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https://www.readbyqxmd.com/read/28918503/coq0-induced-mitochondrial-ptp-opening-triggers-apoptosis-via-ros-mediated-vdac1-upregulation-in-hl-60-leukemia-cells-and-suppresses-tumor-growth-in-athymic-nude-mice-xenografted-nude-mice
#1
You-Cheng Hseu, Varadharajan Thiyagarajan, Ting-Tsz Ou, Hsin-Ling Yang
Coenzyme Q (CoQ) analogs with variable numbers of isoprenoid units have been demonstrated as anticancer and antioxidant/pro-oxidant molecules. This study examined the in vitro and in vivo antitumor and apoptosis activities of CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero isoprenoid side-chains) through upregulation of the Voltage-dependent anion channel 1 (VDAC1) signaling pathway on human promyelocytic leukemia. CoQ0 (0-40 μg/mL) treatment significantly reduced HL-60 cell viability, and up-regulated mitochondrial VDAC1 expression...
September 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28918463/apoptotic-mechanisms-after-repeated-noise-trauma-in-the-mouse-medial-geniculate-body-and-primary-auditory-cortex
#2
Felix Fröhlich, Arne Ernst, Ira Strübing, Dietmar Basta, Moritz Gröschel
A correlation between noise-induced apoptosis and cell loss has previously been shown after a single noise exposure in the cochlear nucleus, inferior colliculus, medial geniculate body (MGB) and primary auditory cortex (AI). However, repeated noise exposure is the most common situation in humans and a major risk factor for the induction of noise-induced hearing loss (NIHL). The present investigation measured cell death pathways using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the dorsal, medial and ventral MGB (dMGB, mMGB and vMGB) and six layers of the AI (AI-1 to AI-6) in mice (NMRI strain) after a second noise exposure (double-exposure group)...
September 16, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28918039/crispr-cas9-mediated-knockin-application-in-cell-therapy-a-non-viral-procedure-for-bystander-treatment-of-glioma-in-mice
#3
Oscar Meca-Cortés, Marta Guerra-Rebollo, Cristina Garrido, Salvador Borrós, Nuria Rubio, Jeronimo Blanco
The use of non-viral procedures, together with CRISPR/Cas9 genome-editing technology, allows the insertion of single-copy therapeutic genes at pre-determined genomic sites, overcoming safety limitations resulting from random gene insertions of viral vectors with potential for genome damage. In this study, we demonstrate that combination of non-viral gene delivery and CRISPR/Cas9-mediated knockin via homology-directed repair can replace the use of viral vectors for the generation of genetically modified therapeutic cells...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918011/nucleic-acid-polymers-with-accelerated-plasma-and-tissue-clearance-for-chronic-hepatitis-b-therapy
#4
Ingo Roehl, Stephan Seiffert, Celia Brikh, Jonathan Quinet, Catherine Jamard, Nadine Dorfler, Jennifer A Lockridge, Lucyna Cova, Andrew Vaillant
REP 2139 is a nucleic acid polymer (NAP) currently under clinical development for chronic hepatitis B (HBV) therapy. This preclinical study investigated different REP 2139 analogs that would display reduced accumulation in the serum and tissues, while retaining an antiviral effect against HBV infection. REP 2139 analogs were evaluated in human plasma, CD-1 mice, cynomolgus monkeys, and Pekin ducks. Discrete ribose transformation to 2'OH in selected riboadenosines resulted in a slow degradation in acidified human plasma that plateaued after 48 hr...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917978/sen1500-a-novel-oral-amyloid-%C3%AE-aggregation-inhibitor-attenuates-brain-pathology-in-a-mouse-model-of-alzheimer-s-disease
#5
D Brunner, S Flunkert, J Neddens, S Duller, D I C Scopes, J M Treherne, B Hutter-Paier
INTRODUCTION: Amyloid-β (Aβ) aggregation is thought to be a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The development of new drugs inhibiting the Aβ aggregation process is, therefore, important. SEN1500, an orally bioavailable and CNS-penetrant Aβ aggregation inhibitor, has previously been shown to reduce spatial learning and memory deficits in an APP transgenic mouse model. To verify that the pharmacological properties of SEN1500 are not unique to this model, we investigated brain Aβ pathology, neuroinflammation, as well as memory in a different mouse model of AD expressing the human amyloid precursor protein with Swedish and London mutations (APPSL)...
September 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28917835/antitumor-activity-pharmacokinetics-tumor-homing-effect-and-hepatotoxicity-of-a-species-cross-reactive-c-met-antibody
#6
Hyunkyu Park, Donggeon Kim, Eunju Son, Sunhwa Shin, Jason K Sa, Seok-Hyung Kim, Yeup Yoon, Do-Hyun Nam
The receptor tyrosine kinase c-Met plays critical roles in promoting tumor growth, invasion, metastasis, and angiogenesis in various types of cancer and is a promising therapeutic target. The development of a species cross-reactive therapeutic antibody could provide useful to comprehensive preclinical assessment in animal models. Towards this goal, we developed human/mouse cross-reactive c-Met antibodies using an antibody phage library. IRCR201, a c-Met antibody with species cross-reactivity, successfully inhibited the HGF/c-Met signaling pathway via degradation of c-Met and disruption of the binding with its partners, and demonstrated strong in vivo antitumor activity...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28917663/leucine-rich-%C3%AE-2-glycoprotein-overexpression-in-the-brain-contributes-to-memory-impairment
#7
Chihiro Akiba, Madoka Nakajima, Masakazu Miyajima, Ikuko Ogino, Masami Miura, Ritsuko Inoue, Eri Nakamura, Fumio Kanai, Norihiro Tada, Miyuki Kunichika, Mitsutaka Yoshida, Kinya Nishimura, Akihide Kondo, Hidenori Sugano, Hajime Arai
We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg. Y-maze and Morris water maze tests indicated retained spatial memory in 8- and 24-week-old LRG-Tg, while deteriorated in 48-week-old LRG-Tg compared with age-matched controls...
August 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28917649/evaluation-of-novel-111-in-labeled-gonadotropin-releasing-hormone-peptides-for-human-prostate-cancer-imaging
#8
Jingli Xu, Changjian Feng, Yubin Miao
The purpose of this study was to evaluate the tumor targeting and imaging properties of novel (111)In-labeled gonadotropin-releasing hormone (GnRH) peptides for human prostate cancer. Three new 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linker-d-Phe-(d-Lys(6)-GnRH) peptides with different hydrocarbon linkers were designed to evaluate their effects on GnRH receptor binding affinities. The Aoc (aminooctanoic acid) linker was better than βAla (3-aminopropanoic acid) and Aun (aminoundecanoic acid) linkers in retaining strong receptor binding affinity...
September 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28917322/high-genetic-diversity-in-toxoplasma-gondii-isolates-from-pigs-at-slaughterhouses-in-para%C3%A3-ba-state-northeastern-brazil-circulation-of-new-genotypes-and-brazilian-clonal-lineages
#9
Thais Ferreira Feitosa, Vinícius Longo Ribeiro Vilela, João Leite de Almeida-Neto, Antonielson Dos Santos, Dayana Firmino de Morais, Bruna Farias Alves, Fabiana Nakashima, Solange Maria Gennari, Ana Célia Rodrigues Athayde, Hilda Fátima Jesus Pena
The consumption of raw or undercooked pig meat containing Toxoplasma gondii cysts is an important transmission route of this protozoon to animals and humans. This study aimed to serologically diagnose, isolate and genotype T. gondii from pigs slaughtered for human consumption in the state of Paraíba, northeastern Brazil. Blood and tissue samples (heart, tongue and brain) were collected from 120 pigs at slaughterhouses in the state of Paraíba. Serological examinations were performed with an indirect immunofluorescent antibody test (IFAT) with a cut-off point of 1:64...
September 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28917045/radioactive-75-se-labeling-and-detection-of-selenoproteins
#10
Sun Hee Yim, Ryuta Tobe, Anton A Turanov, Bradley A Carlson
The trace element selenium (Se) is incorporated into proteins as the amino acid selenocysteine (Sec), which is cotranslationally inserted into specific proteins in response to a UGA codon. Proteins containing Sec at these specific positions are called selenoproteins. Most selenoproteins function as oxidoreductases, while some serve other important functions. There are 25 known selenoprotein genes in humans and 24 in mice. The use of Sec allows selenoproteins to be detected by a convenient method involving metabolic labeling with (75)Se...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28916838/functionally-distinct-tendons-from-elastin-haploinsufficient-mice-exhibit-mild-stiffening-and-tendon-specific-structural-alteration
#11
Jeremy D Eekhoff, Fei Fang, Lindsey G Kahan, M G Espinosa, Austin J Cocciolone, Jessica E Wagenseil, Robert P Mecham, Spencer P Lake
Elastic fibers are present in low quantities in tendon, where they are located both within fascicles near tenocytes and more broadly in the interfascicular matrix. While elastic fibers have long been known to be significant in the mechanics of elastin-rich tissue (i.e. vasculature, skin, lungs), recent studies have suggested a mechanical role for elastic fibers in tendons that is dependent on specific tendon function. However, the exact contribution of elastin to properties of different types of tendons (e...
September 16, 2017: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/28916811/an-enu-induced-splice-site-mutation-of-mouse-col1a1-causing-recessive-osteogenesis-imperfecta-and-revealing-a-novel-splicing-rescue
#12
Koichi Tabeta, Xin Du, Kei Arimatsu, Mai Yokoji, Naoki Takahashi, Norio Amizuka, Tomoka Hasegawa, Karine Crozat, Tomoki Maekawa, Sayuri Miyauchi, Yumi Matsuda, Takako Ida, Masaru Kaku, Kasper Hoebe, Kinji Ohno, Hiromasa Yoshie, Kazuhisa Yamazaki, Eva Marie Y Moresco, Bruce Beutler
GU-AG consensus sequences are used for intron recognition in the majority of cases of pre-mRNA splicing in eukaryotes. Mutations at splice junctions often cause exon skipping, short deletions, or insertions in the mature mRNA, underlying one common molecular mechanism of genetic diseases. Using N-ethyl-N-nitrosourea, a novel recessive mutation named seal was produced, associated with fragile bones and susceptibility to fractures (spine and limbs). A single nucleotide transversion (T → A) at the second position of intron 36 of the Col1a1 gene, encoding the type I collagen, α1 chain, was responsible for the phenotype...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916789/whole-body-and-hematopoietic-adam8-deficiency-does-not-influence-advanced-atherosclerotic-lesion-development-despite-its-association-with-human-plaque-progression
#13
Kosta Theodorou, Emiel P C van der Vorst, Marion J Gijbels, Ine M J Wolfs, Mike Jeurissen, Thomas L Theelen, Judith C Sluimer, Erwin Wijnands, Jack P Cleutjens, Yu Li, Yvonne Jansen, Christian Weber, Andreas Ludwig, Jacob F Bentzon, Jörg W Bartsch, Erik A L Biessen, Marjo M P C Donners
Although A Disintegrin And Metalloproteinase 8 (ADAM8) is not crucial for tissue development and homeostasis, it has been implicated in various inflammatory diseases by regulating processes like immune cell recruitment and activation. ADAM8 expression has been associated with human atherosclerosis development and myocardial infarction, however a causal role of ADAM8 in atherosclerosis has not been investigated thus far. In this study, we examined the expression of ADAM8 in early and progressed human atherosclerotic lesions, in which ADAM8 was significantly upregulated in vulnerable lesions...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916757/muscle-pathology-from-stochastic-low-level-dux4-expression-in-an-fshd-mouse-model
#14
Darko Bosnakovski, Sunny S K Chan, Olivia O Recht, Lynn M Hartweck, Collin J Gustafson, Laura L Athman, Dawn A Lowe, Michael Kyba
Facioscapulohumeral muscular dystrophy is a slowly progressive but devastating myopathy caused by loss of repression of the transcription factor DUX4; however, DUX4 expression is very low, and protein has not been detected directly in patient biopsies. Efforts to model DUX4 myopathy in mice have foundered either in being too severe, or in lacking muscle phenotypes. Here we show that the endogenous facioscapulohumeral muscular dystrophy-specific DUX4 polyadenylation signal is surprisingly inefficient, and use this finding to develop an facioscapulohumeral muscular dystrophy mouse model with muscle-specific doxycycline-regulated DUX4 expression...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916755/protein-o-fucosylation-in-plasmodium-falciparum-ensures-efficient-infection-of-mosquito-and-vertebrate-hosts
#15
Sash Lopaticki, Annie S P Yang, Alan John, Nichollas E Scott, James P Lingford, Matthew T O'Neill, Sara M Erickson, Nicole C McKenzie, Charlie Jennison, Lachlan W Whitehead, Donna N Douglas, Norman M Kneteman, Ethan D Goddard-Borger, Justin A Boddey
O-glycosylation of the Plasmodium sporozoite surface proteins CSP and TRAP was recently identified, but the role of this modification in the parasite life cycle and its relevance to vaccine design remain unclear. Here, we identify the Plasmodium protein O-fucosyltransferase (POFUT2) responsible for O-glycosylating CSP and TRAP. Genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms in humanized chimeric liver mice...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916723/fibroblast-growth-factor-2-fgf2-regulates-cytoglobin-expression-and-activation-of-human-hepatic-stellate-cells-via-jnk-signaling
#16
Misako Sato-Matsubara, Tsutomu Matsubara, Atsuko Daikoku, Yoshinori Okina, Lisa Longato, Krista Rombouts, Le Thi Thanh Thuy, Jun Adachi, Takeshi Tomonaga, Kazuo Ikeda, Katsutoshi Yoshizato, Massimo Pinzani, Norifumi Kawada
Cytoglobin (CYGB) belongs to the mammalian globin family and is exclusively expressed in hepatic stellate cells (HSCs) in the liver. In addition to its gas-binding ability, CYGB is relevant to hepatic inflammation, fibrosis, and cancer because of its antioxidative properties; however, the regulation of CYGB gene expression remains unknown. Here, we sought to identify factors that induce CYGB expression in HSCs and to clarify the molecular mechanism involved. We used the human HSC cell line HHSteC and primary human HSCs isolated from intact human liver tissues...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916717/nlrps-the-subcortical-maternal-complex-and-genomic-imprinting
#17
David Monk, Marta Sanchez-Delgado, Rosemary Fisher
Before activation of the embryonic genome, the oocyte provides many of the RNAs and proteins required for the epigenetic reprogramming and the transition to a totipotent state. Targeted disruption of a subset of oocyte-derived transcripts in mice results in early embryonic lethality and cleavage stage embryonic arrest as highlighted by the members of the Subcortical Maternal Complex (SCMC). Maternal-effect recessive mutations of NLRP7, KHDC3L and NLRP5 in humans are associated with variable reproductive outcomes, biparental hydatidiform moles (BiHM) and widespread multi-locus imprinting disturbances...
September 15, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28916654/biallelic-dicer1%C3%A2-loss-mediated-by-ap2-cre-drives-angiosarcoma
#18
Jason A Hanna, Catherine J Drummond, Matthew R Garcia, Jonathan C Go, David Finkelstein, Jerold E Rehg, Mark E Hatley
Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Due to the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to microRNA biogenesis, and germline DICER1 mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here we show that biallelic Dicer1 deletion with aP2-Cre drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916639/small-rna-seq-during-acute-maximal-exercise-reveal-rnas-involved-in-vascular-inflammation-and-cardiometabolic-health
#19
Ravi Shah, Ashish S Yeri, Avash Das, Amanda Courtright-Lim, Olivia Ziegler, Ernest Gervino, Jeffrey Ocel, Pablo Quintero Pinzon, Luke Wooster, Cole Shields Bailey, Kahraman Tanriverdi, Lea Beaulieu, Jane E Freedman, Ionita Ghiran, Gregory D Lewis, Kendall Van Keuren-Jensen, Saumya Das
OBJECTIVE: Exercise improves cardiometabolic and vascular function, though mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. Approach and Results: We performed plasma small RNA sequencing (RNA-seq) in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry...
September 15, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28916638/pharmacological-and-physiological-assessment-of-serotonin-formation-and-degradation-in-isolated-preparations-from-mouse-and-human-heart
#20
Ulrich Gergs, Franziska Jung, Igor B Buchwalow, Britt Hofmann, Andreas Simm, Hendrik Treede, Joachim Neumann
Using transgenic mice (TG) that overexpress the human 5-HT4a-receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor, 5-hydroxy-tryptophan (5-HTP), can exert inotropic and chronotropic effects in cardiac preparations from TG but not from wild type (WT): similar results were found in human atrial preparations, as well as in intact TG animals using echocardiography...
September 15, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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