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https://www.readbyqxmd.com/read/28550681/antibiotic-associated-manipulation-of-the-gut-microbiota-and-phenotypic-restoration-in-nod-mice
#1
James R Fahey, Bonnie L Lyons, Haiyan L Olekszak, Anthony J Mourino, Jeremy J Ratiu, Jeremy J Racine, Harold D Chapman, David V Serreze, Dina L Baker, N Ken Hendrix
Segmented filamentous bacterium (SFB) a gram-positive, anaerobic, and intestinal commensal organism directly influencesthe development of Th17 helper cells in the small intestine of mice. In NOD mice, SFB colonization interferes with the developmentof type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, suggesting that SFB may influence Th17 cells to inhibit Th1populations associated with the anti-β-cell immune response. This effect is a serious concern for investigators who use NOD micefor diabetes research because the expected incidence of disease decreases markedly when they are colonized by SFB...
May 26, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28550662/-effects-of-simvastatin-on-the-proliferation-invasion-and-radiosensitivity-in-lewis-lung-cancer-cell-line
#2
S F Yu, J Cheng, S Geng, S Gao
Objective: To investigate the effects of simvastatin on proliferation, invasion and radiosensitivity of mouse Lewis lung cancer cell line in vitro. Methods: The inhibitory effects of simvastatin on proliferation of Lewis lung cancer cells were detected by MTT assay. Matrigel invasion and migration assay was used to determine the invasion and motility ability of the Lewis cells. P38 activity was measured by p38 activity detection kit, and the expressions of p-p38, MKP-1, RhoA and MMP-2 were analyzed by Western blot...
April 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28550529/single-administration-of-hbk-15-a-triple-5-ht1a-5-ht7-and-5-ht3-receptor-antagonist-reverses-depressive-like-behaviors-in-mouse-model-of-depression-induced-by-corticosterone
#3
Karolina Pytka, Monika Głuch-Lutwin, Magdalena Kotańska, Anna Waszkielewicz, Agnieszka Kij, Maria Walczak
Studies suggest that the blockade of 5-HT1A, 5-HT7, and 5-HT3 receptor may increase the speed of antidepressant response. 1-[(2,6-Dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15), dual 5-HT1A and 5-HT7 antagonists, showed significant antidepressant- and anxiolytic-like properties in our previous tests in rodents. In this study, we aimed to investigate their antidepressant potential using mouse model of corticosterone-induced depression...
May 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#4
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#5
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28550381/treatment-of-dyslipidemia-using-crispr-cas9-genome-editing
#6
REVIEW
Alexandra C Chadwick, Kiran Musunuru
PURPOSE OF REVIEW: Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) has recently emerged as a top genome editing technology and has afforded investigators the ability to more easily study a number of diseases. This review discusses CRISPR/Cas9's advantages and limitations and highlights a few recent reports on genome editing applications for alleviating dyslipidemia through disruption of proprotein convertase subtilisin/kexin type 9 (PCSK9)...
July 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28550361/prolyl-hydroxylase-inhibition-induces-sdf-1-associated-with-increased-cxcr4-cd11b-subpopulations-and-cardiac-repair
#7
Santhosh Kumar Ghadge, Moritz Messner, Thi Van Pham, Maximilian Doppelhammer, Andreas Petry, Agnes Görlach, Britta Husse, Wolfgang-Michael Franz, Marc-Michael Zaruba
SDF-1/CXCR4 activation facilitates myocardial repair. Therefore, we aimed to activate the HIF-1α target genes SDF-1 and CXCR4 by dimethyloxalylglycine (DMOG)-induced prolyl-hydroxylase (PH) inhibition to augment CXCR4+ cell recruitment and myocardial repair. SDF-1 and CXCR4 expression was analyzed under normoxia and ischemia ± DMOG utilizing SDF-1-EGFP and CXCR4-EGFP reporter mice. In bone marrow and heart, CXCR4-EGFP was predominantly expressed in CD45+/CD11b+ leukocytes which significantly increased after myocardial ischemia...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28550268/improving-reproducibility-of-phenotypic-assessments-in-the-dyw-mouse-model-of-laminin-%C3%AE-2-related-congenital-muscular-dystrophy
#8
Raffaella Willmann, Heather Gordish-Dressman, Sarina Meinen, Markus A Rüegg, Qing Yu, Kanneboyina Nagaraju, Ayar Kumar, Mahasweta Girgenrath, Caroline B M Coffey, Vivian Cruz, Pam M Van Ry, Laurent Bogdanik, Cathleen Lutz, Anne Rutkowski, Dean J Burkin
Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing...
May 24, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28550259/transport-of-non-transferrin-bound-iron-to-the-brain-implications-for-alzheimer-s-disease
#9
Ajai K Tripathi, Shilpita Karmakar, Abhishek Asthana, Ajay Ashok, Vilok Desai, Shounak Baksi, Neena Singh
A direct correlation between brain iron and Alzheimer's disease (AD) raises questions regarding the transport of non-transferrin-bound iron (NTBI), a toxic but less researched pool of circulating iron that is likely to increase due to pathological and/or iatrogenic systemic iron overload. Here, we compared the distribution of radiolabeled-NTBI (59Fe-NTBI) and transferrin-bound iron (59Fe-Tf) in mouse models of iron overload in the absence or presence of inflammation. Following a short pulse, most of the 59Fe-NTBI was taken up by the liver, followed by the kidney, pancreas, and heart...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550243/apomorphine-therapy-for-neuronal-insulin-resistance-in-a-mouse-model-of-alzheimer-s-disease
#10
Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T Yanagihara, Kyoko M Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun-Ichi Kira
Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550196/il-6-signaling-regulates-small-intestinal-crypt-homeostasis
#11
Victoria Jeffery, Andrew J Goldson, Jack R Dainty, Marcello Chieppa, Anastasia Sobolewski
Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550161/lymphoid-differentiation-of-hematopoietic-stem-cells-requires-efficient-cxcr4-desensitization
#12
Christelle Freitas, Monika Wittner, Julie Nguyen, Vincent Rondeau, Vincent Biajoux, Marie-Laure Aknin, Françoise Gaudin, Sarah Beaussant-Cohen, Yves Bertrand, Christine Bellanné-Chantelot, Jean Donadieu, Françoise Bachelerie, Marion Espéli, Ali Dalloul, Fawzia Louache, Karl Balabanian
The CXCL12/CXCR4 signaling exerts a dominant role in promoting hematopoietic stem and progenitor cell (HSPC) retention and quiescence in bone marrow. Gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor have been reported in the WHIM Syndrome (WS), a rare immunodeficiency characterized by lymphopenia. The mechanisms underpinning this remain obscure. Using a mouse model with a naturally occurring WS-linked gain-of-function Cxcr4 mutation, we explored the possibility that the lymphopenia in WS arises from defects at the HSPC level...
May 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28550087/transcriptional-networks-in-rodent-models-support-a-role-for-gut-brain-communication-in-neurogenic-hypertension-a-review-of-the-evidence
#13
Jasenka Zubcevic, Ashley Baker, Christopher J Martyniuk
Hypertension (HTN) is the most prevalent condition observed in primary health care. Hypertension shows complex etiology, and neuroinflammation, overactive sympathetic drive, and the microbiome are associated with the disease. To obtain mechanistic perspective into neurogenic HTN, we first constructed a framework for transcriptional regulators of the disease using the Comparative Toxicogenomics Database. This approach yielded a core group of 178 transcripts that are prevalent in HTN, including leptin and neuropeptide Y...
May 26, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28550083/normal-and-cancerous-tissues-release-extrachromosomal-circular-dna-eccdna-into-the-circulation
#14
Pankaj Kumar, Laura Dillon, Yoshiyuki Shibata, Amir A Jazaeri, David R Jones, Anindya Dutta
Cell-free circulating linear DNA is being explored for non-invasive diagnosis and management of tumors and fetuses, the so-called liquid biopsy. Previously, we observed the presence of small extrachromosomal circular DNA (eccDNA), called microDNA, in the nuclei of mammalian tissues and cell lines. Now, we demonstrate that cell-free microDNA derived from uniquely mapping regions of the genome is detectable in plasma and serum from both mice and humans and that they are significantly longer (30-60% >250 bases) than cell-free circulating linear DNA (~150 bases)...
May 26, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28550051/pd-1-expression-on-tams-suppresses-tumor-cell-phagocytosis
#15
(no author information available yet)
PD-1/PD-L1 blockade increases TAM phagocytosis of tumor cells to extend survival in mouse cancer models.
May 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28550049/recovery-of-ethanol-induced-akkermansia-muciniphila-depletion-ameliorates-alcoholic-liver-disease
#16
Christoph Grander, Timon E Adolph, Verena Wieser, Patrick Lowe, Laura Wrzosek, Benedek Gyongyosi, Doyle V Ward, Felix Grabherr, Romana R Gerner, Alexandra Pfister, Barbara Enrich, Dragos Ciocan, Sophie Macheiner, Lisa Mayr, Matthias Drach, Patrizia Moser, Alexander R Moschen, Gabriel Perlemuter, Gyongyi Szabo, Anne Marie Cassard, Herbert Tilg
OBJECTIVE: Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD. DESIGN: The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A...
May 26, 2017: Gut
https://www.readbyqxmd.com/read/28550041/central-nervous-system-involvement-in-acute-lymphoblastic-leukemia-is-mediated-by-vascular-endothelial-growth-factor
#17
Vera Münch, Luca Trentin, Julia Herzig, Salih Demir, Felix Seyfried, Johann M Kraus, Hans A Kestler, Rolf Köhler, Thomas F E Barth, Geertruy Te Kronnie, Klaus-Michael Debatin, Lüder H Meyer
In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite non-detectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse free survival indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia cell entry into the CNS need to be understood in order to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28550040/kras-g12d-expression-in-lung-resident-myeloid-cells-promotes-pulmonary-lch-like-neoplasm-sensitive-to-statin-treatment
#18
Tamihiro Kamata, Susan Giblett, Catrin Pritchard
Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/ERK signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulmonary, but not in non-pulmonary, LCH cases, suggesting organ-specific contribution of oncogenic RAS to LCH pathogenesis. Using a mouse model expressing KRAS(G12D) in the lung by nasal delivery of adenoviral Cre, here we show that KRAS(G12D) expression in lung-resident myeloid cells induces pulmonary LCH-like neoplasms comprised of pathogenic CD11c(high)F4/80+CD207+ cells...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28550015/statistical-methods-for-latent-class-quantitative-trait-loci-mapping
#19
Shuyun Ye, Rhonda Bacher, Mark P Keller, Alan D Attie, Christina Kendziorski
Identifying the genetic basis of complex traits is an important problem with the potential to impact a broad range of biological endeavors. A number of effective statistical methods are available for quantitative trait loci (QTL) mapping that allow for the efficient identification of multiple, potentially interacting, loci under a variety of experimental conditions. Although proven useful in hundreds of studies, the majority of these methods assume a single model common to each subject and consequently sacrifice power and accuracy when genetically distinct subclasses exist...
May 26, 2017: Genetics
https://www.readbyqxmd.com/read/28549991/pancreatic-derived-factor-impaired-glucagon-like-peptide-1-production-from-glutag-enterendorine-l-cell-line-and-intestines
#20
Fenghua Lai, Yan Chen, Huimei Lin, Xuelan Wang, Xiaonan Zhu, Yanbing Li, Haipeng Xiao, Xiaopei Cao
PURPOSE: Pancreatic-derived factor (PANDER) is a pancreatic islet-specific cytokine that co-secretes with insulin. However, its biological function remains largely unknown. We have recently shown that the intestine might be its novel target tissue. The aim of this study was to clarify whether PANDER impacts the production of glucagon-like peptide-1 (GLP-1). METHODS: We treated GLUTag cells from the mouse intestine L cell line with recombinant PANDER protein and hepatic overexpression of PANDER in an obese murine model...
May 23, 2017: Molecular and Cellular Endocrinology
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