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https://www.readbyqxmd.com/read/28549091/regional-retinal-ganglion-cell-axon-loss-in-a-murine-glaucoma-model
#1
Julie A Schaub, Elizabeth C Kimball, Matthew R Steinhart, Cathy Nguyen, Mary E Pease, Ericka N Oglesby, Joan L Jefferys, Harry A Quigley
Purpose: To determine if retinal ganglion cell (RGC) axon loss in experimental mouse glaucoma is uniform in the optic nerve. Methods: Experimental glaucoma was induced for 6 weeks with a microbead injection model in CD1 (n = 78) and C57BL/6 (B6, n = 68) mice. From epoxy-embedded sections of optic nerve 1 to 2 mm posterior to the globe, total nerve area and regional axon density (axons/1600 μm2) were measured in superior, inferior, nasal, and temporal zones. Results: Control eyes of CD1 mice have higher axon density and more total RGCs than control B6 mice eyes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28548945/soluble-antigens-from-the-neurotropic-pathogen-angiostrongylus-cantonensis-directly-induce-thymus-atrophy-in-a-mouse-model
#2
Zhen Liu, Dong-Ming Su, Zi-Long Yu, Feng Wu, Rui-Feng Liu, Shi-Qi Luo, Zhi-Yue Lv, Xin Zeng, Xi Sun, Zhong-Dao Wu
The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infectedmouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548934/ikbke-regulates-cell-proliferation-and-epithelial-mesenchymal-transition-of-human-malignant-glioma-via-the-hippo-pathway
#3
Jie Lu, Yi Yang, Gaochao Guo, Yang Liu, Zhimeng Zhang, Shicai Dong, Yang Nan, Zhenyi Zhao, Yue Zhong, Qiang Huang
IKBKE is increased in several types of cancers and is associated with tumour malignancy. In this study, we confirmed that IKBKE promoted glioma proliferation, migration and invasion in vitro. Then, we further discovered that IKBKE increased Yes-associated protein 1 (YAP1) and TEA domain family member 2 (TEAD2), two important Hippo pathway downstream factors, to induce an epithelial-mesenchymal transition (EMT), thus contributing to tumour invasion and metastasis. We also testified that YAP1 and TEAD2 promoted epithelial-mesenchymal transition (EMT) in malignant glioma...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548932/lncrna-tincr-attenuates-cardiac-hypertrophy-by-epigenetic-silencing-of-camkii
#4
Mingjing Shao, Guangdong Chen, Fengli Lv, Yanyan Liu, Hongjun Tian, Ran Tao, Ronghuan Jiang, Wei Zhang, Chuanjun Zhuo
In the previous study, we established a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and found that the expression of long non-coding RNAs TINCR was downregulated in myocardial tissue. The present study was designed to determine the potential role of TINCR in the pathogenesis of cardiac hypertrophy. Our results showed that enforced expression of TINCR could attenuate cardiac hypertrophy in TAC mice. Angiotensin II (Ang-II) was found to be associated with reduced TINCR expression and increased hypertrophy in cultured neonatal cardiomyocytes...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548682/arthrotomy-based-pre-clinical-models-of-particle-induced-osteolysis-a-systematic-review
#5
REVIEW
Meghan M Moran, Brittany M Wilson, Ryan D Ross, Amarjit S Virdi, D Rick Sumner
We completed a systematic literature review of in vivo animal models that use arthrotomy-based methods to study particle-induced peri-implant osteolysis. The purpose of the review was to characterize the models developed to date, to determine the questions addressed, to assess scientific rigor and transparency and to identify gaps in knowledge. We probed three literature databases (Medline, Embase and Scopus) and found 77 manuscripts that fit the search parameters. In the most recent 10 years, researchers mainly used rat and mouse models, whereas in the previous 20 years large animal, canine and rabbit models were more common...
May 26, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28548225/single-and-combined-effects-of-delta-9-tetrahydrocannabinol-and-cannabidiol-in-a-mouse-model-of-chemotherapy-induced-neuropathic-pain
#6
Kirsten M King, Alyssa M Myers, Ariele J Soroka-Monzo, Ronald F Tuma, Ronald J Tallarida, Ellen A Walker, Sara Jane Ward
BACKGROUND AND PURPOSE: It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28548090/synergistic-il-6-and-il-8-paracrine-signalling-pathway-infers-a-strategy-to-inhibit-tumour-cell-migration
#7
Hasini Jayatilaka, Pranay Tyle, Jonathan J Chen, Minsuk Kwak, Julia Ju, Hyun Ji Kim, Jerry S H Lee, Pei-Hsun Wu, Daniele M Gilkes, Rong Fan, Denis Wirtz
Following uncontrolled proliferation, a subset of primary tumour cells acquires additional traits/mutations to trigger phenotypic changes that enhance migration and are hypothesized to be the initiators of metastasis. This study reveals an adaptive mechanism that harnesses synergistic paracrine signalling via IL-6/8, which is amplified by cell proliferation and cell density, to directly promote cell migration. This effect occurs in metastatic human sarcoma and carcinoma cells- but not in normal or non-metastatic cancer cells-, and likely involves the downstream signalling of WASF3 and Arp2/3...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547925/blockade-of-the-dissociation-of-nmmhc-iia-from-tnfr2-by-d39-a-saponin-from-liriope-muscari-suppresses-tissue-factor-expression-and-venous-thrombosis
#8
Ke-Feng Zhai, Jin-Rong Zheng, You-Mei Tang, Fang Li, Yan-Ni Lv, Yuan-Yuan Zhang, Zhen Gao, Jin Qi, Bo-Yang Yu, Jun-Ping Kou
BACKGROUND AND PURPOSE: Non-muscular myosin heavy chain IIA (NMMHC IIA) has been demonstrated to play a key role in tissue factor (TF) expression and venous thrombosis. However, whether natural products could inhibit thrombosis via NMMHC IIA remains unclear. In this study, we identified that a representative natural saponin D39 from Liriope muscari showed anti-thrombotic activity by targeting NMMHC IIA. EXPERIMENTAL APPROACH: TF expression and activity in endothelial cells were analysed in vitro by western blot and simplified chromogenic assays...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28547530/reduced-cam-kinase-ii-and-cam-kinase-iv-activities-underlie-cognitive-deficits-in-nckx2-heterozygous-mice
#9
Shigeki Moriguchi, Satomi Kita, Yasushi Yabuki, Ryo Inagaki, Hisanao Izumi, Yuzuru Sasaki, Hideaki Tagashira, Kyoji Horie, Junji Takeda, Takahiro Iwamoto, Kohji Fukunaga
Among five members of the K(+)-dependent Na(+)/Ca(2+) exchanger (NCKX) family (NCKX1-5), only NCKX2 is highly expressed in mouse brain. NCKX2 in plasma membranes mediates cytosolic calcium excretion through electrogenic exchange of 4 Na(+) for 1 Ca(2+) and 1 K(+). Here, we observed significantly decreased levels of NCKX2 protein and mRNA in the CA1 region of APP23 mice, a model of Alzheimer's disease. We also found that, like APP23 mice, heterozygous NCKX2-mutant mice exhibit mildly impaired hippocampal LTP and memory acquisition, the latter based on novel object recognition and passive avoidance tasks...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28547157/shikonin-induces-necroptosis-by-reactive-oxygen-species-activation-in-nasopharyngeal-carcinoma-cell-line-cne-2z
#10
Zixuan Zhang, Zhirui Zhang, Qixiang Li, Hao Jiao, Dianlong Chong, Xiaojin Sun, Pei Zhang, Qiang Huo, Hao Liu
Shikonin, a natural small agent, has shown inhibitory effect in many kinds of cells, which increases intracellular reactive oxygen species (ROS) level and causes mitochondrial injury. In this study, shikonin showed good inhibitory effect on nasopharyngeal carcinoma CNE-2Z cells in vivo and vitro. The results presented here revealed that ROS levels increased markly after shikonin treated. The electron microscopy displays the change in ultrastructure of CNE-2Z cells after treatment for shikonin, which indicated that shikonin induced necroptosis...
May 25, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28547077/effects-of-the-combined-treatment-of-bone-marrow-stromal-cells-with-mild-exercise-and-thyroid-hormone-on-brain-damage-and-apoptosis-in-a-mouse-focal-cerebral-ischemia-model
#11
Kobar Akhoundzadeh, Abedin Vakili, Hamid Reza Sameni, Abbas Ali Vafaei, Ali Rashidy-Pour, Manouchehr Safari, Razieh Mohammadkhani
This study examined whether post-stroke bone marrow stromal cells (BMSCs) therapy combined with exercise (EX) and/or thyroid hormone (TH) could reduce brain damage in an experimental ischemic stroke in mice. Focal cerebral ischemia was induced under Laser Doppler Flowmetry (LDF) guide by 45 min of middle cerebral artery occlusion (MCAO), followed by 7 days of reperfusion in albino mice. BMSCs were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of T3 (20 μg/100 g weight S...
May 25, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28547002/oncolytic-herpes-simplex-virus-inhibits-pediatric-brain-tumor-migration-and-invasion
#12
Julia V Cockle, Anke Brüning-Richardson, Karen J Scott, Jill Thompson, Timothy Kottke, Ewan Morrison, Azam Ismail, Angel M Carcaboso, Ailsa Rose, Peter Selby, Joe Conner, Susan Picton, Susan Short, Richard Vile, Alan Melcher, Elizabeth Ilett
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via immune-mediated mechanisms. Here we investigate a previously unreported mechanism of action: the inhibition of migration and invasion in pediatric brain tumors. We evaluated the effect of oncolytic herpes simplex virus 1716 (HSV1716) on the migration and invasion of pHGG and DIPG both in vitro using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays and in vivo using an orthotopic xenograft model of DIPG invasion...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28546638/effects-of-obesity-on-liver-cytochromes-p450-in-various-animal-models
#13
Veronika Tomankova, Pavel Anzenbacher, Eva Anzenbacherova
The prevalence of obesity and other obesity-related diseases is increasing worldwide. Obesity is a disease characterized by increased body weight, or a condition resulting from excessive accumulation of body fat. Due to increased body fat deposits, obesity has also been associated with increased mortality resulting from higher incidence rates of hypertension, diabetes, or various types of cancer, such as breast, colorectal, cervical and prostate cancer. Physiological changes associated with obesity are likely to result in altered drug biotransformation...
May 25, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28546505/role-of-cyp2b-in-phenobarbital-induced-hepatocyte-proliferation-in-mice
#14
Lei Li, Xiaochen Bao, Qing-Yu Zhang, Masahiko Negishi, Xinxin Ding
Phenobarbital (PB) promotes liver tumorigenesis in rodents, in part through activation of the constitutive androstane receptor (CAR) and the consequent changes in hepatic gene expression and increases in hepatocyte proliferation. A typical effect of CAR activation by PB is a marked induction of Cyp2b10 expression in the liver; the latter has been suspected to be vital for PB-induced hepatocellular proliferation. This hypothesis was tested here, by using a Cyp2a(4/5)bgs-null (null) mouse model, in which all Cyp2b genes are deleted...
May 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28546219/inos-derived-nitric-oxide-induces-integrin-linked-kinase-endocytic-lysosome-mediated-degradation-in-the-vascular-endothelium
#15
Paula Reventun, Matilde Alique, Irene Cuadrado, Susana Marquez, Rocio Toro, Carlos Zaragoza, Marta Saura
OBJECTIVE: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. APPROACH AND RESULTS: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with inducible NO synthase knockout mice...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28546087/region-specific-oligodendrocyte-transcription-factor-expression-in-a-model-of-neonatal-hypoxic-injury
#16
Bethann M Affeldt, Andre Obenaus, Jonathan Chan, Andrea C Pardo
White matter injury (WMI) of prematurity is associated with a spectrum of neurological disorders ranging from mild cognitive and behavioral deficits to cerebral palsy. Translational studies have implicated impaired oligodendrocyte development after hypoxia as the primary cause of WMI, but the underlying mechanisms remain poorly understood. The goal of this study was to identify alterations in the expression of oligodendrocyte precursor cell transcription factors in a mouse model of transient mild global hypoxia...
May 22, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28546081/targeting-nuclear-receptors-for-the-treatment-of-fatty-liver-disease
#17
REVIEW
Naoki Tanaka, Toshifumi Aoyama, Shioko Kimura, Frank J Gonzalez
Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farn esoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis...
May 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28546072/dendrimer-conjugated-peptide-vaccine-enhances-clearance-of-chlamydia-trachomatis-genital-infection
#18
Ingrid S Ganda, Qian Zhong, Mirabela Hali, Ricardo L C Albuquerque, Francine F Padilha, Sandro R P da Rocha, Judith A Whittum-Hudson
Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness...
May 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28546003/thymic-epithelial-cell-specific-deletion-of-jmjd6-reduces-aire-protein-expression-and-exacerbates-disease-development-in-a-mouse-model-of-autoimmune-diabetes
#19
Toyoshi Yanagihara, Takahiro Tomino, Takehito Uruno, Yoshinori Fukui
Thymic epithelial cells (TECs) establish spatially distinct microenvironments in which developing T cells are selected to mature or die. A unique property of medullary TECs is their expression of thousands of tissue-restricted self-antigens that is largely under the control of the transcriptional regulator Aire. We previously showed that Jmjd6, a lysyl hydroxylase for splicing regulatory proteins, is important for Aire protein expression and that transplantation of Jmjd6-deficient thymic stroma into athymic nude mice resulted in multiorgan autoimmunity...
May 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28545977/elevated-glutaric-acid-levels-in-dhtkd1-gcdh-double-knockout-mice-challenge-our-current-understanding-of-lysine-metabolism
#20
Caroline Biagosch, RagaDeepthi Ediga, Svenja-Viola Hensler, Michael Faerberboeck, Ralf Kuehn, Wolfgang Wurst, Thomas Meitinger, Stefan Kölker, Sven Sauer, Holger Prokisch
Glutaric aciduria type I (GA-I) is a rare organic aciduria caused by the autosomal recessive inherited deficiency of glutaryl-CoA dehydrogenase (GCDH). GCDH deficiency leads to disruption of L-lysine degradation with characteristic accumulation of glutarylcarnitine and neurotoxic glutaric acid (GA), glutaryl-CoA, 3-hydroxyglutaric acid (3-OHGA). DHTKD1 acts upstream of GCDH, and its deficiency leads to none or often mild clinical phenotype in humans, 2-aminoadipic 2-oxoadipic aciduria. We hypothesized that inhibition of DHTKD1 may prevent the accumulation of neurotoxic dicarboxylic metabolites suggesting DHTKD1 inhibition as a possible treatment strategy for GA-I...
May 22, 2017: Biochimica et Biophysica Acta
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