuji, Akihiko Kato, Hiroaki Miyajima, Hideo Yasuda
In the original publication, an error occurred in Table 4 (B), under Nighttime group. The value of "Nighttime Log U-AGT/Cr" for model 3 (under R = 0.68) was incorrectly published as 0.11. The correct value should read as -0.31.
December 13, 2018: Clinical and Experimental Nephrology
Mitsuhiro Tawada, Chieko Hamada, Yasuhiro Suzuki, Fumiko Sakata, Ting Sun, Hiroshi Kinashi, Takayuki Katsuno, Yoshifumi Takei, Shoichi Maruyama, Kazuho Honda, Masashi Mizuno, Yasuhiko Ito
BACKGROUND: The morphological changes induced by bio-incompatible peritoneal dialysis (PD) solutions are well known. However, the morphological damage induced by long-term low-glucose degradation product (GDP), pH-neutral solutions has not been reported in detail. The aim of this study was to investigate the long-term effects of pH-neutral PD solutions on morphological and functional changes in the peritoneal membrane. METHODS: We assessed peritoneal membrane biopsy samples from PD patients treated with acidic (Conventional group) or pH-neutral solutions (pH-neutral group) using pathology and immunopathology techniques...
December 13, 2018: Clinical and Experimental Nephrology
Mohamad Nasser, Pia Chedid, Ali Salami, Mariam Khalifeh, Said El Shamieh, Wissam H Joumaa
Rapid growing of mobile phones users has raised about the possible effects of these electromagnetic waves (EMW) on human health. Many studies have examined the role of these EMW on biological systems, but the results are still contradictory and controversial. In addition to EMW, over-activation of angiotensin type 1 receptor (AT1R) has been associated with cognitive decline, incidence and progression of neurodegenerative diseases. Candesartan, an AT1R blocker, is well recognized for treatment of hypertension...
December 2018: Data in Brief
Ahmed Samir Elshikha, Ye Yuan, Yuanqing Lu, Mong-Jen Chen, Georges Abboud, Mohammad Ahsanul Akbar, Henrike Plate, Hedwig Wolney, Tanja Hoffmann, Eleni Tagari, Leilani Zeumer, Laurence Morel, Sihong Song
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by high levels of pathogenic autoantibodies and tissue damage. Multiple studies showed that dendritic cell (DC) activation plays a critical role in SLE pathogenesis. Human alpha 1 antitrypsin (hAAT) is a serine proteinase inhibitor with potent anti-inflammatory and cytoprotective properties. In this study, we first examined the effects of hAAT on the functions of DCs from lupus-prone mice, and we showed that hAAT treatment efficiently inhibited CpG- (TLR9 agonist) induced activation of bone marrow-derived conventional and plasmacytoid DCs as well as the production of pro-inflammatory cytokines...
December 14, 2018: Molecular Therapy. Methods & Clinical Development
Desmond J Bokor, Sumit Raniga, Petra L Graham
Background: The axillary nerve is at risk during repair of a humeral avulsion of the glenohumeral ligament (HAGL). Purpose: To measure the distance between the axillary nerve and the free edge of a HAGL lesion on preoperative magnetic resonance imaging (MRI) and compare these findings to the actual intraoperative distance measured during open HAGL repair. Study Design: Case series; Level of evidence, 4. Methods: A total of 25 patients with anterior instability were diagnosed as having a HAGL lesion on MRI and proceeded to open repair...
December 2018: Orthopaedic Journal of Sports Medicine
Aaron J Fields, Alexander Ballatori, Ellen C Liebenberg, Jeffrey C Lotz
Purpose of review: The endplates form the interface between the rigid vertebral bodies and compliant intervertebral discs. Proper endplate function involves a balance between conflicting biomechanical and nutritional demands. This review summarizes recent data that highlight the importance of proper endplate function and the relationships between endplate dysfunction, adjacent disc degeneration, and axial low back pain. Recent findings: Changes to endplate morphology and composition that impair its permeability associate with disc degeneration...
December 2018: Current Molecular Biology Reports
Julia Krombach, Roman Hennel, Nikko Brix, Michael Orth, Ulrike Schoetz, Anne Ernst, Jessica Schuster, Gabriele Zuchtriegel, Christoph A Reichel, Susanne Bierschenk, Markus Sperandio, Thomas Vogl, Steffen Unkel, Claus Belka, Kirsten Lauber
The major goal of radiotherapy is the induction of tumor cell death. Additionally, radiotherapy can function as in situ cancer vaccination by exposing tumor antigens and providing adjuvants for anti-tumor immune priming. In this regard, the mode of tumor cell death and the repertoire of released damage-associated molecular patterns (DAMPs) are crucial. However, optimal dosing and fractionation of radiotherapy remain controversial. Here, we examined the initial steps of anti-tumor immune priming by different radiation regimens (20 Gy, 4 × 2 Gy, 2 Gy, 0 Gy) with cell lines of triple-negative breast cancer in vitro and in vivo ...
2019: Oncoimmunology
Zhiwu Tan, Li Liu, Mei Sum Chiu, Ka-Wai Cheung, Chi Wing Yan, Zhe Yu, Boon Kiat Lee, Wan Liu, Kwan Man, Zhiwei Chen
Antitumor cytotoxic T lymphocytes (CTLs) are essential for immune surveillance, yet the blockade of eliciting such CTLs during oncolytic virotherapy remains incompletely understood. Here, we show that oncolysis of mesothelioma by modified vaccinia Tiantan (MVTT) induces damage-associated molecular patterns exposure. Although MVTT leads to regression of established mesothelioma dose-dependently, antitumor CTLs are rarely induced. Mechanistically, MVTT virotherapy generates C-X-C chemokines that recruit CXCR2-expressing polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into tumor microenvironment, where they suppress dendritic cells (DCs) by producing IL-10 and halt CTL responses...
2019: Oncoimmunology
Frank Erhard Uschner, Florian Schueller, Ivelina Nikolova, Sabine Klein, Robert Schierwagen, Fernando Magdaleno, Stefanie Gröschl, Sven Loosen, Thomas Ritz, Christoph Roderburg, Michael Vucur, Glen Kristiansen, Twan Lammers, Tom Luedde, Jonel Trebicka
Background and Aims: Angiogenesis is critically involved in the development of liver fibrosis, portal hypertension (PHT) and hepatocellular carcinoma (HCC). Regorafenib is a novel second-line therapy for HCC, but might also be beneficial in fibrosis and PHT even in absence of HCC. This study investigated the effects of regorafenib in experimental models without HCC. Methods: Fibrosis ( in vivo and in vitro ), inflammation, liver damage (aminotransferases), angiogenesis (matrigel implantation) and in vivo systemic and portal hemodynamics were assessed in different mouse and rat models (bile duct ligation, CCl4 , partial portal vein ligation) after acute and chronic treatment with regorafenib...
November 16, 2018: Oncotarget
Valentina Masola, Gloria Bellin, Gisella Vischini, Luigi Dall'Olmo, Simona Granata, Giovanni Gambaro, Antonio Lupo, Maurizio Onisto, Gianluigi Zaza
Renal ischemia/reperfusion (I/R) injury occurs in patients undergoing renal transplantation and with acute kidney injury and is responsible for the development of chronic allograft dysfunction as characterized by parenchymal alteration and fibrosis. Heparanase (HPSE), an endoglycosidase that regulates EMT and macrophage polarization, is an active player in the biological response triggered by ischemia/reperfusion (I/R) injury. I/R was induced in vivo by clamping left renal artery for 30 min in wt C57BL/6J mice...
November 16, 2018: Oncotarget
Huifang Liu, Siming Tao, Hongxia Ma, Jing Jin, Jing Jing, Li Yao, Xiulan Ma, Fengsen Li
The aim of this study was to investigated the functional changes of airway epithelial cells and mitochondria in rat models of asthenic lung and phlegm blocking combined with cough variant asthma (CVA). Sixteen Sprague-Dawley rats were randomly divided into two groups: Control and model group, with 8 rats in each group. On the basis of the CVA rat model induced and sensitized by ovalbumin and aluminum hydroxide, the rat models with asthenic lung and phlegm blocking combined with CVA were established via smoking stimulation...
December 2018: Experimental and Therapeutic Medicine
Romina Burla, Mattia La Torre, Giorgia Zanetti, Alex Bastianelli, Chiara Merigliano, Simona Del Giudice, Alessandro Vercelli, Ferdinando Di Cunto, Marina Boido, Fiammetta Vernì, Isabella Saggio
Epilepsy is a complex clinical condition characterized by repeated spontaneous seizures. Seizures have been linked to multiple drivers including DNA damage accumulation. Investigation of epilepsy physiopathology in humans imposes ethical and practical limitations, for this reason model systems are mostly preferred. Among animal models, mouse mutants are particularly valuable since they allow conjoint behavioral, organismal, and genetic analyses. Along with this, since aging has been associated with higher frequency of seizures, prematurely aging mice, simulating human progeroid diseases, offer a further useful modeling element as they recapitulate aging over a short time-window...
2018: Frontiers in Genetics
Justine Claverie, Suzanne Balacey, Christelle Lemaître-Guillier, Daphnée Brulé, Annick Chiltz, Lucie Granet, Elodie Noirot, Xavier Daire, Benoît Darblade, Marie-Claire Héloir, Benoit Poinssot
Damage-associated molecular patterns (DAMPs) are endogenous molecules that can activate the plant innate immunity. DAMPs can derive from the plant cell wall, which is composed of a complex mixture of cellulose, hemicellulose, and pectin polysaccharides. Fragments of pectin, called oligogalacturonides (OG), can be released after wounding or by pathogen-encoded cell wall degrading enzymes (CWDEs) such as polygalacturonases (PGs). OG are known to induce innate immune responses, including the activation of mitogen-activated protein kinases (MAPKs), production of H2 O2 , defense gene activation, and callose deposition...
2018: Frontiers in Plant Science
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