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https://www.readbyqxmd.com/read/29332180/cd39-adenosinergic-axis-in-renal-pathophysiology-and-therapeutics
#1
REVIEW
Bellamkonda K Kishore, Simon C Robson, Karen M Dwyer
Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis...
January 13, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29332041/in-vivo-visualization-of-tau-accumulation-microglial-activation-and-brain-atrophy-in-a-mouse-model-of-tauopathy-rtg4510
#2
Ai Ishikawa, Masaki Tokunaga, Jun Maeda, Takeharu Minamihisamatsu, Masafumi Shimojo, Hiroyuki Takuwa, Maiko Ono, Ruiqing Ni, Shigeki Hirano, Satoshi Kuwabara, Bin Ji, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Naruhiko Sahara
BACKGROUND: Tau imaging using PET is a promising tool for the diagnosis and evaluation of tau-related neurodegenerative disorders, but the relationship among PET-detectable tau, neuroinflammation, and neurodegeneration is not yet fully understood. OBJECTIVE: We aimed to elucidate sequential changes in tau accumulation, neuroinflammation, and brain atrophy by PET and MRI in a tauopathy mouse model. METHODS: rTg4510 transgenic (tg) mice expressing P301L mutated tau and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers: tg = 17, non-tg = 13; age 2...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332037/increased-vulnerability-of-the-hippocampus-in-transgenic-mice-overexpressing-app-and-triple-repeat-tau
#3
Andrew Arner, Edward Rockenstein, Michael Mante, Jazmin Florio, Deborah Masliah, Bahar Salehi, Anthony Adame, Cassia Overk, Eliezer Masliah, Robert A Rissman
 Alzheimer's disease (AD) is the most common tauopathy, characterized by progressive accumulation of amyloid-β (Aβ) and hyperphosphorylated tau. While pathology associated with the 4-repeat (4R) tau isoform is more abundant in corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau isoforms accumulate in AD. Many studies have investigated interactions between Aβ and 4R tau in double transgenic mice, but few, if any, have examined the effects of Aβ with 3R tau. To examine this relationship, we crossed our APP751 mutant line with our recently characterized 3R tau mutant model to create a bigenic line (hAPP-3RTau) to model AD neuropathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331419/the-therapeutic-potential-of-human-adipose-derived-mesenchymal-stem-cells-producing-cxcl10-in-a-mouse-melanoma-lung-metastasis-model
#4
Hamed Mirzaei, Hossein Salehi, Reza Kazemi Oskuee, Ali Mohammadpour, Hamid Reza Mirzaei, Mohammad Reza Sharifi, Reza Salarinia, Hossein Yousofi Darani, Mojgan Mokhtari, Aria Masoudifar, Amirhossein Sahebkar, Rasoul Salehi, Mahmoud Reza Jaafari
Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29331379/effect-of-histidine-on-sorafenib-induced-vascular-damage-analysis-using-novel-medaka-fish-model
#5
Yoko Shinagawa-Kobayashi, Kenya Kamimura, Ryo Goto, Kohei Ogawa, Ryosuke Inoue, Takeshi Yokoo, Norihiro Sakai, Takuro Nagoya, Akira Sakamaki, Satoshi Abe, Soichi Sugitani, Masahiko Yanagi, Koichi Fujisawa, Yoshizu Nozawa, Naoto Koyama, Hiroshi Nishina, Makoto Furutani-Seiki, Isao Sakaida, Shuji Terai
BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29331340/hsp72-protects-from-liver-injury-via-attenuation-of-hepatocellular-death-oxidative-stress-and-jnk-signaling
#6
Kateryna Levada, Nurdan Guldiken, Xiaoji Zhang, Giovanna Vella, Fa-Rong Mo, Laura P James, Johannes Haybaeck, Sonja M Kessler, Alexandra K Kiemer, Thomas Ott, Daniel Hartmann, Norbert Hüser, Marianne Ziol, Christian Trautwein, Pavel Strnad
BACKGROUND AND AIMS: Heat shock protein (Hsp) 72 is a molecular chaperone that is upregulated in response to stress and possesses broad cytoprotective functions. To determine its hepatic function, we studied its expression in human liver disorders and its biological significance in newly generated transgenic animals. AIM AND METHODS: Double transgenic mice overexpressing Hsp72 (gene HSPA1A) under the control of a tissue-specific tetracycline-inducible system (Hsp72-LAP mice) were produced...
January 10, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29330804/in-vivo-manipulation-of-hif-1%C3%AE-expression-during-glioma-genesis
#7
Patricia D B Tiburcio, Séan B Lyne, L Eric Huang
Hypoxia has long been recognized as a driving force of tumor progression and therapeutic resistance, and the transcription factor HIF-1α is believed to play a crucial role in these processes. Here we describe an efficient RCAS/Nes-TVA system that allows for in vivo manipulation of HIF-1α expression in the mouse neural progenitor cells. Simple production of the recombinant avian virus RCAS enables quick delivery of gene of interest through injection into the neural progenitors of transgenic mice expressing the viral cognate receptor TVA under the nestin promoter...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330472/amyloid-deposition-in-a-mouse-model-humanized-at-the-transthyretin-and-retinol-binding-protein-4-loci
#8
Xiangshun Li, Yanyi Lyu, Jingling Shen, Yanshuang Mu, Lixia Qiang, Li Liu, Kimi Araki, Bruno P Imbimbo, Ken-Ichi Yamamura, Shoude Jin, Zhenghua Li
Familial amyloidotic polyneuropathy is an autosomal dominant disorder caused by a point mutation in the transthyretin (TTR) gene. The process of TTR amyloidogenesis begins with rate-limiting dissociation of the TTR tetramer. Thus, the TTR stabilizers, such as Tafamidis and Diflunisal, are now in clinical trials. Mouse models will be useful to testing the efficacy of these drugs. Although several mouse models have been generated, they all express mouse Rbp4. Thus, human TTR associates with mouse RBP4, resulting in different kinetic and thermodynamic stability profiles of TTR tetramers...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29330323/il-10-deficiency-reveals-a-role-for-tlr2-dependent-bystander-activation-of-t-cells-in-lyme-arthritis
#9
Sarah K Whiteside, Jeremy P Snook, Ying Ma, F Lynn Sonderegger, Colleen Fisher, Charisse Petersen, James F Zachary, June L Round, Matthew A Williams, Janis J Weis
T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4+ and CD8+ T cells leads to arthritis-promoting IFN-γ, similar to the inflammatory environment seen in the synovial tissue of patients with posttreatment Lyme disease. TCR transgenic mice containing monoclonal specificity toward non-Borrelia epitopes confirmed that bystander T cell activation was responsible for disease development...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29330215/mir-195-regulates-metabolism-in-failing-myocardium-via-alterations-in-sirt3-expression-and-mitochondrial-protein-acetylation
#10
Xiaokan Zhang, Ruiping Ji, Xianghai Liao, Estibaliz Castillero, Peter J Kennel, Danielle L Brunjes, Marcus Franz, Sven Möbius-Winkler, Konstantinos Drosatos, Isaac George, Emily I Chen, Paolo C Colombo, P Christian Schulze
Background -Heart failure (HF) leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. Interestingly, unique cardiac and systemic miRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium...
January 12, 2018: Circulation
https://www.readbyqxmd.com/read/29328972/establishment-of-tusmi003-a-an-induced-pluripotent-stem-cell-ipsc-line-from-a-62-year-old-chinese-han-patient-with-alzheimer-s-disease-with-apoe3-4-genetic-background
#11
Ying Wang, Hongxiang Yu, Yue Zhang, Jing Zhang, Keni Chen, Heng Sun, Shulin Meng, Gang Li, Ying Lei, Jian Zhao
A 62-year old Chinese Han Alzheimer's disease (AD) female patient with ApoE3/4 genetic background donated her Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system was used to reprogrammed PBMCs with the human OKSM transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency markers and by the ability of the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a normal karyotype...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29327084/bace1-inhibition-more-effectively-suppresses-initiation-than-progression-of-%C3%AE-amyloid-pathology
#12
Finn Peters, Hazal Salihoglu, Eva Rodrigues, Etienne Herzog, Tanja Blume, Severin Filser, Mario Dorostkar, Derya R Shimshek, Nils Brose, Ulf Neumann, Jochen Herms
BACE1 is the rate-limiting protease in the production of synaptotoxic β-amyloid (Aβ) species and hence one of the prime drug targets for potential therapy of Alzheimer's disease (AD). However, so far pharmacological BACE1 inhibition failed to rescue the cognitive decline in mild-to-moderate AD patients, which indicates that treatment at the symptomatic stage might be too late. In the current study, chronic in vivo two-photon microscopy was performed in a transgenic AD model to monitor the impact of pharmacological BACE1 inhibition on early β-amyloid pathology...
January 11, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#13
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29326160/hypoxia-inducible-lipid-droplet-associated-protein-inhibits-adipose-triglyceride-lipase
#14
Krishna M Padmanabha Das, Lisa Wechselberger, Márton Liziczai, Montserrat De la Rosa Rodriguez, Gernot F Grabner, Christoph Heier, Roland Viertlmayr, Claudia Radler, Joerg Lichtenegger, Robert Zimmermann, Jan Willem Borst, Rudolf Zechner, Sander Kersten, Monika Oberer
Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are critically involved in the maintenance of energy homeostasis. Hypoxia inducible lipid droplet associated protein (HILPDA)/Hypoxia inducible gene-2 (Hig-2) has been shown to affect intracellular TAG levels, yet, the underlying molecular mechanisms are unclear. Here, we show that HILPDA inhibits adipose triglyceride lipase (ATGL), the enzyme catalyzing the first step of intracellular TAG hydrolysis. HILPDA shares structural similarity with G0/G1 switch gene 2 (G0S2), an established inhibitor of ATGL...
January 11, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29326144/a-new-secretory-peptide-of-natriuretic-peptide-family-osteocrin-suppresses-the-progression-of-congestive-heart-failure-after-myocardial-infarction
#15
Takahiro Miyazaki, Kentaro Otani, Ayano Chiba, Hirohito Nishimura, Takeshi Tokudome, Haruko Watanabe-Takano, Ayaka Matsuo, Hiroyuki Ishikawa, Keiko Shimamoto, Hajime Fukui, Yugo Kanai, Akihiro Yasoda, Soshiro Ogata, Kunihiro Nishimura, Naoto Minamino, Naoki Mochizuki
Rationale: An increase of severe ischemic heart diseases results in an increase of the patients with congestive heart failure (CHF). Therefore, new therapies are expected in addition to recanalization of coronary arteries. Previous clinical trials using natriuretic peptides (NPs) prove the improvement of CHF by NPs. Objective: We aimed at investigating whether osteocrin (OSTN) peptide potentially functioning as an NP clearance receptor (NPR3)-blocking peptide can be used as a new therapeutic peptide for treating CHF after myocardial infarction (MI) using animal models...
January 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29325430/rapid-and-sensitive-assessment-of-globin-chains-for-gene-and-cell-therapy-of-haemoglobinopathies
#16
Constantinos Christos Loucari, Petros Patsali, Thamar B van Dijk, Coralea Stephanou, Panayiota Papasavva, Maria Zanti, Ryo Kurita, Yukio Nakamura, Soteroulla Christou, Maria Sitarou, Sjaak Philipsen, Carsten Werner Lederer, Marina Kleanthous
The β-haemoglobinopathies sickle cell anaemia and β-thalassaemia are the focus of many gene-therapy studies. A key disease parameter is the abundance of globin chains, because it indicates the level of anaemia, likely toxicity of excess or aberrant globins, and therapeutic potential of induced or exogenous β-like globins. Reversed-phase high-performance liquid chromatography (HPLC) allows versatile and inexpensive globin quantification, but commonly applied protocols suffer either from long run times, high sample requirements or inability to separate murine from human β-globin chains...
January 12, 2018: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29325032/effect-of-diazoxide-on-friedreich-ataxia-models
#17
Antonella Santoro, Sara Anjomani Virmouni, Eleonora Paradies, Valentina L Villalobos Coa, Sahar Al-Mahdawi, Mee Khoo, Vito Porcelli, Angelo Vozza, Mara Perrone, Nunzio Denora, Franco Taroni, Giuseppe Merla, Luigi Palmieri, Mark A Pook, Carlo M T Marobbio
Friedreich ataxia (FRDA) is an inherited recessive disorder caused by a deficiency in the mitochondrial protein frataxin. There is currently no effective treatment for FRDA available, especially for neurological deficits. In this study, we tested diazoxide, a drug commonly used as vasodilator in the treatment of acute hypertension, on cellular and animal models of FRDA. We first showed that diazoxide increases frataxin protein levels in FRDA lymphoblastoid cell lines, via the mTOR pathway. We then explored the potential therapeutic effect of diazoxide in frataxin-deficient transgenic YG8sR mice and we found that prolonged oral administration of 3mpk/d diazoxide was found to be safe, but produced variable effects concerning efficacy...
January 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29324900/internal-carotid-artery-stenosis-a-novel-surgical-model-for-moyamoya-syndrome
#18
Jill M Roberts, Michael E Maniskas, Justin F Fraser, Gregory J Bix
Moyamoya is a cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries. There are two forms: Disease and Syndrome, with each characterized by the sub-population it affects. Moyamoya syndrome (MMS) is more prominent in adults in their 20's-40's, and is often associated with autoimmune diseases. Currently, there are no surgical models for inducing moyamoya syndrome, so our aim was to develop a new animal model to study this relatively unknown cerebrovascular disease...
2018: PloS One
https://www.readbyqxmd.com/read/29324859/magnetic-resonance-spectroscopy-detects-differential-lipid-composition-in-mammary-glands-on-low-fat-high-animal-fat-versus-high-fructose-diets
#19
Dianning He, Devkumar Mustafi, Xiaobing Fan, Sully Fernandez, Erica Markiewicz, Marta Zamora, Jeffrey Mueller, Joseph R Sachleben, Matthew J Brady, Suzanne D Conzen, Gregory S Karczmar
The effects of consumption of different diets on the fatty acid composition in the mammary glands of SV40 T-antigen (Tag) transgenic mice, a well-established model of human triple-negative breast cancer, were investigated with magnetic resonance spectroscopy and spectroscopic imaging. Female C3(1) SV40 Tag transgenic mice (n = 12) were divided into three groups at 4 weeks of age: low fat diet (LFD), high animal fat diet (HAFD), and high fructose diet (HFruD). MRI scans of mammary glands were acquired with a 9...
2018: PloS One
https://www.readbyqxmd.com/read/29324843/beta-hpv38-oncoproteins-act-with-a-hit-and-run-mechanism-in-ultraviolet-radiation-induced-skin-carcinogenesis-in-mice
#20
Daniele Viarisio, Karin Müller-Decker, Rosita Accardi, Alexis Robitaille, Matthias Dürst, Katrin Beer, Lars Jansen, Christa Flechtenmacher, Matthias Bozza, Richard Harbottle, Catherine Voegele, Maude Ardin, Jiri Zavadil, Sandra Caldeira, Lutz Gissmann, Massimo Tommasino
Cutaneous beta human papillomavirus (HPV) types are suspected to be involved, together with ultraviolet (UV) radiation, in the development of non-melanoma skin cancer (NMSC). Studies in in vitro and in vivo experimental models have highlighted the transforming properties of beta HPV E6 and E7 oncoproteins. However, epidemiological findings indicate that beta HPV types may be required only at an initial stage of carcinogenesis, and may become dispensable after full establishment of NMSC. Here, we further investigate the potential role of beta HPVs in NMSC using a Cre-loxP-based transgenic (Tg) mouse model that expresses beta HPV38 E6 and E7 oncogenes in the basal layer of the skin epidermis and is highly susceptible to UV-induced carcinogenesis...
January 2018: PLoS Pathogens
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