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https://www.readbyqxmd.com/read/29793137/3-o-sulfation-of-heparin-leads-to-hepatotropism-and-longer-circulatory-half-life
#1
Colton M Miller, Yongmei Xu, Katrina M Kudrna, Blake E Hass, Brianna M Kellar, Andrew W Egger, Jian Liu, Edward N Harris
INTRODUCTION: Heparins are common blood anticoagulants that are critical for many surgical and biomedical procedures used in modern medicine. In contrast to natural heparin derived from porcine gut mucosa, synthetic heparins are homogenous by mass, polymer length, and chemistry. MATERIALS & METHODS: Stable cell lines expressing the human and mouse Stabilin receptors were used to evaluate endocytosis of natural and synthetic heparin. We chemoenzymatically produced synthetic heparin consisting of 12 sugars (dodecamers) containing 14 sulfate groups resulting in a non-3-O sulfated structure (n12mer)...
May 17, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29793131/tlr2-4-ligand-amplified-liver-inflammation-promotes-initiation-of-autoimmune-hepatitis-due-to-sustained-il-6-il-12-il-4-il-25-expression
#2
Gang Chi, Xin-Xia Feng, Ying-Xia Ru, Ting Xiong, Yuan Gao, Han Wang, Zhen-Long Luo, Ran Mo, Fang Guo, Yong-Pei He, Gui-Mei Zhang, De-An Tian, Zuo-Hua Feng
Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl4 ) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4...
May 21, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29793116/patterns-of-invasive-growth-in-malignant-gliomas-the-hippocampus-emerges-as-an-invasion-spared-brain-region
#3
Awais A Mughal, Lili Zhang, Artem Fayzullin, Andres Server, Yuping Li, Yingxi Wu, Rainer Glass, Torstein Meling, Iver A Langmoen, Trygve B Leergaard, Einar O Vik-Mo
BACKGROUND: Widespread infiltration of tumor cells into surrounding brain parenchyma is a hallmark of malignant gliomas, but little data exist on the overall invasion pattern of tumor cells throughout the brain. METHODS: We have studied the invasive phenotype of malignant gliomas in two invasive mouse models and patients. Tumor invasion patterns were characterized in a patient-derived xenograft mouse model using brain-wide histological analysis and magnetic resonance (MR) imaging...
May 21, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29792915/the-cd44-ha-axis-and-inflammation-in-atherosclerosis-a-temporal-perspective
#4
REVIEW
Mia Krolikoski, James Monslow, Ellen Puré
Cardiovascular disease (CVD) due to atherosclerosis is a disease of chronic inflammation at both the systemic and the tissue level. CD44 has previously been implicated in atherosclerosis in both humans and mice. This multi-faceted receptor plays a critical part in the inflammatory response during the onset of CVD, though little is known of CD44's role during the latter stages of the disease. This review focuses on the role of CD44-dependent HA-dependent effects on inflammatory cells in several key processes, from disease initiation throughout the progression of atherosclerosis...
May 21, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29792889/ros-triggered-degradable-iron-chelating-nanogels-safely-improving-iron-elimination-in-vivo
#5
Zhi Liu, Jing Qiao, Tamas Nagy, May P Xiong
Iron-mediated generation of highly toxic Reactive Oxygen Species (ROS) plays a major role in the process leading to iron overload-related diseases. The long-term subcutaneous administration of Deferoxamine (DFO) is currently clinically-approved to improve patient symptoms and survival. However, non-specific toxicity and short circulation times of the drug in humans often leads to poor patient compliance. Herein, thioketal-based ROS-responsive polymeric nanogels containing DFO moieties (rNG-DFO) were designed to chelate iron and to degrade under oxidative stimuli into fragments <10 nm to enhance excretion of iron-bound chelates...
May 21, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29792863/identification-of-immunodominant-cd8-epitope-in-the-stalk-domain-of-influenza-b-viral-hemagglutinin
#6
Abenaya Muralidharan, Caroline Gravel, Amparo Duran, Louise Larocque, Changgui Li, Adrian Zetner, Gary Van Domselaar, Lisheng Wang, Xuguang Li
Human infections by type B influenza virus constitute about 25% of all influenza cases. The viral hemagglutinin is comprised of two subunits, HA1 and HA2. While HA1 is constantly evolving in an unpredictable fashion, the HA2 subunit is highly conserved, making it a potential candidate for a universal vaccine. However, immunodominant epitopes in the HA2 subunit remain largely unknown. To delineate MHC Class I epitopes, we first identified 9-mer H-2Kd -restricted CD8 T cell epitopes in the HA2 domain by in silico analyses, followed by evaluating the immunodominance of these peptides in mice challenged with the virus...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29792386/disparate-effects-of-shb-gene-deficiency-on-disease-characteristics-in-murine-models-of-myeloid-b-cell-and-t-cell-leukemia
#7
Maria Jamalpour, Xiujuan Li, Karin Gustafsson, Jeffrey W Tyner, Michael Welsh
The Src homology-2 domain protein B is an adaptor protein operating downstream of tyrosine kinases. The Shb gene knockout has been found to accelerate p210 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced leukemia. In human myeloid leukemia were tumors with high Src homology-2 domain protein B mRNA content, tumors were, however, associated with decreased latency and myeloid leukemia exhibiting immune cell characteristics. Thus, the aim of this study was to investigate the effects of Shb knockout on the development of leukemia in three additional models, that is, colony stimulating factor 3 receptor-T618I-induced neutrophilic leukemia, p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced B-cell leukemia, and G12D-Kras-induced T-cell leukemia/thymic lymphoma...
April 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29792351/peroxiredoxin-6-inhibits-osteogenic-differentiation-and-bone-formation-through-human-dental-pulp-stem-cells-and-induces-delayed-bone-development
#8
Kyung-Ran Park, Hyung-Mun Yun, In Jun Yeo, Sehyung Cho, Jin Tae Hong, Yong Seok Jeong
AIMS: Peroxiredoxins (PRDXs) are thiol-specific antioxidant enzymes that regulate redox balance that are critical for maintaining the cellular potential for self-renewal and stemness. Stem cell-based regenerative medicine is a promising approach in tissue reconstruction. However, to obtain functional cells for use in clinical applications, stem cell technology still requires improvements. RESULTS: In the present study, we found that PRDX6 levels were decreased during osteogenic differentiation in human dental pulp stem cells (hDPSCs)...
May 24, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29792309/metabolic-and-physiologic-imaging-biomarkers-of-the-tumor-microenvironment-predict-treatment-outcome-with-radiation-or-a-hypoxia-activated-prodrug-in-mice
#9
Shingo Matsumoto, Shun Kishimoto, Keita Saito, Yoichi Takakusagi, Jeeva P Munasinghe, Nallathamby Devasahayam, Charles Hart, Robert J Gillies, James B Mitchell, Murali C Krishna
Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here we define two imaging biomarkers that predict differences in tumor response to therapy: 1) partial oxygen pressure (pO2), measured by EPR imaging; and 2) [1-13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa-2, and Su...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29792298/nanobody-antigen-conjugates-elicit-hpv-specific-anti-tumor-immune-responses
#10
Andrew W Woodham, Ross W Cheloha, Jingjing Ling, Mohammad Rashidian, Stephen C Kolifrath, Maia Mesyngier, Joao N Duarte, Justin M Bader, Joseph G Skeate, Diane M Da Silva, W Martin Kast, Hidde L Ploegh
High-risk human papillomavirus-associated cancers express viral oncoproteins (e.g., E6 and E7) that induce and maintain the malignant phenotype. The viral origin of these proteins makes them attractive targets for development of a therapeutic vaccine. Camelid-derived single-domain antibody fragments (nanobodies or VHHs) that recognize cell surface proteins on antigen-presenting cells (APCs) can serve as targeted delivery vehicles for antigens attached to them. Such VHHs were shown to induce CD4+ and CD8+ T-cell responses against model antigens conjugated to them via sortase, but antitumor responses had not yet been investigated...
May 23, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29792201/cerium-dioxide-nanoparticles-exacerbate-house-dust-mite-induced-type-ii-airway-inflammation
#11
Kirsty Meldrum, Sarah B Robertson, Isabella Römer, Tim Marczylo, Lareb S N Dean, Andrew Rogers, Timothy W Gant, Rachel Smith, Terry D Tetley, Martin O Leonard
BACKGROUND: Nanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Cerium dioxide nanoparticles (CeO2 NPs) have the ability to modify disease outcome but have not been investigated for their effect on models of asthma and inflammatory lung disease. The aim of this study was to examine the impact of CeO2 NPs in a house dust mite (HDM) induced murine model of asthma. RESULTS: Repeated intranasal instillation of CeO2 NPs in the presence of HDM caused the induction of a type II inflammatory response, characterised by increased bronchoalveolar lavage eosinophils, mast cells, total plasma IgE and goblet cell metaplasia...
May 23, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29791869/ghrelin-and-the-heart
#12
Takeshi Tokudome, Kentaro Otani, Mikiya Miyazato, Kenji Kangawa
Ghrelin, a growth hormone-releasing peptide that was first discovered in the stomach of rats in 1999, is an endogenous ligand of growth hormone secretagogue receptor. Ghrelin exerts its potent growth hormone-releasing and orexigenic activities by binding to specific receptors in the brain. Subsequent studies showed that ghrelin participates in the regulation of diverse processes, including energy balance, body weight maintenance, and glucose and fat metabolism, and demonstrated that ghrelin is beneficial for treatment of cardiac diseases...
May 20, 2018: Peptides
https://www.readbyqxmd.com/read/29791513/vaccine-induced-antibodies-to-herpes-simplex-virus-glycoprotein-d-epitopes-involved-in-virus-entry-and-cell-to-cell-spread-correlate-with-protection-against-genital-disease-in-guinea-pigs
#13
Lauren M Hook, Tina M Cairns, Sita Awasthi, Benjamin D Brooks, Noah T Ditto, Roselyn J Eisenberg, Gary H Cohen, Harvey M Friedman
Herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit antigen is included in many preclinical candidate vaccines. The rationale for including gD2 is to produce antibodies that block crucial gD2 epitopes involved in virus entry and cell-to-cell spread. HSV-2 gD2 was the only antigen in the Herpevac Trial for Women that protected against HSV-1 genital infection but not HSV-2. In that trial, a correlation was detected between gD2 ELISA titers and protection against HSV-1, supporting the importance of antibodies...
May 23, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29791507/a-novel-mouse-model-of-campylobacter-jejuni-enteropathy-and-diarrhea
#14
Natasa Giallourou, Gregory L Medlock, David T Bolick, Pedro Hqs Medeiros, Solanka E Ledwaba, Glynis L Kolling, Kenneth Tung, Patricia Guerry, Jonathan R Swann, Richard L Guerrant
Campylobacter infections are among the leading bacterial causes of diarrhea and of 'environmental enteropathy' (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection...
May 23, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29791435/immunogenicity-and-efficacy-following-sequential-parenterally-administered-doses-of-salmonella-enteritidis-cops-flic-glycoconjugates-in-infant-and-adult-mice
#15
Scott M Baliban, Brittany Curtis, Deanna Toema, Sharon M Tennant, Myron M Levine, Marcela F Pasetti, Raphael Simon
In sub-Saharan Africa, invasive nontyphoidal Salmonella (iNTS) infections with serovars S. Enteritidis, S. Typhimurium and I 4,[5],12:i:- are widespread in children < 5 years old. Development of an efficacious vaccine would provide an important public health tool to prevent iNTS disease in this population. Glycoconjugates of S. Enteritidis core and O-polysaccharide (COPS) coupled to the homologous serovar phase 1 flagellin protein (FliC) were previously shown to be immunogenic and protected adult mice against death following challenge with a virulent Malian S...
May 23, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29791305/commercial-frozen-mice-used-by-owners-to-feed-reptiles-are-highly-externally-contaminated-with-salmonella-enteritidis-pt8
#16
Clara Marin, Francesca Martelli, André Rabie, Robert Davies
Salmonella remains one of the most prevalent zoonoses worldwide. Although salmonellosis is commonly associated with the consumption of contaminated food, it has been estimated that up to 11% of Salmonella infections overall are acquired from direct or indirect contact with animals, including reptiles. In 2016, an outbreak of Salmonella Enteritidis involving multiple cases, especially children, associated with reptile contact and contaminated feeder mice was reported in the United Kingdom. The aim of this study was to investigate Salmonella external and internal contamination of stored commercial frozen feeder mice used to feed reptiles and obtained from the same supplier involved in the outbreak...
May 23, 2018: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/29791203/short-term-thermoneutral-housing-alters-glucose-metabolism-and-markers-of-adipose-tissue-browning-in-response-to-a-high-fat-diet-in-lean-mice
#17
Zachary Stephen Clayton, Carrie E McCurdy
Systemic insulin resistance and glucose intolerance occur with as little as 3 days of a high-fat diet (HFD) in mice and humans; the mechanisms that initiate acute insulin resistance are unknown. Most laboratories house mice at 22{degree sign}C, which is below their thermoneutral temperature (~30{degree sign}C). Cold stress has been shown to increase white adipose tissue (WAT) browning, alter lipid trafficking and impair immune function, while energy intake and expenditure decrease with increasing ambient temperature; importantly, dysregulation of these parameters have been strongly linked to obesity-induced insulin resistance...
May 23, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29790972/isolation-and-biological-characterization-of-mesenchymal-stem-cells-from-goose-dermis
#18
Jingjing Wang, Xulun Wu, Yanjie Zheng, Hebao Wen, Hongda Ji, Yuhua Zhao, Weijun Guan
The skin is a natural target of stem cell research because of its large size and easy accessibility. Cutaneous mesenchymal stem cells have shown to be a promising source of various adult stem cell or progenitor cell populations, which provide an important source of stem cell-based investigation. Nowadays, much work has been done on dermal-derived mesenchymal stem cells (DMSCs) from humans, mice, sheep, and other mammals, but the literature on avian species has been rarely reported. As an animal model, the goose is an endemic species abounding in dermal tissues which is important in the global economy...
May 21, 2018: Poultry Science
https://www.readbyqxmd.com/read/29790918/temporal-and-tissue-specific-variability-of-smn-protein-levels-in-mouse-models-of-spinal-muscular-atrophy
#19
Ewout Jn Groen, Elena Perenthaler, Natalie L Courtney, Crispin Y Jordan, Hannah K Shorrock, Dinja van der Hoorn, Yu-Ting Huang, Lyndsay M Murray, Gabriella Viero, Thomas H Gillingwater
Spinal muscular atrophy (SMA) is a progressive motor neuron disease caused by deleterious variants in SMN1 that lead to a marked decrease in survival motor neuron (SMN) protein expression. Humans have a second SMN gene (SMN2) that is almost identical to SMN1. However, due to alternative splicing the majority of SMN2 mRNA is translated into a truncated, unstable protein that is quickly degraded. Because the presence of SMN2 provides a unique opportunity for therapy development in SMA patients, the mechanisms that regulate SMN2 splicing and mRNA expression have been elucidated in great detail...
May 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29790809/characterization-of-in-vitro-and-in-vivo-metabolism-of-leelamine-using-liquid-chromatography-tandem-mass-spectrometry
#20
Riya Shrestha, Jung Jae Jo, DooHyun Lee, Taeho Lee, Sangkyu Lee
1. Leelamine is a diterpene compound found in the bark of pine trees and has garnered considerable interest owing to its potent anticancer properties. The aim of the present study was to investigate the metabolic profile of leelamine in human liver microsomes (HLMs) and mice using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 2. We found that leelamine undergoes only Phase I metabolism, which generates one metabolite that is mono-hydroxylated at the C9 carbon of the octahydrophenanthrene ring (M1) both in vitro and in vivo...
May 23, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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