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https://www.readbyqxmd.com/read/28644884/ligand-induced-rapid-skeletal-muscle-atrophy-in-hsa-fv2e-perk-transgenic-mice
#1
Masato Miyake, Masashi Kuroda, Hiroshi Kiyonari, Kenji Takehana, Satoshi Hisanaga, Masatoshi Morimoto, Jun Zhang, Miho Oyadomari, Hiroshi Sakaue, Seiichi Oyadomari
BACKGROUND: Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly. OBJECTIVE: The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly. MATERIAL AND METHODS: A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly...
2017: PloS One
https://www.readbyqxmd.com/read/28644737/circulatory-cnp-rescues-craniofacial-hypoplasia-in-achondroplasia
#2
S Yamanaka, Kazumasa Nakao, N Koyama, Y Isobe, Y Ueda, Y Kanai, E Kondo, T Fujii, M Miura, A Yasoda, Kazuwa Nakao, K Bessho
Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28644090/transdermal-administration-of-melatonin-coupled-to-cryopass-laser-treatment-as-noninvasive-therapy-for-prostate-cancer
#3
Laura Terraneo, Paola Bianciardi, Eleonora Virgili, Elena Finati, Michele Samaja, Rita Paroni
Melatonin, a pineal gland hormone, exerts oncostatic activity in several types of human cancer, including prostate, the most common neoplasia and the third most frequent cause of male cancer death in the developed world. The growth of androgen-sensitive LNCaP prostate cancer cells in mice is inhibited by 3 mg/kg/week melatonin (0.09 mg/mouse/week) delivered by i.p. injections, which is equivalent to a dose of 210 mg/week in humans. The aim of this study is to test an alternative noninvasive delivery route based on transdermal administration of melatonin onto the tumor area followed by cryopass-laser treatment...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28644012/sigma-2-receptor-tmem97-agonists-produce-long-lasting-anti-neuropathic-pain-effects-in-mice
#4
James J Sahn, Galo L Mejia, Pradipta R Ray, Stephen F Martin, Theodore John Price
Neuropathic pain is an important medical problem with few effective treatments. The sigma 1 receptor (σ1R) is a potential target for neuropathic pain therapeutics, and antagonists for this receptor are effective in preclinical models and are currently in phase II clinical trials. Relatively little is known about the σ2R, which has recently been identified as transmembrane protein 97 (Tmem97). We generated a series of σ1R and σ2R/Tmem97 agonists and antagonists and tested them for efficacy in the mouse spared nerve injury (SNI) model...
June 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28643914/the-use-of-cell-culture-platforms-to-identify-novel-markers-of-bone-and-dentin-resorption
#5
W J Rody, O Krokhin, V Spicer, C A Chamberlain, M Chamberlain, K P McHugh, S M Wallet, A K Emory, J D Crull, L S Holliday
OBJECTIVES: 1) To test the hypothesis that there would be proteomic differences in the composition of exosomes isolated from osteoclasts and odontoclasts and 2) to determine the clinical usefulness of these in vitro biomarker candidates. MATERIALS AND METHODS: Mouse bone marrow-derived precursors were cultured on either dentin or bone slices and allowed to mature and begin resorption. Exosomes were isolated from cell culture media and characterized by mass spectrometry...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643912/mouse-models-for-the-study-of-cranial-base-growth-and-anomalies
#6
REVIEW
S R Vora
The cranial base is a central and integral component of the cranioskeleton, yet little is known about its growth. Despite the dissimilarities between human and murine cranioskeletal form, mouse models are proving instrumental in studying craniofacial growth. The objectives of this review are to summarize recent findings from numerous mouse models that display growth defects in one or more cranial base synchondroses, with accompanying changes in chondrocyte cellular zones. Many of these models also display altered growth of the cranial vault and/or the facial region...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643892/calcitriol-exerts-an-anti-tumor-effect-in-osteosarcoma-by-inducing-the-endoplasmic-reticulum-er-stress-response
#7
Takatsune Shimizu, Walied A Kamel, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Akihiro Muto, Hideyuki Saya
Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of FDA-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS)...
June 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28643456/irf6-expression-in-basal-epithelium-partially-rescues-irf6-knockout-mice
#8
Youssef A Kousa, Dina Moussa, Brian C Schutte
BACKGROUND: Mutations in IRF6, CHUK (IKKA) and RIPK4 can lead to a disease spectrum that includes cutaneous, limb and craniofacial malformations. Loss of these alleles in the mouse leads to perinatal lethality and severe cutaneous, limb and craniofacial defects. Genetic rescue in the mouse has been shown for Ikka and Ripk4. RESULTS: Here, we show partial genetic rescue of Irf6 knockout embryos using the KRT14 promoter to drive Irf6 expression in the basal epithelium...
June 23, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28643328/drug-repurposing-by-simulating-flow-through-protein-protein-interaction-networks
#9
M Manczinger, V Bodnár, B T Papp, B Sz Bolla, K Szabó, B Balázs, E Csányi, E Szél, G Erős, L Kemény
As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and uses Support Vector Machine to identify potentially effective drugs in our model disease, psoriasis...
June 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28643250/genome-editing-in-mouse-zygotes-and-embryonic-stem-cells-by-introducing-sgrna-cas9-expressing-plasmids
#10
Taichi Noda, Asami Oji, Masahito Ikawa
In mammalian cells, genome editing with the single guide RNA (sgRNA)/Cas9 complex allows for high targeting efficiency within a relatively short time frame with the added benefits of being low cost and easy to design. sgRNA/Cas9-mediated editing in mouse zygotes has accelerated the analysis of gene functions and the generation of mouse models of human diseases. Despite the benefits, this method still suffers from several problems, such as mosaicism in the founder generation which complicates genotyping and phenotypical analyses, and the low efficiency of more complicated genome editing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28643248/computational-prediction-of-crispr-cas9-target-sites-reveals-potential-off-target-risks-in-human-and-mouse
#11
Qingbo Wang, Kumiko Ui-Tei
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system is a prominent genome engineering technology. In the CRISPR/Cas system, the RNA-guided endonuclease Cas protein introduces a DNA double-stranded break at the genome position recognized by a guide RNA (gRNA) based on complementary base-pairing of about 20-nucleotides in length. The 8- or 12-mer gRNA sequence in the proximal region is especially important for target recognition, and the genes with sequence complementarity to such regions are often disrupted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28643153/a-3e8-scfv-cys-ir800-conjugate-targeting-tag-72-in-an-orthotopic-colorectal-cancer-model
#12
Li Gong, Haiming Ding, Nicholas E Long, Brandon J Sullivan, Edward W Martin, Thomas J Magliery, Michael F Tweedle
PURPOSE: Optical surgical navigation (OSN) will be a potent tool to help surgeons more accurately and efficiently remove tumors. The purpose of this study was to evaluate a novel humanized 3E8 antibody (3E8 MAb) fragment site-specifically conjugated with IR800, 3E8.scFv.Cys-IR800, as a potential OSN agent to target colorectal adenocarcinoma. PROCEDURES: An engineered single-chain variable fragment of 3E8 MAb (targeted to TAG-72), appending a C-terminal cysteine residue (3E8...
June 22, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28642803/transcriptomic-profiles-of-aging-in-na%C3%A3-ve-and-memory-cd4-cells-from-mice
#13
Jackson Taylor, Lindsay Reynolds, Li Hou, Kurt Lohman, Wei Cui, Stephen Kritchevsky, Charles McCall, Yongmei Liu
BACKGROUND: CD4+ T cells can be broadly divided into naïve and memory subsets, each of which are differentially impaired by the aging process. It is unclear if and how these differences are reflected at the transcriptomic level. We performed microarray profiling on RNA derived from naïve (CD44(low)) and memory (CD44(high)) CD4+ T cells derived from young (2-3 month) and old (28 month) mice, in order to better understand the mechanisms of age-related functional alterations in both subsets...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28642444/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#14
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642332/morphine-worsens-the-severity-and-prevents-pancreatic-regeneration-in-mouse-models-of-acute-pancreatitis
#15
Usman Barlass, Raini Dutta, Hassam Cheema, John George, Archana Sareen, Ajay Dixit, Zuobiao Yuan, Bhuwan Giri, Jingjing Meng, Santanu Banerjee, Sulagna Banerjee, Vikas Dudeja, Rajinder K Dawra, Sabita Roy, Ashok K Saluja
BACKGROUND: Opioids such as morphine are widely used for the management of pain associated with acute pancreatitis. Interestingly, opioids are also known to affect the immune system and modulate inflammatory pathways in non-pancreatic diseases. However, the impact of morphine on the progression of acute pancreatitis has never been evaluated. In the current study, we evaluated the impact of morphine on the progression and severity of acute pancreatitis. METHODS: Effect of morphine treatment on acute pancreatitis in caerulein, L-arginine and ethanol-palmitoleic acid models was evaluated after induction of the disease...
June 22, 2017: Gut
https://www.readbyqxmd.com/read/28642245/a-reporter-mouse-model-for-in-vivo-tracing-and-in-vitro-molecular-studies-of-melanocytic-lineage-cells-and-their-diseases
#16
Melissa Crawford, Valerie Leclerc, Lina Dagnino
Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, as well as melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations...
June 22, 2017: Biology Open
https://www.readbyqxmd.com/read/28642198/treatment-of-intestinal-fibrosis-in-experimental-inflammatory-bowel-disease-by-the-pleiotropic-actions-of-a-local-rho-kinase-inhibitor
#17
Tom Holvoet, Sarah Devriese, Karolien Castermans, Sandro Boland, Dirk Leysen, Yves-Paul Vandewynckel, Lindsey Devisscher, Lien Van den Bossche, Sophie Van Welden, Melissa Dullaers, Roosmarijn E Vandenbroucke, Riet De Rycke, Karel Geboes, Arnaud Bourin, Olivier Defert, Pieter Hindryckx, Martine De Vos, Debby Laukens
BACKGROUND: Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ1-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side-effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium and adoptive T cell transfer...
June 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28642195/how-lipid-droplets-tag-along-glycerolipid-synthetic-enzymes-and-lipid-storage
#18
REVIEW
Huan Wang, Michael V Airola, Karen Reue
Triacylglycerols (TAG) serve as the predominant form of energy storage in mammalian cells, and TAG synthesis influences conditions such as obesity, fatty liver, and insulin resistance. In most tissues, the glycerol 3-phosphate pathway enzymes are responsible for TAG synthesis, and the regulation and function of these enzymes is therefore important for metabolic homeostasis. Here we review the sites and regulation of glycerol-3-phosphate acyltransferase (GPAT), acylglycerol-3-phosphate acyltransferase (AGPAT), lipin/phosphatidic acid phosphatase (PAP), and diacylglycerol acyltransferase (DGAT) enzyme action...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28642129/fucoxanthin-inhibits-profibrotic-protein-expression-in-vitro-and-attenuates-bleomycin-induced-lung-fibrosis-in-vivo
#19
Sun Young Ma, Won Sun Park, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Won-Kyo Jung, Sae Gwang Park, Su-Kil Seo, Sung Jae Park, Il Yong Han, Yung Hyun Choi, Il-Whan Choi
Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-β1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated...
June 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28642030/cyclic-mog35-55-ameliorates-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis
#20
Athanasios Lourbopoulos, George Deraos, Minos-Timotheos Matsoukas, Olga Touloumi, Aggeliki Giannakopoulou, Hubert Kalbacher, Nikolaos Grigoriadis, Vasso Apostolopoulos, John Matsoukas
EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell. Altered peptide ligand (APL) vaccination is a novel approach based on an effort to induce T-cell tolerance or alter cytokine profile from pro-inflammatory to anti-inflammatory. In the present study we synthesized the MOG35-55 peptide and altered its 3-dimensional conformation to make it a cyclic one (c-MOG35-55)...
June 7, 2017: Bioorganic & Medicinal Chemistry
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